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science.scientific_papers_summarization_single_doc_arxiv | science.scientific_papers_summarization_single_doc_arxiv.192442 | [
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"content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\neven though the presence of dark matter has been firmly established in recent years , the nature of the dark matter particle remains an outstanding problem in particle physics .\nthe idea that the dark matter particle may perhaps be detected indirectly via the detection of potential annihilation products is promising .\none particularly interesting aspect of indirect demodulation is the detection of @xmath0-rays from dark matter annihilations because it will be readily tested with the _ gamma - ray large area telescope _ ( glast ) in the next few years .\nthe presence of sub solar mass subhalos ( microhalos ) in the milky way can be probed by searching for the proper motion of @xmath0-rays emitted from dark matter annihilations @xcite .\nsuch a detection is of profound importance .\nfirst and foremost , it will be a detection of dark matter .\nin addition , it will provide information on the survival rate of microhalos in the solar neighborhood , and will place bounds on the mass of the dark matter particle , its annihilation cross section and its kinetic decoupling temperature @xcite .\nin the cold dark matter ( cdm ) paradigm , the first bound structures form at high redshifts .\nthe minimum mass is set by the rms dark matter particle velocities dictated at kinetic decoupling at a temperature @xmath1 @xcite .\nfor the particular case of supersymmetric ( susy ) dark matter , this scale is @xmath2 @xcite .\nthe abundance of microhalos in the solar neighborhood is still under debate @xcite . as such\n, it can be paremetrized by assuming that a certain fraction of the local dark matter density ( @xmath3 ) is in microhalos in a logarithmic mass interval @xcite , @xmath4 in this parameterization , @xmath5 takes the maximum value of @xmath6 when all of the local dark matter density is in objects in the logarithmic interval @xmath7 .\nwe can get an estimate on the range of values it may take by considering the subhalo mass function of dark matter halos .\nthe subhalo mass function has been studied in numerical simulations and found to be described by @xmath8 , normalized in a way such that for a milky way size halo , 10% of the mass of the halo is in subhalos of mass greater than @xmath9 .\npreliminary results from n - body simulations @xcite , as well as approximate analytical arguments find that this mass function is preserved down to microhalo scales , with the exception that on sub solar mass scales the survival probability is reduced to only @xmath10$]% due to early rapid merging processes as well as potential interactions with stars @xcite . in this case\n, the value of @xmath5 as defined above reduces to @xmath11\n. a microhalo at a distance @xmath12 and with a velocity @xmath13 will exhibit a proper motion of magnitude @xmath14 $ ] in a time interval @xmath15 . given\na velocity distribution function @xmath16 ( assumed to be described by a maxwell - boltzmann , see @xcite ) , the number of microhalos with a proper motion greater than some threshold @xmath17 is then given by @xmath18 \\\n, dv \\ , dd.\\ ] ] here , @xmath19 $ ] , and @xmath20 is the maximum distance at which a microhalo is detectable ( see next section ) . the expected flux of @xmath0-rays from a microhalo of mass @xmath7 at a distance @xmath12 depends on the annihilation cross section @xmath21 and mass @xmath22 of the dark matter particle , the density profile of the microhalo , as well as the redshift at which the microhalo collapsed , @xmath23 . assuming an navarro - frenk - white profile @xcite and a spectrum given in @xcite the number of photons per unit area and time with energy greater than @xmath24 can be written as : @xmath25\n[ cols=\"^,^ \" , ] in order to detect the proper motion of microhalos that may be present in the solar neighborhood , it is necessary to survey the whole sky in the @xmath0-ray part of the spectrum .\nthis is where glast is ideal in performing a search for the proper motion of nearby microhalos .\nglast will survey the whole sky with an integral sensitivity of @xmath26 for photons with energy above a few gev .\nassuming an effective area of @xmath27 , and an exposure time of 10 years ( assuming the sky will be exposed uniformly for @xmath28 seconds per year based on the orbit configuration of the spacecraft @xcite ) , the sensitivity threshold for glast is @xmath29 photons .\nthe left panel of fig .\n1 shows the number of photons expected from microhalos as a function of distance for the same effective area and exposure time as mentioned above . for this particular example\n, the mass of the dark matter particle was assumed to be @xmath30 , with an annihilation cross - section of @xmath31 .\nthis particular choice of parameters represents an optimistic scenario for supersymmetric dark matter . the shaded area in fig .\n1 shows the radius of the volume needed in order to enclose at least 1 microhalo for different values of the parameter @xmath5 .\nthe lower limit comes from assuming that @xmath32 , while the upper bound corresponds to @xmath33 . as can be gleaned from fig .\n1 , within reasonable distance ( e.g. within the shaded area ) , the number of photons on earth in a 10 year exposure is between 100 - 1000 for microhalos with masses @xmath34 .\nthis number is well above the sensitivity threshold for glast , suggesting that glast will be able to perform a search for microhalos in the solar neighborhood .\nif the fraction of the local dark matter density in microhalos of mass less than @xmath35 is more than 0.2% , then there should be at least one microhalo potentially detectable with glast at a high signal - to - noise ratio .\nthe dot - dashed lines show the distance where the maximum proper motion is greater or equal to 1 & 9 arcminutes .\nthe single photon angular resolution of glast is better than @xmath36 arcminutes for photons of energy above few gev .\nhowever , the localization of a source which emits @xmath37 photons is improved by a factor of @xmath38 , thus placing a proper motion threshold of detection of @xmath39 .\nthe solid line shows the threshold at which microhalos will be resolved as extended objects in glast ( assuming a psf of 9 arcminutes ) . in this case , the prospects for proper motion detection are much better because the excess photon flux from adjacent resolution bins in extended objects could be used to better localize the position of the source @xcite .\nthe right panel of fig .\n1 shows the number of microhalos per logarithmic mass interval that will be detectable based on the integral sensitivity of glast as a function of microhalo mass and the particle physics properties of the dark matter particle . here , @xmath40 , and the quantity @xmath41 is left as a free parameter ( where @xmath42 de $ ] ) .\nthe particular case of an optimistic choice of parameters for supersymmetric dark matter is shown with the dashed line .\nhowever , it should be emphasized that the quantity @xmath43 can attain higher values than the optimistic case of supersymmetry , e.g. kaluza klein dark matter @xcite .\nthe solid lines represent iso - number contours of the number of microhalos detected that will also exhibit proper motion greater than @xmath17 .\nsuch a detection can place constraints on the properties of the dark matter particle .\nmore specifically , the detection of at least 1 microhalo with proper motion places a bound on the mass of the lightest supersymmetric particle to be less than 600 gev , and its kinetic decoupling temperature to be @xmath44 { \\rm mev}$ ] ( see @xcite for more details on the range of values of @xmath1 for supersymmetric dark matter ) .\nthe potential detection of microhalos in the solar neighborhood has profound consequences in our understanding of the nature of the dark matter particle .\nit is therefore essential that glast includes a search for proper motion of @xmath0-rays in the data analysis .\nsuch an analysis can benefit significantly if the lifetime of glast is maximized , thus increasing the baseline for proper motion detection .",
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"content": "i discuss the prospects for detecting the dark matter via the proper motion of sub solar mass dark matter halos in the vicinity of the solar neighbourhood . \n microhalos that survive tidal disruption could exhibit proper motion of order few arcminutes per year . \n for dark matter particles that couple to photons , such as the lightest supersymmetric or kaluza - klein particles , microhalos could be detected via their @xmath0-ray photon emission from annihilations . \n a detection of proper motion of a microhalo in the @xmath0-ray part of the spectrum contains not only information about the particle physics properties of the dark matter particle , but also provides an insight into hierarchical structure formation at very early times . \n address = theoretical division & isr division , los alamos national laboratory , los alamos , nm 87545 , usa",
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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.13469 | [
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"content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Flexible resonance in prefrontal networks with strong feedback inhibition\nContent:\nAbstract:\nOscillations are ubiquitous features of brain dynamics that undergo task-related changes in synchrony, power, and frequency. The impact of those changes on target networks is poorly understood. In this work, we used a biophysically detailed model of prefrontal cortex( PFC) to explore the effects of varying the spike rate, synchrony, and waveform of strong oscillatory inputs on the behavior of cortical networks driven by them. Interacting populations of excitatory and inhibitory neurons with strong feedback inhibition are inhibition-based network oscillators that exhibit resonance( i. e., larger responses to preferred input frequencies). We quantified network responses in terms of mean firing rates and the population frequency of network oscillation; and characterized their behavior in terms of the natural response to asynchronous input and the resonant response to oscillatory inputs. We show that strong feedback inhibition causes the PFC to generate internal( natural) oscillations in the beta/gamma frequency range( >15 Hz) and to maximize principal cell spiking in response to external oscillations at slightly higher frequencies. Importantly, we found that the fastest oscillation frequency that can be relayed by the network maximizes local inhibition and is equal to a frequency even higher than that which maximizes the firing rate of excitatory cells; we call this phenomenon population frequency resonance. This form of resonance is shown to determine the optimal driving frequency for suppressing responses to asynchronous activity. Lastly, we demonstrate that the natural and resonant frequencies can be tuned by changes in neuronal excitability, the duration of feedback inhibition, and dynamic properties of the input. Our results predict that PFC networks are tuned for generating and selectively responding to beta- and gamma-rhythmic signals due to the natural and resonant properties of inhibition-based oscillators. They also suggest strategies for optimizing transcranial stimulation and using oscillatory networks in neuromorphic engineering.\nIntroduction:\nOscillatory neural activity is a common feature of brain dynamics. In vitro experiments have demonstrated that different brain regions can produce network oscillations at different frequencies[1, 2]. In vivo experiments have shown that field potential oscillations in prefrontal cortex( PFC) at beta-( 15-35Hz) and gamma-( 35-80Hz) frequencies undergo task-related modulations in their power[3] and synchrony[4] and that multiple frequencies can appear in the same region[5, 6]. Despite the wealth of experimental evidence suggesting changes in oscillation frequency and synchrony are functionally significant, little remains known about the mechanisms by which they affect processing in downstream networks( but see[7]). In this paper, we will explore the natural, resonant, and competitive dynamics of PFC networks and how the task-modulated properties of oscillatory signals affect those dynamics. Neural systems at multiple spatial scales are known to exhibit larger responses to oscillatory inputs at preferred( resonant) frequencies. For instance, neurons can exhibit resonance in subthreshold voltage fluctuations[8, 9], and networks can exhibit resonance in the amplitude of suprathreshold instantaneous firing rates of self-inhibiting interneurons( INs)[10] and reciprocally connected populations of principal cells( PCs) and INs[11]. Given weak inputs, these systems often exhibit response amplitudes that scale linearly with the input, and they oscillate with the same frequency as the input. In the linear regime, analytical methods can be applied to fully characterize network responses[11]. However, the results of such analyses no longer hold when inputs are strong and responses become strongly nonlinear. Neural models of fast network oscillations, like those observed in PFC, often involve populations of cells receiving strong feedback inhibition to synchronize the network and strong excitatory input to drive the oscillation[6]. Under a constant( possibly noisy) tonic input, self-inhibiting populations of INs and reciprocally connected PC and IN populations can generate( natural) gamma-frequency network oscillations, termed ING[1, 12] and PING[12, 13], respectively. Due to the strong input and oscillatory response to a tonic drive, the earlier work on network resonance does not extend to these inhibition-based oscillators. In this article, we present a numerical study of the natural and resonant behavior of an inhibition-based PC/IN network oscillator. In contrast to the linear regime, we will show that the frequency of the network oscillation equals the input up to a maximal frequency, above which, it decreases; we call this phenomenon population frequency resonance. We will show that different input frequencies maximize inhibition and excitation when inputs are strong and that the population frequency peaks when inhibition is maximized. The importance of this phenomenon will be demonstrated by showing that the optimal driving frequency for suppressing responses to asynchronous input is that which maximizes population frequency and not that which maximizes the firing rate of excitatory PCs. Finally, we will show how network resonance depends on dynamic, task-modulated properties of the input as well as intrinsic properties of the resonant network. Our quantitative results identify mechanisms that are not model specific, as will be shown by analogous simulations in a Hodgkin-Huxley type model of PFC and a generic integrate-and-fire network model that exhibit qualitatively similar behavior. The paper will begin with a characterization of network responses to asynchronous and oscillatory inputs. Responses will be characterized in terms of firing rate and population frequency, and then the latter will be shown to determine the maximal suppression of asynchronous activity. The dependence of response on experimentally-motivated input parameters will be described. Finally, the paper will end with a discussion of the functional relevance of these findings for flexible neural processing.\nDiscussion:\nResonance phenomena have been studied in neural systems at multiple scales. Peaks in the single neuron membrane potential response to subthreshold oscillatory inputs have been studied in terms of the interplay between intrinsic ion currents[9]; their ability to influence spiking has been demonstrated in single neurons[42]; and relationships between subthreshold resonance and the natural network frequency of electrically coupled excitatory cells have been shown[43]. Our PC model, in isolation, exhibits subthreshold resonance at delta frequencies( 2Hz)( S1A Fig) that translates into an input strength-independent spiking resonance at the same frequency for suprathreshold inputs( S1B and S1C Fig). The addition of strong feedback inhibition suppresses the spiking response to delta-frequency inputs while a higher-frequency, input strength-dependent spiking resonance emerges in response to strong inputs( S1D Fig). We have explored this higher-frequency resonance in this work and shown how it depends on the strength of input( S1Ei and S1Eii Fig) and the time constant of feedback inhibition( S1Eiii Fig). The mechanism that determines the precise value of f R P C in the inhibition-based PC/IN oscillator is not fully understood. Insight into the locking of an inhibition-based IN network oscillator to periodic drive with heterogeneous phases has been obtained using a timing map[18]; a similar analysis might provide insight in the present case of a PC/IN network locking preferentially to a particular periodic drive with heterogeneous spike times but is beyond the scope of this work. The work in[18] and our results suggest the value of f R P C is related to the number of PC spikes that are necessary to engage INs on a given cycle. Changing the network size while keeping the synaptic strengths constant did not affect f R P C( compare Fig 2Bi to S4 Fig). This is in contrast to work showing that resonant frequency in a network model of Wilson-Cowan oscillators depended strongly on network size[44]. Further work is needed to understand the differences between resonances in spiking versus activity-based networks.[11] showed that strong feedback inhibition is required for firing rate resonance in integrate-and-fire networks of excitatory and inhibitory cells driven by sinusoidal inputs; they also showed that stronger inputs increase resonant frequencies. We have reproduced these qualitative findings in a more detailed network model and extended the results by showing how firing rate resonance relates to the natural and peak oscillation frequencies in the strong-input regime, and how they all depend on other properties of the oscillatory input( i. e., waveform and spike synchrony). Compared to the integrate-and-fire networks( S3 Fig), the prefrontal network exhibited lower natural and resonant frequencies.[45] showed that heterogeneity of PC intrinsic properties in a PC/IN network produces a range of resonant frequencies that supports combining, instead of selecting, inputs. In contrast, our PC population is homogeneous, and the network produces more selective responses favoring outputs with fpop-resonant inputs. See Methods for a comparison of output measures used in this and other studies of spiking resonance.[46] investigated the response of an inhibition-paced IN population to physiologically-relevant periodic pulse inputs, but their work did not include PC cells or examine resonance. The model investigated in this work made the following simplifications: no NMDA synapses, usage of all-to-all connectivity between PCs and INs, no PC-to-PC or IN-to-IN connectivity, and the lack of noise driving INs. Preliminary simulations demonstrated that probabilistic connectivity, weak noise, and weak NMDA synapses did not disrupt the results. For strong noise to INs, additional IN-to-IN feedback inhibition is necessary to synchronize the IN population. Furthermore, IN-to-IN and PC-to-PC connectivity have been shown to modulate resonant frequencies[36]. We suspect the main requirement for our results to hold is that the network is in a regime that produces a natural oscillation in response to an asynchronous input to the PCs( i. e., external noise to INs must be weak enough, feedback inhibition strong enough, and PC-to-IN drives strong and fast enough for a fraction of spiking PC cells to control IN activity from cycle to cycle). Another important limitation of the present work pertains to the role of modulatory intrinsic currents. We have focused on regimes where PCs are roughly regular spiking and INs are fast spiking. More work is needed to understand how the dynamics reported here would be affected by PCs that are intrinsically bursting( as observed in deep layers of cortex and thalamus) and INs exhibiting low-threshold spiking. Furthermore, our account of the effects of knocking out modulatory currents is limited to effects on overall activity levels across the PC population. In contrast, work by[47] shows that modulatory currents can impact the cycle-to-cycle probability of individual cells participating in the population rhythm. The work reported here has introduced a distinction between time-averaged firing rate resonance in excitatory PCs and inhibitory INs that arises when inputs are strong. We have also introduced a new form of network resonance observed in strongly-driven inhibition-based PC/IN oscillators, called population frequency resonance that depends on firing rate resonance in INs; and demonstrated its importance for suppressing responses to asynchronous activity. These results have also made a significant contribution to understanding how PC/IN networks with strong feedback inhibition are affected by task-modulated changes in oscillatory inputs, in general, and why beta rhythms are so frequently associated with prefrontal activity.",
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"content": "The prefrontal cortex ( PFC ) flexibly encodes task-relevant representations and outputs biases to mediate higher cognitive functions . The relevant neural ensembles undergo task-related changes in oscillatory dynamics at beta- and gamma frequencies . Using a computational model of the PFC network , we show that strong feedback inhibition causes the PFC to generate internal oscillations and to prefer external oscillations at similar frequencies . The precise frequencies that are generated and preferred can be flexibly tuned by varying the synchrony and strength of input network activity , the level of background excitation , and neuromodulation of intrinsic ion currents . We also show that the peak output frequency in response to external oscillations , which depends on the synchrony and strength of the input as well as the strong inhibitory feedback , is faster than the internally generated frequency , and that this difference enables exclusive response to oscillatory inputs . These properties enable changes in oscillatory dynamics to govern the selective processing and gating of task-relevant signals in service of cognitive control .",
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science.craftchem_ner | science.craftchem_ner.1886 | [
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"content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nTheDNApelletwaswashedin70%EtOHandresuspendedin100-150mulTEbuffer.",
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"content": "[\"EtOH\"]",
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science.craftchem_ner | science.craftchem_ner.3996 | [
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"content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nInsurveyingthetissuesofthePGC-1alpha-/-mice,structuralabnormalitiesofthebrainwereobserved.",
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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.3038 | [
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"content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Genetic Analysis of a Novel Tubulin Mutation That Redirects Synaptic Vesicle Targeting and Causes Neurite Degeneration in C. elegans\nContent:\nAbstract:\nNeuronal cargos are differentially targeted to either axons or dendrites, and this polarized cargo targeting critically depends on the interaction between microtubules and molecular motors. From a forward mutagenesis screen, we identified a gain-of-function mutation in the C. elegans α-tubulin gene mec-12 that triggered synaptic vesicle mistargeting, neurite swelling and neurodegeneration in the touch receptor neurons. This missense mutation replaced an absolutely conserved glycine in the H12 helix with glutamic acid, resulting in increased negative charges at the C-terminus of α-tubulin. Synaptic vesicle mistargeting in the mutant neurons was suppressed by reducing dynein function, suggesting that aberrantly high dynein activity mistargeted synaptic vesicles. We demonstrated that dynein showed preference towards binding mutant microtubules over wild-type in microtubule sedimentation assay. By contrast, neurite swelling and neurodegeneration were independent of dynein and could be ameliorated by genetic paralysis of the animal. This suggests that mutant microtubules render the neurons susceptible to recurrent mechanical stress induced by muscle activity, which is consistent with the observation that microtubule network was disorganized under electron microscopy. Our work provides insights into how microtubule-dynein interaction instructs synaptic vesicle targeting and the importance of microtubule in the maintenance of neuronal structures against constant mechanical stress.\nIntroduction:\nMicrotubule and molecular motors mediate polarized transport of neuronal proteins to either axons or dendrites[1]. Microtubules are oriented uniformly with their plus ends towards the distal end of the axon, which facilitates kinesin-dependent targeting of presynaptic proteins[2]. By contrast, targeting of postsynaptic molecules to the dendrite, such as glutamate receptors, requires the minus end-oriented dynein motors[3], consistent with the fact that many microtubules in the dendrites orient the minus end distally[4]. Mislocalization of presynaptic proteins to the dendrite occurs when this polarized pattern of axon-dendritic microtubule arrays is disrupted[5],[6], when kinesin function is compromised[7],[8], or when dynein activity is inadvertently increased[3],[7],[8]. Synaptic vesicle( SV) precursors are generated in the neuronal cell body and transported to the synapses by the unidirectional motor Kinesin 3/KIF1A[1]. On the other hand, the dynein motor complex mediates retrograde SV transport in the axon[1],[9]. Since SVs are cargos for both KIF1A and dynein, it is intriguing that they are exclusively targeted to the axon and prevented from entering the dendrites. Previous biochemical and structural studies suggest that kinesin and dynein share an overlapping binding region at the C-terminus of α-tubulin[10]. The N-terminus of the H12 helix of the α-tubulin contains a stretch of absolutely conserved acidic residues( 414EEGE, equivalent to 415EEGE in the yeast α-tubulin) and interacts with ATP-bound KIF1A[11]. A recent study on dynein structures also implicates this region in the interaction between microtubule and the microtubule-binding domain( MTBD) of dynein[12], although validation of this model in the context of in vivo, eukaryotic system is still lacking. Mutations of any of the three glutamic acids in the yeast α-tubulin to alanine dramatically reduced the frequency of kinesin binding to the microtubules[13]. Mutations of several conserved, acidic residues in the H12 helix of β-tubulin( E410, E412, D417) to alanine similarly reduced microtubule affinity for kinesins. Interestingly, E410K, D417H and D417N in the human β-tubulin TUBB3, among other point mutations, had been found in patients with congenital neurological syndrome with ophthalmoparesis and peripheral neuropathy[14]. In particular, TUBB3( E410K) and TUBB3( D417H), but not other disease-related TUBB3 mutations, were shown to impair the bindings of Kinesin 1/KIF5, Kinesin 3/KIF1A and KIF21 when expressed in cultured mammalian neurons[15]. The interaction between dynein and microtubule was not affected by these TUBB3 mutants[15]. These studies established the critical importance of negative charge in the H12 helix of the α- and β-tubulins in mediating microtubule-kinesin interaction, but the molecular mechanisms governing microtubule-dynein interaction and its physiological significance remain unexplored. Here we describe a novel mutation of G416 in the α-tubulin MEC-12 of C. elegans to glutamic acid( G416E). Homologous mutations at this site of α-tubulin had not been reported in human diseases or tested in genetic model organisms. In C. elegans, mec-12 is highly expressed in the six touch receptor neurons that detect gentle mechanical stimulation on the worm cuticle[16],[17]. MEC-12 and the touch neuron-specific β-tubulin MEC-7 are required to form the unusual, 15-protofilament giant microtubules in these neurons[16]. These giant microtubules had been implicated in the transduction of mechanosensation, although the mechanisms remain enigmatic[18]. We show that this gain-of-function G416E mutation redirects SVs to non-axon compartment in the C. elegans mechanosensory neuron PLM, and it does so by increasing microtubule affinity for dynein.\nDiscussion:\nIn the present study, we characterized a gain-of-function mec-12/tubulin mutant that displayed synaptic vesicle mistargeting and neurite swelling phenotypes, which were absent in the mec-12 null mutant. In this mutant, single amino acid substitution augments microtubule-dynein interaction, thereby mistargeting synaptic vesicles to non-axon compartments. This observation extends previous structural studies on the charged cluster of the α-tubulin H12 helix and provides a biological context for such charge-based coupling between microtubule and dynein. The neurite swelling and degeneration phenotypes could bear important implications for human neurological diseases associated with missense tubulin mutations, as discussed below. Previous structural studies suggest that dynein binds the H12 helix of α-tubulin, and the interaction between dynein and microtubule is not as strong as that between kinesins and microtubule[10],[12]. One advantage for this suboptimal dynein-microtubule affinity is flexibility and dynamic range for dynein processivity on the microtubule scaffolds. The hypothesis that dynein-microtubule interaction is not optimized also suggests that it is possible to further enhance dynein-microtubule affinity by mutating residues at this interface. Here, we show that this is indeed the case: by increasing negative charges of the α-tubulin H12 helix or augmenting positive charges of the dynein MTBD, microtubule-dynein interaction was strengthened. More importantly, we show that this aberrantly high affinity of microtubule for dynein redistributed synaptic vesicles to ectopic compartments in the neurons. We speculate that the suboptimal affinity of microtubule for dynein prevents initial SV entry into the dendrite, yet allows for retrograde SV transport within the axon. The G416E mutation of MEC-12 increased microtubule affinity for dynein probably at the expense of dynein processivity: we found that motility of the mistargeted SVs in the PLM posterior process was profoundly compromised( Figure 1J). Consistent with this view, Redwine et al. showed that E3378K mutation of MTBD caused about 40% reduction in the velocity of dynein movements on microtubules. By contrast, none of the G416 substitutions restored the UNC-104/KIF1A-dependent, anterograde SV transport in the mec-12( e1607) null mutant. This is also consistent with the observation by Redwine et al. that microtubule-kinesin interaction was molecularly optimized, therefore changes to the tubulin residues at the microtubule-kinesin interface will only compromise but not compensate for or even further improve this interaction. Rather than merely serving as a track, mounting evidence indicates that microtubules play an active role in directing axon transport[2]. One such example is the various posttranslational modifications on microtubules, which regulate axon transport by restricting different kinesin motors to discrete subcellular compartments[31],[32]. The intrinsic organization of microtubule is another critical factor regulating polarized axon transport. UNC-33 and UNC-44, the C. elegans homologs for the Collapsin Response Mediator Protein 2( CRMP2) and neuronal ankyrin, respectively[33],[34], regulate axon transport by maintaining uniform microtubule polarity in the axon and the dendrite[5]. In C. elegans head neurons, microtubules are uniformly oriented with their minus-ends towards the distal of the dendrite. In the unc-33 and the unc-44 mutants, dendritic microtubules showed mixed polarity, which resulted in aberrant sorting of axonal proteins into the dendrite[5]. In these mutants, the dendritic localization of SVs requires UNC-104. Of note, mistargeting of axonal proteins in the unc-33 and unc-44 mutants occurred to the SVs and multiple active zone components. By contrast, SYD-2 was not mistargeted in the mec-12( gm379) mutant, and we found that SV transport in the touch neurons was not affected in unc-33 and unc-44 mutants. These observations indicate that while perturbation to the gross architecture of microtubule causes extensive mistargeting of multiple axonal cargos, changes at a restricted, yet functionally critical site of microtubule could lead to targeting defects of specific axonal proteins. Many tubulin mutations associated with human diseases are point mutations that alter protein function rather than eliminating protein products[35]–[37]. Mutant tubulins are still incorporated into microtubule polymers; phenotypes presumably arise from altered microtubule dynamics or disrupted interactions with molecular motors or microtubule-associated proteins[14],[15],[38]. The G416E mutation of MEC-12 caused extensive neurite swellings that eventually led to degeneration of the touch neurons. Ultrastructurally, there were unbundling of microtubules and accumulation of mitochondria at focal neurite swellings. Interestingly, these neurite defects were independent of dynein activity, but could be suppressed by genetic paralysis of locomotion. In light of two recent studies that showed touch neurite buckling or swelling when unc-70/β-spectrin or mec-17/tubulin acetyltransferase was mutated[21],[22], this suggests that microtubules confer resistance of touch neurites to deformation imposed by constant muscle activity. When this structural resilience is compromised, touch neurons are likely to degenerate presumably in a wear-and-tear fashion induced by the animal's constant movements. Supporting this notion, commissural axons in unc-70 mutants also increasingly break as the animals grow and move, and paralysis of the animals prevents axon interruption[39]. Unlike the mec-17 mutant, in which defective tubulin acetylation was associated with abnormal microtubule protofilament number, tubulin acetylation and microtubule protofilaments were unaffected in the mec-12( gm379) mutant. We hypothesize that the G416E substitution may alter the association of microtubule-binding proteins with microtubules, changing the stability or structure of microtubule lattice and rendering the neurites susceptible to mechanical strain. It would be interesting to test whether any of the tubulin mutations found in human diseases generates similar axon defects and could also be ameliorated by reduced activity of neighboring musculature. The molecular mechanism by which G416E mutant microtubules cause axon degeneration awaits future investigation.",
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"content": "Axons and dendrites are two classes of neuronal process that differ in their functions and molecular compositions . Proteins important for synaptic functions are mostly synthesized in the cell body and sorted differentially into the axon or dendrites . Microtubules in the axon and dendrite maintain their structural integrity and regulate polarized protein transport into these compartments . We identified a novel α-tubulin mutation in C . elegans that caused mistargeting of synaptic vesicles and induced progressive neurite swelling , which resulted in late-onset neurodegeneration . We showed that this tubulin mutation weakened microtubule network and abnormally increased microtubule affinity for dynein , a motor protein responsible for cargo sorting to the dendrite . This enhanced microtubule-dynein affinity is due to augmented negative charge at the carboxyl terminus of α-tubulin . Neurite swelling and neurodegeneration could be ameliorated by reduced physical activity , suggesting that recurrent mechanical strain from muscle contraction jeopardized neurite integrity in the long run . Mutations in α- and β-tubulins are found in human neurological diseases; our findings therefore contribute to understanding the pathogenic mechanism of human neurological diseases associated with tubulin mutations .",
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science.bc7_litcovid_topic_classification | science.bc7_litcovid_topic_classification.2975 | [
{
"content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nBACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging serious global health problem. Gastrointestinal symptoms are common in COVID-19 patients, and SARS-CoV-2 RNA has been detected in stool specimens. However, the relationship between the gut microbiome and disease remains to be established. METHODS: We conducted a cross-sectional study of 30 COVID-19 patients, 24 influenza A (H1N1) patients, and 30 matched healthy controls (HC) to identify differences in the gut microbiota by 16S ribosomal RNA (rRNA) gene V3-V4 region sequencing. RESULTS: Compared with HC, COVID-19 patients had significantly reduced bacterial diversity, a significantly higher relative abundance of opportunistic pathogens, such as Streptococcus, Rothia, Veillonella and Actinomyces, and a lower relative abundance of beneficial symbionts. Five biomarkers showed high accuracy for distinguishing COVID-19 patients from HC with an area under the curve (AUC) up to 0.89. Patients with H1N1 displayed lower diversity and different overall microbial composition compared with COVID-19 patients. Seven biomarkers were selected to distinguish the two cohorts with an AUC of 0.94. CONCLUSION: The gut microbial signature of patients with COVID-19 was different from that of H1N1 patients and HC. Our study suggests the potential value of the gut microbiota as a diagnostic biomarker and therapeutic target for COVID-19, but further validation is needed.",
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"content": "[\"Diagnosis\", \"Treatment\"]",
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science.craftchem_ner | science.craftchem_ner.339 | [
{
"content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nTheeyesofCBA/CaJandBALB/cJmicewerealsofixedandprocessedforplasticembedding(Historesin,Leica,Heidelberg,Germany),andsectionedaspreviouslyreported[14,79].",
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science.chemprot_ner | science.chemprot_ner.846 | [
{
"content": "Analyze the following text to identify specific entities. Focus on the categories provided: [\"Chemical\", \"Protein\"].\n\nDeliver your findings as a JSON structure: {\"Chemical\": [\"ExampleChemical\", ...], \"Protein\": [\"ExampleProtein\", ...]}. Each key represents an entity type, and the associated list contains the entities found. \n\nEnsure the response is strictly the JSON format without any extra text.\n\nSource:\n\nSubstrates of IAP ubiquitin ligases identified with a designed orthogonal E3 ligase, the NEDDylator.\nInhibitors of Apoptosis Protein (IAPs) are guardian ubiquitin ligases that keep classic proapoptotic proteins in check. Systematic identification of additional IAP substrates is challenged by the heterogeneity and sheer number of ubiquitinated proteins (>5,000). Here we report a powerful catalytic tagging tool, the NEDDylator, which fuses a NEDD8 E2-conjugating enzyme, Ubc12, to the ubiquitin ligase, XIAP or cIAP1. This permits transfer of the rare ubiquitin homolog NEDD8 to the ubiquitin E3 substrates, allowing them to be efficiently purified for LC-MS/MS identification. We have identified >50 potential IAP substrates of both cytosolic and mitochondrial origin that bear hallmark N-terminal IAP binding motifs. These substrates include the recently discovered protein phosphatase PGAM5, which we show is proteolytically processed, accumulates in cytosol during apoptosis, and sensitizes cells to death. These studies reveal mechanisms and antagonistic partners for specific IAPs, and provide a powerful technology for labeling binding partners in transient protein-protein complexes.",
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"content": "{\"Chemical\": [\"N\"], \"Protein\": [\"ubiquitin E3\", \"NEDD8\", \"ubiquitin\", \"E2-conjugating enzyme\", \"ubiquitin ligases\", \"IAP\", \"PGAM5\", \"Ubc12\", \"protein phosphatase\", \"ubiquitin ligase\", \"IAPs\", \"E3 ligase\", \"Inhibitors of Apoptosis Protein\", \"XIAP\", \"cIAP1\"]}",
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science.covid_deepset_qa | science.covid_deepset_qa.115 | [
{
"content": "Analyze the following excerpt from a biomedical text. Identify the relevant information needed to respond to the inquiry. Provide only the necessary details in your answer.\n\nContext: The risk of developing at least one of the major sequelae was estimated as 6% after an ambulatory pneumonia event and 14% after an episode of hospitalized pneumonia. Because respiratory diseases affect almost 1 billion people globally and are a major cause of mortality and morbidity [10] , childhood pneumonia might contribute to substantial morbidity across the life course. Chest radiologic changes have been considered the gold standard for defining a pneumonia event [11] because clinical findings can be subjective and clinical definitions of pneumonia can be nonspecific. In 2005, to aid in defining outcomes of pneumococcal vaccine studies, the World Health Organization's (WHO) standardized chest radiograph description defined a group of children who were considered most likely to have pneumococcal pneumonia [12] . The term \"end-point consolidation\" was described as a dense or fluffy opacity that occupies a portion or whole of a lobe, or the entire lung. \"Other infiltrate\" included linear and patchy densities, peribronchial thickening, minor patchy infiltrates that are not of sufficient magnitude to constitute primary end-point consolidation, and small areas of atelectasis that in children can be difficult to distinguish from consolidation. \"Primary end-point pneumonia\" included either end-point consolidation or a pleural effusion associated with a pulmonary parenchymal infiltrate (including \"other\" infiltrate). Widespread use of pneumococcal conjugate vaccination and Haemophilus influenzae type B conjugate vaccination has decreased the incidence of radiologic pneumonia. In a review of four randomized controlled trials and two case-control studies of Haemophilus influenzae type B conjugate vaccination in high-burden communities, the vaccination was associated with an 18% decrease in radiologic pneumonia [13] . Introduction of pneumococcal conjugate vaccination was associated with a 26% decrease in radiologic pneumonia in California between 1995 and 1998 [14] . In vaccine efficacy trials in low-and middle-income countries, pneumococcal conjugate vaccination reduced radiologic pneumonia by 37% in the Gambia [15] , 25% in South Africa [16] and 26% in the Philippines [17] . The WHO radiologic case definition was not intended to distinguish bacterial from viral etiology but rather to define a sub-set of pneumonia cases in which pneumococcal infection was considered more likely and to provide a set of standardized definitions through which researchers could achieve broad agreement in reporting chest radiographs. However, despite widespread field utilization, there are concerns regarding inter-observer repeatability. There has been good consensus for the description of lobar consolidation but significant disagreement on the description of patchy and perihilar infiltrates [18, 19] . In addition, many children with clinically severe lung disease do not have primary end-point pneumonia: in one pre-pneumococcal conjugate vaccination study, only 34% of children hospitalized with pneumonia had primary end-point pneumonia [20] . A revised case definition of \"presumed bacterial pneumonia\" has been introduced, and this definition includes pneumonia cases with WHO-defined alveolar consolidation, as well as those with other abnormal chest radiograph infiltrates and a serum C-reactive protein of at least 40 mg/L [21, 22] . This definition has been shown to have greater sensitivity than the original WHO radiologic definition of primary end-point pneumonia for detecting the burden of pneumonia prevented by pneumococcal conjugate vaccination [23] . Using the revised definition, the 10-valent pneumococcal conjugate vaccine (pneumococcal conjugate vaccination-10), had a vaccine efficacy of 22% in preventing presumed bacterial pneumonia in young children in South America [22] , and pneumococcal conjugate vaccination-13 had a vaccine efficacy of 39% in preventing presumed bacterial pneumonia in children older than 16 weeks who were not infected with human immunodeficiency virus (HIV) in South Africa [21] . Thus there is convincing evidence that pneumococcal conjugate vaccination decreases the incidence of radiologic pneumonia; however there is no evidence to suggest that pneumococcal conjugate vaccination modifies the radiologic appearance of pneumococcal pneumonia. Empyema is a rare complication of pneumonia. An increased incidence of empyema in children was noted in some high-income countries following pneumococcal conjugate vaccination-7 introduction, and this was attributed to pneumococcal serotypes not included in pneumococcal conjugate vaccination-7, especially 3 and 19A [24] . In the United States, evidence from a national hospital database suggests that the incidence of empyema increased 1.9-fold between 1996 and 2008 [25] . In Australia, the incidence rate ratio increased by 1.4 times when comparing the pre-pneumococcal conjugate vaccination-7 period (1998 to 2004) to the post-pneumococcal conjugate vaccination-7 period (2005 to 2010) [26] . In Scotland, incidence of empyema in children rose from 6.5 per million between 1981 and 1998, to 66 per million in 2005 [27] . These trends have been reversed since the introduction of pneumococcal conjugate vaccination-13. Data from the United States suggest that empyema decreased by 50% in children younger than 5 years [28] ; similarly, data from the United Kingdom and Scotland showed substantial reduction in pediatric empyema following pneumococcal conjugate vaccination-13 introduction [29, 30] . Several national guidelines from high-income countries, as well as the WHO recommendations for low-and middleincome countries, recommend that chest radiography should not be routinely performed in children with ambulatory pneumonia [31] [32] [33] . Indications for chest radiography include hospitalization, severe hypoxemia or respiratory distress, failed initial antibiotic therapy, or suspicion for other diseases (tuberculosis, inhaled foreign body) or complications. However, point-of-care lung ultrasound is emerging as a promising modality for diagnosing childhood pneumonia [34] . In addition to the effect on radiologic pneumonia, pneumococcal conjugate vaccination reduces the risk of hospitalization from viral-associated pneumonia, probably by reducing bacterial-viral co-infections resulting in severe disease and hospitalization [35] . An analysis of ecological and observational studies of pneumonia incidence in different age groups soon after introduction of pneumococcal conjugate vaccination-7 in Canada, Italy, Australia, Poland and the United States showed decreases in all-cause pneumonia hospitalizations ranging from 15% to 65% [36] . In the United States after pneumococcal conjugate vaccination-13 replaced pneumococcal conjugate vaccination-7, there was a further 17% decrease in hospitalizations for pneumonia among children eligible for the vaccination, and a further 12% decrease among unvaccinated adults [28] . A systematic review of etiology studies prior to availability of new conjugate vaccines confirmed S. pneumoniae and H. influenzae type B as the most important bacterial causes of pneumonia, with Staphylococcus aureus and Klebsiella pneumoniae associated with some severe cases. Respiratory syncytial virus was the leading viral cause, identified in 15-40% of pneumonia cases, followed by influenza A and B, parainfluenza, human metapneumovirus and adenovirus [37] . More recent meta-analyses of etiology data suggest a changing pathogen profile, with increasing recognition that clinical pneumonia is caused by the sequential or concurrent interaction of more than one organism. Severe disease in particular is often caused by multiple pathogens. With high coverage of pneumococcal conjugate vaccination and Haemophilus influenzae type B conjugate vaccination, viral pathogens increasingly predominate [38] . In recent case-control studies, at least one virus was detected in 87% of clinical pneumonia cases in South Africa [39] , while viruses were detected in 81% of radiologic pneumonia cases in Sweden [40] . In a large multi-center study in the United States, viral pathogens were detected in 73% of children hospitalized with radiologic pneumonia, while bacteria were detected in only 15% of cases [41] . A meta-analysis of 23 case-control studies of viral etiology in radiologically confirmed pneumonia in children, completed up to 2014, reported good evidence of causal attribution for respiratory syncytial virus, influenza, metapneumovirus and parainfluenza virus [42] . However there was no consistent evidence that many other commonly described viruses, including rhinovirus, adenovirus, bocavirus and coronavirus, were more commonly isolated from cases than from controls. Further attribution of bacterial etiology is difficult because it is often not possible to distinguish colonizing from pathogenic bacteria when they are isolated from nasal specimens [43] . Another etiology is pertussis. In the last decade there has also been a resurgence in pertussis cases, especially in highincome countries [44] . Because pertussis immunity after acellular pertussis vaccination is less long-lasting than immunity after wild-type infection or whole-cell vaccination, many women of child-bearing age have waning pertussis antibody levels. Their infants might therefore be born with low transplacental anti-pertussis immunoglobulin G levels, making them susceptible to pertussis infection before completion of the primary vaccination series [45] . In 2014, more than 40,000 pertussis cases were reported to the Centers for Disease Control and Prevention in the United States; in some states, population-based incidence rates are higher than at any time in the last 70 years [44] . In contrast, most low-and middleincome countries use whole-cell pertussis vaccines and the numbers of pertussis cases in those countries were stable or decreasing until 2015 [46] . However recent evidence from South Africa (where the acellular vaccine is used) shows an appreciable incidence of pertussis among infants presenting with acute pneumonia: 2% of clinical pneumonia cases among infants enrolled in a birth cohort were caused by pertussis [39] , and 3.7% of infants and young children presenting to a tertiary academic hospital had evidence of pertussis infection [47] . Similarly, childhood tuberculosis is a major cause of morbidity and mortality in many low-and middle-income countries, and Mycobacterium tuberculosis has increasingly been recognized as a pathogen in acute pneumonia in children living in high tuberculosis-prevalence settings. Postmortem studies of children dying from acute respiratory illness have commonly reported M. tuberculosis [48, 49] . A recent systematic review of tuberculosis as a comorbidity of childhood pneumonia reported culture-confirmed disease in about 8% of cases [50] . Because intrathoracic tuberculosis disease is only culture-confirmed in a minority of cases, the true burden could be even higher; tuberculosis could therefore be an important contributor to childhood pneumonia incidence and mortality in high-prevalence areas. Childhood pneumonia and clinically severe disease result from a complex interaction of host and environmental risk factors [37] . Because of the effectiveness of pneumococcal conjugate vaccination and Haemophilus influenzae type B conjugate vaccination for prevention of radiologic and clinical pneumonia, incomplete or inadequate vaccination must be considered as a major preventable risk factor for childhood pneumonia. Other risk factors include low birth weight, which is associated with 3.2 times increased odds of severe pneumonia in low-and middle-income countries, and 1.8 times increased odds in high-income countries [51] . Similarly, lack of exclusive breastfeeding for the first 4 months of life increases odds of severe pneumonia by 2.7 times in low-and middle-income countries and 1.3 times in highincome countries. Markers of undernutrition are strong risk factors for pneumonia in low-and middle-income countries only, with highly significant odds ratios for underweight for age (4.5), stunting (2.6) and wasting (2.8) . Household crowding has uniform risk, with odds ratios between 1.9 and 2.3 in both low-and middle-income countries and high-income countries. Indoor air pollution from use of solid or biomass fuels increases odds of pneumonia by 1.6 times; lack of measles vaccination by the end of the first year of age increases odds of pneumonia by 1.8 times [51] . It is estimated that the prevalence of these critical risk factors in low-and middle-income countries decreased by 25% between 2000 and 2010, contributing to reductions in pneumonia incidence and mortality in low-and middle-income countries, even in countries where conjugate vaccines have not been available [3] . The single strongest risk factor for pneumonia is HIV infection, which is especially prevalent in children in sub-Saharan Africa. HIV-infected children have 6 times increased odds of developing severe pneumonia or of death compared to HIV-uninfected children [52] . Since the effective prevention of mother-to-child transmission of HIV, there is a growing population of HIV-exposed children who are uninfected; their excess risk of pneumonia, compared to HIV unexposed children, has been described as 1.3-to 3.4-fold higher [53] [54] [55] [56] [57] . The pneumococcal conjugate vaccination and Haemophilus influenzae type B conjugate vaccination have been effective tools to decrease pneumonia incidence, severity and mortality [58, 59] . However, equitable coverage and access to vaccines remains sub-optimal. By the end of 2015, Haemophilus influenzae type B conjugate vaccination had been introduced in 73 countries, with global coverage estimated at 68%. However, inequities are still apparent among regions: in the Americas coverage is estimated at 90%, while in the Western Pacific it is only 25%. By 2015, pneumococcal conjugate vaccination had been introduced into 54 countries, with global coverage of 35% for three doses of pneumococcal conjugate vaccination for infant populations [60] . To address this issue, the WHO's Global Vaccine Access Plan initiative was launched to make life-saving vaccines more equitably available.\n\nInquiry: What is responsible for the reduction of radiologic pneumonia?",
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"content": "Widespread use of pneumococcal conjugate vaccination and Haemophilus influenzae type B conjugate vaccination has decreased the incidence of radiologic pneumonia.",
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science.bc7_litcovid_topic_classification | science.bc7_litcovid_topic_classification.4556 | [
{
"content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nBACKGROUNDT cell responses to the common cold coronaviruses have not been well characterized. Preexisting T cell immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported, and a recent study suggested that this immunity was due to cross-recognition of the novel coronavirus by T cells specific for the common cold coronaviruses.METHODSWe used the enzyme-linked immunospot (ELISPOT) assay to characterize the T cell responses against peptide pools derived from the spike protein of 3 common cold coronaviruses (HCoV-229E, HCoV-NL63, and HCoV-OC43) and SARS-CoV-2 in 21 healthy donors (HDs) who were seronegative for SARS-CoV-2 and had no known exposure to the virus. An in vitro expansion culture assay was also used to analyze memory T cell responses.RESULTSWe found responses to the spike protein of the 3 common cold coronaviruses in many of the donors. We then focused on HCoV-NL63 and detected broad T cell responses to the spike protein and identified 22 targeted peptides. Interestingly, only 1 study participant had a significant response to SARS-CoV-2 spike or nucleocapsid protein in the ELISPOT assay. In vitro expansion studies suggested that T cells specific for the HCoV-NL63 spike protein in this individual could also recognize SARS-CoV-2 spike protein peptide pools.CONCLUSIONHDs have circulating T cells specific for the spike proteins of HCoV-NL63, HCoV-229E, and HCoV-OC43. T cell responses to SARS-CoV-2 spike and nucleocapsid proteins were present in only 1 participant and were potentially the result of cross-recognition by T cells specific for the common cold coronaviruses. Further studies are needed to determine whether this cross-recognition influences coronavirus disease 2019 (COVID-19) outcomes.",
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{
"content": "[\"Mechanism\", \"Treatment\"]",
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science.scitldr_aic | science.scitldr_aic.1440 | [
{
"content": "Review the provided sections from a computer science paper and distill the primary contribution into a single sentence. Provide only the summary sentence.\n\nSections:\n\nSearch space is a key consideration for neural architecture search.\nRecently, Xie et al. (2019a) found that randomly generated networks from the same distribution perform similarly, which suggest we should search for random graph distributions instead of graphs.\nWe propose graphon as a new search space.\nA graphon is the limit of Cauchy sequence of graphs and a scale-free probabilistic distribution, from which graphs of different number of vertices can be drawn.\nThis property enables us to perform NAS using fast, low-capacity models and scale the found models up when necessary.\nWe develop an algorithm for NAS in the space of graphons and empirically demonstrate that it can find stage-wise graphs that outperform DenseNet and other baselines on ImageNet.\nNeural architecture search (NAS) aims to automate the discovery of neural architectures with high performance and low cost.\nOf primary concern to NAS is the design of the search space [23] , which needs to balance multiple considerations.\nFor instance, too small a space would exclude many good solutions, whereas a space that is too large would be prohibitively expensive to search through.\nAn ideal space should have a one-to-one mapping to solutions and sufficiently smooth in order to accelerate the search.\nA common technique [37, 17, 35, 19, 24, 34] to keep the search space manageable is to search for a small cell structure, typically containing about 10 operations with 1-2 input sources each.\nWhen needed, identical cells are stacked to form a large network.\nThis technique allows cells found on, for instance, CIFAR-10 to work on ImageNet.\nThough this practice is effective, it cannot be used to optimize the overall network structure.\nIn both manual and automatic network design, the overall network structure is commonly divided into several stages, where one stage operates on one spatial resolution and contains several nearidentical layers or multi-layer structures (i.e., cells).\nFor example, ResNet-34 [11] contains 4 stages with 6, 8, 12 , and 6 convolutional layers, respectively.\nDenseNet-121 [12] contains 4 stages with 6, 12, 24, and 16 two-layer cells.\nAmoebaNet-A [24] has 3 stages, within each 6 cells are arranged sequentially.\nAmong cells in the same stage, most connections are sequential with skip connections occasionally used.\nAs an exception, DenseNet introduces connections between every pairs of cells within the same stage.\nHere we emphasize the difference between a stage and a cell.\nA cell typically contains about 10 operations, each taking input from 1-2 other operations.\nIn comparison, a stage can contain 60 or more operations organized in repeated patterns and the connections can be arbitrary.\nA network usually contains only 3-4 stages but many more cells.\nIn this paper, we focus on the network organization at the level of stage rather than cell.\n[32] recently showed that the stage structure can be sampled from probabilistic distributions of graphs, including Erdős-Rényi (ER) (1960), Watts-Strogatz (WS) (1998), and Barabási-Albert (BA) (1999), yielding high-performing networks with low in-group variance.\nThis finding suggests the random graph distribution, rather than the exact graph, is the main causal factor behind network performance.\nThus, searching for the graph is likely not as efficient as searching for the random (c) m0 = m = 100, n = 1000 Figure 1 : Three adjacency matrices of graphs generated by the Barabási-Albert model with m = m 0 = 0.1n.\nA black dot at location (i, j) denotes an edge from node i to node j.\nThe sequence of matrices converges to its limit, the graphon, as n → ∞.\nFigure 2: Graphons for common random graph models.\nDifferent shades denote different probabilities (e.g., p and 1 − p).\nThe Erdős-Rényi model has two parameters: number of nodes n and probability p.\nThe Watts-Strogatz (WS) model has three parameters: number of nodes n, replacement probability p, and initial neighborhood width k.\nTechnically, the WS model has a constant number of edges, violating exchangeability for random graphs; graphs sampled from (b) converges in probability to the same number of edges as n increases.\ngraph distribution.\nThe parameter space of random graph distributions may appear to be a good search space.\nWe propose a different search space, the space of graphons [20] , and argue for its superiority as an NAS search space.\nFormally introduced in Section 3, a graphon is a measurable function defined on [0, 1] 2 → [0, 1] and a probabilistic distribution from which graphs can be drawn.\nGraphons are limit objects of Cauchy sequences of finite graphs under the cut distance metric.\nFigure 1 visualizes three adjacency matrices randomly generated by the Barabási-Albert (BA) model with increasing numbers of nodes.\nIt is easy to see that, as the number of nodes increases, the sequence of random graphs converges to its limit, a graphon.\nThe BA model starts with an initial seed graph with m 0 nodes and arbitrary interconnections.\nHere we choose a complete graph as the seed.\nIt sequentially adds new nodes until there are n nodes in the graph.\nFor every new node v new , m edges are added, with the probability of adding an edge between v new and the node v i being proportional to the degree of v i .\nIn Figure 1 , we let m = m 0 = 0.1n.\nThe fact that different parameterization results in the same adjacency matrix suggests that directly searching in the parameter space will revisit the same configuration and is less efficient than searching in the graphon space.\nAdditionally, graphon provides a unified and more expressive space than common random graph models.\nFigure 2 illustrates the graphons for the WS and the ER models.\nWe can observe that these random models only capture a small proportion of all possible graphons.\nThe graphon space allows new possibilities such as interpolation or striped combination of different random graph models.\nFinally, graphon is scale-free, so we should be able to sample an arbitrary-sized stage-wise architecture with identical layers (or cells) from a graphon.\nThis allows us to perform expensive NAS on small datasets (e.g., CIFAR-10) using low-capacity models and obtain large stage-wise graphs to build large models.\nBy relating graphon theory to NAS, we provide theoretically motivated techniques that scale up stage-wise graphs, which are shown to be effective in practice.\nOur experiments aim to fairly compare the stage-wise graphs found by our method against DenseNet and the WS random graph model by keeping other network structures and other hyperparameters constant.\nThe results indicate that the graphs found outperform the baselines consistently across a range of model capacities.\nThe contribution of this paper revolves around building a solid connection between theory and practice.\nMore specifically,\n• We propose graphon, a generalization of random graphs, as a search space for stage-wise neural architecture that consists of connections among mostly identical units.\n• We develop an operationalization of the theory on graphon in the representation, scaling and search of neural stage-wise graphs that perform well in fair comparisons.\nWe attribute the performance differences to the stage-wise graphs, since we have strictly applied the same setting, including the global network structure, the cell structure, and hyperparameter settings.\nThe first conclusion we draw is the effectiveness of the theoretically motivated scaling technique for graphon.\nWe scaled up the 11-node graph found by the search to graphs with up to 64 nodes in the experiments.\nWe also scaled the WS(4, 0.25) network, initially defined for 32 nodes in [32] , to 64 nodes in the DenseNet-264 group.\nThe experiments show that after scaling, the relative rankings of these methods are maintained, suggesting that the proposed scaling technique incurs no performance loss.\nSecond, we observe the standard deviations for most methods are low, even though they edge a bit higher for ImageNet V2 where model selection has been carried out.\nThis is consistent with the findings of [32] and reaffirms that searching for random graphs is a valid approach for NAS.\nFinally, we emphasize that these results are created for the purpose of fair comparisons and not for showcasing the best possible performance.\nOur goal is to show that the graphon space and the associated cut distance metric provide a feasible approach for NAS and the empirical evidences support our argument.\nThe design of search space is of paramount importance for neural architecture search.\nRecent work [32] suggests that searching for random graph distributions is an effective strategy for the organization of layers within one stage.\nInspired by mathematical theories on graph limits, we propose a new search space based on graphons, which are the limits of Cauchy sequences of graphs based on the cut distance metric.\nThe contribution of this paper is the operationalization of the graphon theory as practical NAS solutions.\nFirst, we intuitively explain why graphon is a superior search space than the parameter space of random graph models such as the Erdős-Rényi model.\nFurthermore, we propose a technique for scaling up random graphs found by NAS to arbitrary size and present a theoretical analysis under the cut distance metric associated with graphon.\nFinally, we describe an operational algorithm that finds stage-wise graphs that outperform manually designed DenseNet as well as randomly wired architectures in [32] .\nAlthough we find neural architectures with good performance, we remind the reader that absolute performance is not the goal of this paper.\nFuture work involves expanding the work to different operators in the same stage graph.\nThis can be achieved, for example, in the same manner that digraphon accommodates different types of connections.\nWe contend that the results achieved in this paper should not be considered an upper bound, but only the beginning, of what can be achieved.\nWe believe this work opens the door toward advanced NAS algorithms in the space of graphon and the cut distance metric.\nA The DenseNet network contains a stem network before the first stage, which contains a 3 × 3 convolution, batch normalization, ReLU and max-pooling.\nThis is followed by three stages for CIFAR-10 and four stages for ImageNet.\nBetween every two stages, there is a transition block containing a 1×1 convolution for channel reduction and a 2 × 2 average pool with stride 2 for downsampling.\nThe network ends with a 7 × 7 global average pooling and a linear layer before a softmax.\nFigure 4 shows the cell structure for DenseNet, which contains two convolutions with different kernel size: 1 × 1 and 3 × 3.\nEach of the two convolutions are immediately preceded by a batch normalization and ReLU.\nEvery cell in the same stage outputs c channels.\nThe input to the n th cell is the concatenation of outputs from the cell 1 to cell n − 1, for a total of c(n − 1) channels.\nAs every cell increments the number of input channels by c, it is called the growth rate.\nTheorem 5 shows the k-fold blow-up method is a better approximation of the original graph in terms of the cut distance δ than the 1D linear interpolation.\nBut the exact k-fold blow-up is only applicable when k is an integer.\nIf a graph of size n + m(0 < m < n) is desired, we need to resort to the fractional blow-up method, which has been analyzed in Theorems 3 and 4.\nWe show that when m is 1 or n − 1, this partial blowup operation does not cause δ to change more than O(β ∆ /n).\nHowever, when m is n/2, δ between the original graph and the new graph could be up to β ∆ /6.\nThis suggests that the fractional upsampling results in a graph that is similar to the original when only a small number of nodes (relative to n) is added.",
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"content": "Graphon is a good search space for neural architecture search and empirically produces good networks.",
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science.covid_deepset_qa | science.covid_deepset_qa.782 | [
{
"content": "Analyze the following excerpt from a biomedical text. Identify the relevant information needed to respond to the inquiry. Provide only the necessary details in your answer.\n\nContext: SARS to novel coronavirus – old lessons and new lessons\n\nhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026896/\n\nSHA: 5d254ed178c092d 3 6 9ce70ae965 59 acc471f9\n\nAuthors: McCloskey, Brian; Heymann, David L.\nDate: 2020-02-05\nDOI: 10.1017/s0950268820000254\nLicense: cc-by\n\nAbstract: The response to the novel coronavirus outbreak in China suggests that many of the lessons from the 200 SARS epidemic have been implemented and the response improved as a consequence. Nevertheless some questions remain and not all lessons have been successful. The national and international response demonstrates the complex link between public health, science and politics when an outbreak threatens to impact on global economies and reputations. The unprecedented measures implemented in China are a bold attempt to control the outbreak – we need to understand their effectiveness to balance costs and benefits for similar events in the future. Text: On 29 December 2019 clinicians in a hospital in Wuhan City, China noticed a clustering of cases of unusual pneumonia (with the first case identified at that time on 12 December) with an apparent link to a market that sells live fish, poultry and animals to the public. This event was reported to the World Health Organisation (WHO) on 1 December [1]. Within 4 weeks, by 26 January 2020, the causative organism had been identified as a novel coronavirus, the genome of the virus had been sequenced and published, reverse transcription polymerase chain reaction tests had been developed, the WHO R&D Blueprint had been activated to accelerate diagnostics, therapeutics and vaccine development and a candidate vaccine was ready for initial laboratory testing. Currently Chinese health authorities are building a 1000 bed hospital in Wuhan in 10 days. By 26 January also, almost 50 million people in Wuhan and neighbouring cities had effectively been placed in quarantine while the WHO had determined that the event should not yet be declared as a Public Health Emergency of International Concern (PHEIC) [2] and had recommended no specific travel restrictions. The WHO have emphasised the importance of exit screening at ports in countries showing transmission of the novel coronavirus and have provided guidance for countries implementing entry screening at airports while acknowledging that evidence for the effectiveness of entry screening is equivocal. This response is one of the swiftest, coordinated global responses to an emerging infectious disease the world has seen in modern times, but is it the appropriate response, will it be effective and is it sustainable? According to the situation report published by the WHO on 28 January 2020 [ ], a total of 2798 confirmed 2019-nCoV cases have been reported globally; of these, 2761 cases were from China, including Hong Kong (8 cases), Macau (5) and Taipei (4). Thirty-seven confirmed cases have been reported outside of China in eleven countries in Europe, North America, Australia and Asia; of these 7 exported cases, 6 had a travel history from China or an epidemiological link to a case from China. Of the confirmed cases in China, 461 have been reported as severely ill, with 80 deaths to date. This outbreak and the response to it illustrate some key issues about how global preparedness and response capacity for outbreaks have evolved over almost two decades since the severe acute respiratory syndrome (SARS) epidemic of 2002/ and what lessons have, or have not, been learned. It also raises questions about the impact these lessons have had on the way agencies and governments respond to these events and about the role of the WHO and the International Health Regulations (IHR). One of the critical lessons from the SARS experience was the absolute necessity to be able to coordinate the international resources that are available in an outbreak and to get them focussed on identifying priorities and solving problems. The WHO established the means to do this for SARS and it has since been further developed and integrated into global preparedness, especially after the West Africa Ebola epidemic. Organisations such as the Global Outbreak Alert and Response Network (GOARN), the Coalition for Epidemic Preparedness Innovations (CEPI), the Global Research Collaboration For Infectious Disease Preparedness (GloPID-R) and the Global Initiative on Sharing All Influenza Data (GISAID) have been supported by the WHO Research Blueprint and its Global Coordinating Mechanism to provide a forum where those with the expertise and capacity to contribute to managing new threats can come together both between and during outbreaks to develop innovative solutions to emerging problems. This global coordination has been active in the novel coronavirus outbreak. WHO's response system includes three virtual groups based on those developed for SARS to collate real time information to inform real time guidelines, and a first candidate vaccine is ready for laboratory testing within 4 weeks of the virus being identified. Another key factor in successfully preventing and managing emerging threats is the rapid and transparent sharing of information between countries and agencies. There was extensive criticism of China for its perceived failure to share information about the emerging SARS infection early enough in the outbreak to allow countries to prepare and respond. There were similar concerns about information sharing as Middle East Respiratory Syndrome (MERS) emerged and evolved in the Middle East in 2012, particularly in Saudi Arabia, and about the emergence of Ebola in West Africa in 2014. On this occasion information sharing seems to have been rapid and effective (while recognising that the information available in the early stages of an outbreak is always less than the global community would like). The WHO was notified of the original clustering within days and the full genomic sequence of the new virus was published less than 2 weeks after the cluster was first detected. The WHO has expressed its satisfaction with the actions of the Chinese authorities in sharing information with the WHO. Working with journalists and the media to help them understand the science and epidemiology, particularly in a fast moving event, will improve risk communication to the public and reduce inappropriate concerns and panic. While reporting of this outbreak shows signs of the efforts of epidemiologists, infectious disease experts, national and international public health agencies and others engaging with journalists, there are also signs that this is not yet achieving it's goal. For example, the public perception is that the increase in case numbers reported daily by the Chinese authorities represents a daily escalation in the epidemic while the reality is that these numbers are also the result of active, aggressive, case finding in China and some of these cases are 'old' cases newly recognised as being due to the novel coronavirus. Similarly the virus is usually described by the media as 'deadly' and although this is true in the sense that it has caused deaths, the nuances of uncertain case fatality rates in the early stages of an outbreak are not being communicated. The current estimated case fatality rate seems to be around % which is significant but not comparable to the 10% rate for SARS or 4% reported for MERS. These misperceptions are still driving public anxiety. To supplement formal reporting mechanisms between countries and with WHO (including the IHR), the use of informal mechanisms such as media and social media reports was advocated in the light of the SARS experience. There are now globally several systems that provide collated information from informal reporting including networks of experts and scanning of media and social media. These contribute to, and amplify, epidemic intelligence and are being integrated with national and international surveillance systems. The value, and the challenges, of this additional source of information has been evident in the current outbreak. The value comes from ensuring that early indications of cases beyond the initial outbreak city have been detected and can supplement the global risk assessment and monitoring of the evolution of the outbreak. The challenges lie in the volume and diversity of the information available and the relative lack of verification mechanisms, such that one of these systems (ProMed) has commented that it was becoming increasingly difficult to assimilate the information being supplied [4] and to make meaningful interpretations. Early in the outbreak it was reported that health workers had not been infected. This was reassuring because it is health workers who many times, and inadvertently, amplify transmission. Failure to wash hands between patients, for example, can result not only in autoinfection, but also in infection of patients hospitalised for other causes when they provide care. Autoinfection is not only a risk for the health worker, but also for their families and the communities in which they live, depending on the transmissibility and means of transmission. More recently infection, and at least one death, in health workers has been confirmed. Although not unexpected this does add to the epidemiological risk. A characteristic of the SARS outbreak was the variability of transmissibility between cases and the occurrence of 'superspreading events' where a case infected significantly more contacts than the average. This was also seen with MERS in the outbreak in the Republic of Korea (RoK). In this current novel coronavirus outbreak, such superspreading events have not been documented but the epidemiology is still not clear. Confirming whether or not this is happening must be an urgent task for the Chinese investigation. Modellers have suggested reproductive rates (R 0 ) of .8 (95% confidence interval, .6-4.0) [5] and 2.6 (1.5- .5) [6] ; R 0 for SARS was estimated at around in the absence of control measures [7] . The economic impact of major outbreaks can be substantial for the affected country. This was seen clearly in SARS, MERS in RoK and Ebola in West Africa. One analyst estimates that the current coronavirus outbreak's likely impact will range from a 0.8% cut to real GDP if the epidemic is controlled within months, to a 1.9% cost to GDP if the epidemic lasts 9 months [8] . This may increase substantially in the light of the extended restrictions on movement, and therefore trade and commerce, within China. The emergence of a significant respiratory illness linked to a novel coronavirus represents a test of the global capacity to detect and mange emerging disease threats. Its emergence in China adds an additional dimension in the light of previous experience with SARS. The timing of the outbreak immediately before the Chinese Lunar New Year with its attendant population movements adds extra risk and urgency to the response. The rapid sharing of information in this outbreak and the speed of the coordinated response both in the country and internationally suggest that lessons have been learned from SARS that improve global capacity. The international networks and forums that now exist have facilitated the bringing together of expertise from around the world to focus research and development efforts and maximise the impact. At this early stage in the outbreak information remains incomplete and key clinical and epidemiological questions have not yet been answered, but the deficit seems to be due more to the constraints of investigating an emerging disease than to any unwillingness to engage and share information with partners. There are some indications of areas where further improvement is necessary. The global media response to the unfolding events has been relatively balanced and informed but the nuances of the evolving situation have not been critically examined in partnership with the media and as a result the public perception of the risk may be exaggeratedalthough it of course remains possible that the outbreak will develop in a way that matches up to the perceived risk. The lack of appreciation of the uncertainties in determining a meaningful case fatality rate and the significance of ascertainment bias at the beginning of an outbreak, along with the impact of aggressive case finding on case numbers, are examples of where understanding could be improved. This is always a challenging process when balancing the resources focussed on analysing the situation on the ground with resources directed at interpreting the information for journalists but in SARS, the R 0 was seen to decrease in response to information reaching the public and the public then adopting risk reduction actions [6] ; so accurate public risk communication is critical to success. It would be helpful to find a forum where this can be explored with the media community after the event. The increase in access to early information from diverse sources including media and social media adds an important dimension to identifying and tracking new events globally and is a key part of the overall epidemic intelligence system. However, it is also a potential source of disinformation. When, as has been seen in this outbreak, the volume of information coming in exceeds any capacity to collate and analyse it and to attempt to cross-reference and verify separate items, there is a risk that the information fuels speculation and media and public concern. Again there is a fine balance between information that encourages appropriate risk avoidance actions and information that encourages inappropriate actions; however the public health is usually better served by more information rather than less. The role of a declaration of a PHEIC in managing a serious outbreak has been questioned in the light of Ebola in West Africa and in the Democratic Republic of Congo [9] and has been challenged again with this outbreak. The binary nature of a PHEIC declaration (either an event is a PHEIC or it isn'tthere are no intermediate options) and the specificity of the three defined criteria for a PHEIC have caused difficulty for Emergency Committees in considering whether a given event should be a PHEIC. The lack of a clear understanding of what a PHEIC declaration is meant to achieve adds to the Emergency Committee's difficulties, as does the relative paucity of clinical and epidemiological answers at this stage of the investigation. In this instance the Emergency Committee were divided in coming to a conclusion but decided on balance that the current situation, although an emergency, should not as yet be declared a PHEIC [2]. As with Ebola in the DRC, there has been criticism of the WHO for this decision but, as with Ebola, it is not immediately clear what would be different in the response if a PHEIC was declared. The WHO is working on improving the way in which Emergency Committees develop their advice for the Director General but, as recommended by this Emergency Committee and the post-Ebola IHR Review Committee in 2015, the development of an intermediate alert alongside WHO's risk assessment process may be helpful. A key function of a PHEIC declaration is that it is the (only) gateway to the WHO Temporary Recommendations on possible travel and trade restrictions to limit international spread of a disease. In this case several countries globally had already implemented entry screening at airports and China had begun closing down international travel from Wuhan before the Emergency Committee had finished their deliberations. While the WHO would not, and could not, interfere with the sovereign decisions of member states, the lack of influence on travel and trade decisions could prove problematic. Alongside the speed of the response in this outbreak, we have seen dramatic changes in the scale of the response. The imposition of very extensive quarantine measures on millions of people as an attempt to break the transmission of the virus is unprecedented. We do not know whether they will be effective; indeed we do not know how we will determine if they have been effectivewhat end point can we measure that will provide an answer to that question? If recent suggestions that people infected with this coronavirus may be infectious while incubating or asymptomatic, and the reports that up to 5 m people left Wuhan before the travel restrictions were imposed, are confirmed, the efficacy of these control measures will be more challenged. Given the likely impact on at least the Chinese economy and probably the global economy, it will be important to understand the role and the effectiveness of public health measures on this scale for the future. However, the imposition of these dramatic measures does also raise a wider question: if there is an impact from these measures, what other countries would (or could) implement such measures? Would other countries accept the self-imposed economic damage that China has accepted to try and contain this outbreak? Is it reasonable to consider that national governments would close down public transport into and out of London, New York or Paris in the week before Christmas even if it were shown to be an effective control measure? These decisions and questions cross the interface between public health, science and politics.\n\nInquiry: What was the R0 of SARS in absence of control measures?",
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"content": "3",
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science.data_reco_mcq_sc | science.data_reco_mcq_sc.1458 | [
{
"content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: I want to train a supervised model on images.\n\nKeywords: supervised learning images\n\nDataset Information:\nCIFAR-10: The CIFAR-10 dataset (Canadian Institute for Advanced Research, 10 classes) is a subset of the Tiny Images dataset and consists of 60000 32x32 color images. The images are labelled with one of 10 mutually exclusive classes: airplane, automobile (but not truck or pickup truck), bird, cat, deer, dog, frog, horse, ship, and truck (but not pickup truck).\nConvAI2: The ConvAI2 NeurIPS competition aimed at finding approaches to creating high-quality dialogue agents capable of meaningful open domain conversation. The ConvAI2 dataset for training models is based on the PERSONA-CHAT dataset.\nCLUECorpus2020: CLUECorpus2020 is a large-scale corpus that can be used directly for self-supervised learning such as pre-training of a language model, or language generation. It has 100G raw corpus with 35 billion Chinese characters, which is retrieved from Common Crawl.\nYouTube-8M: The YouTube-8M dataset is a large scale video dataset, which includes more than 7 million videos with 4716 classes labeled by the annotation system. The dataset consists of three parts: training set, validate set, and test set.\n\nAvailable Datasets: A: CIFAR-10 B: ConvAI2 C: CLUECorpus2020 D: YouTube-8M",
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"content": "CIFAR-10",
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.18566 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nDisruption of gingipain oligomerization into non-covalent cell-surface attached complexes\n\nContent Extracts:\n\n<p>Arguably, periodontitis is the most prevalent infection-driven chronic inflammatory disorder of mankind and Porphyromonas gingivalis is considered the pivotal aetiologic organism responsible for the development and progression of the disease (Albandar and Rams, 2002; Cobb et al., 2009). This anaerobic, asaccharolytic Gram-negative bacterium is well armed with virulence factors and the gingipain cysteine protease family plays a key role in P. gingivalis pathogenesis (Guo et al., 2010). Except for one laboratory strain of P. gingivalis (HG66) which secretes soluble gingipains, in all other strains, the gingipains are associated with the bacterial outer membrane (Potempa et al., 1995). While RgpB is a single chain protease (Mikolajczyk-Pawlinska et al., 1998), membrane-associated Kgp and RgpA are assembled into very large (>300 kDa), multifunctional (Tam et al. 2008, 2009; O'Brien-Simpson et al., 2009; Pathirana et al., 2008), non-covalent complexes composed of two individual unique protease domains (RgpAcat and Kgpcat) and several hemagglutinin-adhesin domains (RgpAHA1, KgpHA1, RgpAHA2, KgpHA2, RgpAHA3, and KgpHA3) (Bhogal et al., 1997) (Fig. 1). All domains are generated by limited proteolysis of a single, nascent polypeptide chain encoded by rgpA or kgp genes, with the hemagglutinin-adhesin (HA) domains being located in the C-terminal extension of the translation products of the two genes (Pike et al., 1994; Pavloff et al., 1995, 1997). In addition, some adhesin domains in the complexes are derived from HagA (Pathirana et al., 2006), a large protein encompassing up to 4 HA-domain repeats (Kozarov et al., 1998). With the exception of Lys-Pro peptide bond being cleaved downstream of the hemoglobin-binding domain (HA2), the initial proteolytic processing of other domains occurs at Arg-Xaa peptide bonds (Fig. 1). The initial cleavage is followed by progressive truncation of the C-terminus at Lys-Xaa sites by Kgp and removal of the resulting C-terminal Lys by surface located carboxypeptidase (Fig. 1) (Veith et al., 2002, 2004). Individual domains generated in this sequence of proteolytic events remain tightly associated via non-covalent, protein-protein interactions.</p><p>A conserved sequence (PVxNLT) present on the catalytic, HA1 and HA3 domains referred to as the adhesin-binding motif (ABM); was suggested to be responsible for oligomerization and assembly of multidomain complexes (Slakeski et al., 1998). To test this hypothesis, we have disrupted this motif in Kgpcat by insertion of hexahistidine residues or by mutation of six consecutive residues of ABM into histidine residues (Fig. 1). The accuracy of these genetic manipulations was confirmed by DNA resequencing of the entire kgp gene and secretion of gingipains by different mutants was characterized in comparison to the wild-type parental strain.</p><p>The kgp gene mutation had no effect on Rgp activity and subcellular distribution. In the mutants, the vast majority of Rgps are cell-associated as in the wild-type strain. However, ABM mutants produced approximately only one-third total Kgp activity of the parental strain and in stark contrast to the wild-type strain, this activity was found almost exclusively in a soluble form in the growth medium regardless of the age of the culture (Fig. 2). This decreased production of Kgp was not related to hindered gene expression since qRT-PCR analysis revealed the same level the kgp gene transcription in mutants and in the parental strain (data not shown). Since disintegration of bacteria by sonication did not release any additional Kgp activity, we assumed that lower level of Kgp activity produced by the ABM mutants is due to disturbed folding and impaired maturation of Kgp due to added hexahistidine motif. To assess this possibility, we have subjected the mutants to Western blot analysis.</p><p>In accordance with the cellular distribution of Kgp activity in the ABM mutants, a single band representing the Kgp catalytic domain (Kgpcat) was located exclusively in the media fraction but absent from cell extracts (Fig. 3A) in Western blot using Kgpcat-specific mAbs. Interestingly, cell extracts of P. gingivalis cultured only for 24h revealed the presence of additional weak but clear bands of molecular mass higher than the Kgpcat in the ABM mutants (Fig. 3B). The highest band (200 kDa) in ABM2 cell extract may represent a full-length proKgp while the others are proKgp-derived fragments containing Kgpcat. No such bands were found in the wild-type P. gingivalis regardless of the culture age. Therefore, the presence of intermediate forms of Kgp in cell extracts of ABM mutants suggests that indeed, a portion of mutated kgp translation products were misfolded and were inefficiently processed explaining why mutants produce less Kgp activity than the wild-type P. gingivalis strain. In concordance with unaffected Rgp activity and cellular distribution, mutations in Kgp had no effect on Rgps band patterns (Fig. 3C).</p><p>The partially processed Kgp was also detected in 24 h culture medium of ABM2 and ABM3 mutants (Fig. 3B). Western blots with anti-hexahistidine antibodies revealed strong immunoreactive bands only in the media from ABM1 and ABM3 mutants and barely visible band in the ABM2 mutant (Fig. 3D) arguing that proKgp polypeptide proteolytic processing occurs downstream of hexahistidine tag in the former two mutants and mostly within or upstream of the tag in the latter strain. Similarly, two higher molecular mass (60- and 70-kDa) forms of Kgp bearing the hexahistidine tags were detected in the media of ABM3 mutant cultured for 24h (Fig. 3E).</p><p>The presence of His-tags on Kgp secreted by ABM1 and ABM3 mutants allows for their affinity purification on Ni-Sepharose (Fig. 4A). Surprisingly, only a small fraction (6–7%) of the total Kgp activity was recovered from Ni-Sepharose after ABM1 and ABM3 media were applied onto Ni-chelating matrix. The bulk of Kgp was found unbound in the Ni-Sepharose flow-through fraction. Western blot analysis of bound and unbound Kgp forms separated on the affinity column clearly showed that the latter sample did not interact with anti-hexahistidine antibody (Fig. 4BC). The lack of interaction with anti-6His antibody and Ni-Sepharose was found to be due to the lack of hexahistidine motif as inferred from nanoL-ESI-MS/MS analysis of the unbound forms of Kgp. Tryptic-digests of Ni-Sepharose bound Kgp forms returned QIQVGEPHHHHHH and QIQVGEPSPYQPHHHHHH peptides in proteins produced by ABM1 and ABM3 mutants, respectively. In stark contrast, in the unbound Kgp variants from all three mutants, no peptides containing the hexahistidine motif were identified. Interestingly, peptides bearing mono- and/or dihistidine at the C-terminus (QIQVGEPH(H), QIQVGEPPSH(H) and QIQVGEPSPYQPH(H)) were found in unbound Kgp produced by ABM1, ABM2, and AMB3 mutants, respectively. In addition, peptides with tetrahistidine (QIQVGEPHHHH and QIQVGEPSPYQPHHHH) were also identified in unbound Kgp from the ABM1 and AMB3 mutants. Results of the nanoL-ESI-MS/MS analysis are in agreement with reactivity of these forms with polyclonal Abs reactive with tetra-, penta-and hexahistidine (Fig. 4B) but not with monoclonal Abs specific only for the hexahistidine tag (Fig. 4C).</p><p>All forms of Kgp obtained by affinity-chromatography and purified by ion-exchange and gel-filtration chromatography from Ni-Sepharose non-binding fraction were subjected to Edman degradation. Regardless which mutant the 50 kDa band was derived from, the same N-terminal sequence of the mature Kgp catalytic domain was found (DVYTDHGDLYNT). Conversely, no sequence was detected in the 60- and 70-kDa forms isolated from the ABM3 mutant, suggestive of a blocked N-terminus. Therefore, 50-, 60-, and 70-kDa protein bands were analysed by MS to verify protein identity. In tryptic digests of the 70 kDa band, peptides derived from the entire Kgp profragment and catalytic domain were identified. One hundred and ten N-terminal residues of the profragment were missing in the 60 kDa form. Finally, no peptides derived from the profragment were found in the 50 kDa form. Together, it is clear that Kgp isoforms purified from the ABM3 mutant media represent the Kgp catalytic domain alone (50 kDa), with intact (70 kDa) and truncated profragment (60 kDa). As shown by nearly identical Km and kcat values (Table 1), the soluble fully processed Kgpcat released by mutants have the same catalytic activity on Ac-Lys-pNA and Z-Lys-pNA synthetic substrates as the native 110 kDa Kgp purified from P. gingivalis HG66 growth medium, which is the full protein complex comprising of the catalytic and HA domains (Pike et al., 1994).</p><p>Presence of the profragment in the 70- and 60-kDa forms of Kgp prompted us to investigate if they are proteolytically active. To this end, affinity purified Kgp forms secreted by the ABM1, AMB2, and ABM3 mutants were treated with an active site probe, a biotinylated irreversible Kgp-specific inhibitor (Kato et al., 2005). In this reaction, only 50-and 60-kDa Kgp forms but not 70-kDa band (Fig. 4) were labelled arguing that the full length profragment exerts latency on Kgp activity.</p><p>The molecular weight of hexahistidine labelled or unlabelled 50 kDa forms derived from different ABM mutants is indistinguishable by SDS-PAGE but visibly lower than that of Kgpcat in wild-type P. gingivalis W83 (Fig. 3) or derived from the enzyme purified from the HG66 strain (Fig. 4). Along with similar Km and kcat values between the wild-type Kgp and the hexahistidine-inserted Kgp variants, it can be inferred that insertion of the tag into ABM interferes with a normal proteolytic processing but has no deleterious effect on folding of the Kgp catalytic domain. As indicated by the nanoL-ESI-MS/MS analysis of the purified Kgp forms, the aberrant promiscuous proteolysis apparently occurred at a number of sites directly after (Ni-Sepharose bound forms) and within the hexahistidine sequence (Ni-Sepharose unbound forms) (Fig. 1D). Generated in this way, C-terminally truncated Kgp variants have molecular weight indistinguishable one from the other in SDS-PAGE but clearly lower than that of wild-type Kgp since proteolysis occurred at least several residues upstream from the native cleavage site in the wild-type protein (Fig. 1). Subsequently, the major part of the oligomerization motif was lost and the Kgp catalytic domain was released into the medium together with the truncated or intact profragment. Apparently, the remaining N-terminal fragment of the oligomerization motif GEPSP and GEPSPYQP in ABM2 and ABM3, respectively, is insufficient to mediate oligomerization of the catalytic domain to the hemagglutinin/adhesin domains. Of note, the mode of association of the Kgp/RgpA complex on the P. gingivalis surface is unclear. Nevertheless, it can be hypothesized that glycosylated HA4 anchors the remaining domains to the outer membrane of the organism. The presence of the conservative C-terminal domain (CTD) essential for RgpB glycosylation and anchorage in the outer membrane (Nguyen et al., 2007) in RgpA and Kgp supports this hypothesis.</p><p>Cumulatively, we have confirmed the ABM role in oligomerization of the catalytic and HA domains of Kgp into the non-covalent complex. Alteration of the ABM leads to aberrant proteolysis at the junction between proKgpcat and HA1, resulting in secretion of the soluble catalytic domain. The mutated Kgps are truncated at the C-terminus in comparison to wild-type Kgp but with catalytic properties indistinguishable from the native, multidomain Kgpcat-HA complex. Purification of the Kgp catalytic domain alone opens the possibility to solve the crystal structure of this gingipain and investigate the role of HA domains in Kgp function as the major virulence factor of P. gingivalis.</p>",
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"content": "RgpA and Kgp gingipains are non-covalent complexes of endoprotease catalytic and hemagglutinin-adhesin domains on the surface of Porphyromonas gingivalis. A motif conserved in each domain has been suggested to function as an oligomerization motif. We tested this hypothesis by mutating motif residues to hexahistidine or insertion of hexahistidine tag to disrupt the motif within the Kgp catalytic domain. All modifications led to the secretion of entire Kgp activity into the growth media, predominantly in a form without functional His-tag. This confirmed the role of the conserved motif in correct posttranslational proteolytic processing and assembly of the multidomain complexes.",
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science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.4253 | [
{
"content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nMany security issues have come to the fore with the increasingly widespread adoption of Internet-of-Things (IoT) devices. The Mirai attack on Dyn DNS service, in which vulnerable IoT devices such as IP cameras, DVRs and routers were infected and used to propagate large-scale DDoS attacks, is one of the more prominent recent examples. IoT botnets, consisting of hundreds-of-thousands of bots, are currently present in-the-wild'' at least and are only expected to grow in the future, with the potential to cause significant network downtimes and financial losses to network companies. We propose, therefore, to build testbeds for evaluating IoT botnets and design suitable mitigation techniques against them. A DETERlab-based IoT botnet testbed is presented in this work. The testbed is built in a secure contained environment and includes ancillary services such as DHCP, DNS as well as botnet infrastructure including CnC and scanListen loading servers. Developing an IoT botnet testbed presented us with some unique challenges which are different from those encountered in non-IoT botnet testbeds and we highlight them in this paper. Further, we point out the important features of our testbed and illustrate some of its capabilities through experimental results.\n\nCited Works Summary:\n[1]: There is an urgent need for a pro-active approach to botnet detection and mitigation that will enable computer network defenders to characterize emerging and future botnet threats and design effective defense techniques before these threats materialize. To this end, we have developed a System for Live Investigation of Next Generation bots (SLINGbot). SLINGbot is an extensible, composable bot framework that enables researchers to construct benign bots for the purposes of generating and characterizing botnet Command and Control (C2) traffic. This enables researchers to simulate current and potential future botnet traffic, characterize it, and design effective defense techniques. In this paper, we describe the SLINGbot system and how it can be used for the pro-active development of botnet defenses.\n\n[2]: An in-depth understanding of botnet behavior is a precursor to building effective defenses against this serious and growing threat. In this paper we describe our initial steps toward building a flexible and scalable laboratory testbed for experiments with bots and botnets. Our Botnet Evaluation Environment (BEE) is designed to enable individual bots or networks of up to thousands of bots to be tested in a secure, self-contained framework. BEE is being developed as a toolkit for Emulab-enabled network testbeds; a design choice made to obviate the need for building user experiment management functions and to enable access to collections of computing hosts. The focus of our implementation efforts has been on building a library of OS Bot images that can be run on individual systems or on virtual machines. The library currently includes images generated from source code of four well known bots (Agobot, GTbot, Spybot, SDbot) and from binary code for several unknown bots, and a number of Windows OS variants. BEE also includes a set of services that are required for botnets including DHCP, DynDNS, and IRC, as well as other tools that are useful for botnet measurement and evaluation such as VM monitors and honeypots. To demonstrate the utility of BEE, we describe a simple set of tests that characterizes command and control traffic from three different botnet configurations.",
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"content": "There have been several research works on the study of botnets through testbeds. [2] have presented a toolkit for Emulab-enabled testbeds (such as DETERlab) called Botnet Evaluation Environment (BEE), designed to provide bots and botnets for experimentation in a scalabale and secure self-contained environment. BEE includes a library of OS bot images to be run on physical and virtual machines as well as a set of services and tools required for botnet evaluation such as DHCP, DNS, IRC, VM monitors and honeypots. [1] has proposed a composable botnet framework called SLINGbot which can be used to construct botnets with different (Command and Control) C2 structures (including potential future botnet C2 structures), simulate botnet traffic, characterize it and develop botnet defense techniques.",
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science.chemdner_ner | science.chemdner_ner.744 | [
{
"content": "Analyze the given text to identify specific entities. Focus on extracting relevant data.\n\nProvide your findings in JSON format. Each category should list the entities found.\n\nText:\n\nGarlic oil attenuates the cardiac apoptosis in hamster-fed with hypercholesterol diet. Hypercholesterolemia is a well established risk factor for cardiac cell apoptosis. The purpose of this study is to evaluate the effects of garlic oil on cardiac apoptosis induced by a hypercholesterol diet. Twenty-four male Golden-Syrian hamsters at 3 months of age were randomly divided into three groups, control, cholesterol and garlic oil groups received a chow diet, chow diet with 2% cholesterol, and chow diet with 2% cholesterol and 1% garlic oil for 8 weeks, respectively. The TUNEL-positive apoptotic cells, and several apoptotic proteins were significantly induced in the excised left ventricle in cholesterol group, whereas significant reduction was observed in cholesterol plus garlic oil group. The IGFI receptor dependent survival pathway was inhibited in cholesterol group whereas it was obviously reversed in cholesterol plus garlic oil group. Our results suggest that administration of garlic oil shows protective effects on cardiac apoptosis in rats with high cholesterol intake.",
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"content": "{\"Chemical\": [\"cholesterol\"]}",
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science.healthver_entailment | science.healthver_entailment.4219 | [
{
"content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: coronavirus started at some point before December 2019 in Wuhan, but COVID-19 doesn't come the Wuhan wet market that was initially blamed for the outbreak.\n\nResearch Abstract:\nOrigin of the COVID-19 virus has been intensely debated in the scientific community since the first infected cases were detected in December 2019.\nThe disease has caused a global pandemic, leading to deaths of thousands of people across the world and thus finding origin of this novel coronavirus is important in responding and controlling the pandemic.\nRecent research results suggest that bats or pangolins might be the original hosts for the virus based on comparative studies using its genomic sequences.\nThis paper investigates the COVID-19 virus origin by using artificial intelligence (AI) and raw genomic sequences of the virus.\nMore than 300 genome sequences of COVID-19 infected cases collected from different countries are explored and analysed using unsupervised clustering methods.\nThe results obtained from various AI-enabled experiments using clustering algorithms demonstrate that all examined COVID-19 virus genomes belong to a cluster that also contains bat and pangolin coronavirus genomes.\nThis provides evidences strongly supporting scientific hypotheses that bats and pangolins are probable hosts for the COVID-19 virus.\nAt the whole genome analysis level, our findings also indicate that bats are more likely the hosts for the COVID-19 virus than pangolins.",
"role": "user"
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{
"content": "{\"verdict\": \"NEI\", \"evidence\": []}",
"role": "assistant"
}
]
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science.pico_ner | science.pico_ner.3980 | [
{
"content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nAbsence of central effects in man of the benzodiazepine antagonist Ro 15-1788 . The benzodiazepines are typified by a profile of side effects which includes drowsiness , ataxia and incoordination . Ro 15-1788 , an imidazodiazepine derivative , exhibits marked antagonism of the behavioural and biochemical effects of the benzodiazepines in animals and man . It is devoid of any behavioural activity in animals , except at very high doses . In the present study the effects of single rising oral doses of Ro 15-1788 on cognitive , psychomotor and subjective function in man have been assessed using a battery of psychometric tests designed to identify the sedative action of the benzodiazepines . At all doses up to 600 mg , Ro 15-1788 demonstrated none of the classical behavioural effects of the benzodiazepines .",
"role": "user"
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{
"content": "{\"Intervention\": [\"benzodiazepine\", \"Ro 15-1788\"], \"Outcome\": [\"incoordination\", \"psychomotor\", \"psychometric tests\", \"central effects\", \"subjective function\", \"sedative action\", \"behavioural effects\", \"cognitive\", \"drowsiness\", \"ataxia\"], \"Participant\": [\"in man\"]}",
"role": "assistant"
}
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science.healthver_entailment | science.healthver_entailment.1843 | [
{
"content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: In patients with both COVID-19 and cancer, immunotherapy might increase the immune system response, which could already be overactive because of the COVID-19 infection.\n\nResearch Abstract:\nSeveral related human coronaviruses (HCoVs) are endemic in the human population, causing mild respiratory infections1.\nSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiologic agent of Coronavirus disease 2019 (COVID-19), is a recent zoonotic infection that has quickly reached pandemic spread2,3.\nZoonotic introduction of novel coronaviruses is thought to occur in the absence of pre-existing immunity in the target human population.\nUsing diverse assays for detection of antibodies reactive with the SARS-CoV-2 Spike (S) glycoprotein, we demonstrate the presence of pre-existing immunity in uninfected and unexposed humans to the new coronavirus.\nSARS-CoV-2 S-reactive antibodies, exclusively of the IgG class, were readily detectable by a sensitive flow cytometry-based method in SARS-CoV-2-uninfected individuals with recent HCoV infection and targeted the S2 subunit.\nIn contrast, SARS-CoV-2 infection induced higher titres of SARS-CoV-2 S-reactive IgG antibodies, as well as concomitant IgM and IgA antibodies throughout the observation period of 6 weeks since symptoms onset.\nHCoV patient sera also variably reacted with SARS-CoV-2 S and nucleocapsid (N), but not with the S1 subunit or the receptor binding domain (RBD) of S on standard enzyme immunoassays.\nNotably, HCoV patient sera exhibited specific neutralising activity against SARS-CoV-2 S pseudotypes, according to levels of SARS-CoV-2 S-binding IgG and with efficiencies comparable to those of COVID-19 patient sera.\nDistinguishing pre-existing and de novo antibody responses to SARS-CoV-2 will be critical for serology, seroprevalence and vaccine studies, as well as for our understanding of susceptibility to and natural course of SARS-CoV-2 infection.",
"role": "user"
},
{
"content": "{\"verdict\": \"NEI\", \"evidence\": []}",
"role": "assistant"
}
]
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.1560 | [
{
"content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: Scene Flow Estimation: A Survey \nChapter Title: The modification of methods in the future \n1. Abstract of Cited Paper (BIB001): This paper proposes a novel approach to non-rigid, markerless motion capture from synchronized video streams acquired by calibrated cameras. The instantaneous geometry of the observed scene is represented by a polyhedral mesh with fixed topology. The initial mesh is constructed in the first frame using the publicly available PMVS software for multi-view stereo [7]. Its deformation is captured by tracking its vertices over time, using two optimization processes at each frame: a local one using a rigid motion model in the neighborhood of each vertex, and a global one using a regularized nonrigid model for the whole mesh. Qualitative and quantitative experiments using seven real datasets show that our algorithm effectively handles complex nonrigid motions and severe occlusions. \n2. Abstract of Cited Paper (BIB002): In this paper a novel approach for estimating the three dimensional motion field of the visible world from stereo image sequences is proposed. This approach combines dense variational optical flow estimation, including spatial regularization, with Kalman filtering for temporal smoothness and robustness. The result is a dense, robust, and accurate reconstruction of the three-dimensional motion field of the current scene that is computed in real-time. Parallel implementation on a GPU and an FPGA yields a vision-system which is directly applicable in real-world scenarios, like automotive driver assistance systems or in the field of surveillance. Within this paper we systematically show that the proposed algorithm is physically motivated and that it outperforms existing approaches with respect to computation time and accuracy. \n3. Abstract of Cited Paper (BIB003): We propose a depth and image scene flow estimation method taking the input of a binocular video. The key component is motion-depth temporal consistency preservation, making computation in long sequences reliable. We tackle a number of fundamental technical issues, including connection establishment between motion and depth, structure consistency preservation in multiple frames, and long-range temporal constraint employment for error correction. We address all of them in a unified depth and scene flow estimation framework. Our main contributions include development of motion trajectories, which robustly link frame correspondences in a voting manner, rejection of depth/motion outliers through temporal robust regression, novel edge occurrence map estimation, and introduction of anisotropic smoothing priors for proper regularization. \n4. Abstract of Cited Paper (BIB004): We present a method for extracting depth information from a rectified image pair. We train a convolutional neural network to predict how well two image patches match and use it to compute the stereo matching cost. The cost is refined by cross-based cost aggregation and semiglobal matching, followed by a left-right consistency check to eliminate errors in the occluded regions. Our stereo method achieves an error rate of 2.61% on the KITTI stereo dataset and is currently (August 2014) the top performing method on this dataset. \n5. Abstract of Cited Paper (BIB005): Recent work has shown that optical flow estimation can be formulated as a supervised learning task and can be successfully solved with convolutional networks. Training of the so-called FlowNet was enabled by a large synthetically generated dataset. The present paper extends the concept of optical flow estimation via convolutional networks to disparity and scene flow estimation. To this end, we propose three synthetic stereo video datasets with sufficient realism, variation, and size to successfully train large networks. Our datasets are the first large-scale datasets to enable training and evaluation of scene flow methods. Besides the datasets, we present a convolutional network for real-time disparity estimation that provides state-of-the-art results. By combining a flow and disparity estimation network and training it jointly, we demonstrate the first scene flow estimation with a convolutional network. \n6. Abstract of Cited Paper (BIB006): In the past year, convolutional neural networks have been shown to perform extremely well for stereo estimation. However, current architectures rely on siamese networks which exploit concatenation followed by further processing layers, requiring a minute of GPU computation per image pair. In contrast, in this paper we propose a matching network which is able to produce very accurate results in less than a second of GPU computation. Towards this goal, we exploit a product layer which simply computes the inner product between the two representations of a siamese architecture. We train our network by treating the problem as multi-class classification, where the classes are all possible disparities. This allows us to get calibrated scores, which result in much better matching performance when compared to existing approaches.\n\nReview Chapter:",
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"content": "By checking the error map provided by KITTI benchmark, it's clear that inaccuracy mainly exists in the boundaries of objects. Since this is a common issue for all computer vision tasks, edge-preserving and reasonable filtering is the first priority. GPU implementation has shown a great efficiency improvement, and the duality-based optimization has proved to enhance the efficiency of global variational methods without accuracy sacrifice. These kind of methods may be a routine in the future for better efficiency. With the development of a robust and efficient estimation between two frames, some papers have studied motion estimation under a long sequence BIB001 BIB003 BIB002 BIB004 . The multi-fames estimation with temporal prior knowledges deserves more attention. A robust temporal constraint can benefit the methods with a better initial value or a better feature BIB004 to match. The challenges like varying illumination and occlusion can be handled with the help of it. The emerging learning based methods and light field technique has brought fresh blood to scene flow estimation. Learning method with CNN shows an upward tendency in the relevant issues of scene flow estimation like stereo matching and optical flow with promising accuracy and computational cost BIB005 BIB007 . With the help of the up-to-date large scale training dataset BIB006 , learning-based method has a profound potential to achieve an accurate and fast estimation. Light field camera provides more data than existing data source, which brings diverse possibilities for this field. Similar to the emergence of RGB-D cameras, this new source of data may lead to a new attractive branch. On account of the fact that scene flow estimation relies highly on texture and intensity information, application will suffer in the night or an insufficient illumination circumstance. Moreover, the car headlights and lighting on the building that are frequent in the autonomous driving scene may interfere motion estimation significantly. Hence, the scene flow estimation with insufficient illumination is worth studying.",
"role": "assistant"
}
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science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.2540 | [
{
"content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nDeep Convolution Neural Networks (CNN) have achieved significant performance on single image super-resolution (SR) recently. However, existing CNN-based methods use artificially synthetic low-resolution (LR) and high-resolution (HR) image pairs to train networks, which cannot handle real-world cases since the degradation from HR to LR is much more complex than manually designed. To solve this problem, we propose a real-world LR images guided bi-cycle network for single image super-resolution, in which the bidirectional structural consistency is exploited to train both the degradation and SR reconstruction networks in an unsupervised way. Specifically, we propose a degradation network to model the real-world degradation process from HR to LR via generative adversarial networks, and these generated realistic LR images paired with real-world HR images are exploited for training the SR reconstruction network, forming the first cycle. Then in the second reverse cycle, consistency of real-world LR images are exploited to further stabilize the training of SR reconstruction and degradation networks. Extensive experiments on both synthetic and real-world images demonstrate that the proposed algorithm performs favorably against state-of-the-art single image SR methods.\n\nCited Works Summary:\n[1]: We present a new method for digitally interpolating images to higher resolution. It consists of two phases: rendering and correction. The rendering phase is edge-directed. From the low resolution image data, we generate a high resolution edge map by first filtering with a rectangular center-on-surround-off filter and then performing piecewise linear interpolation between the zero crossings in the filter output. The rendering phase is based on bilinear interpolation modified to prevent interpolation across edges, as determined from the estimated high resolution edge map. During the correction phase, we modify the mesh values on which the rendering is based to account for the disparity between the true low resolution data, and that predicted by a sensor model operating on the high resolution output of the rendering phase. The overall process is repeated iteratively. We show experimental results which demonstrate the efficacy of our interpolation method.\n\n[2]: Recently, Convolutional Neural Network (CNN) based models have achieved great success in Single Image Super-Resolution (SISR). Owing to the strength of deep networks, these CNN models learn an effective nonlinear mapping from the low-resolution input image to the high-resolution target image, at the cost of requiring enormous parameters. This paper proposes a very deep CNN model (up to 52 convolutional layers) named Deep Recursive Residual Network (DRRN) that strives for deep yet concise networks. Specifically, residual learning is adopted, both in global and local manners, to mitigate the difficulty of training very deep networks, recursive learning is used to control the model parameters while increasing the depth. Extensive benchmark evaluation shows that DRRN significantly outperforms state of the art in SISR, while utilizing far fewer parameters. Code is available at https: github.com tyshiwo DRRN_CVPR17.\n\n[3]: Despite the breakthroughs in accuracy and speed of single image super-resolution using faster and deeper convolutional neural networks, one central problem remains largely unsolved: how do we recover the finer texture details when we super-resolve at large upscaling factors? The behavior of optimization-based super-resolution methods is principally driven by the choice of the objective function. Recent work has largely focused on minimizing the mean squared reconstruction error. The resulting estimates have high peak signal-to-noise ratios, but they are often lacking high-frequency details and are perceptually unsatisfying in the sense that they fail to match the fidelity expected at the higher resolution. In this paper, we present SRGAN, a generative adversarial network (GAN) for image super-resolution (SR). To our knowledge, it is the first framework capable of inferring photo-realistic natural images for 4x upscaling factors. To achieve this, we propose a perceptual loss function which consists of an adversarial loss and a content loss. The adversarial loss pushes our solution to the natural image manifold using a discriminator network that is trained to differentiate between the super-resolved images and original photo-realistic images. In addition, we use a content loss motivated by perceptual similarity instead of similarity in pixel space. Our deep residual network is able to recover photo-realistic textures from heavily downsampled images on public benchmarks. An extensive mean-opinion-score (MOS) test shows hugely significant gains in perceptual quality using SRGAN. The MOS scores obtained with SRGAN are closer to those of the original high-resolution images than to those obtained with any state-of-the-art method.\n\n[4]: \n\n[5]: This paper presents a novel edge orientation adaptive interpolation scheme for resolution enhancement of still images. In order to achieve ideal orientation adaptation, we propose to estimate the local covariance characteristics at low resolution but cleverly use them to direct the interpolation at high resolution based on the resolution invariant property of edge orientation. The orientation adaptive property guarantees the interpolation always go along the edge orientation but not across it. Our new interpolation scheme can generate images with dramatically higher visual quality than linear interpolation techniques while keeping the computational complexity still modest.\n\n[6]: \n\n[7]: \n\n[8]: \n\n[9]: Recent years have witnessed the unprecedented success of deep convolutional neural networks (CNNs) in single image super-resolution (SISR). However, existing CNN-based SISR methods mostly assume that a low-resolution (LR) image is bicubicly downsampled from a high-resolution (HR) image, thus inevitably giving rise to poor performance when the true degradation does not follow this assumption. Moreover, they lack scalability in learning a single model to nonblindly deal with multiple degradations. To address these issues, we propose a general framework with dimensionality stretching strategy that enables a single convolutional super-resolution network to take two key factors of the SISR degradation process, i.e., blur kernel and noise level, as input. Consequently, the super-resolver can handle multiple and even spatially variant degradations, which significantly improves the practicability. Extensive experimental results on synthetic and real LR images show that the proposed convolutional super-resolution network not only can produce favorable results on multiple degradations but also is computationally efficient, providing a highly effective and scalable solution to practical SISR applications.\n\n[10]: \n\n[11]: Recent research on super-resolution has progressed with the development of deep convolutional neural networks (DCNN). In particular, residual learning techniques exhibit improved performance. In this paper, we develop an enhanced deep super-resolution network (EDSR) with performance exceeding those of current state-of-the-art SR methods. The significant performance improvement of our model is due to optimization by removing unnecessary modules in conventional residual networks. The performance is further improved by expanding the model size while we stabilize the training procedure. We also propose a new multi-scale deep super-resolution system (MDSR) and training method, which can reconstruct high-resolution images of different upscaling factors in a single model. The proposed methods show superior performance over the state-of-the-art methods on benchmark datasets and prove its excellence by winning the NTIRE2017 Super-Resolution Challenge.\n\n[12]: We propose an image super-resolution method (SR) using a deeply-recursive convolutional network (DRCN). Our network has a very deep recursive layer (up to 16 recursions). Increasing recursion depth can improve performance without introducing new parameters for additional convolutions. Albeit advantages, learning a DRCN is very hard with a standard gradient descent method due to exploding vanishing gradients. To ease the difficulty of training, we propose two extensions: recursive-supervision and skip-connection. Our method outperforms previous methods by a large margin.\n\n[13]: \n\n[14]:",
"role": "user"
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{
"content": "Early methods [1] [5] [10] super-resolve images based on the the interpolation-based theory. However, it is difficult to reconstruct detailed textures in the super-resolved results. Dong al [8] propose a pioneer 3-layer CNN (SRCNN) for bicubic up-sampled image SR, which then brings outs a series of CNN-based SISR methods with more descent effectiveness and higher efficiency. On one hand, more effective CNN architectures are designed to improve SR performance, including very deep CNN with residual learning [4] , residual and dense block [3] [11] , recursive structure [12] [2] and channel attention [14] . On the other hand, separate research efforts are paid to speed up computational efficiency, where deep features are extracted from original LR image [13] [6] [7] . Taking both effectiveness and efficiency into account, this speed up strategy has also been succesively adopted in [3] [11] [9] [14] .",
"role": "assistant"
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science.craftchem_ner | science.craftchem_ner.4191 | [
{
"content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nVariablesthatwereanalyzedincludedthetotalnumberofambulations,aswellasthenumberofentries,thetimespent,andthedistancetraveledinthecenterareaaswellasthedistancetraveledintheperipherysurroundingthecenter.",
"role": "user"
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{
"content": "[]",
"role": "assistant"
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science.anat_em_ner | science.anat_em_ner.431 | [
{
"content": "Analyze the provided text from a biomedical study. Your task is to detect and list entities based on predefined categories.\n\nPresent your results in a JSON format: {\"AnatomicalEntity\": [\"entity1\", \"entity2\", ...]}. Each category should have a corresponding list of identified entities. \n\nText:\n\nLMP1 of Epstein-Barr virus induces proliferation of primary mouse embryonic fibroblasts and cooperatively transforms the cells with a p16-insensitive CDK4 oncogene. \nThe latent membrane protein LMP1 of Epstein-Barr virus (EBV) is often present in EBV-associated malignancies including nasopharyngeal carcinoma and Hodgkin's lymphoma. Previous work demonstrates that the LMP1 gene of EBV is sufficient to transform certain established rodent fibroblast cell lines and to induce the tumorigenicity of some human epithelial cell lines. In addition, LMP1 plays pleiotropic roles in cell growth arrest, differentiation, and apoptosis, depending on the background of the target cells. To examine the roles of LMP1 in cell proliferation and growth regulation in primary culture cells, we constructed a recombinant retrovirus containing an LMP1 gene. With this retrovirus, LMP1 was shown to stimulate the proliferation of primary mouse embryonic fibroblasts (MEF cells). It has a mitogenic activity for MEF cells, as demonstrated by an immediate induction of cell doubling time. In addition, it significantly extends the passage number of MEF cells to more than 30 after retroviral infection, compared with less than 5 for uninfected MEF cells. Furthermore, LMP1 cooperates with a p16-insensitive CDK4(R24C) oncogene in transforming MEF cells. Our results provide the first evidence of the abilities of the LMP1 gene, acting alone, to effectively induce the proliferation of primary MEF cells and of its cooperativity with another cellular oncogene in transforming primary cells.",
"role": "user"
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{
"content": "{\"AnatomicalEntity\": [\"malignancies\", \"embryonic fibroblasts\", \"epithelial cell lines\", \"nasopharyngeal carcinoma\", \"cell\", \"culture cells\", \"fibroblast cell lines\", \"MEF cells\", \"cells\", \"Hodgkin\\u0027s lymphoma\", \"cellular\"]}",
"role": "assistant"
}
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science.healthver_entailment | science.healthver_entailment.3659 | [
{
"content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: Vitamin D Lower Your Risk of COVID-19\n\nResearch Abstract:\nThe severity of coronavirus 2019 infection (COVID-19) is determined by the presence of pneumonia, severe acute respiratory distress syndrome (SARS-CoV-2), myocarditis, microvascular thrombosis and/or cytokine storms, all of which involve underlying inflammation.\nA principal defence against uncontrolled inflammation, and against viral infection in general, is provided by T regulatory lymphocytes (Tregs).\nTreg levels have been reported to be low in many COVID-19 patients and can be increased by vitamin D supplementation.\nLow vitamin D levels have been associated with an increase in inflammatory cytokines and a significantly increased risk of pneumonia and viral upper respiratory tract infections.\nVitamin D deficiency is associated with an increase in thrombotic episodes, which are frequently observed in COVID-19.\nVitamin D deficiency has been found to occur more frequently in patients with obesity and diabetes.\nThese conditions are reported to carry a higher mortality in COVID-19.\nIf vitamin D does in fact reduce the severity of COVID-19 in regard to pneumonia/ARDS, inflammation, inflammatory cytokines and thrombosis, it is our opinion that supplements would offer a relatively easy option to decrease the impact of the pandemic.",
"role": "user"
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{
"content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"A principal defence against uncontrolled inflammation, and against viral infection in general, is provided by T regulatory lymphocytes (Tregs).\", \"Treg levels have been reported to be low in many COVID-19 patients and can be increased by vitamin D supplementation.\", \"Low vitamin D levels have been associated with an increase in inflammatory cytokines and a significantly increased risk of pneumonia and viral upper respiratory tract infections.\", \"Vitamin D deficiency is associated with an increase in thrombotic episodes, which are frequently observed in COVID-19.\", \"Vitamin D deficiency has been found to occur more frequently in patients with obesity and diabetes.\", \"These conditions are reported to carry a higher mortality in COVID-19.\", \"If vitamin D does in fact reduce the severity of COVID-19 in regard to pneumonia/ARDS, inflammation, inflammatory cytokines and thrombosis, it is our opinion that supplements would offer a relatively easy option to decrease the impact of the pandemic.\"]}",
"role": "assistant"
}
]
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science.bc7_litcovid_topic_classification | science.bc7_litcovid_topic_classification.4196 | [
{
"content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nThe aim of this study is to examine the use of an inflammasome competitor as a preventative agent. Coronaviruses have zoonotic potential due to the adaptability of their S protein to bind receptors of other species, most notably demonstrated by SARS-CoV. The binding of SARS-CoV-2 to TLR (Toll-like receptor) causes the release of pro-IL-1beta, which is cleaved by caspase-1, followed by the formation and activation of the inflammasome, which is a mediator of lung inflammation, fever, and fibrosis. The NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome is implicated in a variety of human diseases including Alzheimer's disease (AD), prion diseases, type 2 diabetes, and numerous infectious diseases. By examining the use of 4,4'-diaminodiphenyl sulfone (DDS) in the treatment of patients with Hansen's disease, also diagnosed as Alzheimer's disease, this study demonstrates the diverse mechanisms involved in the activation of inflammasomes. TLRs, due to genetic polymorphisms, can alter the immune response to a wide variety of microbial ligands, including viruses. In particular, TLR2Arg(677)Trp was reported to be exclusively present in Korean patients with lepromatous leprosy (LL). Previously, mutation of the intracellular domain of TLR2 has demonstrated its role in determining the susceptibility to LL, though LL was successfully treated using a combination of DDS with rifampicin and clofazimine. Of the three tested antibiotics, DDS was effective in the molecular regulation of NLRP3 inflammasome activators that are important in mild cognitive impairment (MCI), Parkinson's disease (PD), and AD. The specific targeting of NLRP3 itself or up-/downstream factors of the NLRP3 inflammasome by DDS may be responsible for its observed preventive effects, functioning as a competitor.",
"role": "user"
},
{
"content": "[\"Treatment\", \"Mechanism\"]",
"role": "assistant"
}
]
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science.bioasq_factoid_qa | science.bioasq_factoid_qa.1273 | [
{
"content": "Given the following biomedical passages, answer the question succinctly. Ensure your response is precise and limited to the answer only.\n\nQuestion: Fingolimod is a selective antagonist for which molecule?\n\nPassages: Pharmacologically, fingolimod was characterized as a non-selective agonist of all of the S1P receptors (S1PR), with the exception of S1P2, and in addition, as a selective S1P1 functional antagonist by induction of irreversible S1P1 internalization and degradation.",
"role": "user"
},
{
"content": "S1P1",
"role": "assistant"
}
]
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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.15999 | [
{
"content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Estimating Divergence Time and Ancestral Effective Population Size of Bornean and Sumatran Orangutan Subspecies Using a Coalescent Hidden Markov Model\nContent:\nAbstract:\nDue to genetic variation in the ancestor of two populations or two species, the divergence time for DNA sequences from two populations is variable along the genome. Within genomic segments all bases will share the same divergence—because they share a most recent common ancestor—when no recombination event has occurred to split them apart. The size of these segments of constant divergence depends on the recombination rate, but also on the speciation time, the effective population size of the ancestral population, as well as demographic effects and selection. Thus, inference of these parameters may be possible if we can decode the divergence times along a genomic alignment. Here, we present a new hidden Markov model that infers the changing divergence( coalescence) times along the genome alignment using a coalescent framework, in order to estimate the speciation time, the recombination rate, and the ancestral effective population size. The model is efficient enough to allow inference on whole-genome data sets. We first investigate the power and consistency of the model with coalescent simulations and then apply it to the whole-genome sequences of the two orangutan sub-species, Bornean( P. p. pygmaeus) and Sumatran( P. p. abelii) orangutans from the Orangutan Genome Project. We estimate the speciation time between the two sub-species to be thousand years ago and the effective population size of the ancestral orangutan species to be, consistent with recent results based on smaller data sets. We also report a negative correlation between chromosome size and ancestral effective population size, which we interpret as a signature of recombination increasing the efficacy of selection.\nIntroduction:\nThere is a growing awareness that the genomic sequences now available for closely related species or sub-species may provide detailed information on the population genetics process in the ancestors of these species and about the speciation process itself[1]. This is because the divergence patterns of a set of( sub-) species vary along their genomes due to polymorphism in the ancestral species. Different parts of the genome have different histories because recombination has brought together the genome from different ancestors. Viewed back in time, two sequences are therefore, at any given point in the genome, a sample of two individuals in the ancestral species and the identity of these individuals vary along the sequence, as illustrated in Figure 1. The varying sequence-divergence times provide information that allows us to examine the speciation process[2],[3] and enable inference of parameters for the population genetics of the ancestral species, such as the effective population size or speciation-divergence or population-divergence times[4]–[6]. Coalescent theory[7] tells us that the variation in coalescence time in an ancestral population is directly proportional to the effective population size of the ancestral population. This was exploited by Takahata[8] in order to derive a simple estimator of the ancestral effective population size, but when applied to human and chimpanzee the estimate was associated with a large variance, because of the limited divergence of these species. Takahata[9] showed that including an outgroup improved the results, and Yang[10] showed that mutation rate heterogeneity is confounded with the estimate. These early approaches estimated a fixed phylogeny for different sequence fragments. Later approaches have exploited the fact that if speciation times are sufficiently close together, incomplete lineage sorting( cases where the gene tree is different from the species tree) may occur. Wall[11] allowed for recombination and several species in the likelihood estimation of population parameters and Patterson et al.[2], Hobolth et al.[5], and Dutheil et al.[12] made simple models of changes in genealogy along a multi-species alignment with incomplete lineage sorting. Detailed modeling using MCMC of the genealogies supporting a data set[13], or the ancestral recombination graph[3] in a model that includes recombination, has the advantage of allowing modeling more complex aspects of the data such as gene flow through migration, but scaling these to whole genome data is challenging. In contrast, approaches based on hidden Markov models( HMMs), such as Hobolth et al.[5], and Dutheil et al.[12], provide computationally fast inference algorithms, which are scalable to whole-genome data sets. Nevertheless, modeling complex demographic models in terms of transition matrices and emission probabilities is mathematically challenging. Here we present a new approach for constructing transition matrices for HMM approaches and use it to capture the variation in coalescence time between the genomes of two individuals from two divergent populations or two closely related species. The model traces the ancestry of the two sequences using the coalescence process with recombination[14]–[16], and this process determines the switching probabilities from one coalescent time to another along the pair of sequences. Considering a junction between two nucleotides, and going back in time, two types of events may occur: a sequence can split up in two fragments( a recombination event) and two fragments can merge again to become one( a coalescence event). We model the two species using an isolation model( recall Figure 1). Initially, the sequences from the two populations evolve independently, meaning that coalescence events always involves sequences from within the same population. After the population split event, the two populations become one, and the two( fragmented) sequences can now start finding most recent common ancestors. As a result of these events, the sequence divergence varies as we scan along the genomic sequences. The patterns of sequence divergence, and the distribution of recombination events separating segments with constant divergence, are informative of the coalescent processes in the separate populations and that of the ancestor. The model is parameterized with the split time between the two populations, the effective population size of the ancestral population, and the recombination rate, which is assumed to be constant along the segment of the genome analysed. The model assumes that no migration occurs after the population split. We validate the model by simulations and then apply it to the recently sequenced genomes of the two orangutan subspecies Bornean( P. p. pygmaeus) and Sumatran( P. p. abelii)[17]. We estimate the sub-species divergence time to be thousand years ago( kya), and the effective population size of the ancestral orangutan to be estimated from the autosomal chromosomes, and about of that for the X chromosome:.\nDiscussion:\nThe present model assumes a simple population split or an allopatric speciation. To test the consequences of this assumption, we simulated data sets where a single population first splits into two populations with some gene-flow between the populations, and some time later the gene-flow stops( see Protocol S1). In this setting, the divergence time we infer is between the first and the second time point; usually closer to the time point where gene-flow stopped unless the migration rate is very low. This makes sense since the split time modeled in our approach is exactly the termination of genetic flow between the two lineages, and not the introduction of structure in the ancestral population. Only the split time parameter seemed to be affected to a larger extend by gene-flow. The effective population size was slightly over-estimated when gene-flow is present, more so if the time interval and migration rate are large, but the effect is small relative to the variance on the estimates. The recombination rate is estimated to be somewhat higher with gene-flow, again higher when the time interval and mutation rate are high, but is still biased and estimated below the simulated rate. Our model assumes that the input data is an alignment of two haploid genomes where neighboring nucleotides are linked on the same chromosome, but in the analysis we use reference genome sequences that each are a mosaic of at least two haploid genomes. A consequence of this is that the assumption we make about the two neighbouring nucleotides being linked at the present day is incorrect( see also Figure 3). If the recombination/coalescence process is close to equilibrium, assumptions about the starting point are irrelevant, but with an effective size on the order of and speciation time of years we do not expect that the process has reached equilibrium, and thus the unknown phase could potentially affect our estimates. However, varying the present day effective population size parameters an order of magnitude in either direction( see Supplemental Figure 10 of Protocol S1) gave essentially identical results for the parameter estimates, so we trust that treating the reference genome sequences as if they were present day haploid genomes is not a source of bias. Our estimates on effective sizes and speciation time are in close agreement with an analysis based on SNP frequencies from full genome sequencing of five individuals of each of the subspecies( included in the Orangutan Genome paper[17]). Results disagree with Bequet and Przeworski[3] who reported a split time of 1. 4 million years and an ancestral effective size of( C. I.). They used MIMAR to infer parameters. The same authors have shown that MIMAR is quite sensitive to population structure in the ancestral species. Furthermore, their parameters correspond to an average divergence time of the two subspecies of 1. 4 my plus years. If we assume years per generation then years will be million years and a total divergence of million years. This does not seem to be supported by the average divergence of the subspecies which is estimated close to million years[17], therefore we believe there must be a bias in the estimates by Becquet and Przeworski. The X chromosome is found to have an effective population size almost exactly 3/4 of the autosome average. This suggests that selection has not affected the X chromosomes in a different way than the autosomes between the two orangutan sub-species, in contrast to the reports from the human-chimpanzee analyses[2],[5]. Further validation that the model contains information in addition to a simple sliding window analysis of divergence is provided by the observation that small chromosomes are found to have higher recombination rate estimates. This is in line with genetic maps of the human genome( and other genomes) and is believed to be a consequence of the necessity of a least one crossover event per chromosomes for proper segregation in meiosis. The observed correlation between GC content and recombination rate was also expected from similar correlations in other species. This leads us to the negative correlation between effective size and chromosome size observed. Why should smaller chromosomes have higher effective population sizes? We suggest that this is due to their higher average recombination rates, which reduces the effects of background selection and hitch-hiking, both of which tend to increase coalescence rates and thus decrease estimates of effective population size. If this suggestion is true, it shows a large role for selection on determining effective population size, in accordance with the large role proposed in the recent study by McVicker et al.[21]. The simple model presented here can be extended to more populations by extending the number of transition states. It may therefore also be combined with the HMM models that analyse incomplete lineage sorting[5],[12]. This would allow better consideration of substitution rate heterogeneity along the genome. The limiting factor in a straightforward extension of the method to more genomes is the state explosion in the CTMC as more and more combinations of sequences must be considered. While the single sequence CTMC has two states and two non-zero transition-rates, and the two sequence CTMC has 15 states and 44 non-zero transition-rates, three sequences would have 203 states and 1, 118 non-zero rates and four sequences would have 4, 140 states and 35, 446 non-zero rates, making the approach impractical for more than a few genomes. We do, however, believe that it is possible to extend the method to three genomes, combining the CTMC approach presented here with the incomplete lineage sorting model used in our previous CoalHMMs[5],[12]. We also believe that the approach of computing transition probabilities based on coalescence calculations on two neighboring nucleotides can be extended to more complex scenarios such as gene flow following the population split or( sub-) speciation. Since we are explicitly modeling the coalescence process for two nucleotides, the framework generalizes to essentially all scenarios that can be modeled with the coalescence process, without the need for approximating these. Posterior decoding of the states is also a promising avenue for inferring changes in population size over time in the ancestral population[1],[5],[12],[21]. Likewise, posterior decoding might be a powerful approach to the detection of selective sweeps in the ancestral population as long segments with the same divergence time. A simulation study is presently exploring this opportunity of ancestral demographics and we believe that the present model is ideally suited for this.",
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"content": "We present a hidden Markov model that uses variation in coalescence times between two distantly related populations , or closely related species , to infer population genetics parameters in ancestral population or species . The model infers the divergence times in segments along the alignment . Using coalescent simulations , we show that the model accurately estimates the divergence time between the two populations and the effective population size of the ancestral population . We apply the model to the recently sequenced orangutan sub-species and estimate their divergence time and the effective population size of their ancestor population .",
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science.data_reco_mcq_sc | science.data_reco_mcq_sc.10756 | [
{
"content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: We propose a hierarchical reinforcement learning framework to generate detailed descriptions for videos. The model takes in a video\n\nKeywords: video captioning\n\nDataset Information:\nComposable activities dataset: The Composable activities dataset consists of 693 videos that contain activities in 16 classes performed by 14 actors. Each activity is composed of 3 to 11 atomic actions.\nBDD100K: Datasets drive vision progress, yet existing driving datasets are impoverished in terms of visual content and supported tasks to study multitask learning for autonomous driving. Researchers are usually constrained to study a small set of problems on one dataset, while real-world computer vision applications require performing tasks of various complexities.\nMineRL: MineRLis an imitation learning dataset with over 60 million frames of recorded human player data. The dataset includes a set of tasks which highlights many of the hardest problems in modern-day Reinforcement Learning: sparse rewards and hierarchical policies.\nCharades: The Charades dataset is composed of 9,848 videos of daily indoors activities with an average length of 30 seconds, involving interactions with 46 objects classes in 15 types of indoor scenes and containing a vocabulary of 30 verbs leading to 157 action classes. Each video in this dataset is annotated by multiple free-text descriptions, action labels, action intervals and classes of interacting objects.\n\nAvailable Datasets: A: Composable activities dataset B: BDD100K C: MineRL D: Charades",
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"content": "Charades",
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science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.2997 | [
{
"content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nWe present a new method to localize a camera within a previously unseen environment perceived from an egocentric point of view. Although this is, in general, an ill-posed problem, humans can effortlessly and efficiently determine their relative location and orientation and navigate into a previously unseen environments, e.g., finding a specific item in a new grocery store. To enable such a capability, we design a new egocentric representation, which we call ECO (Egocentric COgnitive map). ECO is biologically inspired, by the cognitive map that allows human navigation, and it encodes the surrounding visual semantics with respect to both distance and orientation. ECO possesses three main properties: (1) reconfigurability: complex semantics and geometry is captured via the synthesis of atomic visual representations (e.g., image patch); (2) robustness: the visual semantics are registered in a geometrically consistent way (e.g., aligning with respect to the gravity vector, frontalizing, and rescaling to canonical depth), thus enabling us to learn meaningful atomic representations; (3) adaptability: a domain adaptation framework is designed to generalize the learned representation without manual calibration. As a proof-of-concept, we use ECO to localize a camera within real-world scenes---various grocery stores---and demonstrate performance improvements when compared to existing semantic localization approaches.\n\nCited Works Summary:\n[1]: This paper explores the possibility of using Sun altitude for localization of a robot in totally unknown territory. A set of Sun altitudes is obtained by processing a sequence of time-indexed images of the sky. Each altitude constrains the viewer to a circle on the surface of a celestial body, called the circle of equal altitude. A set of circles of equal altitude can be intersected to yield viewer position. We use this principle to obtain the position on Earth. Since altitude measurements are corrupted by noise, a least-square estimate is numerically calculated from the sequence of altitudes. The paper discusses the necessary theory for Sun-based localization, the technical issues of camera calibration and image processing, and presents preliminary results with real data.\n\n[2]: In this paper we present a prototype system for image based localization in urban environments. Given a database of views of city street scenes tagged by GPS locations, the system computes the GPS location of a novel query view. We first use a wide-baseline matching technique based on SIFT features to select the closest views in the database. Often due to a large change of viewpoint and presence of repetitive structures, a large percentage of matches (> 50 ) are not correct correspondences. The subsequent motion estimation between the query view and the reference view, is then handled by a novel and efficient robust estimation technique capable of dealing with large percentage of outliers. This stage is also accompanied by a model selection step among the fundamental matrix and the homography. Once the motion between the closest reference views is estimated, the location of the query view is then obtained by triangulation of translation directions. Approximate solutions for cases when triangulation cannot be obtained reliably are also described. The presented system is tested on the dataset used in ICCV 2005 Computer Vision Contest and is shown to have higher accuracy than previous reported results.\n\n[3]: A key problem in widely distributed camera networks is locating the cameras. This paper considers three scenarios for camera localization: localizing a camera in an unknown environment, adding a new camera in a region with many other cameras, and localizing a camera by finding correlations with satellite imagery. We find that simple summary statistics (the time course of principal component coefficients) are sufficient to geolocate cameras without determining correspondences between cameras or explicitly reasoning about weather in the scene. We present results from a database of images from 538 cameras collected over the course of a year. We find that for cameras that remain stationary and for which we have accurate image times- tamps, we can localize most cameras to within 50 miles of the known location. In addition, we demonstrate the use of a distributed camera network in the construction a map of weather conditions.\n\n[4]: Estimating geographic information from an image is an excellent, difficult high-level computer vision problem whose time has come. The emergence of vast amounts of geographically-calibrated image data is a great reason for computer vision to start looking globally - on the scale of the entire planet! In this paper, we propose a simple algorithm for estimating a distribution over geographic locations from a single image using a purely data-driven scene matching approach. For this task, we leverage a dataset of over 6 million GPS-tagged images from the Internet. We represent the estimated image location as a probability distribution over the Earthpsilas surface. We quantitatively evaluate our approach in several geolocation tasks and demonstrate encouraging performance (up to 30 times better than chance). We show that geolocation estimates can provide the basis for numerous other image understanding tasks such as population density estimation, land cover estimation or urban rural classification.\n\n[5]: This paper presents a method for estimating geographic location for sequences of time-stamped photographs. A prior distribution over travel describes the likelihood of traveling from one location to another during a given time interval. This distribution is based on a training database of 6 million photographs from Flickr.com. An image likelihood for each location is defined by matching a test photograph against the training database. Inferring location for images in a test sequence is then performed using the Forward-Backward algorithm, and the model can be adapted to individual users as well. Using temporal constraints allows our method to geolocate images without recognizable landmarks, and images with no geographic cues whatsoever. This method achieves a substantial performance improvement over the best-available baseline, and geolocates some users' images with near-perfect accuracy.\n\n[6]: This paper presents a method for extracting distinctive invariant features from images that can be used to perform reliable matching between different views of an object or scene. The features are invariant to image scale and rotation, and are shown to provide robust matching across a substantial range of affine distortion, change in 3D viewpoint, addition of noise, and change in illumination. The features are highly distinctive, in the sense that a single feature can be correctly matched with high probability against a large database of features from many images. This paper also describes an approach to using these features for object recognition. The recognition proceeds by matching individual features to a database of features from known objects using a fast nearest-neighbor algorithm, followed by a Hough transform to identify clusters belonging to a single object, and finally performing verification through least-squares solution for consistent pose parameters. This approach to recognition can robustly identify objects among clutter and occlusion while achieving near real-time performance.\n\n[7]: Given a picture taken somewhere in the world, automatic geo-localization of that image is a task that would be extremely useful e.g. for historical and forensic sciences, documentation purposes, organization of the world's photo material and also intelligence applications. While tremendous progress has been made over the last years in visual location recognition within a single city, localization in natural environments is much more difficult, since vegetation, illumination, seasonal changes make appearance-only approaches impractical. In this work, we target mountainous terrain and use digital elevation models to extract representations for fast visual database lookup. We propose an automated approach for very large scale visual localization that can efficiently exploit visual information contours and geometric constraints consistent orientation at the same time. We validate the system on the scale of a whole country Switzerland, 40 000km2 using a new dataset of more than 200 landscape query pictures with ground truth.",
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"content": "Image localization techniques often incorporate other correlated sensory data. Cozman and Krotkov [1] introduced localization of an image taken from unknown environment using temporal changes in sun altitudes. [3] incorporated weather data reported by satellite imagery to localize widely distributed cameras. They find matches between weather conditions on images over an year and the expected weather changes indicated by satellite imagery. As GPS became a viable solution for localization in many applications, GPS-tagged images can help to localize images that do not have such tags. Zhang and Kosecka [2] built a GPS-tagged image repository in urban environments and found correspondences between a query image and the database using SIFT features [3]5 . Hays and Efros [4] leveraged GPS-tagged internet images to estimate a location probability distribution over Earth. [5] extended the work to disambiguate locations of the images without distinct landmarks. [7] estimated image location based on a 3D elevation model of mountainous terrains and evaluated their method on the scale of a country (Switzerland).",
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science.drug_combo_extraction_re | science.drug_combo_extraction_re.1056 | [
{
"content": "Analyze the given paragraph from a biomedical study. Focus on identifying drug pairings within a specified sentence. Your goal is to determine the nature of these pairings.\n\nPresent your findings as a JSON array. Each element should be an array containing the drug names and their interaction type. Use the exact names from the sentence.\n\nOnly consider the specified sentence for your analysis. The paragraph is for context only.\n\nReturn solely the JSON array. If no pairings are found, return an empty array.\n\nContext Paragraph: Bevacizumab and ranibizumab tachyphylaxis in the treatment of choroidal neovascularisation. To evaluate the effect of switching to bevacizumab or ranibizumab after developing tachyphylaxis during anti-vascular endothelial growth factor ( VEGF ) therapy for choroidal neovascularisation ( CNV ) . ### methods The authors reviewed the records of all patients who received both ranibizumab and bevacizumab for treatment of CNV to identify those who developed tachyphylaxis, defined as optical coherence tomography evidence of initial decreased exudation followed by lack of further reduction or an increase in exudation. Signs of exudation included subretinal fluid (SRF), pigment epithelial detachment (PED) and/or cystoid macular oedema (CMO). ### results 26 eyes were included. 10 were initially treated with bevacizumab and then changed to ranibizumab for persistent SRF, PED and/or CMO. Of these, seven had occult CNV and three had predominantly classic CNV. One eye in the occult CNV group did not respond after being switched to ranibizumab. Six eyes had a positive therapeutic response, after one injection in four eyes, and after two or three injections in one eye each. In the classic group, two responded to ranibizumab and one did not. Sixteen eyes were initially treated with ranibizumab before changing to bevacizumab. Of these, 15 had occult CNV and 1 was predominantly classic. Three of the 16 eyes failed to respond to bevacizumab; 6 improved after one injection and 5 after two injections. ### conclusions Patients with CNV who develop tachyphylaxis to ranibizumab or bevacizumab may respond to another anti-VEGF drug. The majority of cases (81%) in this series demonstrated at least some response after switching therapies.\n\nTarget Sentence: To evaluate the effect of switching to bevacizumab or ranibizumab after developing tachyphylaxis during anti-vascular endothelial growth factor ( VEGF ) therapy for choroidal neovascularisation ( CNV ) .",
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"content": "[]",
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science.bioasq_factoid_qa | science.bioasq_factoid_qa.491 | [
{
"content": "Given the following biomedical passages, answer the question succinctly. Ensure your response is precise and limited to the answer only.\n\nQuestion: Which cells secretes alpha defensin 5?\n\nPassages: The major tissue in which HD5 is expressed is the crypt of the small intestine, an anaerobic niche that should allow for substantial pools of both oxidized and (partly) reduced HD5.\nHuman α-defensin 5 (HD5) exhibits broad spectrum antimicrobial activity and plays an important role in mucosal immunity of the small intestine.\nHuman enteric α-defensins (HD5 and HD6), major antimicrobial peptides produced by Paneth cells in the intestine, play important roles in intestinal innate immunity.\nHuman α-defensin 5 (HD5), the most abundant enteric antimicrobial peptide,\nHD5, naturally present at very high concentrations in the mucosa of the small intestine,\nHuman α-defensin 5 (HD5) is an innate immune effector peptide secreted by epithelial cells in the genitourinary tract\nHuman α-defensin 5 (HD5) is a 32-residue cysteine-rich host-defense peptide that exhibits broad-spectrum antimicrobial activity and contributes to innate immunity in the human gut and other organ systems.\nThe concentrations of lactoferrin and defensins in preterm breast milk have antimicrobial activity against common neonatal pathogens.",
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"content": "Intestinal Paneth cells secretes alpha-defensin 5",
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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.10188 | [
{
"content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Probing the canonicity of the Wnt/Wingless signaling pathway\nContent:\nAbstract:\nThe hallmark of canonical Wnt signaling is the transcriptional induction of Wnt target genes by the beta-catenin/TCF complex. Several studies have proposed alternative interaction partners for beta-catenin or TCF, but the relevance of potential bifurcations in the distal Wnt pathway remains unclear. Here we study on a genome-wide scale the requirement for Armadillo( Arm, Drosophila beta-catenin) and Pangolin( Pan, Drosophila TCF) in the Wnt/Wingless( Wg)-induced transcriptional response of Drosophila Kc cells. Using somatic genetics, we demonstrate that both Arm and Pan are absolutely required for mediating activation and repression of target genes. Furthermore, by means of STARR-sequencing we identified Wnt/Wg-responsive enhancer elements and found that all responsive enhancers depend on Pan. Together, our results confirm the dogma of canonical Wnt/Wg signaling and argue against the existence of distal pathway branches in this system.\nIntroduction:\nWnt proteins are highly conserved signaling molecules specifying the fate and behavior of cells in multicellular animals ranging from nematodes to humans[1]. They play crucial roles in embryogenesis, pattern formation and tissue homeostasis during development and in adult life. Therefore it is not surprising that aberrant Wnt signaling has been found to be implicated in many human diseases[2]. Following the identification of Wnt proteins nearly 40 years ago[3–5] genetic and biochemical studies have revealed mechanistic details of how the signaling cascade operates when cells receive a Wnt signal[for review see 6]. As a consequence of Wnt/Wg proteins binding their cognate receptors, beta-catenin is no longer marked for degradation and accumulates in the cytoplasm and nucleus[7–10]. In the prevailing model, TCF is targeted through its DNA binding domain to Wnt-responsive elements( WREs) in the promoters or enhancers of target genes[11] and initiates the transcription of Wnt/Wg-responsive genes when complexed with beta-catenin. In the absence of Wnt/Wg ligand, beta-catenin is phosphorylated and degraded while TCF is bound by transcriptional repressors, such as Groucho and Coop[12–15]. In contrast to the well-studied mechanism of gene activation, the mechanisms by which beta-catenin and TCF promote target gene repression are not well understood[16]. Several reports suggest that, in addition to beta-catenin and TCFs, other factors are involved in Wnt-mediated repression, such as Prop1, Mad or Zic[17–19]. Furthermore it is not clear, in which context alternative[20] or traditional TCF binding sites are used for transcriptional repression[21–23]. A recent study showed that TCF4 is a predominant factor in mediating the Wnt response and for recruiting beta-catenin to DNA[24], however ongoing research on the Wnt signaling pathway has repeatedly demonstrated that beta-catenin as well as TCF interacts with various other proteins. Yet it remains to be determined, whether alternative transcriptional complexes also regulate the expression of Wnt/Wg target genes. For example, an interaction between beta-catenin and FOXO-transcription factors in mouse and DLD-1 human colon carcinoma cells has been demonstrated resulting in the activation of genes involved in oxidative stress and colon cancer metastasis[25–27]. Furthermore in mouse embryonic stem cells it was shown that beta-catenin forms a complex with Oct4 to promote Oct4-driven transcription and pluripotency[28]. In addition, studies in Xenopus reported an interaction between beta-catenin and Sox17, promoting expression of Sox17 target genes[29], and more recently it was suggested that beta-catenin complexes with YAP1 and TBX5 in human cancer cell lines[30]. In addition, alternative binding partners have also been reported for TCF, such as Plakoglobin or Mad[31, 18]. In this study, we address the question of whether alternative routes exist that bypass beta-catenin or TCF to promote the transcription of Wnt/Wg target genes in Drosophila cells. Using cells that lack either Arm or Pan and functional read-outs( i. e. RNA-seq and STARR-seq), we show that both, Arm and Pan, are absolutely required for target gene activation and repression. Consistent with these findings, we further demonstrate that Wnt/Wg-responsive enhancers also require Pan, arguing against the existence of distal branches in the Wnt signaling pathway.\nDiscussion:\nAccording to the generally accepted dogma the canonical Wnt signaling pathway culminates in the transcriptional induction of target genes via the beta-catenin/TCF complex. During the past decade, several alternative configurations of the Wnt pathway have been proposed in which either beta-catenin or TCF is bypassed. A recent study explored the co-occupancy of TCF4 and beta-catenin using ChIP-seq and showed that TCF4 is the major factor in tethering beta-catenin to DNA[24]. However, the study could not exclude the possibility that other putative factors could compensate the lack of TCF or beta-catenin–an aspect that is still poorly understood in the field of Wnt research. In the present study, we investigate whether and, if yes, to which extent a Wnt response can bypass beta-catenin or TCF. To this aim we used somatic cell genetics in Drosophila cultured cells. As a basis for our analysis, we first carried out a systematic and genome-wide study to explore all Wnt/Wg-related transcriptional outputs in this system. We identified a set of 51 genes that are induced upon Wg stimulation. To probe whether their expression requires Arm or Pan, we generated cells lacking one or the other of these factors using the CRISPR/Cas9 technology. Surprisingly, we found that Arm and Pan are both absolutely required for all Wnt/Wg-related transcriptional outputs in this system. As a transcription factor, Pan binds to DNA regulatory elements up- or downstream of the TSS of its target genes. Thus, next we asked, whether these DNA regulatory elements–enhancers/repressors–are dependent on Pan using STARR-seq. Impressively, consistent with our RNA-seq analysis, we found that the induction of Wnt/Wg-responsive enhancer elements fully depends on Pan. In our work we identified eleven down-regulated target genes and showed that knockout of Arm or Pan is sufficient to abrogate their repression. We observed the same effect for repressed enhancers in pan null mutant cells. These findings are in line with a previous study in Drosophila Kc cells[20], in which it was shown that Pan and Arm are required for the repression of the negative target genes Pxn, Ugt36Bc, Tig and Ugt58Fa[20]. We also found Pxn in our Wnt/Wg target gene set. However, the other genes were less than 2-fold repressed in our system and thus did not pass our selection criteria. This might be due to technical differences in Wnt-pathway stimulation and/or timing. Blauwkamp and colleagues showed also in their study that the negatively regulated targets exhibited lower expression upon Pan reduction in the Wnt OFF state[20], implicating that Pan normally activates their expression even in the absence of Wg ligand. When analyzing our data, we found that only half of the negative target genes appear to be activated in the Wnt OFF state upon Pan abrogation, the remaining targets did not exhibit a significant change in their expression profile. This suggests that they might be indirect targets or independent of Pan. Furthermore, we found that several repressed enhancers possess neither the traditional TCF/Pan binding motif, nor the previously reported alternative binding site important for repression, indicative for a Pan-dependent indirect regulation of repressed enhancers. It is likely that Pan is tethered to the DNA by other co-factors as it was shown for dpp or CDH1[21, 23]. Thus, these Pan-dependent enhancers without any known TCF/Pan binding site provide a good starting point for further molecular studies to gain insight into the still incomplete model of Wnt-mediated repression[16]. In sum our results demonstrate that all Wnt/Wg-related transcriptional output in Drosophila cells requires Arm and Pan and that the induction of Wnt/Wg-responsive enhancers is fully dependent on Pan. Hence, collectively our data argue against the existence of distal branching of the Wnt pathway in this system.",
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"content": "Our manuscript addresses the question of whether either of the canonical transduction components , beta-catenin or TCF , can be bypassed when the Wnt pathway is activated . By using somatic cell genetics in Drosophila cells ( via CRISPR/Cas9 editing ) in combination with RNA-seq and STARR-seq ( Self-transcribing-active-regulatory-region-sequencing ) as functional read-outs , we provide firm evidence against the existence of distal branches in the Wnt pathway .",
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science.bioasq_factoid_qa | science.bioasq_factoid_qa.318 | [
{
"content": "Given the following biomedical passages, answer the question succinctly. Ensure your response is precise and limited to the answer only.\n\nQuestion: Which bone protein is used in archaelogy for dating and species identification?\n\nPassages: Collagen was extracted from modern and archaeological cod bones using a weak HCl solution and analysed for its sulphur isotopic composition by isotope ratio mass spectrometry (IRMS)\nWith the high sensitivity of current generation mass spectrometers, ZooMS provides a non-destructive and highly cost-effective method to characterise collagen peptides.\nArchaeological bones are usually dated by radiocarbon measurement of extracted collagen.\nwe describe three complementary preparative HPLC procedures suitable for separating and isolating single amino acids from bone collagen or hair keratin with minimal isotopic contamination.\nBulk bone collagen isotopic analysis of 11 skeletons of Iron Age and Roman date gave a typical C(3) terrestrial signal (\nComparison of liquid chromatography-isotope ratio mass spectrometry (LC/IRMS) and gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) for the determination of collagen amino acid δ13C values for palaeodietary and palaeoecological reconstruction.\nAlthough the primary focus was the compound-specific stable carbon isotope analysis of bone collagen AAs, because of its growing application for palaeodietary and palaeoecological reconstruction, the results are relevant to any field where AA δ(13)C values are required.\nIn archaeological studies, the isotopic enrichment values of carbon and nitrogen in bone collagen give a degree of information on dietary composition.\nLiquid chromatography/isotope ratio mass spectrometry measurement of δ13C of amino acids in plant proteins.\nA new procedure for extraction of collagen from modern and archaeological bones for 14C dating.\nBones are potentially the best age indicators in a stratigraphic study, because they are closely related to the layer in which they are found. Collagen is the most suitable fraction and is the material normally used in radiocarbon dating.\nThe developed strategy permitted unprecedented biochemical analyses of bone-matrix proteins, including collagen modifications, using nearly nanoscale amounts of exceptionally homogenous bone tissue.\nAmino acid delta13C analysis of hair proteins and bone collagen using liquid chromatography/isotope ratio mass spectrometry: paleodietary implications from intra-individual comparisons.\nWe report a novel method for the chromatographic separation and measurement of stable carbon isotope ratios (delta(13)C) of individual amino acids in hair proteins and bone collagen using the LC-IsoLink system, which interfaces liquid chromatography (LC) with isotope ratio mass spectrometry (IRMS).\nSpecies identification by analysis of bone collagen using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry.\nAnalysis of the collagen from 32 different mammal species identified a total of 92 peptide markers that could be used for species identification, for example, in processed food and animal feed.\nWe used authentication tests developed for ancient DNA to evaluate claims by Asara et al. (Reports, 13 April 2007, p. 280) of collagen peptide sequences recovered from mastodon and Tyrannosaurus rex fossils\nAnalysis of amino acid 13C abundance from human and faunal bone collagen using liquid chromatography/isotope ratio mass spectrometry.\nStable nitrogen (delta(15)N) and carbon (delta(13)C) isotope ratios were measured in bone collagen and dentine from human skeletons excavated from this site in order to establish a weaning curve in mid-Holocene hunter-gatherers.\nMass spectrometric analysis of the stable carbon isotope composition (13C/12C or delta 13C) of bone collagen from human remains recovered at archaeological sites provides a direct chemical method for investigating dietary patterns of prehistoric human populations.\nCoupled with more traditional archaeological methods, stable carbon isotope analysis of bone collagen can significantly enhance reconstruction of dietary patterns of prehistoric humans.",
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"content": "Collagen",
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science.mslr2022_ms2_multidoc_summarization | science.mslr2022_ms2_multidoc_summarization.3123 | [
{
"content": "Analyze the following collection of medical RCT summaries. Your goal is to craft a concise synthesis of the findings. Focus on the core insights and present them succinctly. Only include the synthesis in your response. Below are the RCT summaries:\n\n\n\nReport 1:\nTitle: Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial.\nSummary: BACKGROUND There are presently no available therapeutic options for patients with peanut allergy . OBJECTIVE We sought to investigate the safety , efficacy , and immunologic effects of peanut sublingual immunotherapy ( SLIT ) . METHODS After a baseline oral food challenge ( OFC ) of up to 2 g of peanut powder ( approximately 50 % protein ; median successfully consumed dose [ SCD ] , 46 mg ) , 40 subjects , aged 12 to 37 years ( median , 15 years ) , were r and omized 1:1 across 5 sites to daily peanut or placebo SLIT . A 5-g OFC was performed after 44 weeks , followed by unblinding ; placebo-treated subjects then crossed over to higher dose peanut SLIT , followed by a subsequent crossover Week 44 5-g OFC . Week 44 OFCs from both groups were compared with baseline OFCs ; subjects successfully consuming 5 g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders . RESULTS After 44 weeks of SLIT , 14 ( 70 % ) of 20 subjects receiving peanut SLIT were responders compared with 3 ( 15 % ) of 20 subjects receiving placebo ( P < .001 ) . In peanut SLIT responders , median SCD increased from 3.5 to 496 mg . After 68 weeks of SLIT , median SCD significantly increased to 996 mg ( compared with Week 44 , P = .05 ) . The median SCD at the Week 44 Crossover OFC was significantly higher than baseline ( 603 vs 71 mg , P = .02 ) . Seven ( 44 % ) of 16 crossover subjects were responders ; median SCD increased from 21 to 496 mg among responders . Of 10,855 peanut doses through the Week 44 OFCs , 63.1 % were symptom free ; excluding oral-pharyngeal symptoms , 95.2 % were symptom free . CONCLUSIONS Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared with placebo . Longer duration of therapy showed statistically significant increases in the SCD\n\n\nReport 2:\nTitle: A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response.\nSummary: BACKGROUND Open-label oral immunotherapy ( OIT ) protocol s have been used to treat small numbers of patients with peanut allergy . Peanut OIT has not been evaluated in double-blind , placebo-controlled trials . OBJECTIVE To investigate the safety and effectiveness of OIT for peanut allergy in a double-blind , placebo-controlled study . METHODS In this multicenter study , children ages 1 to 16 years with peanut allergy received OIT with peanut flour or placebo . Initial escalation , build-up , and maintenance phases were followed by an oral food challenge ( OFC ) at approximately 1 year . Titrated skin prick tests ( SPTs ) and laboratory studies were performed at regular intervals . RESULTS Twenty-eight subjects were enrolled in the study . Three peanut OIT subjects withdrew early in the study because of allergic side effects . During the double-blind , placebo-controlled food challenge , all remaining peanut OIT subjects ( n = 16 ) ingested the maximum cumulative dose of 5000 mg ( approximately 20 peanuts ) , whereas placebo subjects ( n = 9 ) ingested a median cumulative dose of 280 mg ( range , 0 - 1900 mg ; P < .001 ) . In contrast with the placebo group , the peanut OIT group showed reductions in SPT size ( P < .001 ) , IL-5 ( P = .01 ) , and IL-13 ( P = .02 ) and increases in peanut-specific IgG(4 ) ( P < .001 ) . Peanut OIT subjects had initial increases in peanut-specific IgE ( P < .01 ) but did not show significant change from baseline by the time of OFC . The ratio of forkhead box protein 3 (FoxP3)(hi ) : FoxP3(intermediate ) CD4 + CD25 + T cells increased at the time of OFC ( P = .04 ) in peanut OIT subjects . CONCLUSION These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation . The current study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance\n\n\nReport 3:\nTitle: Sublingual immunotherapy for peanut allergy: clinical and immunologic evidence of desensitization.\nSummary: BACKGROUND There are no treatments currently available for peanut allergy . Sublingual immunotherapy ( SLIT ) is a novel approach to the treatment of peanut allergy . OBJECTIVE We sought to investigate the safety , clinical effectiveness , and immunologic changes with SLIT in children with peanut allergy . METHODS In this double-blind , placebo-controlled study subjects underwent 6 months of dose escalation and 6 months of maintenance dosing followed by a double-blind , placebo-controlled food challenge . RESULTS Eighteen children aged 1 to 11 years completed 12 months of dosing and the food challenge . Dosing side effects were primarily oropharyngeal and uncommonly required treatment . During the double-blind , placebo-controlled food challenge , the treatment group safely ingested 20 times more peanut protein than the placebo group ( median , 1,710 vs 85 mg ; P = .011 ) . Mechanistic studies demonstrated a decrease in skin prick test wheal size ( P = .020 ) and decreased basophil responsiveness after stimulation with 10(-2 ) μg/mL ( P = .009 ) and 10(-3 ) μg/mL ( P = .009 ) of peanut . Peanut-specific IgE levels increased over the initial 4 months ( P = .002 ) and then steadily decreased over the remaining 8 months ( P = .003 ) , whereas peanut-specific IgG4 levels increased during the 12 months ( P = .014 ) . Lastly , IL-5 levels decreased after 12 months ( P = .015 ) . No statistically significant changes were found in IL-13 levels , the percentage of regulatory T cells , or IL-10 and IFN-γ production . CONCLUSION Peanut SLIT is able to safely induce clinical desensitization in children with peanut allergy , with evidence of immunologic changes suggesting a significant change in the allergic response . Further study is required to determine whether continued peanut SLIT is able to induce long-term immune tolerance\n\n\nReport 4:\nTitle: Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract.\nSummary: BACKGROUND Immediate hypersensitivity to peanuts is a frequent cause of anaphylactic reactions and deaths in children and adults . Currently , preventive treatment consists of avoidance , which is difficult because of the widespread and often disguised use of peanuts in the food industry . METHODS Twelve patients with immediate hypersensitivity to ingestion of peanuts were recruited . Half were treated with injections of peanut extract : a maintenance level of tolerance was first achieved by a rush protocol , then maintained with weekly injections for at least 1 year . The other six were untreated control subjects . All patients underwent double-blind , placebo-controlled , oral peanut challenges initially , after approximately 6 weeks , and after 1 year . RESULTS All treated patients achieved the maintenance dose of 0.5 ml of 1:100 wt/vol peanut extract by the rush injection protocol . All experienced increased tolerance to double-blind , placebo-controlled peanut challenge and decreased sensitivity on titrated skin prick testing with peanut extract , whereas the threshold to oral peanut challenge and cutaneous reactivity to peanut extract were unchanged in the untreated control subjects . Systemic reactions were common in the treated group both during rush immunotherapy and with maintenance injections . Only three patients remained tolerant of the full maintenance dose . The increased tolerance to oral peanut challenge was maintained in the three subjects who received full maintenance doses , but there was partial ( n = 2 ) or complete ( n = 1 ) loss of protection in the patients who required dose reduction because of systemic reactions . CONCLUSIONS Injections of peanut extract increase the tolerance of patients with peanut allergy to oral ingestion of peanuts . Injections result in repeated systemic reactions in most patients , even during maintenance injections . For clinical application of this method of treatment , a modified peanut extract is needed\n\n\nReport 5:\nTitle: Treatment of peanut allergy with rush immunotherapy.\nSummary: Peanut and peanut products are a common food in the diet . Peanuts are also one of the most common foods responsible for food-induced anaphylaxis . Patients rarely lose sensitivity to peanuts . Although the ideal treatment is avoidance , this is often not possible because of hidden exposures ; therefore , a more effective treatment is needed . Subjects with confirmed peanut allergy were treated in a double-blind , placebo-controlled study with peanut immunotherapy or placebo . Objective measures of efficacy included changes in symptom score during double-blind placebo-controlled peanut challenge ( DBPCPC ) and titrated end point prick skin tests ( PST ) . Three subjects treated with peanut immunotherapy completed the study . These subjects displayed a 67 % to 100 % decrease in symptoms induced by DBPCPC . Subjects also had a 2- to 5-log reduction in end point PST reactivity to peanut extract . One placebo-treated subject completed the study . This subject had essentially no change in DBPCPC symptom scores or PST sensitivity to peanut . Two other placebo-treated subjects underwent a second PST session . These subjects had a 1- to 2-log increase in skin test sensitivity to peanut . All peanut-treated subjects were able to reach maintenance dose , and in no case did an anaphylactic reaction occur secondary to the peanut immunotherapy . The current study provides preliminary data demonstrating the efficacy of injection therapy with peanut extract and provides a future line of clinical investigation for the treatment of this potentially lethal disease . It should be noted , however , that the rate of systemic reactions with rush immunotherapy was 13.3 % . ( ABSTRACT TRUNCATED AT 250 WORDS\n\n\nReport 6:\nTitle: Oral and sublingual peanut immunotherapy is not ready for general use.\nSummary: Food oral immunotherapy ( OIT ) is an investigational peanut allergy treatment aim ed to achieve specific oral tolerance induction . Allergic children are given titrated oral ( or sublingual ) doses of their allergen on a daily basis , unlike in subcutaneous immunotherapy ( SCIT ) . OIT is theorized to cause a shift from a Th2 to a Th1 regulatory environment , reflected by increases in food-specific IgG4/IgE , and the production of FoxP3 . Peanut OIT holds special promise because peanut allergy has an unfavorable natural history and is rarely outgrown . A high percentage of the participants experience symptoms during peanut OIT , including anaphylaxis , warranting epinephrine and /or discontinuation of therapy . This is a concerning fact given that the studies have mostly targeted only older children , with less historical reactivity for enrollment . The h and ful of peanut OIT studies have shown that some participants can be desensitized to peanut , but none have shown that long-term tolerance can be reestablished . Factors predictive of which patients are most likely to succeed and become desensitized through OIT are unknown . Some private practice s have begun offering peanut OIT as a therapy . Such practice is potentially dangerous given the safety and efficacy of OIT in r and omized controlled clinical trials is still not well established . Therefore , until further investigation emerges that conclusively demonstrates OIT is safe , intermediate and long-term outcomes are better established , the number of participants that experience symptoms is reduced , and proof of concept established in patients of all ages , ( irrespective of past reaction severity ) , OIT is not ready for use in the general allergy practice\n\n\nReport 7:\nTitle: Emergency treatment of anaphylactic reactions--guidelines for healthcare providers.\nSummary: * The UK incidence of anaphylactic reactions is increasing . * Patients who have an anaphylactic reaction have life-threatening airway and , or breathing and , or circulation problems usually associated with skin or mucosal changes . * Patients having an anaphylactic reaction should be treated using the Airway , Breathing , Circulation , Disability , Exposure ( ABCDE ) approach . * Anaphylactic reactions are not easy to study with r and omised controlled trials . There are , however , systematic review s of the available evidence and a wealth of clinical experience to help formulate guidelines . * The exact treatment will depend on the patient 's location , the equipment and drugs available , and the skills of those treating the anaphylactic reaction . * Early treatment with intramuscular adrenaline is the treatment of choice for patients having an anaphylactic reaction . * Despite previous guidelines , there is still confusion about the indications , dose and route of adrenaline . * Intravenous adrenaline must only be used in certain specialist setting s and only by those skilled and experienced in its use . * All those who are suspected of having had an anaphylactic reaction should be referred to a specialist in allergy . * Individuals who are at high risk of an anaphylactic reaction should carry an adrenaline auto-injector and receive training and support in its use . * There is a need for further research about the diagnosis , treatment and prevention of anaphylactic reactions",
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"content": "This study showed a statistically significant benefit of peanut immunotherapy in patients with peanut allergy .",
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science.bc7_litcovid_topic_classification | science.bc7_litcovid_topic_classification.2761 | [
{
"content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nPURPOSE: Glucocorticoids (GCs), alone or associated to other drugs, were widely used in the management of patients affected by severe acute respiratory syndrome caused by SARS-CoV-2 infection, during the recent COVID-19 outbreak. This review summarizes the available data on HPA axis impairment in GC-treated SARS-CoV-2 patients, focusing on the risk of adrenal insufficiency and on potential drug interactions during concomitant treatments. METHODS: Literature on the impact of GCs therapy on HPA axis and on the consequences of coadministration of GCs and other drugs in SARS-CoV-2 patients has been reviewed. RESULTS: GC treatment can cause symptoms of hypercortisolism, especially in patients with individual hypersensibility, or hypoadrenalism after drug withdrawal, due to hypothalamic-pituitary-adrenal (HPA) axis suppression, with consequences in terms of increased morbidity and mortality risk. On the other hand, in SARS-CoV-2-infected patient's cortisol secretion could be insufficient also due to critical illness-related corticosteroid insufficiency (CIRCI). In addition, in this clinical context, the co-administration of antiretroviral drugs and corticosteroids may trigger drug-drug interaction and enhance the exposure to the latter ones, metabolized through the CYP450 CYP3A pathway, severely impacting on HPA axis. CONCLUSION: Physicians involved in the management of patients affected by COVID-19 should be aware of the need of an appropriate GC dose tapering, and of potential interaction of GCs with antiviral therapy and drugs used to treat associated co-morbidities.",
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"content": "[\"Treatment\"]",
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science.data_reco_mcq_sc | science.data_reco_mcq_sc.2938 | [
{
"content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: We propose a novel method for source separation of the vocal track from a musical mixture. Our method relies on\n\nKeywords: source separation audio\n\nDataset Information:\nMusic21: Music21 is an untrimmed video dataset crawled by keyword query from Youtube. It contains music performances belonging to 21 categories.\niKala: The iKala dataset is a singing voice separation dataset that comprises of 252 30-second excerpts sampled from 206 iKala songs (plus 100 hidden excerpts reserved for MIREX data mining contest). The music accompaniment and the singing voice are recorded at the left and right channels respectively.\nCCMixter: CCMixter is a singing voice separation dataset consisting of 50 full-length stereo tracks from ccMixter featuring many different musical genres. For each song there are three WAV files available: the background music, the voice signal, and their sum.\nSlakh2100: The Synthesized Lakh (Slakh) Dataset is a dataset for audio source separation that is synthesized from the Lakh MIDI Dataset v0.1 using professional-grade sample-based virtual instruments. This first release of Slakh, called Slakh2100, contains 2100 automatically mixed tracks and accompanying MIDI files synthesized using a professional-grade sampling engine.\n\nAvailable Datasets: A: Music21 B: iKala C: CCMixter D: Slakh2100",
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"content": "iKala",
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science.craftchem_ner | science.craftchem_ner.4245 | [
{
"content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nThelevelofsignificancewassetatp<0.05inallcases.",
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"content": "[]",
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science.scicite_classification | science.scicite_classification.3400 | [
{
"content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nidentify and manage people with an ARMS for psychosis, even in a deprived inner-city area with a high proportion of people from ethnic minorities (Broome et al. 2005).",
"role": "user"
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"content": "Background",
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.20453 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nDiscovery of a New Molecular Probe ML228: An Activator of the Hypoxia Inducible Factor (HIF) Pathway\n\nContent Extracts:\n\n<p>Hypoxia and ischemia are linked to several serious public health problems that affect most major organ systems. Specific examples include diseases of the cardiovascular, pulmonary, renal, neurologic, and musculoskeletal systems. The hypoxia inducible factor (HIF) pathway is the major pathway required for intracellular adaptation initiated by lower oxygen availability in the bloodstream. The HIF pathway is known to take part in the angiogenesis processes enhancing blood supply required for tissue repair and regeneration. A unique gene transcription program involving the activation of multiple transcriptional factors known as the hypoxia inducible factors (HIFs) is triggered in response to hypoxia.1 HIFs exists as a heterodimeric complex containing one of three α subunits (HIF-1α, HIF-2α, or HIF-3α) associated with the aryl hydrocarbon receptor nuclear translocator (ARNT), also known as HIF-1β. Although the hypoxic response requires multiple HIF subunits to be functional, hypoxia only leads to changes in both the accumulation and the activity of the HIF-1α subunit.</p><p>In most cells the HIF pathway is primarily regulated by the inhibition of the HIF-1α subunit degradation during hypoxia.2 In normoxia, the intracellular level of HIF-1α protein is typically low due to its on-going ubiquitination and proteasomal degradation. The degradation of the HIF-1α subunit is initiated through hydroxylation on a conserved proline residue, which is a process mediated by three prolyl hydroxylase (PHD) isoforms known as PHD1, PHD2, and PHD3.3 The presence of iron, oxygen, and 2-oxoglutarate (2-OG) are required for hydroxylation. Prolyl hydroxylation is blocked during hypoxia, which leads to the stabilization of HIF-1α and the establishment of a negative feedback loop whereby hypoxia and HIF-1α both upregulate PHD2 expression.4 Once HIF-1α is stabilized, it accumulates in the cells, dimerizes with ARNT, and translocates into the nucleus. Inside the nucleus, the HIF-1α/ARNT complex through interaction with its binding partners initiates the transactivation of HIF-responsive genes, such as the glucose transporter Glut1 and the angiogenic factor vascular endothelial growth factor (VEGF).5 Several strategies have been explored for manipulation of the HIF pathway at various points to either promote or retard angiogenesis.6</p><p>To date, the most common strategy for HIF activation is through inhibition of PHDs. General iron chelators such as desferrioxamine (DFO) and the inorganic salt cobalt chloride (CoCl2) have been explored clinically. DFO activates HIF-1α by chelating iron, whereas cobalt displaces iron from PHDs. Both compounds have been shown to increase HIF activation in vitro and in vivo and have demonstrated an ability to promote angiogenesis and produce a similar response to ischemia.7 Although these agents have been investigated clinically in certain disease settings, they have also been associated with toxicity.8 As such, more recent approaches to PHD inhibition have centered on small molecules.9 In many cases, known PHD inhibitors contain functional groups that are isosteric analogs of 2-OG (Figure 1). Common examples are N-acylated glycine analogs such as 1 and 2.10 Most known PHD inhibitors contain a carboxylic acid group, and in the case of compounds such as pyrazole 3, this functional group participates in a key interaction that mimics that of 2-OG.11 PHD inhibitors without a carboxylic acid group, such as 4 and 5, posses other acidic proton donors.12</p><p>In order to identify novel and interesting HIF activators, a phenotypic cell-based high-throughput screen was conducted on the NIH's Molecular Libraries Small Molecule Repository, which contains more than 300K compounds. The primary screening assay utilized a previously described cell-based gene reporter assay with stably transfected human U2OS osteosarcoma cell line expressing luciferase under control of hypoxia response elements (HREs).13 DFO (100 μM) was used as a positive control, with a previously determined EC50 of 17.8 μM in the same assay. Compounds were initially screened in the HRE-luciferase assay at a concentration of 7.5 μM. Using a cutoff at 10% or more of the activity obtained with the positive control DFO identified approximately 1200 primary hits. Complete dose response curves were subsequently generated for these compounds using the primary HRE-luciferase assay. These compounds were also tested in a high content imaging assay examining the accumulation and nuclear translocation of HIF-1α in USOS cells expressing HIF-1α fused to the Green Fluorescent Protein (GFP).14 Finally, each of these compounds was also submitted to a commercially available cell-based proteasome inhibition assay in order to eliminate any compounds acting as general proteasome inhibitors. 15</p><p>Among the compounds emerging from the screening process, isoxazoles 6 and 7 and triazines 8 and 9 represented particularly interesting starting points for chemistry as they were dissimilar to known PHD inhibitor scaffolds and lacked the acidic functional groups common to such scaffolds (Figure 2). Such facts increased the potential likelihood that these compounds may activate HIF through alternative mechanisms to PHD inhibition, or if they did act through PHD, may at the very least bind in a much different manner. Furthermore, recent reports have demonstrated that HIF activation increases cell viability and potentiates dopamine release in dopaminergic cells, which may indicate a potential application in certain neurodegenerative disorders such as Parkinson's disease.16 Since highly acidic functional groups can often limit the ability of small molecules to penetrate the blood-brain barrier, new chemical starting points for HIF activators without such functionality are considered interesting.</p><p>A 35 member amide library was rapidly prepared through standard coupling conditions with commercially available 5-phenylisoxazole-3-carboxylic acid and structurally diverse amines. In addition to the aforementioned HRE-luciferase and high content imaging nuclear translocation assays, the compounds were also tested in a real time PCR assay for their ability to induce VEGF transcription.14 Compounds were also subjected to the proteasome inhibition assay and were found to be generally inactive. The activity of the isoxazole series in the HRE-luciferase assay was uniformly disappointing. Representative results with some of the active compounds are shown here (Table 1). In fact, resynthesis of hit 6 revealed that compound to be 3–4 fold less potent than originally indicated. Although further work could certainly be done within this chemotype, early results in the triazine series were more compelling and focus was directed there.</p><p>The synthetic route for the synthesis of triazine HIF activators such as 8 and 9 was relatively straightforward (Scheme 1).17 Reaction of 2-cyanopyridine 13 with hydrazine afforded imidohydrazide 14, which was subsequently reacted with ethyl 2-oxo-2-phenylacetate in a condensation reaction to provide triazin-5(4H)-one 15. Treatment with phosphorous oxychloride under thermal conditions provided the chloride 16, which was directly reacted with commercially available amines in an SNAr reaction to afford the final compounds.</p><p>An initial library of 24 compounds (including resynthesized batches of 8 and 9) focused on variation of the amine moiety was prepared within the triazine series, and results there were much more promising (Table 2). As with the isoxazole series, these compounds were also inactive in the proteasome inhibition assay. The potency of the resynthesized batches of 8 and 9 closely matched those found during analysis of the initial hits. Not surprisingly, cyclopropylmethanamine 17 was similar in potency to 8. Increasing the size of the aliphatic group on the amine (18 and 19) led to improvements in potency relative to 8. Such modifications led to increasingly lipophilic compounds; however, incorporation of the more polar functional groups (20–22) was not favorable. Tertiary amine analogs of hit 9 were also prepared, but these analogs (23–24) failed to improve potency. Some heteroaryl secondary amine analogs such as 25 and 26 were also prepared but were also not improvements. Although, the simple benzyl amine analog 27 had similar activity to hit 8, it was noted that methyl substitution of the benzyl group at any of the positions on the aromatic ring (28–30) enhanced potency relative to 27. Having an initial survey of the SAR in hand, attention was turned to the synthesis of a second generation library that would refine the SAR around the amine moiety. First, additional aliphatic amine analogs would be prepared in an attempt to improve upon analogs 18 and 19. Second, more meta and para substituted analogs of 27 would be prepared.</p><p>Selected aliphatic amine analogs of 18 and 19 are presented here (Table 3). Introduction of a methyl group on the sp3 carbon adjacent to the secondary amine of 18 afforded analogs 31 and 32. This modification had little effect on activity, and any preference for one enantiomer over the other was minimal. Wanting to continue to explore opportunities to reduce lipophilicity, tetrahydropyran 33 was prepared; however, such a modification again failed to yield positive results. Replacement of the t-butyl group of 19 with phenyl gave analog 34, which was similarly potent in the primary assay but less active in the secondary assays. Modification of 34 by installation of a pyridyl ring (35) reduced activity. Clearly, polar functional groups, whether installed in saturated or aromatic systems, were not advantageous. Additional meta and para substituted analogs of 27 are also shown here (Table 4). Both 3,4-dimethylphenyl analog 36 and 3-chlorophenyl analog 37 were noted improvements over both 27 and previously prepared methylphenyl analogs 29 and 30. Conversely, methoxyphenyl analogs 38 and 39 were less active than 36 and 37. Substitution of 27 with a para-t-butyl group (40) gave one of the most potent compounds tested. As was demonstrated in other analogs, attempts to introduce polarity through installation of pyridine rings (41 and 42) significantly reduced activity. Installation of a phenyl ring at either the meta (43) or para (ML228) position of the benzyl amine 27, on the other hand, quite enhanced potency.</p><p>ML228 was selected for further characterization since it showed the most improved potency within the chemotype and was viewed as an interesting tool compound. The probe compound ML228 was among the top active compounds in each of the three HIF-specific activity assays and was inactive in the proteasome inhibition counterscreen assay (Figure 3). In order to gain an understanding of the broad pharmacology of this compound, ML228 was submitted to a radioligand binding assay panel of 68 GPCRs, ion channels, kinases, and transporters.18 ML228 was found to inhibit greater than 75% of radioligand binding in six assays when tested at a concentration of 10 μM (Table 5). An additional ten molecular targets were identified where binding inhibition was moderate (50–75% inhibition),19 while there was no significant binding (<50% inhibition) at the remaining 52 targets. Lipophilic compounds such as ML228 sometimes exhibit non-specific binding in assays such as these; however, this binding assay profile provides some basic information for future users of the probe compound to consider.</p><p>Most compounds that are known to activate HIF act through metal chelation. In order to provide some further insight into the possible mechanisms by which ML228 acts on the HIF pathway, the role of metal chelation was investigated (Figure 4). To achieve this task, excess iron or zinc (50 μM) were added in the media with the probe and tested in the primary HRE-luciferase assay. Results were compared to those with only media and probe. The presence of iron produced a dramatic effect, shifting the dose response curve to the right and substantially decreasing the magnitude of response. The addition of zinc produced a much smaller rightward shift and the magnitude of response was similar to compound alone. These results suggest that ML228 can chelate iron, which is consistent with some known mechanisms of HIF activation. A cell toxicity assay20 was also performed in the same cell line and ruled out that the changes in activity observed with the addition of these metals was due to cell death (data not shown).</p><p>Recent publication of PHD inhibitor 3 and related analogs disclosed x-ray co-crystal structures of some inhibitors from this chemotype bound to the PHD2 active site.11 Although ML228 has not been shown to act through PHD, molecular modeling of ML228 was deemed an expeditious method for determining whether it could reasonably bind at this known binding site. Flexible superposition of an ensemble of 30 low energy structures of ML228 with a structural hypothesis taken from a mutual flexible alignment of all ligands bound to the published PHD2 active site using SurflexSim21 gave a rather low shape based similarity score of 5.5 (normalized similarity on a 1–10 scale) (Figure 5). Generally, compounds with a higher likelihood to bind a similar protein site based on shape and surface considerations typically score above 7.0 in a SurflexSim shape-based similarity score. Furthermore, manual docking of ML228 positioned to chelate iron in the active site revealed multiple negative steric interactions and a lack of favorable contacts. While not conclusive, molecular modeling suggests a low probability that ML228 shares a similar mode of binding to PHD2 as those reported for analogs of 3.</p><p>ML228 represents a novel chemotype available to the research community for the study of HIF activation and its therapeutic potential. Not only is the compound substantially different in structure from known HIF activators, ML228 lacks the acidic functional group almost universally present in PHD inhibitors, which may be important for certain disease applications. ML228 was demonstrated to potently activate HIF in vitro as well as its downstream target VEGF. Further biological evaluation of ML228 is ongoing and will be reported in due course.</p>",
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"content": "Hypoxia and ischemia are linked to several serious public health problems that affect most major organ systems. Specific examples include diseases of the cardiovascular, pulmonary, renal, neurologic, and musculoskeletal systems. The most significant pathway for cellular response to hypoxia is the hypoxia inducible factor (HIF) pathway. HIFs are transcription factors responsible for the activation of genes which encode proteins that mediate adaptive responses to reduced oxygen availability. A high-throughput cell-based HIF-mediated gene reporter screen was carried out using the NIH\\xe2\\x80\\x99s Molecular Libraries Small Molecule Repository to identify activators of the HIF pathway. This communication describes the subsequent medicinal chemistry optimization of a triazine scaffold that led to the identification of the new molecular probe ML228. A discussion of HIF activation SAR within this chemotype as well as detailed in vitro characterization of the probe molecule is presented here.",
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}
]
|
science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.783 | [
{
"content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Integration of Evolutionary Features for the Identification of Functionally Important Residues in Major Facilitator Superfamily Transporters\nContent:\nAbstract:\nThe identification of functionally important residues is an important challenge for understanding the molecular mechanisms of proteins. Membrane protein transporters operate two-state allosteric conformational changes using functionally important cooperative residues that mediate long-range communication from the substrate binding site to the translocation pathway. In this study, we identified functionally important cooperative residues of membrane protein transporters by integrating sequence conservation and co-evolutionary information. A newly derived evolutionary feature, the co-evolutionary coupling number, was introduced to measure the connectivity of co-evolving residue pairs and was integrated with the sequence conservation score. We tested this method on three Major Facilitator Superfamily( MFS) transporters, LacY, GlpT, and EmrD. MFS transporters are an important family of membrane protein transporters, which utilize diverse substrates, catalyze different modes of transport using unique combinations of functional residues, and have enough characterized functional residues to validate the performance of our method. We found that the conserved cores of evolutionarily coupled residues are involved in specific substrate recognition and translocation of MFS transporters. Furthermore, a subset of the residues forms an interaction network connecting functional sites in the protein structure. We also confirmed that our method is effective on other membrane protein transporters. Our results provide insight into the location of functional residues important for the molecular mechanisms of membrane protein transporters.\nIntroduction:\nThe identification of functionally important cooperative residue is important for understanding the allosteric pathways of proteins. Cooperative residues are responsible for long-range allosteric communication from the substrate binding sites to the translocation pathways of membrane protein transporters[1]. A number of methods have been proposed for the identification of functionally important residues in proteins. Based on the notion that functionally important residues tend to be conserved within a protein family[2],[3], sequence conservation analyses have been applied to identify specific functional sites, such as substrate/ligand binding residues[4], protein-protein interfaces[5], active sites of enzymes[6], and residues responsible for functional specificity[7]. Meanwhile, co-evolutionary analyses, which were introduced by the observation that functionally important residues are likely to co-evolve with other functional residues to reduce the effects of mutations[8], have been applied to identify energetically and/or evolutionarily coupled interactions between the domains of complex proteins[9], the interaction sites of protein complexes[10], and the allosteric pathways of proteins[11],[12]. One drawback of these approaches is that residues may be conserved or co-evolved due to several underlying causes, such as the maintenance of protein structure, interaction, and folding, as well as functional constraint[13],[14]. Therefore, a method that can quantify and detect functional constraints from the evolutionary information in protein sequences would greatly aid the identification of functionally important residues in proteins[15]. Membrane protein transporters are involved in two-state allosteric communication, which mediates the propagation of regulatory information from the substrate binding site to the translocation pathway through large conformational changes[1]. These conformational changes could be brought about through cooperative residues[16]. Recent studies have suggested that cooperative residues are conserved[17] or evolutionary coupled[18] to maintain allosteric communication. Furthermore, it has been proposed that co-evolved pairs of moderately conserved residues are important for protein function[19]. Thus, it may be possible to combine sequence conservation and co-evolutionary analyses to identify the cooperative residues of membrane protein transporters. To do this, we derived a new method for identifying the cooperative residues of membrane protein transporters by integrating two different evolutionary features. We extracted functional information from multiple evolutionary constraints based on the following deduction: we took advantage of the fact that clusters of cooperative residues might be co-evolutionary connected not only by proximal but also distal residues in order to mediate allosteric communication[18]. When we considered a protein as a co-evolving network of residues, high connectivity described the functional essentiality of a single residue. Based on these, we hypothesized that cooperative residues lining the substrate binding and translocation pathway are likely to be conserved and have more co-evolutionarily coupled partners than non-functional residues, showing high connectivity in a co-evolution network. To test our hypothesis, we introduced a co-evolutionary coupling number( CN) to measure the connectivity of co-evolving residue pairs in a co-evolution network. We then integrated CN with sequence conservation score and investigated the functional roles and structural positions of the conserved cores of co-evolutionarily coupled residues. We initially applied our method to the MFS transporters, LacY, GlpT, and EmrD, for which crystal structures have been solved and whose functional residues have been characterized well enough to evaluate the performance of our method. MFS transporters represent one of the largest and most diverse superfamily of membrane protein transporters and are ubiquitous to all three kingdoms[20]. The identification of cooperative residues of MFS transporters may be helpful in inferring their allosteric mechanisms, including substrate recognition and translocation. MFS transporters move various substrates( e. g., sugar, drug, metabolites, and anions) in different directions across cell membranes using a unique combination of residues in their transmembrane regions[21]. One MFS transporter, lactose permease( LacY), is a symporter that catalyzes the coupled translocation of lactose and H+[22]. Another, glycerol-3-phosphate transporter( GlpT), mediates the exchange of glycerol-3-phosphate and inorganic phosphate in an antiport manner[23]. Multi-drug transporter, EmrD, is an antiporter that exports a diverse group of chemically unrelated drugs[24]. Using our method, we found that conserved cores of evolutionarily coupled residues comprise residue interaction networks connecting the specific substrate recognition site and translocation pathway of MFS transporters. We also tested our method on other proteins and confirmed that it is effective in identifying the cooperative residues of membrane protein transporters.\nDiscussion:\nIn this study, we attempted to identify the functionally important cooperative residues of membrane protein transporters from amino acid sequences by integrating two different evolutionary features. We demonstrated that the conserved cores of evolutionarily coupled residues of MFS transporters were mainly located in the substrate translocation pathway. One may question why functionally important residues are conserved and have evolved in a co-dependent manner. It has been suggested that protein sequences may have been robust to environmental and mutational perturbations in the course of evolution in order to preserve protein function[48]. These residues have evolved at a rate that was slow enough to avoid the loss of function[49]. Indeed, we observed that central cavity residues of MFS transporters are moderately conserved and enriched between the 75th and 90th percentile of sequence conservation scores( Figure S1). This slow evolution rate allows correlative substitutions among functional residues, resulting in high co-evolutionary coupling numbers[26]. The presence of an interaction network of cooperative residues is strongly correlated with the pathway of substrate translocation described in other studies[27],[50]. We found that the cluster of cooperative residues comprised an interaction network that may constitute an allosteric pathway connecting the substrate binding site and translocation pathway of MFS transporters. Yifrach and colleagues found that allosteric pathway-lining residues are energetically coupled over long distances and showed that these residues are important for the sequential conformational transition of the Kv channel using electrophysiology recordings techniques[1],[51]. In addition, other researchers have shown that perturbations of conserved residues impair the allosteric communication of protein residues[52],[53]. These results suggest that cooperative residues are evolutionarily coupled and conserved to mediate long-range allosteric communication from the substrate binding site to the translocation pathway of membrane protein transporters. The efficient regulation of allosteric communication is achieved through the interaction of cooperative residues. Recent network-based structural analyses by Nussinov and colleagues have shown that centrally positioned residues in protein structures maintain the robustness of allosteric pathways through residue-residue interactions[29],[54]. By mapping the detected residues onto the ligand-free( PDB ID: 2CFQ) and ligand-bound( PDB ID: 1PV7) structures, we observed the rearrangement of residue-residue interactions. In particular, irreplaceable substrate binding residues, E126 and R144, had different interatomic contacts between ligand-free and ligand-bound structures( Figure S6). In the ligand-free structure, the guanidine group of R144 forms a salt bridge with the carboxyl group of E126; whereas, in the ligand-bound structure, the two atomic groups directly interact with the substrate by breaking the salt bridge[55],[56]. Also, the rearrangements of hydrogen bonds and salt bridges between residues Y236, D240, R302, K319, H322, and E325 are known to involve conformational changes in LacY[27]. Taken together, we reasoned that the connectivity of the detected residues was changed because efficient conformational changes for substrate transport are regulated by the formation and breakage of interactions between cooperative residues. We found that some of the high-IS residues in MFS transporters are non-cavity residues, while most of them are positioned in the central cavity to control substrate transport. It may be possible that some of the detected non-cavity residues are also involved in the transport mechanism. For example, it has been reported that a non-cavity residue, R302, of LacY is irreplaceable for substrate transport[27] and connected with central cavity residues, K319, Y236, D240, and H322( Figure 4B and Table 1). Furthermore, we noticed that some non-cavity residues that have high-IS were found from the residue interaction networks of other membrane protein transporters( Figures S4). The detected non-cavity residues that surround the cavity region may have functional roles in membrane protein transporters. Different MFS transporters may have diverse interaction networks of cooperative residues. We believe that the diversity of the networks occurs because evolution likely favors functional diversification of MFS transporters. Interestingly, we found that the interaction network of the detected residues in EmrD were found from only one symmetric half( where H+ translocation occurs); whereas, the networks of LacY and GlpT covered both symmetric halves. In EmrD, proton translocation and drug transport may occur at different sites in the central cavity[24]. EmrD has a large and flexible substrate recognition pocket that transports various chemically unrelated drug compounds; therefore, different drugs may interact with different sites of the pocket[57]. We suspect that the substrate recognition pocket of EmrD is not conserved so that functional residue detection is limited. In summary, our integrative evolutionary analysis effectively shows that the conserved cores of evolutionarily coupled residues arose from functional constraints, providing information to characterize specific functional residues of MFS transporters. We believe this method can be applied to other proteins to narrow down the potential candidates of functional residues and to save time and reduce the cost incurred by molecular biology, biochemical, and biophysical approaches. We provide downloadable source code at our website( http://sbi. postech. ac. kr/IS/) for wide application of this method.",
"role": "user"
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{
"content": "Major Facilitator Superfamily ( MFS ) transporters are one of the largest families of membrane protein transporters and are ubiquitous to all three kingdoms of life . Structural studies of MFS transporters have revealed that the members of this superfamily share structural homology; however , due to weak sequence similarity , their structural similarity has only been found after structural determination . Even after the structures were solved , painstaking efforts were needed to detect functionally important residues . The identification of functionally important cooperative residues from sequences may provide an alternative way to understanding the function of this important class of proteins . Here , we show that it is possible to identify functionally important residues of MFS transporters by integrating two different evolutionary features , sequence conservation and co-evolutionary information . Our results suggest that the conserved cores of evolutionarily coupled residues are involved in specific substrate recognition and translocation of membrane protein transporters . Also , a subset of the identified residues comprises an interaction network connecting functional sites in the protein structure . The ability to identify functional residues from protein sequences may be helpful for locating potential mutagenesis targets in mechanistic studies of membrane protein transporters .",
"role": "assistant"
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science.craftchem_ner | science.craftchem_ner.3907 | [
{
"content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nAbatteryoftestswasperformedtofurtherevaluatethegeneralsensorimotorphenotypeofthePGC-1alpha-/-mice.",
"role": "user"
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{
"content": "[]",
"role": "assistant"
}
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science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.2903 | [
{
"content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nDedicated lanes for connected and automated vehicles (CAVs) can not only provide the technological accommodation, but also the desired market incentive for road user to adapt CAVs. Thus far, the majority of the impact assessment of CAV focused on the network-wide benefits. In this paper, we investigate the change of the traffic flow characteristic with two configurations of dedicated CAV lane across levels of market penetration. The traffic flow characteristics are quantified from the perspectives of headway distribution, communication density, and speed-flow diagram. The results highlight the contributions of the CAV lane. First, CAV lanes significantly improves the speed-flow characteristics by extending the stable region of the speed-flow curve and yielding a greater optimum flow. The highest value of optimum flow is 3400 vehicle per lane per hour at 90 MPR with one CAV lane. Furthermore, the concentration of CAVs at a lane results a narrower headway distribution (with smaller standard deviation), even with partial market penetration. Moreover, the CAV lane creates a more consistent CAV density which maintains the communication density level at a predictable level, hence decreasing the probability of packet drop.\n\nCited Works Summary:\n[1]: Automated vehicles have the potential to bring about transformative safety, mobility, energy, and environmental benefits to the surface transportation system. They are also being introduced into a complex transportation system, where second-order impacts, such as the possibility of increased vehicle-miles traveled, are of significant concern. Given the complexity of the impacts, a modeling framework is needed to ensure that they are adequately captured. This report presents a framework for estimating the potential benefits and dis-benefits of technologies contributing to the automation of the Nation’s surface transportation system. Components of the framework include (1) Safety: exposure to near-crash situations, crash prevention, and crash severity reduction; (2) Vehicle mobility: vehicle throughput, both in car following situations and at intersections; (3) Energy environment: fuel consumption and tailpipe emissions; (4) Accessibility: personal mobility, for motorists and nonmotorists; (5) Transportation system usage: response of travelers to changes in mobility and accessibility, as well as potential new modes of transportation such as increased car sharing; (6) Land use: effects of automation on land use, and (7) Economic analysis: the macro-economic impacts of all of the above changes.",
"role": "user"
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"content": "An analytical modeling framework for assessing the benefits of CAV operations was proposed in [1] . The overall results indicated that CAV improved network mobility performance, when the MPR was low, even in the absence of ML policies. Throughput without managed lane increased by 4 Nearly all of the previous studies evaluated the benefits of CAV at a aggregated level with the emphasis of the overall improvement. In this paper, we further the impact analysis to a traffic flow level, aiming to investigate the traffic flow characteristic with the presence of CAV lanes.",
"role": "assistant"
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science.medmentions_ner | science.medmentions_ner.2547 | [
{
"content": "Analyze the provided paragraph from a scientific document. Your goal is to identify and extract relevant entities.\n\nFormat your findings as a JSON object, where each key represents a category of entities, and the corresponding value is a list of entities identified in that category. If no entities are found for a category, return an empty list.\n\nFocus on precision and ensure that the output is strictly in JSON format.\n\nDocument:\n\nMulticenter Patch Testing With Methylchloroisothizoline/Methylisothiazolinone in 100 and 200 ppm Within the International Contact Dermatitis Research Group The preservative methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) is a well-known contact sensitizer. Historically, there have been different opinions on the optimal patch test concentration of MCI/MI, and both 0.01% and 0.02% aqueous (aq.) have been proposed. In 2011, based on literature reviews, it was recommended that the concentration of 0.02% aq. should be used in the international baseline series. The aim of this study was to verify the recommendation from 2011 by comparing the patch test results from consecutive patch testing with MCI/MI 0.01% and 0.02% in clinics representing countries around the world. Two thousand seven hundred three consecutive patients with dermatitis in 8 dermatology clinics representing 8 countries were patch tested with MCI/MI 0.01% aq. and, in parallel with MCI/MI 0.02% aq., provisionally included in the baseline series. Contact allergy to MCI/MI at 0.01% and 0.02% was found in 3.7% and 5.6% of the patients, respectively (P < 0.001). Methylchloroisothiazolinone/MI 0.02% aq. (dose, 6 μg/cm) diagnoses significantly more contact allergy than 0.01% (dose, 3 μg/cm), without resulting in more adverse reactions. Methylchloroisothiazolinone/MI at 0.02% aq. should therefore be continuously used in the international baseline series.",
"role": "user"
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{
"content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"dermatitis\", \"Contact allergy\", \"contact allergy\", \"adverse reactions\"], \"BiomedicalOccupationOrDiscipline\": [\"dermatology\"], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"Methylchloroisothiazolinone/MI\", \"preservative\", \"methylchloroisothiazolinone/methylisothiazolinone\", \"contact sensitizer\", \"Methylchloroisothizoline/Methylisothiazolinone\", \"MCI/MI\"], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"results\", \"diagnoses\"], \"Food\": [], \"HealthCareActivity\": [\"Multicenter Patch Testing\", \"patch testing\", \"patch test\", \"patch tested\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"baseline series\", \"literature reviews\", \"international baseline series\"], \"MedicalDevice\": [], \"Organization\": [\"International Contact Dermatitis Research Group\", \"clinics\"], \"PopulationGroup\": [\"world\"], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"study\", \"parallel\"], \"SpatialConcept\": [\"countries\"], \"Virus\": []}",
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science.data_reco_mcq_sc | science.data_reco_mcq_sc.7584 | [
{
"content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: This is an end-to-end tracking system with high tracking accuracy and efficiency.\n\nKeywords: visual tracking video\n\nDataset Information:\nE2E: End-to-End NLG Challenge (E2E) aims to assess whether recent end-to-end NLG systems can generate more complex output by learning from datasets containing higher lexical richness, syntactic complexity and diverse discourse phenomena.\nTUM RGB-D: TUM RGB-D is an RGB-D dataset. It contains the color and depth images of a Microsoft Kinect sensor along the ground-truth trajectory of the sensor.\nOTB: Object Tracking Benchmark (OTB) is a visual tracking benchmark that is widely used to evaluate the performance of a visual tracking algorithm. The dataset contains a total of 100 sequences and each is annotated frame-by-frame with bounding boxes and 11 challenge attributes.\nTUM monoVO: TUM monoVO is a dataset for evaluating the tracking accuracy of monocular Visual Odometry (VO) and SLAM methods. It contains 50 real-world sequences comprising over 100 minutes of video, recorded across different environments – ranging from narrow indoor corridors to wide outdoor scenes.\n\nAvailable Datasets: A: E2E B: TUM RGB-D C: OTB D: TUM monoVO",
"role": "user"
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{
"content": "OTB",
"role": "assistant"
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science.healthver_entailment | science.healthver_entailment.2650 | [
{
"content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: Should you wear a mask to prevent contracting the coronavirus? there's little scientific evidence to show that medical face masks or other forms of facial protective gear alone are effective in keeping healthy individuals from inhaling infectious particles.\n\nResearch Abstract:\nEvidence that face masks provide effective protection against respiratory infections in the community is scarce.\nHowever, face masks are widely used by health workers as part of droplet precautions when caring for patients with respiratory infections.\nIt would therefore be reasonable to suggest that consistent widespread use of face masks in the community could prevent further spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2).\nIn this study we examine public face mask wearing in Uganda where a proportion wears masks to protect against acquiring, and the other to prevent from transmitting SARS-CoV-2.\nThe objective of this study was to determine what percentage of the population would have to wear face masks to reduce susceptibility to and infectivity of COVID-19 in Uganda, keeping the basic reproduction number below unity and/or flattening the curve.\nWe used an SEIAQRD model for the analysis.\nResults show that implementation of facemasks has a relatively large impact on the size of the coronavirus epidemic in Uganda.\nWe find that the critical mask adherence is 5 per 100 when 80% wear face masks.\nA cost-effective analysis shows that utilizing funds to provide 1 public mask to the population has a per capita compounded cost of USD 1.34.\nIf provision of face masks is done simultaneously with supportive care, the per capita compounded cost is USD 1.965, while for the case of only treatment and no provision of face masks costs each Ugandan USD 4.0579.\nWe conclude that since it is hard to achieve a 100% adherence to face masks, government might consider provision of face masks in conjunction with provision of care.",
"role": "user"
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{
"content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"Evidence that face masks provide effective protection against respiratory infections in the community is scarce.\", \"However, face masks are widely used by health workers as part of droplet precautions when caring for patients with respiratory infections.\", \"It would therefore be reasonable to suggest that consistent widespread use of face masks in the community could prevent further spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2).\"]}",
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]
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science.data_reco_mcq_mc | science.data_reco_mcq_mc.1943 | [
{
"content": "Consider the following research inquiry and associated key terms. Review the dataset summaries provided and determine which datasets are suitable for addressing the research question. Base your decision on your understanding of machine learning datasets.\nProvide your answer as a JSON list. For example, for the inquiry \"Semi supervised image classification\", a possible response could be: [\"CIFAR-10\", \"CIFAR-100\"]. Ensure the response contains only the dataset names in JSON format.\n\nResearch Inquiry: We propose a biologically-inspired deep network, called shuttleNet, for sequence learning. We embed shuttleNet\n\nKey Terms: action recognition video\n\nDataset Summaries:\nSet11: Set11 is a dataset of 11 grayscale images. It is a dataset used for image reconstruction and image compression.\nUCF101: UCF101 dataset is an extension of UCF50 and consists of 13,320 video clips, which are classified into 101 categories. These 101 categories can be classified into 5 types (Body motion, Human-human interactions, Human-object interactions, Playing musical instruments and Sports).\nHMDB51: The HMDB51 dataset is a large collection of realistic videos from various sources, including movies and web videos. The dataset is composed of 6,766 video clips from 51 action categories (such as “jump”, “kiss” and “laugh”), with each category containing at least 101 clips.\nUASOL: The UASOL an RGB-D stereo dataset, that contains 160902 frames, filmed at 33 different scenes, each with between 2 k and 10 k frames. The frames show different paths from the perspective of a pedestrian, including sidewalks, trails, roads, etc.\nPlaces: The Places dataset is proposed for scene recognition and contains more than 2.5 million images covering more than 205 scene categories with more than 5,000 images per category.\nREDS: The realistic and dynamic scenes (REDS) dataset was proposed in the NTIRE19 Challenge. The dataset is composed of 300 video sequences with resolution of 720×1,280, and each video has 100 frames, where the training set, the validation set and the testing set have 240, 30 and 30 videos, respectively\n\nDataset Options: A: Set11 B: UCF101 C: HMDB51 D: UASOL E: Places F: REDS",
"role": "user"
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{
"content": "[\"UCF101\", \"HMDB51\"]",
"role": "assistant"
}
]
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science.bc7_litcovid_topic_classification | science.bc7_litcovid_topic_classification.2201 | [
{
"content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nBACKGROUND: Skilled nursing facilities (SNFs) are high-risk settings for SARS-CoV-2 transmission. Infection rates among employees are infrequently described. OBJECTIVE: To describe SARS-CoV-2 rates among SNF employees and residents during a non-outbreak time period, we measured cross-sectional SARS-CoV-2 prevalence across multiple sites in the Seattle area. DESIGN: SARS-CoV-2 testing was performed for SNF employees and residents using quantitative real-time reverse transcription polymerase chain reaction. A subset of employees completed a sociodemographic and symptom questionnaire. PARTICIPANTS: Between March 29 and May 13, 2020, we tested 1583 employees and 1208 residents at 16 SNFs for SARS-CoV-2. MAIN MEASURE: SARS-CoV-2 testing results and symptom report among employees and residents. KEY RESULTS: Eleven of the 16 SNFs had one or more resident or employee test positive. Overall, 46 (2.9%) employees had positive or inconclusive testing for SARS-CoV-2, and among those who completed surveys, most were asymptomatic and involved in direct patient care. The majority of employees tested were female (934, 73%), and most employees were Asian (392, 30%), Black (360, 28%), or white (360, 28%). Among the 1208 residents tested, 110 (9.1%) had positive or inconclusive results. There was no association between the presence of positive residents and positive employees within a SNF (p = 0.62, McNemar's test). CONCLUSIONS: In the largest study of SNFs to date, SARS-CoV-2 infections were detected among both employees and residents. Employees testing positive were often asymptomatic and involved in direct patient care. Surveillance testing is needed for SNF employees and residents during the pandemic response.",
"role": "user"
},
{
"content": "[\"Prevention\", \"Diagnosis\"]",
"role": "assistant"
}
]
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.759 | [
{
"content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: A survey on Hamilton cycles in directed graphs \nChapter Title: Hamilton cycles in directed graphs \n1. Abstract of Cited Paper (BIB001): This result is best possible for k = 3 since the Petersen graph is a nonhamiltonian, 2-connected, 3-regular graph on 10 vertices. It is essentially best possible for k > 4 since there exist non-hamiltonian, 2-connected, kregular graphs on 3k + 4 vertices for k even, and 3k + 5 vertices for all k. Examples of such graphs are given in [ 1, 3 1. The problem of determining the values of k for which all 2-connected, k-regular graphs on n vertices are hamiltonian was first suggested by G. Szekeres. Erdijs and Hobbs [ 3 ] proved that such graphs are hamiltonian if n < 2k + ck”*, where c is a positive constant. Subsequently, Bollobas and Hobbs [ 1 ] showed that G is hamiltonian if n < +k. We shall in fact prove a result slightly stronger than Theorem 1.\n\nReview Chapter:",
"role": "user"
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{
"content": "2.1. Minimum degree conditions. For an analogue of Dirac's theorem in directed graphs it is natural to consider the minimum semidegree δ 0 (G) of a digraph G, which is the minimum of its minimum outdegree δ + (G) and its minimum indegree δ − (G). (Here a directed graph may have two edges between a pair of vertices, but in this case their directions must be opposite.) The corresponding result is a theorem of Ghouila-Houri BIB001 . Theorem 1 (Ghouila-Houri BIB001 ). Every strongly connected digraph on n vertices with δ + (G) + δ − (G) ≥ n contains a Hamilton cycle. In particular, every digraph with δ 0 (G) ≥ n/2 contains a Hamilton cycle. (When referring to paths and cycles in directed graphs we usually mean that these are directed, without mentioning this explicitly.) For undirected regular graphs, Jackson BIB002 showed that one can reduce the degree condition in Dirac's theorem considerably if we also impose a connectivity condition, i.e. every 2-connected d-regular graph on n vertices with d ≥ n/3 contains a Hamilton cycle. Hilbig improved the degree condition to n/3 − 1 unless G is the Petersen graph or another exceptional graph. The example in Figure 1 shows that the degree condition cannot be reduced any further. Clearly, the connectivity condition is necessary. We believe that a similar result should hold for directed graphs too. Conjecture 2. Every strongly 2-connected d-regular digraph on n vertices with d ≥ n/3 contains a Hamilton cycle. Replacing each edge in Figure 1 with two oppositely oriented edges shows that the degree condition cannot be reduced. Moreover, it is not hard to see that the strong 2-connectivity cannot be replaced by just strong connectivity.",
"role": "assistant"
}
]
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science.chemdner_ner | science.chemdner_ner.2237 | [
{
"content": "Analyze the given text to identify specific entities. Focus on extracting relevant data.\n\nProvide your findings in JSON format. Each category should list the entities found.\n\nText:\n\nComputational design and biosensor applications of small molecule-sensing allosteric ribozymes. Here I describe accurate and time-efficient computational methods for designing small molecule-sensing allosteric ribozymes that serve as logic gates with NOT or YES Boolean logic functions. Theophylline-sensing ribozymes are engineered to have a high cleavage rate of 1.3 min(-1) under physiologically relevant conditions. They are highly specific to theophylline and do not respond to caffeine, which differs in a single methyl group. These ribozymes are designed by fusing a theophylline aptamer with an extended version of the hammerhead ribozyme by modeling secondary structures. Purine-sensing ribozymes are designed by fusing the minimal version of the hammerhead ribozyme with bacterial guanine or adenine aptamers by modeling 3D interactions. I have developed high-throughput compatible arrays based on purine RNA sensors that can be used for antibacterial drug discovery. The ribozymes can be employed as molecular sensors in various applications, including exogenous control of gene expression, high-throughput screening arrays, and molecular computing.",
"role": "user"
},
{
"content": "{\"Chemical\": [\"guanine\", \"purine\", \"Purine\", \"theophylline\", \"caffeine\", \"methyl\", \"Theophylline\", \"adenine\"]}",
"role": "assistant"
}
]
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science.craftchem_ner | science.craftchem_ner.3150 | [
{
"content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nGiventhattheE-cadherinpromoterisadirecttargetforSnail-mediatedrepressioninvitro[4,12,13],andthatE-cadherinwasdown-regulatedinSnail-expressinghairbuds,weexaminedthestatusofE-cadherinandotherAJproteinswithinregionsofhyperproliferativeepidermiswhereTgSnailwaspresent(Figure4A).",
"role": "user"
},
{
"content": "[\"proteins\"]",
"role": "assistant"
}
]
|
science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.2413 | [
{
"content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nIn big-data analytics, using tensor decomposition to extract patterns from large, sparse multivariate data is a popular technique. Many challenges exist for designing parallel, high performance tensor decomposition algorithms due to irregular data accesses and the growing size of tensors that are processed. There have been many efforts at implementing shared-memory algorithms for tensor decomposition, most of which have focused on the traditional C C++ with OpenMP framework. However, Chapel is becoming an increasingly popular programing language due to its expressiveness and simplicity for writing scalable parallel programs. In this work, we port a state of the art C OpenMP parallel sparse tensor decomposition tool, SPLATT, to Chapel. We present a performance study that investigates bottlenecks in our Chapel code and discusses approaches for improving its performance. Also, we discuss features in Chapel that would have been beneficial to our porting effort. We demonstrate that our Chapel code is competitive with the C OpenMP code for both runtime and scalability, achieving 83 -96 performance of the original code and near linear scalability up to 32 cores.\n\nCited Works Summary:\n[1]: HPC systems are increasingly used for data intensive computations which exhibit irregular memory accesses, non-uniform work distributions, large memory footprints, and high memory bandwidth demands. To address these challenging demands, HPC systems are turning to many-core architectures that feature a large number of energy-efficient cores backed by high-bandwidth memory. These features are exemplified in Intel's recent Knights Landing many-core processor (KNL), which typically has 68 cores and 16GB of on-package multi-channel DRAM (MCDRAM). This work investigates how the novel architectural features offered by KNL can be used in the context of decomposing sparse, unstructured tensors using the canonical polyadic decomposition (CPD). The CPD is used extensively to analyze large multi-way datasets arising in various areas including precision healthcare, cybersecurity, and e-commerce. Towards this end, we (i) develop problem decompositions for the CPD which are amenable to hundreds of concurrent threads while maintaining load balance and low synchronization costs; and (ii) explore the utilization of architectural features such as MCDRAM. Using one KNL processor, our algorithm achieves up to 1.8x speedup over a dual socket Intel Xeon system with 44 cores.\n\n[2]: Tensor decompositions are a powerful technique for enabling comprehensive and complete analysis of real-world data. Data analysis through tensor decompositions involves intensive computations over large-scale irregular sparse data. Optimizing the execution of such data intensive computations is key to reducing the time-to-solution (or response time) in real-world data analysis applications. As high-performance computing (HPC) systems are increasingly used for data analysis applications, it is becoming increasingly important to optimize sparse tensor computations and execute them efficiently on modern and advanced HPC systems. In addition to utilizing the large processing capability of HPC systems, it is crucial to improve memory performance (memory usage, communication, synchronization, memory reuse, and data locality) in HPC systems. In this paper, we present multiple optimizations that are targeted towards faster and memory-efficient execution of large-scale tensor analysis on HPC systems. We demonstrate that our techniques achieve reduction in memory usage and execution time of tensor decomposition methods when they are applied on multiple datasets of varied size and structure from different application domains. We achieve up to 11× reduction in memory usage and up to 7× improvement in performance. More importantly, we enable the application of large tensor decompositions on some important datasets on a multi-core system that would not have been feasible without our optimization.\n\n[3]: The Canonical Polyadic Decomposition (CPD) of tensors is a powerful tool for analyzing multi-way data and is used extensively to analyze very large and extremely sparse datasets. The bottleneck of computing the CPD is multiplying a sparse tensor by several dense matrices. Algorithms for tensor-matrix products fall into two classes. The first class saves floating point operations by storing a compressed tensor for each dimension of the data. These methods are fast but suffer high memory costs. The second class uses a single uncompressed tensor at the cost of additional floating point operations. In this work, we bridge the gap between the two approaches and introduce the compressed sparse fiber (CSF) a data structure for sparse tensors along with a novel parallel algorithm for tensor-matrix multiplication. CSF offers similar operation reductions as existing compressed methods while using only a single tensor structure. We validate our contributions with experiments comparing against state-of-the-art methods on a diverse set of datasets. Our work uses 58 less memory than the state-of-the-art while achieving 81 of the parallel performance on 16 threads.",
"role": "user"
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"content": "Designing and implementing sparse parallel tensor decomposition algorithms has been a rich research area in recent years. There are several shared-memory based tensor decomposition implementations using novel approaches to performing MTTKRP in a scalable and efficient manner [3] [1] [2] . However, to the best of our knowledge, the work presented in this paper is the first to implement parallel sparse tensor decomposition in a high productivity programming language such as Chapel.",
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science.scientific_papers_summarization_single_doc_pubmed | science.scientific_papers_summarization_single_doc_pubmed.2964 | [
{
"content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\nnucleotide sequences diverge over time due to the combined effects of point mutation and homologous recombination .\nrecombination events cause changes to regions of contiguous bases in single events and were generally assumed to be rare in bacteria . however , there is growing evidence that homologous recombination has a significant impact on sequence diversification during bacterial genome evolution .\na recent analysis on the mlst ( multilocus sequence typing ) data of 46 bacterial and two archaeal species revealed 27 ( 56% ) species in which homologous recombination contributed to more nucleotide changes than point mutation . the rapid genetic change introduced by homologous recombination could facilitate ecological adaption and drive pathogenesis in bacterial pathogens .\ncurrently , the mlst scheme , using dna fragments from seven housekeeping genes , has been routinely used to characterize bacterial isolates .\nthe standard mlst scheme has also been extended to construct fine - scale relationships and further subdivide identical multilocus sequence types ( sts ) using more loci or a large amount of shared genomic sequences .\ngiven the common occurrence of homologous recombination , it becomes crucial to investigate the genome - wide extent of homologous recombination , which could also benefit the construction of the strain history and tracking the spread of emerging pathogens .\nidentifying recombinational exchanges in closely related strains is challenging as recombinational exchanges involved in a small number of nucleotides may be mistaken as point mutations . guttman and dykhuizen ( 1994 )\nhave successfully examined the clonal divergence of e. coli strains in the ecor group a by considering the divergence time and mutation rate and showed that recombination has occurred at a rate 50-fold higher than the mutation rate in four loci .\n( 2000 ) estimated the ancestral allele for the isolates that differ only one locus out of the seven mlst loci and assigned recombination based on the number of derived nucleotides from the ancestral allele and on whether the nucleotides are novel in the population .\nwe adopted a new approach ( illustrated in fig . 1 ) to identify recombinant genes in neisseria meningitidis strains with identical sts , which does not require\nthe estimation of divergence time and ancestral alleles and can be applied on any two strains with identical sts . in brief ,\nnucleotide substitution was assumed to follow a binomial distribution and an upper bound of genome - wide divergence ( ) by point mutation was calculated for no observed substitution in all nucleotide sites of the seven mlst loci .\nthe estimated maximum genome - wide divergence was then used as a benchmark to compute a p - value for the observed nucleotide changes of each gene in the genome to be explained by point mutation .\ngenes that have more than the expected number of nucleotide changes at a significance level of 0.001 were deemed as recombinant genes .\nour results revealed that up to 19% of commonly present genes in n. meningitidis strains with identical sts have been affected by homologous recombination .\ninference of homologous recombination in strains with identical sts . under a binomial distribution of nucleotide substitution ,\nthere is a probability for no nucleotide change in the seven mlst loci . that is ( 1- )\n= 0.001 , here n is the number of nucleotides in the seven mlst loci and is the upper bound of genome - wide nucleotide divergence ( ) at 0.001 significance level given no change in the seven mlst loci . at genome - wide divergence , genes that have more than the expected number of nucleotide changes at 0.001 significance level were deemed as nonvertically acquired genes . in another study on e. coli o104 ( st678 ) genomes , we visualized recombinant genes by plotting the pairwise dna distance of orthologous genes along the genome and identified 167 genes in three gene clusters that have likely undergone homologous recombination . a reanalysis on the orthologs between e. coli on2010 and 55989 ( labeled as ec55989 thereafter to avoid unnecessary confusion ) genomes using both pairwise dna distance and the p - values as described in ref .\nin fact , the use of nucleotide divergence between two genomes for homologous recombination detection has been successful in other studies , one of which was on two e. coli st131 strains .\nit has been observed that a higher portion ( at least 9% ) of core genes in the e. coli st131 genomes than in the e. coli st678 genomes ( fig . 2 ) are affected by homologous recombination .\nthe findings in both n. meningitidis and e. coli showed extensive genomic variation within identical sts .\nsince many bacterial species have a comparable or higher level of recombinogenicity than n. meningitidis or e. coli , extensive genomic variation within identical sts should be expected in many bacterial species .\ninferring genes involved in homologous recombination by comparing orthologs between two e. coli strains on2010 and ec55989 .\n( b ) p - values were calculated based on the maximum genome - wide divergence given the seven identical mlst loci as illustrated in figure 1 . for simplicity ,\nplease note that more genes ( 4207 genes in total ) were examined here than in our previous study ( 3794 genes ) , since our previous study focused on the genes present in both the o104 strains and the iai1 strain .\nit is important to note that the high genomic variation discovered within identical sts should not be interpreted as artifacts of these studies .\nthe high level of genomic variation within identical sts could , instead , be explained by that many non - vertical genes within identical sts are deleterious or transiently adaptive and undergo fast rates of evolution .\nin fact , the ratio of recombination to mutation rates was higher in the comparison of clonally related strains than of relatively broadly sampled strains from the corresponding species .\nsuch a discrepancy between the estimated recombination - mutation ratios highlights the need for a population genetics framework for the study of recombination and bacterial genome evolution .\namong the three gene clusters of recombinant genes we identified in e. coli o104 , one gene cluster contained 125 genes and was likely involved in direct chromosomal homologous recombination specific to the on2010 strain .\nthese 125 genes were found in 20 different functional categories and 70 of them were found in all the studied 57 e. coli and shigella genomes .\nthis is consistent with the conclusion that genes from all functional categories are subject to dna exchange .\nfurthermore , the nearest phylogenetic neighbors of these genes were not clustered in a single phylogenetic group .\nwe hypothesized that extensive recombination with a broad spectrum of strains has taken place in one genome , and this highly mosaic genome then recombined with the precursor to the on2010 genome .\nthe other two gene clusters of recombinant genes in e. coli o104 were located in the prophage regions , but the genes in these two gene clusters were identical between on2010 and ec55989 genomes .\nit is noteworthy that the reanalysis with more single - copy genes ( with details in fig . \nthese prophage genes are not present in all o104 strains and the outgroup iai1 strain .\nthis could be explained by frequent recombination of the prophage genes with infecting phages or different prophages from other bacterial chromosomes .\nsince all examined o104 genomes are of conserved genome synteny , our observations support the argument that homologous ( legitimate ) recombination drives module exchange between phages .\ntogether , these findings suggest that homologous recombination takes place frequently in both core genes and dispensable genes .\nas the cost of sequencing drops , the characterization of bacterial isolates has utilized more shared genes or loci and shifted toward phylogenomic analysis .\nquite often , multiple gene alignments were concatenated into a single super - alignment , from which phylogenies were reconstructed using a variety of methodologies .\nsuch a data set , also known as a supermatrix , has been demonstrated to solve previously ambiguous or unresolved phylogenies , even in the presence of a low amount of horizontal gene transfer in the data set .\nunfortunately , the supermatrix approach becomes very sensitive to recombination when applied to strains with identical sts due to limited genuine sequence diversity .\nthe concatenated sequences of 3794 genes in the e. coli o104 strains were overwhelmed by the phylogenetic signal of the 125 recombinant genes , as many other genes are identical among the e. coli o104 strains ( fig . \nthe accuracy and robustness of the constructed evolutionary relationships can be improved by the exclusion of recombinogenic and incongruent sequences .\nin fact , the removal of the 125 recombinant genes from the e. coli o104 data set has resulted in consistent phylogenetic relationships of o104 strains by different phylogenetic approaches .\none interesting finding of our e. coli o104 study is that the number of identical loci implemented in bigsdb was less sensitive to homologous recombination than the concatenated sequences of all loci .\nthis could be explained by the fact that recombination has affected a relatively small number of genes but introduced a substantial amount of diversity in the on2010 genome .\nit is further noteworthy that supertrees , another widely used approach for phylogenomic analysis are not suitable for characterizing strains with identical mlst types , as many individual genes are identical or nearly identical and contain no or very limited phylogenetic information for each individual gene tree .\nhomologous recombination can bring the beneficial mutations arising in different genomes together and have a strong impact on ecological adaptation .\none well - known example was the recombination in the pena genes during the emergence of penicillin resistance in n. meningitidis .\nvariation of the pena gene corresponding to different levels of penicillin susceptibility has also been observed between n. meningitidis strains with the same mlst types .\nfurthermore , genetic variation within the same mlst types has been evident in the capsule gene cluster and genes used for vaccine target in n. meningitidis .\nthese observations suggest a strong relationship between homologous recombination and pathogenic adaptation involved in antibiotic resistance , capsule biosynthesis and vaccine efficacy .\nrecombination has affected fimh which encodes mannose - specific type 1 fimbrial adhesin , resulting in distinct fluoroquinolone - resistance profiles in st131 strains .\na survey of the fimh gene on the 57 e. coli and shigella genomes revealed that on2010 was the only e. coli o104 genome containing a fimh blast hit > 10% of length ( fig . \non the on2010 genome scaffold , fimh is upstream adjacent to a fructuronic acid transporter gene gntp , which is universally present in all e. coli and shigella genomes . the gntp gene in on2010\n2 ) , and most importantly , the most similar sequences to the on2010 gntp were also in e24377a and s88 ( data not shown ) .\nthe shared origin between the adjacent fimh and gntp genes in on2010 suggested that patchily distributed genes involved in pathogenesis could be introduced by homologous recombination of the conserved flanking genes .\nonly informative sites are shown with coordinates at the top . the on2010 sequence and its most similar sequences ( differing by one nucleotide )",
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"content": "due to divergence , genetic variation is generally believed to be high among distantly related strains , low among closely related ones and little or none within the same classified clonal groups . \n several recent genome - wide studies , however , revealed that significant genetic variation resides in a considerable number of genes among strains with identical mlst ( multilocus sequence typing ) types and much of the variation was introduced by homologous recombination . recognizing and understanding genomic variation within clonal bacterial groups \n could shed new light on the evolutionary path of infectious agents and the emergence of particularly pathogenic or virulent variants . \n this commentary presents our recent contributions to this line of work .",
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.41808 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nInhibition of bacterial α-, β- and γ-class carbonic anhydrases with selenazoles incorporating benzenesulfonamide moieties\n\nContent Extracts:\nIntroduction\n<p>Carbonic anhydrases (CAs, EC 4.2.1.1) are a superfamily of ubiquitous metalloenzymes which catalyze the simple but physiologically crucial interconversion of carbon dioxide and water, with the formation of bicarbonate and protons: CO2 + H2O ⇌ HCO3− + H+1–11. The hydration/dehydration of CO2 is a key physiological reaction for the life cycle of most organisms, including bacteria, since it is connected with numerous metabolic pathways, such as the biosynthetic processes requiring CO2 or HCO3− (photosynthesis and carboxylation reactions) and biochemical pathways including pH homeostasis, secretion of electrolytes, transport of CO2 and bicarbonate, etc.12,13. Figure 1 shows the transport of carbon dioxide and bicarbonate assisted by bacterial CAs denoting their pivotal role in the bacterial metabolism. In fact, bacteria encode such enzymes belonging to three different genetic families, the α-, β- and γ-CAs11–13.</p>\n\n\n<p>Proposed role of CAs in Gram-negative bacteria. The α-CAs convert the diffused CO2 inside the periplasmic space into bicarbonate, whereas the cytosolic β-and γ-CAs are responsible for the supplementation of CO2 and bicarbonate for the cellular metabolism. Furthermore, all these enzymes play an important role in the cellular pH homeostasis1.</p>\n\nIntroduction\n<p>Inhibition of one or more of the CAs present in bacteria was shown to interfere with the growth and/or pathogenicity of many such organisms1–5,13. The reason for that is explained as follows: these enzymes participate in tightly controlled metabolic processes, or in the pH homeostasis, which are highly relevant in all organisms, including bacteria1–13. It has been demonstrated that the two CAs (α and β) encoded by the genome of the pathogen Helicobacter pylori, a Gram-negative bacterium colonizing the human stomach, are essential for the acid acclimatization of the pathogen within the human stomach and thus, for the bacterial survival in the host14. On the other hand, Vibrio cholerae (a Gram-negative bacterium provoking cholera) uses its CAs (α, β and γ) for producing sodium bicarbonate, which induces cholera toxin expression15, and for colonizing the host16. Once more, the causative agent of brucellosis, Brucella suis, a non-motile Gram-negative coccobacillus, and the Mycobacterium tuberculosis, an obligate pathogenic bacterium responsible for tuberculosis, were needed of functional CAs for growing17–19. Indeed, a large number of interesting studies were dedicated in the last decade for finding effective in vitro CA inhibitors (CAIs) targeting these pathogenic enzymes8–14,17–19, and possibly translating such results to in vivo and eventually clinical activity1. However, CAIs are not yet seriously considered as potential anti-infectives to date, mainly due to the fact that no relevant drug discovery program has been yet started, although these compounds may show indeed a great promise for fighting drug resistant microbes, such as bacteria, fungi and protozoa20.</p>\n\nChemistry\n<p>Selenazoles 1, 4–5 and 8–11 were reported earlier by our group and were used as follows21.</p>\n\nCA enzyme inhibition assay\n<p>An Sx.18Mv-R Applied Photophysics (Oxford, UK) stopped-flow instrument has been used to assay the catalytic activity of various CA isozymes for CO2 hydration reaction22. Phenol red (at a concentration of 0.2 mM) was used as an indicator, working at the absorbance maximum of 557 nm, with 10 mM Hepes (pH 7.5, for α-CAs) or TRIS (pH 8.3, for β- and γ-CAs) as buffers, 0.1 M Na2SO4 (for maintaining constant ionic strength), following the CA-catalyzed CO2 hydration reaction for a period of 10 s at 25 °C. The CO2 concentrations ranged from 1.7 to 17 mM for the determination of the kinetic parameters and inhibition constants. For each inhibitor, at least six traces of the initial 5–10% of the reaction have been used for determining the initial velocity. The uncatalyzed rates were determined in the same manner and subtracted from the total observed rates. Stock solutions of inhibitors (10 mM) were prepared in distilled-deionized water and dilutions up to 1 nM were done thereafter with the assay buffer. Enzyme and inhibitor solutions were pre-incubated together for 15 min (standard assay at room temperature) prior to assay, in order to allow for the formation of the enzyme–inhibitor complex. The inhibition constants were obtained by non-linear least-squares methods, using GraphPad PRISM 3 and the Cheng–Prusoff equation, as reported earlier23. All CAs were recombinant proteins produced as reported earlier by our groups9–14,24.</p>\n\nChemistry\n<p>Selenazoles are an important class of heterocycles with significant biological effects and considerable pharmacological relevance21,25. Moreover, these five-membered selenium heterocycles are easily synthesized from primary selenoamide bearing benzenesulfonamide 1 as starting materials. This compound has been used for the preparation of various 2,5-disubstituted 1,3-selenazoles 4a-f and 5a-c, as reported earlier (Scheme 1)21.</p>\n\n\n<p>Synthesis of functionalized selenazoles 4a–f and 5a–c.</p>\n\nChemistry\n<p>In order to extend our library of selenazole derivatives, we report the synthesis of a variety of double-functionalized and ionic 1,3-selenazoles, as shown in Scheme 2.</p>\n\n\n<p>Synthesis of substituted 2,5-selenazoles 8–11.</p>\n\nChemistry\n<p>Our main interest was to investigate structure–activity relationship related to the inhibition of different CAs classes from three different pathogenic bacteria: Helicobacter pylori (hpCAα), Vibrio cholerae (VchCAα, VchCAβ and VchCAγ) and, Burkholderia pseudomallei (BpsCAβ and BpsCAγ), relevant pathogens in many diseases for which drug-resistant strains were evidenced1,9–11.</p>\n\nCarbonic anhydrase inhibition\n<p>Selenazole scaffolds showed promising results as antibacterial activity26–28. For this reason, we investigated whether such compounds may act as inhibitors of bacterial CAs, thus being possible candidates for anti-infective studies. We tested in vitro compounds 4–11 for their inhibitory activity against six bacterial enzyme: hpCAα, VchCAα, VchCAβ, VhCAγ, BpsCAβ and BpsCAγ, by means of the stopped-flow carbon dioxide hydration assay22. These activities were compared with those of the standard, clinically used CAI acetazolamide (AAZ) (Table 1).</p>\n\n\n<p>Inhibition data against bacterial enzyme hpCAα, VchCAα, VchCAβ, VchCAγ, BpsCAβ and BpsCAγ of derivates 4–5, 8–11 and acetazolamide AAZ by a stopped-flow CO2 hydrase assay22.</p><p>aMean from three different assays, by a stopped-flow technique (errors were in the range of ±5–10% of the reported values).</p>\n\nCarbonic anhydrase inhibition\n<p>As seen from data of Table 1, all bacterial enzymes investigated here showed inhibition in the low micromolar or submicromolar range, with all selenazoles incorporating benzenesulfonamide mioietes included in the study.</p><p>(i) HpCAα was effectively inhibited, with KIs ranging between 0.79 and 2.84 µM, thus leaving little space to structure–activity relationship (SAR) discussion due to this flat profile. However, all these sulfonamides were at least two orders of magnitude less effective as HpCAα inhibitors compared to acetazolamide, which is a very potent inhibitor of this enzyme.</p><p>(ii) VchCAα was inhibited in the submicromolar range by selenazoles 4–11, with KIs ranging between 0.21 and 0.94 µM, again without any relevant SAR, since the activity was very similar for the entire series of derivatives. However, the β- and γ-class enzymes from the same pathogen had a weaker sensitivity to this class of CAIs, since the KIs ranged between 2.61–9.12 µM for VchCAβ, and 3.64–9.29 µM for VchCAγ (Table 1). Again, AAZ was a better inhibitor for all these CAs compared to the studied derivatives.</p><p>(iii) Some of the selenazole sulfonamides investigated here were, on one hand, more effective BpsCAβ inhibitors compared to the standard drug AAZ, as they showed submicromolar inhibitory power. Among them were 10a (KI of 90 nM), 9b (KI of 320 nM), 5b and 5c (KIs of 0.33–0.36 µM), compared to the KI of 0.74 µM of acetazolamide. These data show that small structural differences lead to drastic effects on the CA inhibition. For example, 10b, possessing an extra methyl group compared to 10a, was 52 times a weaker BpsCAβ inhibitor compared to 10a. BpsCAγ was, on the other hand, less sensitive to these inhibitors compared to the β-class enzyme from the same pathogen, although some compounds (4a–4e, 10c) were submicromolar inhibitors, with KIs ranging between 0.70 and 0.91 µM.</p>\n\nConclusions\n<p>A series of benzenesulfonamides incorporating selenazoles with diverse substitution patterns were investigated as inhibitors of six bacterial CAs from pathogens such as Helicobacter pylori (tested enzyme was hpCAα), Vibrio cholerae (all the three CAs from this pathogen were considered, VchCAα, VchCAβ and VchCAγ) and Burkholderia pseudomallei (with its two CAs, BpsCAβ and BpsCAγ). All these sulfonamides were effective inhibitors, with potencies in the low micromolar or submicromolar range, making this class of CA inhibitors attractive as lead compounds for designing antibacterials with a novel mechanism of action, which could counteract the extensive antibiotic resistance problem encountered with most clinically used such drugs.</p>\n\nDisclosure statement\n<p>No potential conflict of interest was reported by the authors.</p>",
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"content": "AbstractA series of benzenesulfonamides incorporating selenazoles with diverse substitution patterns were investigated as inhibitors of six bacterial carbonic anhydrases (CAs, EC 4.2.1.1) from bacterial pathogens, such as Helicobacter pylori (hpCAα was the investigated enzyme), Vibrio cholerae (all the three CAs from this pathogen were considered, VchCAα, VchCAβ and VchCAγ) and Burkholderia pseudomallei (with its two CAs, BpsCAβ and BpsCAγ). All these sulfonamides were effective CA inhibitors, with potencies in the low micromolar or submicromolar range, making them attractive as lead compounds for designing antibacterials with a novel mechanism of action, which could counteract the extensive resistance problem observed with many clinically used antibiotics.",
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science.mslr2022_cochrane_multidoc_summarization | science.mslr2022_cochrane_multidoc_summarization.1314 | [
{
"content": "Review the provided collection of medical RCT summaries. Your objective is to distill the essential insights into a brief conclusion. Focus solely on the synthesis of findings without additional commentary. The RCT summaries are as follows:\n\n\n\nReport Title 1:\nA double-blind randomised controlled trial of continuous oxygen therapy for compromised fetuses.\nReport Abstract 1:\nTo investigate the effect of chronic oxygen therapy in fetuses with absent end diastolic flow in the umbilical artery assessed by doppler analysis at 24-30 weeks of gestation.\n A double-blind, randomised control trial was performed with patients blindly allocated to receive humidified oxygen or humidified air.\n A tertiary referral hospital in South Africa.\n Thirty-two women who presented between 24 and 30 weeks of gestation with a confirmed finding of absent end diastolic flow in the umbilical artery.\n After randomisation patients were allocated to receive a 40% mixture of humidified oxygen or humidified air from uniform coloured gas cylinders which were marked either 'a' or 'b' All women received betamethasone from 27 weeks of gestation on a weekly basis. Cardiotocographs were used from 28 weeks of gestation; after 28 weeks of gestation an amniocentesis was considered to confirm fetal maturity. Women were expected to breath the allocated gas continuously apart from meals and visits to the toilet.\n Survival of the fetus was the main outcome measure with secondary outcome measures documenting improvement in the fetal condition in utero.\n There were 16 women randomised to receive oxygen and 16 to receive air. There were nine survivors in the oxygen group (56.3%) and six in the air group (37.5%) (relative risk 1.5, 95% confidence interval 0.7-3.2). There was a nonsignificant increase in mean birthweight in the oxygen group (858.3 grammes vs 774.4 grammes) and a nonsignificant increase in mean duration of treatment in the oxygen group (12.8 days vs 10.4 days).\n This study did not demonstrate that chronic oxygen therapy provides any benefits to compromised fetuses between 24 and 30 weeks of gestation. Larger studies with sufficient power are necessary to assess whether oxygen therapy can reduce perinatal mortality by a clinically useful amount in this group of patients.\n\n\nReport Title 2:\nMaternal hyperoxygenation in the treatment of intrauterine growth retardation.\nReport Abstract 2:\nIn the current study the efficacy of maternal hyperoxygenation on growth-retarded fetuses was evaluated.\n Thirty-six pregnant women with intrauterine growth retardation were studied. The patients were divided in oxygen-treated (n = 17) and untreated (n = 19) groups. Doppler analysis of the fetal circulation was performed on the arrival to the hospital, after 12 hours, and thereafter on alternate days until delivery. Fetal blood was sampled by cordocentesis for immediate blood gas analysis at entrance to the study and the day of delivery.\n Significant improvement in Doppler flow patterns in treated patients were found when compared with untreated women. The Doppler variations were associated with complementary modifications in fetal blood gas. These differences resulted in a significant modification in perinatal mortality with an incidence of 29% and 68% (p less than 0.01) in treated and untreated groups, respectively.\n Our data suggest a benefit of maternal hyperoxygenation in the treatment of fetal growth retardation.\n\n\nReport Title 3:\nA prospective randomised comparison of the effect of continuous O2 therapy and bedrest on fetuses with absent end-diastolic flow on umbilical artery Doppler waveform analysis.\nReport Abstract 3:\nnan",
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"content": "There is not enough evidence to evaluate the benefits and risks of maternal oxygen therapy for suspected impaired fetal growth. Further trials of maternal hyperoxygenation seem warranted.",
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science.qasa_abstractive_qa | science.qasa_abstractive_qa.839 | [
{
"content": "Review the following segment from a research document in AI. Answer the subsequent query based solely on the provided information. Limit your response to the answer itself.\n\nResearch Segment: Data augmentation is essential to teach the network the desired invariance and robustness properties, when only few training samples are available. In case of microscopical images we primarily need shift and rotation invariance as well as robustness to deformations and gray value variations. Especially random elastic deformations of the training samples seem to be the key concept to train a segmentation network with very few annotated images.We generate smooth deformations using random displacement vectors on a coarse 3 by 3 grid. The displacements are sampled from a Gaussian distribution with 10 pixels standard deviation. Per-pixel displacements are then computed using bicubic interpolation. Drop-out layers at the end of the contracting path perform further implicit data augmentation. As for our tasks there is very little training data available, we use excessive data augmentation by applying elastic deformations to the available training images. This allows the network to learn invariance to such deformations, without the need to see these transformations in the annotated image corpus. This is particularly important in biomedical segmentation, since deformation used to be the most common variation in tissue and realistic deformations can be simulated efficiently. The value of data augmentation for learning invariance has been shown in Dosovitskiy et al. [2] in the scope of unsupervised feature learning.\n\nInquiry: Can we try to re-generate those unreachable images using recent methods to enhance medical tasks?",
"role": "user"
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"content": "unreachable images can be generated by using elastic deformation based augmentation methods.",
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science.scicite_classification | science.scicite_classification.4339 | [
{
"content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nwhere I(r, z, t) is the dynamic component of the acoustic intensity due to the interaction of the pressure waves [3–5], vi = pi/q0c0, i = a, b, describes the particle velocity for each beam -q0 being the ambient density of the medium – and * denotes the complex conjugate.",
"role": "user"
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{
"content": "Background",
"role": "assistant"
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science.scientific_papers_summarization_single_doc_pubmed | science.scientific_papers_summarization_single_doc_pubmed.10185 | [
{
"content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\nany comprehensive hypothesis concerning the pathogenesis of systemic sclerosis ( ssc , scleroderma ) must account for the varying contributions of vascular damage , extravascular tissue fibrosis , and inflammation . while certain clinical features of ssc are overt expressions of vascular injury ( renal crisis , pulmonary arterial hypertension , and raynaud phenomenon ) , our understanding of other organ involvements is less well understood .\ncomplications from scleroderma do have a negative impact on sexual function and in turn on the overall quality of life . in spite of the 80% female predominance of ssc ,\nmost of the studies on the effect of ssc on sexual function have involved men [ 29 ] . \nmale erectile dysfunction ( med ) has been noted in as many as 81% of afflicted persons . \nmed in ssc can be reasonably attributed to scleroderma vasculopathy although cavernosal fibrosis has been implicated as well . \nlittle is known of the impact of scleroderma on female sexual functioning and on quality of female sex life . \nthe general difficulties in researching female sexual function might explain some of the lack of interest in this area although there has been a marked change in the past year with the publication of several studies [ 1113 ] . \ndaily and long - acting pde-5 inhibitors have been proven to be safe and effective for med in males with ssc . to our knowledge ,\nno studies have been published on successful pharmacological interventions in female ssc patients with sexual impairment .\nmed is defined as the consistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance .\nthe first report of an association between erectile dysfunction and ssc was as recently as 1981 . \nprevalence of med in ssc has been found to range from 12% to 81% [ 9 , 16 ] . \nthe causes of ed associated with ssc are unclear although a number of factors have been suggested including vascular , fibrotic , and neuropathic / dysautonomic factors [ 10 , 15 , 17 ] . while some studies reported correlations between ed in ssc and testosterone and prolactin levels [ 15 , 17 ] others have not [ 1820 ] . \nconclude that there is no support for a hormonal basis for ed in ssc as no consistent abnormalities in serum testosterone , follicle - stimulating hormone , luteinizing hormone , prolactin , estradiol , or thyroid hormones have been found . \nseveral studies have ruled out a neurological basis for ed in ssc [ 17 , 21 ] . \nrecent studies have found links between ed in ssc and penile blood pressure and penile temperature , leading to a link between ed in ssc and vasculopathy . a strong connection between endothelial function and ed has been reported in the general population , supported by the strong linkage of med with coronary artery disease . \nin this construct , endothelial injury and dysfunction result in diminished nitric oxide ( no ) production . during normal penile erection ,\nnitric oxide diffuses into the vascular smooth muscle cells in the penile corpus cavernosum stimulating guanylyl cyclase and production of cyclic guanosine monophosphate ( cgmp ) . \nthis in turn activates cgmp - dependent protein kinase ( pkg ) , phosphorylation of several proteins , lowering of intracellular cell calcium , or sensitivity to calcium leading to muscle relaxation . \nthis relaxation leads to an increase of blood in the corpus cavernosum leading to penile erection . \nan insufficient release of nitric oxide from nerve endings or endothelium can lead to an attenuated production of cgmp . \npenile vascular damage in ssc patients was assessed using duplex ultrasonography [ 2 , 23 ] showing that penile thermal abnormalities are present in almost all ssc patients . \npenile fibrosis has also been shown to be present in almost all ssc patients . \nreport severe veno - occlusive dysfunction based on histological analysis confirming severe corporeal fibrosis from a biopsy evaluation of a single ssc ed patient . \nthey postulate that fibrosis could lead to veno - occlusion leading to a reduction of the trabecular fibroelastic compliance and trabecular smooth muscle tone which depend on neurogenic - and endothelial - dependent vasomotility . \npenile fibrosis has also been shown to occur in almost all ssc patients with the presence of thickening of the tunica albuginea and hyperechoic spots inside the corpera carnevosa . \nconclude that their results showing fibrosis and thermoregulatory dysfunction in ssc patients with ed support the hypothesis that structural modifications induced by ssc lead to a reduced capability of heat exchange and vascular damage . \npde-5 inhibitors enhance erectile function by blocking degradation of cgmp leading to an increase in intracellular cgmp in the corpus cavernosum and penile vasculature . \nthe result is an increase in the relaxation of the smooth muscle leading to an increased blood flow and penile erection . \nthere are three pde-5 inhibitor compounds licensed for treatment of med : sildenafil , vardenafil , and tadalafil . \nstudies in the general population have shown these to be safe and generally effective depending on the etiology and severity of the erectile dysfunction . \nostojic and damjanov described a small case series with unsatisfactory response to on demand sildenafil ( 2550 mg ) . \nan open label randomized cross - over study by aversa et al . compared 20 mg tadalafil on demand versus 20 mg in a fixed alternate day schedule . on the fixed alternate day schedule ,\na significant improvement was reported for the flow - mediated dilatation , peak flow velocities of cavernous arteries , reduced plasma levels of et-1 and vascular cell adhesion molecules ( markers of endothelial function ) , and morning erections . \nno such results were found for the on - demand regimen suggesting that a constant plasma level of pde-5i might be important for the treatment of med in ssc . \nreport the results of a study with a daily 10 mg dose of tadalafil for 12 weeks in 14 ssc patients with varying degrees of ed . \nimprovements were found in erectile function , vascular measures of cavernous arteries , morning erections , and plasma et-1 levels ( reduced levels ) .\nthere is an inequality in the number of studies focusing on male versus female sexual dysfunction ( fsd ) in the general population and the same holds true in ssc although the disease primarily affects women . \nthe complexity and multifactorial nature of female sexual response and female sexual dysfunction adds to the difficulty in research in this area . \nfsd can have psychological and social components in addition to medical and physiological components . \nfsd is defined as persistent or recurring decrease in sexual desire , persistent or recurring decrease in sexual arousal , dyspareunia , and a difficulty in or inability to achieve orgasm . \nit is reported to affect 20%50% of all women and can severely impact quality of life and interpersonal relationships [ 28 , 29 ] . changes associated with ssc can have a negative impact on female sexuality and sexual functioning\n. symptoms such as skin tightening around the vaginal introitus , joint contractures , muscle weakness , changes in skin around the breasts and breast muscle , and joint pain have been found to be associated with lower levels of sexual functioning , desire , arousal , lubrication , and satisfaction [ 4 , 6 , 30 ] . \nmany ssc patients experience significant limitations on exercise capacity with dyspnea , decreased stamina , and coughing that may interfere with certain sexual behaviors [ 4 , 30 ] . \nmedications used to treat ssc - related symptom are also known to impact sexual desire and sexual functioning .\nthe number of women with ssc reporting sexual dysfunction is higher than those reported in the general population and also higher than those reported in studies on other chronic conditions [ 1113 ] . \nbhadauria et al . reported that more than 50% of women with ssc had significantly fewer orgasms and that they reported a decrease in the intensity of their orgasms compared to fewer than 20% of ra patients . in a study by sampaio - barros et al .\nsome female ssc patients are sexually inactive because of complications related to their disease . \none study reported that 17% of subjects were sexually inactive because of issues caused by their disease . while there are many studies on the use of pde-5 inhibitors in the treatment of ed there are few studies on their use in the treatment of female sexual arousal problems and their effectiveness is in question . \nour understanding of the effects of these drugs on female sexual psychophysiology is limited . \nanimal models of female sexual response show a similar physiological effect of pde-5 on vaginal and clitoral tissues compared to males with no synthase ( nos ) being active in the vaginal epithelium and pde5 enzyme found in vaginal smooth muscle tissue and clitoral shaft . \npde5 inhibition with sidenafil in female rabbits have been shown to lead to increased smooth muscle relaxation .\nchivers and rosen conclude that there is clear evidence for the role of no neurotransmitter mechanisms in mediating blood flow and smooth muscle relaxation in the clitoral shaft , vaginal endothelium , and uterine tissues .\nhowever , pde5 inhibitors are not found to be as efficacious in women with sexual dysfunction as in men with ed [ 32 , 33 ] . \nstudies focusing on the physiological effects of pde5 on genital vasocongestion consistently report effects on genital sexual response while those using self - reported measures provide mixed results . \nthis is likely due to problems related to the classification and measurement of fsd in women and difficulties related to finding meaningful endpoints in clinical trials due to the complexity of female sexual response compared to men . \nchivers and rosen attribute this lack of efficacy of pde-5 inhibitors in women to gender differences in the concordance between physiological and psychological components of sexual response . while there are few studies on the effectiveness of pde-5 inhibitors for fsd in the general population , no studies were found in ssc patients .\nthe paper by chivers and rosen regarding the effectiveness of pde-5 inhibitors for fsd did not include any studies on the longer acting drug , tadalafil . as part of a study on the safety , tolerability and effectiveness of tadalafil for raynaud phenomenon ( rp )\n, female subjects were asked to attempt sex at least once weekly to evaluate potential effects on quality of female sexual functioning . \nthis prospective randomized , double - blinded , placebo - controlled , and cross - over study compared oral tadalifil at a fixed 20 mg dose daily for a period of 4 weeks versus placebo in female ssc patients . \ntadalafil was found to be well tolerated but no statistically significant differences were found in raynaud condition score , frequency or duration of rp episodes between treatment periods . \nthe study design can be found in figure 1 . there were a total of 5 visits : a screening visit ( visit 1 ) , three intermediate visits ( visits 24 ) , and an exit visit . \ndata obtained specifically regarding sexual function included the female sexual function index ( fsfi ) and a sexual activity log including the frequency of sexual activity . \nthis was obtained at visit 2 ( baseline ) and visits 3 and 5 ( after treatment or no treatment period ) . \nthe fsfi quantitatively assesses six domains of sexual functioning : desire , subjective arousal , lubrication , orgasm , pain , and satisfaction . \na total of 39 patients met all inclusion criteria , agreed to attempt sexual activity at least once weekly and successfully completed all 5 visits . when comparing change from baseline between drug and placebo on the six domains of the fsfi no statistically significant differences\nwere found although patients reported greater change when on drug versus when on placebo . \na significant difference was found between drug and placebo in the number of sexual activities with ssc patients reporting more frequent sexual activities when receiving drug than when on placebo ( mean number sexual activity drug = 7.24 with sd = 4.53 and a mean of 6.12 and sd of 3.3 on placebo ) . \nthis difference was statistically significant ( p = .021 ; 2-tailed ) as was the change from baseline ( 1.49 and sd = 2.55 on drug and x = .36 and sd = 2.16 ; p = .024 2 tailed ) . \nthe only other statistically significant difference in this study was found in a change from baseline in the sexual desire domain of the fsfi for drug although this was not statistically different from the change in the placebo group . \nsome of the more recent studies on female sexual functioning in ssc confirm the complexity of studying female sexual function as well as the psychological components of it . \ndepressive symptoms were found to be associated with impaired sexual functioning and sexual distress in ssc [ 11 , 13 ] . in our own studies of quality of female sexual function , we found stronger correlations with the mental component of the sf-36 than with the physical component score .\none lesson is that health care professionals should not dismiss consideration of sexual care and advice in any patient with systemic sclerosis .\nsexual dysfunction is a common problem in both men and women with systemic sclerosis . in males ,\nthe dominant issue is erectile dysfunction which in turn seems tightly linked to vascular dysfunction .\nsexual dysfunction in the female patient is no less prevalent but is considerably more complex .\nclitoral engorgement , lubrication , orgasm are but some of the components of quality of sexual life . to our knowledge , only one study with pde5-i has been performed in women with confusing and small effects whereas pde5-i are a mainstay agent in med .\nthe clinician should be reminded that women with scleroderma remain sexually active overall ( 60% ) in spite of a host of physical and psychological difficulties associated with their disease .\ncomplete care should consider agents for vaginal lubrication , advice about positioning and attention to sexual adverse events of therapies .",
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"content": "sexual dysfunction is common in systemic sclerosis ( ssc ) . \n male erectile dysfunction ( med ) has been reported in around 80% of subjects and more than half of female patients fulfill criteria for diagnosis as female sexual arousal disorder ( fsad ) . while some evidence supports a role for cavernosal fibrosis , abundant data suggest that med is yet another clinical feature of ssc related to vasculopathy . \n the contribution of vasculopathy to the more complex issues of female sexual dysfunction is less clear . \n inhibitors of type v phosphodiesterase are effective in men with med secondary to ssc . \n limited study in women suggests inconsistent effects on behavior ( frequency ) but not on measures related to perfusion . \n sexual activity is an important component of quality of life and an important domain for the caregiver to address ; it is not clear that it warrants primary consideration as a consistent measure of scleroderma - related vasculopathy .",
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science.mslr2022_cochrane_multidoc_summarization | science.mslr2022_cochrane_multidoc_summarization.3723 | [
{
"content": "Review the provided collection of medical RCT summaries. Your objective is to distill the essential insights into a brief conclusion. Focus solely on the synthesis of findings without additional commentary. The RCT summaries are as follows:\n\n\n\nReport Title 1:\nEffect of treatment with capsaicin on daily activities of patients with painful diabetic neuropathy. Capsaicin Study Group.\nReport Abstract 1:\nTo establish the effects of topically applied capsaicin on daily activities in patients with painful diabetic neuropathy.\n Investigators at 12 sites enrolled 277 men and women with painful peripheral polyneuropathy and/or radiculopathy in an 8-wk double-blind vehicle-controlled study with parallel randomized treatment assignments. Participants were unresponsive or intolerant to conventional therapy and were experiencing pain that interfered with functional activities and/or sleep. Either 0.075% capsaicin cream or vehicle cream was applied to the painful areas 4 times/day. A visual analogue scale of pain intensity and baseline measurements of the pain's interference with the ability to walk, work, participate in recreational activities, use shoes and socks, sleep, and eat were recorded at onset and at 2-wk intervals. A physician's global evaluation scale assessed changes in pain status from baseline.\n Statistically significant differences are percentage of patients with improvement in favor of capsaicin versus vehicle: 69.5 vs 53.4% with clinical improvement in pain status (P = 0.012), 26.1 vs. 14.6% with improvement in walking (P = 0.029), 18.3 vs. 9.2% with improvement in working (P = 0.019), 29.5 vs. 20.3% with improvement in sleeping (P = 0.036), and 22.8 vs. 12.1% with improvement in participating in recreational activities (P = 0.037).\n The results from this study suggest that topical 0.075% capsaicin is effective for reducing pain in patients with painful diabetic neuropathy with subsequent improvement in daily activities, enhancing the quality of the patient's life.\n\n\nReport Title 2:\nTopical capsaicin treatment of chronic postherpetic neuralgia.\nReport Abstract 2:\nUncontrolled studies have indicated that topically applied capsaicin may be a safe and effective treatment for postherpetic neuralgia. In a double-blind study 32 elderly patients with chronic postherpetic neuralgia were treated with either capsaicin cream or its vehicle for a 6-week period. Response to treatment was evaluated by visual analogue scales of pain and of pain relief, together with changes in a categoric pain scale and in a physician's global evaluation. Significantly greater relief in the capsaicin-treated group compared with vehicle was observed for all efficacy variables. After 6 weeks almost 80% of capsaicin-treated patients experienced some relief from their pain. Because capsaicin avoids problems with drug interactions and systemic toxicity, we suggest that topical capsaicin be considered for initial management of postherpetic neuralgia.\n\n\nReport Title 3:\nDouble-blind, placebo-controlled study of the application of capsaicin cream in chronic distal painful polyneuropathy.\nReport Abstract 3:\nWe have completed a 12-week double-blind, placebo-controlled randomized study on the efficacy of the application of capsaicin (CAPS) cream (0.075%) in the treatment of chronic distal painful polyneuropathy. Forty patients were enrolled and 39 completed the study. The 2 limbs were randomly assigned to CAPS or placebo (PLAC). The cream was applied 4 times a day. The first tube contained the active PLAC, methyl nicotinate. In the final 4 weeks (single-blind wash-out phase), PLAC was administered bilaterally. Efficacy was evaluated using the following scales: (1) investigator global, (2) patient global, (3) visual analog (VAS) of pain severity, (4) VAS of pain relief, (5) activities of daily living, and (6) allodynia. Patients were examined at onset and at monthly intervals using a neurologic disability scale, nerve conduction studies, computer-assisted sensory examination for vibration and thermal cooling and warming, QSART (quantitative sudomotor axon reflex test) and quantitative flare response. There was no statistical evidence of efficacy of CAPS cream over PLAC for any of the pain indices. At early time points (1-4 weeks), there were a small number of indices that favored the PLAC. The percent of limbs that improved on the investigator's global scale were 51.3 vs. 53.8 at 4 weeks, 56.4 vs. 64.1 at 8 weeks and 59 vs. 66.7 at 12 weeks for CAPS vs. PLAC; no statistically significant difference was found. All the safety indices showed no difference between sides. We interpret the early hyperalgesia on the CAPS side as being responsible for the better performance of PLAC at early time points. The large percentage of limbs that improved may be a pronounced PLAC response.\n\n\nReport Title 4:\nA double-blind comparison of topical capsaicin and oral amitriptyline in painful diabetic neuropathy.\nReport Abstract 4:\nAn 8-week double-blind, multicenter, parallel study compared the safety and efficacy of topical capsaicin and oral amitriptyline in patients with painful diabetic neuropathy involving the feet. Two hundred thirty-five patients were randomized to treatment with either capsaicin cream or amitriptyline capsules. Capsaicin-treated patients received inactive capsules, and amitriptyline-treated patients applied vehicle cream. A visual analogue scale of pain intensity and measurements of interference by pain with functional activities were recorded at onset and at 2-week intervals. A visual analogue scale of pain relief and physicians' global evaluation assessed changes in pain status from baseline. Topical capsaicin and oral amitriptyline produced equal and statistically significant improvements in pain over the course of the study. By the end of week 8, 76% of patients in each group experienced less pain, with a mean reduction in intensity of more than 40%. By the end of the study, the interference with daily activities by pain had diminished significantly (P = .001) in both groups, including improvements in sleeping and walking. No systemic side effects were observed in patients treated with topical capsaicin. Most patients receiving amitriptyline experienced at least one systemic side effect, ranging from somnolence (46%) to neuromuscular (23%) and cardiovascular (9%) adverse effects. Topically applied capsaicin is an equally effective but considerably safer alternative to amitriptyline for relief of the pain of diabetic neuropathy.\n\n\nReport Title 5:\nA randomized vehicle-controlled trial of topical capsaicin in the treatment of postherpetic neuralgia.\nReport Abstract 5:\nA large double-blind, vehicle-controlled study of 143 patients with chronic postherpetic neuralgia (PHN) was performed to evaluate the degree of efficacy of topically applied capsaicin 0.075% cream. In addition, the safety and efficacy of long-term application of topical capsaicin in PHN was assessed by following patients in an open-label study for up to 2 years. In the double-blind phase, 143 patients with PHN of 6 months' duration or longer were enrolled. Since epidemiologic studies of patients who receive no treatment have shown that only 10% to 25% of those with PHN after 1 month will still have pain at 1 year, two separate efficacy analyses were performed: one with all evaluable patients (n = 131) and the other with 93 patients whose PHN lasted for longer than 12 months prior to study startup. All efficacy variables, including the physician's global evaluation of reduction in PHN pain, changes in pain severity on the categoric scale, visual analogue scale for pain severity, visual analogue scale for pain relief, and functional capacity scale, showed significant improvement at nearly all time points throughout the study for both patient groups, based on duration of PHN pain. In contrast, the group receiving vehicle cream remained essentially unchanged. Data from the long-term, open-label phase (up to 2 years, n = 77), which immediately followed the 6-week blinded phase, showed that the clinical benefit in patients treated for a short (6-week) period with topical capsaicin could be maintained or amplified in most patients (86%) during prolonged therapy. There were no serious adverse effects observed or reported throughout the trial; in fact, the only side effect associated with capsaicin treatment was the burning or stinging at local sites of application (in 9% of patients) during exposures of up to 2 years (long-term phase). On the basis of these data, we conclude that capsaicin 0.075% cream is a safe and effective treatment for the pain of postherpetic neuralgia and should be considered for initial management of patients with this condition.\n\n\nReport Title 6:\nThe postmastectomy pain syndrome and topical capsaicin: a randomized trial.\nReport Abstract 6:\nThis paper describes a randomized parallel trial of topical 0.075% capsaicin versus vehicle (placebo) in the postmastectomy pain syndrome (PMPS). The study was double-blind in design; however, this was compromised by the burning sensation induced by capsaicin. We could not demonstrate a significant difference in the visual analogue scale (VAS) for steady pain although a trend was present. A significant difference was found, however, in the VAS for jabbing pain, in category pain severity scales, and in overall pain relief scales in favour of capsaicin. Five of 13 patients on capsaicin were categorized as good-to-excellent responses with 8 (62%) having 50% or greater improvement. Only 1 of 10 cases had a good response to vehicle with 3 rated as 50% or better.\n\n\nReport Title 7:\nPhase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients.\nReport Abstract 7:\nA minority of cancer survivors develops long-term postsurgical neuropathic pain. Based on evidence that capsaicin, the pungent ingredient in hot chili peppers, might be useful for treating neuropathic pain, we developed the present clinical trial.\n Ninety-nine assessable patients with postsurgical neuropathic pain were entered onto this study. After stratification, patients were to receive 8 weeks of a 0.075% capsaicin cream followed by 8 weeks of an identical-appearing placebo cream, or vice versa. A capsaicin/placebo cream was to be applied to the painful site four times daily. Treatment evaluation was performed by patient-completed weekly questionnaires.\n During the first 8-week study period, the capsaicin-cream arm was associated with substantially more skin burning, skin redness, and coughing (P < .0001 for each). Nonetheless, treatment was stopped for patient refusal or toxicity just as often while patients were receiving the placebo as compared with the capsaicin. The capsaicin cream arm had substantially more pain relief (P = .01) after the first 8 weeks, with an average pain reduction of 53% versus 17%. On completion of the 16-week study period, patients were asked which treatment period was most beneficial. Of the responding patients, 60% chose the capsaicin arm, 18% chose the placebo arm, and 22% chose neither (P = .001).\n A topical capsaicin cream decreases postsurgical neuropathic pain and, despite some toxicities, is preferred by patients over a placebo by a three-to-one margin among those expressing a preference.",
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"content": "There were insufficient data to draw any conclusions about the efficacy of low-concentration capsaicin cream in the treatment of neuropathic pain. The information we have suggests that low-concentration topical capsaicin is without meaningful effect beyond that found in placebo creams; given the potential for bias from small study size, this makes it unlikely that low-concentration topical capsaicin has any meaningful use in clinical practice. Local skin irritation, which was often mild and transient but may lead to withdrawal, was common. Systemic adverse effects were rare.",
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science.scientific_papers_summarization_single_doc_pubmed | science.scientific_papers_summarization_single_doc_pubmed.2238 | [
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"content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\nthe occurrence of liposarcomas in the gastrointestinal tract is very low and the reported incidence of gastrointestinal liposarcoma is 0.1% to 5.8% at autopsy .\nthe incidence of liposarcomas occurring at the esophagus is particularly low , where they form only 1.2% to 1.5% of all gastrointestinal lipomas .\nthe optimal treatment method for primary esophageal liposarcoma has not been established yet , but all reported cases so far have been treated by surgical means .\nalthough the use of therapeutic esophageal intervention has become increasingly common , nonsurgical therapy of primary esophageal liposarcomas has not been described yet in the literature . here ,\nwe present a case of a large esophageal liposarcoma which was resected by endoscopic submucosal dissection ( esd ) under general anesthesia .\na 44-year - old male patient was admitted to our hospital for 4 months of dysphagia which was exacerbated during the recent weeks . an abdominal computed tomography ( ct ) scan showed a 15 cm long mass protruding into the esophageal lumen on coronal image .\nthe majority of the tumor showed fat attenuation , internal septa - like structures , and soft tissue density ( fig .\n, there was a yellowish , soft , and movable subepithelial tumor ( set ) located 20 to 35 cm away from the upper incisor .\nendoscopic ultrasonography showed a nonhomogeneous submucosal mass located in the posterior wall of upper to mid esophagus ( fig .\nalthough the tumor had a stalk , the stalk was too huge to use a snare .\nthe procedure was done using a cap - fitted gastroscope ( gif - q260 ; olympus , tokyo , japan ) .\nafter submucosal injection of cerol mixture ( glycerin 10% , fructose 5% ; cheiljedang pharma corp . ,\nseoul , korea ) , the first incision was made using a fixed flexible knife ( kachu technology , seoul , korea ) at the center of the stalk .\nafter exposing the submucosal tissue , the mass was dissected along the stalk using the it-2 knife ( kd-611l ; olympus medical systems co. , tokyo , japan ) ( fig .\nmacroscopically , the tumor had a three fingers - like shape and was measured 8.76.03.0 cm .\nthe cut end of the mass revealed multilobulating contoured mass , which was located in the submucosal layer and had yellow color ( fig .\nhistologically , the neoplasm consisted predominantly of mature looking fat tissues which were in variable sizes and the shape of adipocytic element .\nsome lipocytes showed big and bizarre nucleuses , suggesting liposarcoma rather than lipoma ( fig .\nthe tumor had the characteristic features of well - differentiated liposarcoma in general . in some other areas\n, there were lobules of mature adipose tissue with a delineated myxoid tumor in the subepithelial stroma .\nfollowing esd , the patient was followed up for 4 months by chest ct and egd , and signs of recurrence and metastasis have not been found so far ( fig .\nfour main subtypes of liposarcoma include well - differentiated liposarcoma , myxoid liposarcoma , pleomorphic liposarcoma , and dedifferentiated liposarcoma .\nthe only established methods for the diagnosis of liposarcoma are surgical excision and histological examination . although indications for resection have not been established , unconditional resection is not generally recommended because of rare incidence of esophageal liiposarcoma .\nthe prognosis after the resection of esophageal liposarcoma is not well known because the occurrence of esophageal liposarcoma is so rare that there is no long term follow - up study .\nwhen we reviewed previous records , recurrence occurred in two patients among 15 patients whose medical records were available , so the recurrence rate of esophageal liposarcoma does not seem so high .\nalthough there is no esablished guideline on the follow - up after the resection of esophageal liposarcoma yet , it seems that too frequent monitoring is not required because esophageal liposarcoma is known as a slow - growing tumor . here\n, we showed that esd can be a good alternative method for esophageal set to avoid aggressive surgical procedures .\npreviously esophageal liposarcoma cases were treated by various surgical methods including simple enucleation and partial or total esophagectomy via transcervical , transthoracic , and transgastric routes.1,2 however , such surgical approaches are expensive and more invasive , resulting in longer hospital stays compared to endoscopic methods .\nesd is a technique which was originally developed in japan as a method for endoscopic resection of early gastric cancer and adenoma .\nthe use of esd has been expanded to include the removal of gastric sets following reports of its usefulness in the treatment of gastric sets.3 today , esd is also considered to be a useful therapeutic option for the resection of high grade dysplasia or early cancer in the esophagus .\nthere have been several studies investigating the efficacy of esd for the resection of esophageal sets .\nshi et al.4 reported the usefulness of esd in treating esophageal sets originating from the muscularis propria layer . in this study ,\nthe curative resection rate was 100% ( 28/28 ) and there were no recurrences during the follow - up of 3 to 27 months .\nperforation , which occurred in two cases , were closed with metal endoclips and the patients recovered quickly without surgery .\nrecently , there have also been some reports about cases for which submucosal tunnel dissection was used to treat upper gastrointestinal sets.5,6 in these studies , sets were successfully resected in patients with tumors sized 2 to 4 cm without severe complications . to our knowledge\n, there have been no previous reports about the use of esd for the treatment of esophageal liposarcoma , perhaps due to its rare occurrence .\nalthough the postoperative follow - up has been only 4 months long , there have not been any signs of recurrence or complications .\nwe believe that the endoscopic approach is superior to more aggressive surgical approaches ( such as esophagectomies ) because it allows more detailed resection as well as early recovery and less pain for the patient .\nconsidering the fact that the use of esd has been increasing recently , we believe this case report is meaningful and will help to validate the use of esd as a feasible option for the treatment of esophageal liposarcomas .",
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"content": "liposarcoma is one of the most common soft tissue sarcomas occurring in adults , but it rarely occurs in the gastrointestinal tract and more uncommonly in the esophagus . to the best of our knowledge , there are only 19 reported cases of esophageal liposarcoma in the literature published in english language up to the year 2008 , and they were all treated by surgical methods . here \n , we report a case of primary liposarcoma of the esophagus which was treated with endoscopic submucosal dissection ( esd ) . \n esd was well tolerated in this patient , suggesting that it may be a therapeutic option for primary esophageal sarcomas .",
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science.scientific_papers_summarization_single_doc_arxiv | science.scientific_papers_summarization_single_doc_arxiv.169614 | [
{
"content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nmassless triangle feynman diagrams occur in field theoretical perturbative calculations , being one of the primary divergent ( one - particle irreducible ) graphs for the non - abelian gauge theories such as yang - mills fields .\nthis makes this kind of perturbative calculation the more interesting and necessary once we want to check the higher order quantum corrections for many physical processes of interest .\ntwo decades ago , boos and davydychev @xcite were the first to obtain the analytic formulae for the one - loop massless vertex diagram using the mellin - barnes complex contour integral representation for the propagators .\nlater on , suzuki , santos and schmidt @xcite reproduced the same result making use of the negative dimensional integration method ( ndim ) technique of halliday and ricotta @xcite for feynman integrals , where propagators are initially taken to be finite polynomials in the integrand , and once the result is obtained , analytically continued to the realm of positive dimensions .\nthese two widely different methods of calculation yielding the same answer lends to the analytic result obtained a degree of certainty as far as the mathematical soundness is concerned .\nhowever , here i argue that mathematical soundness only is not enough when we are interested in processes of physical content .\nneither the mellin - barnes formulation of boos and davydychev nor the ndim technique employed by suzuki _ et al _ to evaluate the massless triangle graph take into account the basic physical constraint imposed on such a diagram due to the momentum conservation flowing in the three legs .\nmomentum ( that is , energy and three - momentum ) conservation is one of the basic , fundamental tenets of modern natural sciences , and plays a key role in determining the final form for the analytic result for the massles one - loop vertex correction . the system of coupled , simultaneous partial differential equations : @xmath1\\frac{\\partial z}{\\partial x } - ( \\alpha+\\beta+1)y\\frac{\\partial z}{\\partial y}-\\alpha \\beta z = 0 \\nonumber \\\\\ny(1-y)\\frac{\\partial^2 z}{\\partial y^2}-x^2\\frac{\\partial^2 z}{\\partial x^2}-2xy\\frac{\\partial^2 z}{\\partial x \\partial y } + [ \\gamma\\hspace{.05cm}'-(\\alpha+\\beta+1)y]\\frac{\\partial z}{\\partial y } - ( \\alpha+\\beta+1)x\\frac{\\partial z}{\\partial x}-\\alpha \\beta z = 0 \\end{aligned}\\ ] ] has a solution which consists of a linear combination of four hypergeometric functions of type @xmath0 , as follows @xcite : @xmath2 where it is implicit that @xmath3 and @xmath4 are independent variables . now the analytic solution for the massless triangle feynman diagram given by boos and davydychev @xcite and suzuki _ et al _ @xcite has exactly the same structure as the above solution for the simultaneous partial differential equation\n. however , the variables @xmath3 and @xmath4 for the triangle feynman diagram are given by ratios of momentum squared , such as @xmath5 and @xmath6 where @xmath7 , so that the variables @xmath8 and @xmath9 are not independent , but constrained by momentum conservation .\ntherefore , the solution for the feynman diagram can not be a linear combination of four linearly independent hypergeometric functions @xmath0 , but a linear combination of _ three _ linearly independent hypergeometric solutions @xmath0 .\none of the simplest examples where the four - term hypergeometric combination above mentioned does not reproduce the correct result is when it is embedded in a higher two - loop order calculation .\nconsider , for example , the diagrams of figure 1 . for neither of the diagrams the four - term solution for the triangle when embedded into the two - loop graph yields the correct answer .\nthe right result can only be achieved when we use a three - term triangle solution embedded into the two - loop structure @xcite .\none could use the analytic continuation formula for the @xmath0 function @xcite in order to reduce the number of independent functions to three ; however , one has at least two possibilities to do this : either combining ( [ a ] ) and ( [ c ] ) or combining ( [ b ] ) and ( [ d1 ] ) , so that , for example , for the former case @xmath10 therefore , which three of those @xmath0 s should be considered can not be determined by the momentum conservation only ; it needs another physical input to this end . in order to determine the exact structure and content of the analytic result for the triangle diagram i employ the analogy that exists between feynman diagrams and electric circuit networks .\nthe conclusion of the matter can be summarized as follows : since there is a constraint ( call it either a initial condition or a boundary condition ) to the momenta flowing in the legs of a triangle diagram , it means that the overall analytic answer obtained via mellin - barnes or ndim technique , which comes as a sum of four linearly independent hypergeometric functions of type @xmath0 , in fact must contain only three linearly independent ones . which three of these should be is determined by the momentum conservation flowing through the legs of the diagram , _ and _ , by the circuit analogy , by the equivalence between the `` y - type '' and `` @xmath11-type '' resistance networks through which _ conserved _ electric current flows .\nalthough known for a long time and mentioned sometimes in the literature of field theory , the analogy between electric circuit networks and feynman diagrams , more often than not stays as a mere curiosity or at a diagrammatic level in which the drawing is only a representation that helps us out in the `` visualization '' of a given physical process .\nthere is , however , a few exceptions to this . the earliest one that i know of is by mathews @xcite as early as 1958 where he deals with singularities of green s functions and another one by wu @xcite in 1961 , where he gave an algebraic proof for several properties of normal thresholds ( singularities of the scattering amplitudes ) in perturbation theory\nwhat i am going to do here is just to state the well - known result for the equivalence between `` @xmath12''- and `` @xmath11-circuits '' which is used , for example , in analysing the `` kelvin bridge '' in relation to the more commom `` wheatstone brigde '' .\nthe equivalence i consider is for the network of resistors , where energy is dissipated via joule effect .\nthen with this in hands i argue which three out of the overall four hypergeometric functions @xmath0 present in the one - loop vertex obtained via mellin - barnes or via ndim should be considered as physically meaningful .\nconsider then the `` @xmath12''- and `` @xmath11-circuits '' of figure 2 .\nthese two network of resistors are related to each other ; for example , the `` delta - circuit '' can be made equivalent to the `` y - circuit '' when resistors obey the following equations @xcite : @xmath13 in electric circuits a general theorem guarantees that the current density in a conductor distributes itself in such a way that the generation of heat is a minimum @xcite . strictly speaking , since i consider the `` y''- and `` delta - networks '' by themselves and not embedded within an electrical circuit , i can not consider the minimum of power generation , but still i can consider the equivalence between the power generated in one of them say `` y - circuit '' as compared to the power generated in the other one , the `` delta - circuit '' . labelling the currents that flow through resistors\n@xmath14 , @xmath15 and @xmath16 of the `` y - circuit '' by @xmath9 , @xmath17 and @xmath18 , respectively , by reason of current conservation we have that , for example @xmath19 each of these currents will generate heat according to joule s law and the corresponding power will be given by ohm s law .\nso in each leg , the product of the resistance times the square of the current will give the power generated by the current flowing through it .\nthe overall power generated in the `` y - network '' is therefore : @xmath20 from this we have the following system of equations : @xmath21 where for convenience i have defined @xmath22 , @xmath23 , @xmath24 and @xmath25 . multiplying the last equation by @xmath26 and comparing with ( [ d ] ) , @xmath27 it follows that the coefficient of @xmath15 is @xmath28 . multiplying ( [ d ] ) by @xmath29 and comparing with ( [ e ] ) , @xmath30 it follows that the coefficient of @xmath16 is @xmath31 .\nfinally , multiplying ( [ f ] ) by @xmath32 and comparing with ( [ d ] ) , @xmath33 it follows that the coefficient of @xmath14 is @xmath34 . on the other hand ,\nin the `` delta - network '' , let @xmath35 label the current flowing through resistance @xmath36 , so that the power generated in this resistor is , using ( [ ra ] ) @xmath37 now , as the resistances follow the equivalence defined by ( [ ra ] ) , the current @xmath35 that flows through @xmath36 must be such that : @xmath38 where @xmath39 and @xmath40 therefore , the solution for the one - loop triangle feynman diagram must be such that it contains three terms which are proportional to `` currents '' @xmath41 , @xmath42 and @xmath43 .\nthis solution is exactly achieved when i combine ( [ b ] ) and ( [ d1 ] ) in a similar way as was done in ( [ anacont ] ) . combination of ( [ a ] ) and ( [ c ] ) as in ( [ anacont ] ) leaves the term ( [ d1 ] ) in the solution , which is proportional to @xmath44 , and therefore not suitable since it violates the equivalence above demonstrated .\nexplicit analytic solution for the one - loop massless triangle feynman diagram reads therefore @xmath45 where @xmath46 with @xmath47 being the dimensional regularization parameter .\none notes that the variables for the last @xmath0 , though related to those that appear in the first and second @xmath0 s , differ from them .\nusing the basic physical principle of momentum conservation i deduced the correct analytic result for the one - loop massless triangle feynman diagram in terms of three linearly independent hypergeometric functions @xmath48 .\nthe reason why there must be only three linearly independent functions in the solution is due to the fact that the variables @xmath26 and @xmath49 are such that implicit in them is a momentum conservation constraint that must be taken into account properly .\nthe set of which three linearly independent functions @xmath0 should be is given by another physical input , deduced in analogy to the equivalence between `` y''- and `` delta - network '' of electrical resistance circuits .\nwith the conservation of momentum correctly taken into account , the final result for the mentioned feynman diagram is the physically correct and relevant analytic solution to the problem , having only a combination of three linearly independent @xmath0 functions in it .\ne.e.boos and a.i.davydychev , _ vestnik mgu _ * 28 * , ( 1987 ) 8 . cited by v.a.smirnov in his book renormalization and asymptotic expansions \n, page 124 .\nvolume 14 of the series progress in physics , birkhuser verlag , basel , boston , berlim ( 1991 )",
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"content": "different mathematical methods have been applied to obtain the analytic result for the massless triangle feynman diagram yielding a sum of four linearly independent hypergeometric functions @xmath0 . in this paper \n i work out the diagram and show that that result , though mathematically sound , is not physically correct , because it misses a fundamental physical constraint imposed by the conservation of momentum , which should reduce by one the total number of linearly independent ( l.i . ) \n functions @xmath0 in the overall solution . taking into account that the momenta flowing along the three legs of the diagram are constrained by momentum conservation , the number of overall l.i . \n functions that enter the most general solution must reduce accordingly . to determine the exact structure and content of the analytic solution for the three - point function , i use \n the analogy that exists between feynman diagrams and electric circuit networks , in which the electric current flowing in the network plays the role of the momentum flowing in the lines of a feynman diagram . \n this analogy is employed to define exactly which three out of the four hypergeometric functions are relevant to the analytic solution for the feynman diagram . \n the analogy is built based on the equivalence between electric resistance circuit networks of type `` y '' and `` delta '' in which flows a conserved current . \n the equivalence is established via the theorem of minimum energy dissipation within circuits having these structures .",
"role": "assistant"
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science.genia_ner | science.genia_ner.673 | [
{
"content": "Analyze the provided text excerpt from a scientific document. Identify and extract distinct entities based on predefined categories.\n\nDeliver the results as a JSON structure where each key represents an entity category, and the associated value is a list of identified entities. If no entities are found for a category, return an empty list.\n\nText Excerpt:\n\nAbnormal NF-kappa B activity in T lymphocytes from patients with systemic lupus erythematosus is associated with decreased p65-RelA protein expression. Numerous cellular and biochemical abnormalities in immune regulation have been described in patients with systemic lupus erythematosus (SLE), including surface Ag receptor-initiated signaling events and lymphokine production. Because NF-kappa B contributes to the transcription of numerous inflammatory genes and has been shown to be a molecular target of antiinflammatory drugs, we sought to characterize the functional role of the NF-kappa B protein complex in lupus T cells. Freshly isolated T cells from lupus patients, rheumatoid arthritis (RA) patients, and normal individuals were activated physiologically via the TCR with anti-CD3 and anti-CD28 Abs to assess proximal membrane signaling, and with PMA and a calcium ionophore (A23187) to bypass membrane-mediated signaling events. We measured the NF-kappa B binding activity in nuclear extracts by gel shift analysis. When compared with normal cells, the activation of NF-kappa B activity in SLE patients was significantly decreased in SLE, but not in RA, patients. NF-kappa B binding activity was absent in several SLE patients who were not receiving any medication, including corticosteroids. Also, NF-kappa B activity remained absent in follow-up studies. In supershift experiments using specific Abs, we showed that, in the group of SLE patients who displayed undetectable NF-kappa B activity, p65 complexes were not formed. Finally, immunoblot analysis of nuclear extracts showed decreased or absent p65 protein levels. As p65 complexes are transcriptionally active in comparison to the p50 homodimer, this novel finding may provide insight on the origin of abnormal cytokine or other gene transcription in SLE patients.",
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"content": "{\"CellLine\": [], \"CellType\": [\"T cells\", \"T lymphocytes\", \"lupus T cells\", \"normal cells\"], \"DNA\": [\"inflammatory genes\"], \"Protein\": [\"NF - kappa B protein complex\", \"p65 protein\", \"Ag receptor\", \"lymphokine\", \"Abs\", \"anti - CD3\", \"anti - CD28 Abs\", \"TCR\", \"NF - kappa B\", \"abnormal cytokine\", \"p65 complexes\", \"p65 - RelA\"], \"RNA\": []}",
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.3091 | [
{
"content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: A Survey on Software-Defined Wireless Sensor Networks: Challenges and Design Requirements \nChapter Title: B. ROUTING \n1. Abstract of Cited Paper (BIB001): Since the SDN (Software Defined Network) technology based on OpenFlow was born, domestic and foreign research institutions have had increasing attention to this emerging field. The OpenFlow technology which is known for standardization and compatibility network virtualization has brought a lot of innovative solutions in the field of research. As the wireless sensor network node is complex and difficult to move and the network topology is changing rapidly with time, this requires a routing protocol for it to be able to adapt to this high topology change. Because traditional WSNS protocol communication needs to consider energy consumption, load balancing and other factors, it is difficult to find one to take into account all aspects of network algorithms. In this paper, we put forward a new solution for WSNS in accordance with the OpenFlow technology research in the application of traditional network. \n2. Abstract of Cited Paper (BIB002): There has been a decade of extensive research on application specific wireless sensor networks (WSNs). The recent development in communication network technologies makes it practical to realize a new WSN paradigm or controlling the control plane with the new group of by software defined networking (SDN) based on Open Flow. The Open Flow technology which is known for standardization and compatibility network Virtualization has brought a lot of innovative solutions in the field of research. In WSNs, sensor node are complex, highly dense and hence difficult to move. Network topology fast changes with time by using routing protocol, network topology, load balancing, power optimization, security and other factors. In this paper, the concept of SDN in WNS is introduced where Open Flow is the controller part of network.\n\nReview Chapter:",
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"content": "It is worth noting that in SDN's paradigm, the routing functionalities are logically centralised at the controller. Traditional WSN routing protocols runs on the nodes and consumes lot of energy. Such approaches in their current state are not viable for SDWSN; however their algorithmic concepts could be implemented at the controller level, thus requiring a transformation from an infrastructure-based to a software-based approach. The traditional WSN routing methods, as discussed and classified in BIB002 remain to be tailored for SDWSN based on SDN guidelines. The most related current work thus far is found in the routing model architecture proposed by Shanmugapriya and Shivakumar . The authors combine context-aware and policy based routing modules in line with the SDN principles. Fig. 5 depicts the proposed architecture. The model has six phases: Initiation phase: sensor nodes connect to the controller using the Sensor OpenFlow protocol. The nodes also supply the controller with all relevant information such as node status, CPU load, etc. Topology discovery phase: The node supplies the controller not only with its own information but its neighbours' as well. The controller forms a routing map table. The table has all the nodes and their next best hops. The route link has context information such as CPU load, service information and power levels of the next hop. Services are any policies defined for that route such as security, privacy, etc. . Decision phase: The controller uses a recursive destination based lookup algorithm to look for a route in the mapping table. Policy based route phase: The routes are chosen using defined policies. The algorithm lookup will determine all available routes towards the destination and a particular route will be chosen if it matches the policy criteria, i.e. ignore any route with a CPU usage of at least 90%. Should all routes not match the policy, packets could be dropped. Enforcement phase: The controller enforces the routing onto the switch devices. Han and Ren BIB002 propose a cluster-based routing protocol based on SDN. They set an OpenFlow oriented SDN network based on three types of nodes: master node, centre node, and a normal node, where the master node is a controller, the centre node is equivalent to a switch/sensor node (packet forwarding device) and the normal node is only for receiving data. The SDN network uses a NOX controller. They further highlight the use of FlowVisor BIB001 , BIB003 for controller scalability purposes. FlowVisor is a SDN based virtualization application model, which enables multiple controllers to use or manage one switch concurrently. Each controller accesses the switch through a dedicated virtual portion called slice. Like all the OpenFlow based routing, the master node determines the route upon receiving a new request. The routing or the forwarding policy is based on the QoS information. The centre nodes maintain the flow tables. The network is arranged in clusters, with the centre nodes as cluster heads, which then communicates with the master node via a secure channel, as shown in Fig. 6 . The location of the centre node is critical and thus uses a distance aware routing algorithm based on Content Addressable Network (CAN). The authors highlight limited energy on the nodes as a challenge. Yuan et al. , propose a hybrid routing model which combines the ideals of an Ad Hoc On-Demand Distance Vector (AODV) protocol with OpenFlow. AODV is a wireless and mobile ad hoc network routing protocol. They use an AODV daemon to implement the AODV algorithm as well as OpenvSwitch [162] as an OpenFlow agent which enables the communication between the devices and the controller . Fig. 7 depicts the system architecture, which was implemented on a physical device (Raspberry Pi). Most of the current efforts lack qualitative and quantitative evidence of their efficiency in a real network environment. Their performance ought to be tested against common network factors such as latency, QoS, packet delivery, congestion etc. The current SDWSN routing protocols are listed in Table 5 .",
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.10024 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nSyntheses and properties of thienyl-substituted dithienophenazines\n\nContent Extracts:\nIntroduction\n<p>Thiophene based oligomers and polymers have drawn considerable interest as active materials in various fields of organic electronics such as organic light-emitting diodes (OLEDs), organic thin-film transistors (OTFTs), or organic photovoltaics (OPVs) [1][2][3]. Concerning applications, organic materials are highly attractive due to their low cost and their particularly simple deposition from either vacuum or solution (casting or printing), and thus they are already utilized in industrial manufacturing. Particularly, deposition from the solution phase requires sufficiently high solubility, and one approach to cover this aspect is the functionalization with long, flexible alkyl substituents. Additionally, in many cases (short) oligomers are considerably better soluble than their corresponding (long) polymers, and can, as a matter of principle, be obtained in higher purity with respect to defects/polymerization faults. Moreover, they act as model systems allowing estimation of the pure polymer properties by extrapolation of the oligomer properties to infinite molecular weight [4].</p><p>Beside pure thiophene-based (well-established) materials, compounds with additional electron-poor moieties are in focus, as they are known to shift the HOMO and LUMO levels towards lower energies, thus increasing the compounds' stability against oxidation. In addition, the HOMO-LUMO gap is reduced (by the donor-acceptor (DA) approach), thereby red-shifting the absorption edge. This is of special importance, as there is still a need for new materials (exhibiting additionally the above mentioned processability criteria) absorbing the longer wavelength region (> 600 nm) of the sunlight spectrum, being required for photocurrent generation also from respective lowenergy photons and thus enhancing the overall light harvesting yield in organic photovoltaics (OPV). For example, in the field of fused Nand S-heterocycles, thieno [3,4-b]pyrazines with various side groups have already found applications in OPVs [5][6][7][8]. In addition, fused bithiophenes with an enforced planarity, and therefore reduced optical gaps, and an increased π-π overlap of the polycyclic molecule backbone have entered various fields of organic electronics [9][10][11][12][13].</p><p>Apart from their optoelectronic properties, linear and branched as well as cyclic and polycyclic thiophenes are valuable templates for the epitaxial coadsorption of adlayers, in particular for fullerenes and metallacycles [14][15][16][17].</p>\n\nResults and Discussion\n<p>Here we report the syntheses of two isomeric benzodithiophenediones, their respective phenazines and their coupling products with thiophene boronic acids. In both cases the thiophene units of the molecules act as electron rich parts (donors, D), whereas the phenazine moieties serve as electron deficient parts (acceptors, A), leading to a bathochromic shift of the UV-vis spectra in comparison with the non-condensed thiophene analogues. These assignments of the thiophene moieties as donors and the phenazine moieties as acceptors are confirmed by quantumchemical calculations at the density-functional level.</p><p>Additionally, one of the compounds forms a self-assembled monolayer on a HOPG surface, as imaged by scanning tunneling microscopy (STM).</p>\n\nSynthesis\n<p>The synthesis of 4 is shown in Scheme 1. It is obtained in three steps from commercially available starting materials. The syn- thesis of 3 has previously been reported by benzoin condensation of the corresponding bithiophene derivative [18].</p><p>Alternatively, we prepared first 3,3'-thenil (2) by metalation of 3-bromothiophene and reaction with dimethyl oxalate [19]. Subsequent oxidative intramolecular thiophene-thiophene coupling [20] with FeCl 3 yielded 3 as a dark red (nearly black) solid. Bromination of 3 with bromine in acetic acid/chloroform gave 4 in nearly quantitative yield [21,22]. The respective regio isomer 8 was synthesized starting from commercially available 3-bromothiophene 1 and boronic acid 5 in three steps (Scheme 2). By Suzuki-Miyaura coupling we obtained 3,3'bithiophene in good yields. The red diketone 7 was prepared by two-fold acylation with oxalyl chloride [23,24]. Bromination of 7 with NBS failed, however, the reaction with bromine under similar conditions as described for 4 afforded 8 in quantitative yields. Both routes towards the brominated bithiophene-diketones gave high overall yields and can be scaled up easily. Condensation of the diketones 4 and 8 with diaminobenzenes 9a and 9b, containing methyl and hexyl side groups [25], in pure acetic acid at 50 °C gave the phenazines 10 and 11 as yellow solids in 50-93% yield (Scheme 3) [26]. The hexyl derivatives 10b and 11b showed a significantly higher solubility than the methyl analogues and could be more easily purified by column chromatography. Nevertheless, both compounds can serve as starting materials for thiophene oligomers with increased donor ability. Thiophene-and bithiophene boronic acids or esters were coupled via Suzuki-Miyaura reactions forming orange-colored thiophenetetramers 12a, 12b, 14 and 16 and red-colored hexamers 13, 15, 17a, 17b and 18, respectively (Scheme 4 and Scheme 5).</p><p>The low solubility of the methyl derivatives 12a, 16 and 17a made their purification tedious. However, this problem did not occur in the case of the hexyl substituted oligomers. Highly soluble compounds (20-50 mg/mL in chloroform or dichlorobenzene) were obtained by coupling of the hexyl substituted compounds 10b and 11b with alkyl substituted thiophene or bithiophene boronic acids (esters).</p>\n\nUV-Vis spectra\n<p>Figure 1a shows the UV-Vis absorption and emission spectra of 12a, 13, 14 and 15 in solution (CH 2 Cl 2 ). In Figure 1b the spectra of the isomeric compounds 16, 17a and 18 are displayed [27]. All oligomers based on 10 exhibit strong absorption bands at ~250-350 nm and at ~350-450 nm with underlying vibronic structures. As expected, the longest wavelength absorption is for the hexathiophene derivatives shifted bathochromically in comparison to the tetrathiophene derivatives. The spectra of 16, 17a and 18 display two strong bands at ~300-400 nm and at ~400-500 nm, some of them show vibronic fine structures. The maxima of the emission spectra are shifted by ≈3500 to 4600 cm −1 with respect to the longest wavelength absorption maxima (Figure 1, Table 1). At the onset of the absorption, the zero-zero transition and the longest wavelength absorption maxima follow the same (expected) trends, that is the more extended π-systems (13, 15, 17, 18) exhibit a smaller optical gap. Moreover, when compared with the optical spectra of the quater-and sexithiophene [28] (Table 2, 19 and 20), a clear red-shift could be observed for both oligomer series, regardless if they are based on 10 or 11, due to the intramolecular donor-acceptor character of the compounds.</p>\n\nQuantum chemical calculations\n<p>To rationalize the observed trends in the optical absorption spectra of the oligomers, DFT calculations using the ORCA program package [29] were carried out. The ground state geometries of quaterthiophene 19, the compounds 12a, 16, sexithiophene 20 and the compounds 13 and 17a were optimized with the B3LYP functional [30] with a TZVP basis set [31]. Different rotations of the thiophene rings were investigated each corresponding to a different local minimum-energy structure. The differences in the total energy of the ground states are within the typical DFT error range of 3 to 11 kJ/mol. It can therefore be expected that at room temperature all conformations are present. For simplicity we only present results for the most stable structure. For the treatment of excited states time-dependent density functional theory (TD-DFT) was applied. The COSMO model was used to simulate the solution environment of the molecules in CH 2 Cl 2 [32,33].</p><p>The calculated spectra of the most stable conformers and the S n -S 0 difference electron densities of selected compounds are shown in Figure 2. In general, the calculated excitation ener-gies are in reasonable agreement with the experimental results (see also Table 3). It has to be kept in mind that the calculated values correspond to vertical excitation energies between electronic states while the measured optical spectra include vibronic effects.</p><p>The dominating signals in the spectra of quaterthiophene 19 and sexithiophene 20 correspond to the HOMO-LUMO excitation.</p><p>While the calculated S 1 excitation energy of 19 differs by about 0.4 eV from the experimental result, the excitation energy of 20 is within the typical error range of B3LYP (ΔE exp-calc = 0.1 eV) [34]. Both compounds have a similar spectrum, but the transi- tions of 20 are red shifted due to its larger delocalized π-system, which lowers the HOMO-LUMO gap as discussed above.</p><p>The difference density of 12a (Figure 2c) shows that the S 0 -S 1 excitation leads to an intramolecular charge transfer (CT) from the thiophenes to the phenazine part of the molecule. These calculations verify our initial assumption that the electron rich thiophene units act as electron donors and the electron poor phenazine unit as an electron acceptor in this intramolecular CT-complex. This CT state can also be observed in 16 (Figure 2e), but here the calculated difference between the S 1 energies of 12a and 16 (0.27 eV) is larger than the measured value (0.07 eV). Nevertheless, the computed excitation energies show a similar trend as the observed maxima of the absorption spectra.</p><p>The increased length of the thiophene chains in 13 compared to 12a lowers the excitation energies of the CT states by about 0.2 eV due to an extended electron delocalization, as it is also experimentally observed. The same holds for the isomeric series. The calculated and observed optical gap in 17a is considerably smaller than in 16. It is worth noting that in both hexathiophene derivatives the charge reorganization upon excitation includes also the outermost thiophene rings, indicating that an extension of the chain would further reduce the optical gap. In addition, 17a has a nearly degenerate S 2 state, which also has CT properties. This HOMO-1 to LUMO excitation is visible in 17a but not in 13 since the orbital energy and shape of HOMO and HOMO-1 in 17a are nearly the same (ΔE HOMO,HOMO-1 =0.02 eV), while in 13 the energy difference between HOMO and HOMO-1 is larger than 0.6 eV [35].</p>\n\nSTM study\n<p>All synthesized thiophene oligomers 12-18 were investigated concerning their ability to form self-assembled monolayers (SAMs) at the HOPG/TCB interface (highly oriented pyrolytic graphite/1,2,4-trichlorobenzene). In situ STM was applied under typical conditions with typical tunneling parameters normally allowing the visualization of SAMs -if formed [36].</p><p>However, among all the substances only 12b (10 −5 M in TCB) assembles into crystalline monolayers on HOPG (Figure 3a). Bright and dark colors originate from locally high and low tunneling currents, resulting from unsaturated (backbone) and saturated (alkyl side chain) hydrocarbon segments, respectively [37]. A unit cell with a = 2.5 ± 0.1 nm, b = 2.3 ± 0.1 nm, γ = 90 ± 2° could be determined [38]. A proposed molecular model of the adsorbate geometry is shown in Figure 3b.</p><p>The banana-shaped bright features in Figure 3a are attributed to the backbones of 12b, assembling in densely packed double rows. However, short alkyl chains are commonly not visible under the applied conditions. Nevertheless we assume they are oriented along the main crystallographic direction of the HOPG substrate.</p><p>Ordered adlayers were observed only for 12b, but not for 12a. Moreover, additional terminal alkyl chains terminating the endcapping thiophene substituents of 14, 15 and 18 appear to hinder the formation of a self-assembled monolayer, most probably due to sterical hindrance of the molecules to cover the surface densely.</p>\n\nConclusion\n<p>We have developed a simple method for preparing phenazinethiophene oligomers. These compounds show interesting optical characteristics, which can be tuned by attachment of different thiophene substituents. Currently we investigate the electrooptical properties of these compounds and similar derivatives.</p><p>In addition, for one of the compounds a SAM on HOPG could be observed.</p>",
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"content": "A series of dithienophenazines with different lengths of the oligomeric thiophene units (quaterthiophenes and sexithiophenes) was synthesized. The thiophene and phenazine units act as electron donors and acceptors, respectively, resulting in characteristic absorption spectra. The optical spectra were calculated using time-dependent density functional theory at the B3LYP/TZVP level and verify the experimental data. Adsorption of the dithienophenazines on highly ordered pyrolytic graphite (HOPG) was investigated by scanning tunneling microscopy, showing that one of the compounds forms highly organized self-assembled monolayers.",
"role": "assistant"
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.2435 | [
{
"content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: A Survey on Three-Dimensional Wireless Ad Hoc and Sensor Networks \nChapter Title: UWSNs Localization. \n1. Abstract of Cited Paper (BIB001): The past decade has seen a growing interest in ocean sensor networks because of their wide applications in marine research, oceanography, ocean monitoring, offshore exploration, and defense or homeland security. Ocean sensor networks are generally formed with various ocean sensors, autonomous underwater vehicles, surface stations, and research vessels. To make ocean sensor network applications viable, efficient communication among all devices and components is crucial. Due to the unique characteristics of underwater acoustic channels and the complex deployment environment in three dimensional (3D) ocean spaces, new efficient and reliable communication and networking protocols are needed in design of ocean sensor networks. In this paper, we aim to provide an overview of the most recent advances in network design principles for 3D ocean sensor networks, with focuses on deployment, localization, topology design, and position-based routing in 3D ocean spaces. \n2. Abstract of Cited Paper (BIB002): Localization is one of the most important issues associated with underwater acoustic sensor networks, especially when sensor nodes are randomly deployed. Given that it is difficult to deploy beacon nodes at predetermined locations, localization schemes with a mobile beacon on the sea surface or along the planned path are inherently convenient, accurate, and energy-efficient. In this paper, we propose a new range-free Localization with a Mobile Beacon (LoMoB). The mobile beacon periodically broadcasts a beacon message containing its location. Sensor nodes are individually localized by passively receiving the beacon messages without inter-node communications. For location estimation, a set of potential locations are obtained as candidates for a node's location and then the node's location is determined through the weighted mean of all the potential locations with the weights computed based on residuals.\n\nReview Chapter:",
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"content": "Most of the existing localization methods for 3D UWSNs can be classified into different categories by different researchers as shown in Figure 4 . Different localization techniques are mainly categorized into two methods, that is, range-based and range-free BIB002 BIB001 . A range-based method is based on anchor or reference nodes and includes time of arrival (ToA), time difference of arrival (TDoA), or angle of arrival (AoA) to measure distances or angles between nodes. These distance or angle estimations are further recycled to compute the positions of nodes. However, range-based localization is not suitable in all applications due to the cost and limitations of the hardware on sensing nodes. Therefore, range-free is used as an alternative localization method which includes hop count or areas to locate nodes with less expense. Depending on the mobility of anchor nodes in UWSNs, localization methods can also be categorized into stationary, mobile, and hybrid localization algorithms BIB002 BIB003 . In stationary localization algorithms, all sensor nodes are static and attached to surface buoys or ocean floor units having fixed locations. In mobile localization algorithms, all sensor nodes are mobile and freely drift with water, such as AUVs. In hybrid localization algorithms, sensor nodes are both stationary and mobile. Some researchers further grouped these three localization algorithms under centralized and distributed methods. Centralized methods are controlled and operated by center sink or base station which usually collects all kinds of information by underwater known positioned sensors. Where the localization between sensors in distributed methods are performed individually and collaboratively. Thus, to accomplish different requirements of localization in UWSNs, a number of 3D localization methods have been proposed which are summarized in following Table 2. 3D wireless ad hoc and sensor networks localization is based on analysis, evaluation, and interpretation of appropriate input parameters. Most of these parameters are related to the physical characteristics being measurable in a direct or indirect way. From the point of physical localization, three basic techniques are followed, that is, signal strength and network parameters, triangulation/trilateration, and proximity. The signal strength and network parameters measures radio network setu, cell id, timing advances in GSM/GPRS, round trip time (RTT) in UMTS network, and time offset information sent from base transceiver station (BTS). These measurements can be used to determine the distance from the mobile node to the BTS to further reduce the position error. The triangulation technique is the process of finding a distance to a mobile node by calculating the length of one side of a triangle formed by that point and two other reference nodes, given measurements of sides and angles of the triangle as shown in Figure 5 . Such trigonometric methods are used for position determination. In the distance based triangulation such as GPS, the position of an object is computed by measuring its distance from multiple reference points. In AoA triangulation nodes uses omnidirection antenna to estimate angle with the help of known reference axis. Furthermore, the proximity technique is based on the place of an object located nearby a known reference anchor or base station. Thus, monitoring and matching the terminal location with the RSSIs from different base stations. Beside this it also monitoring WLAN radio access points to evaluate the terminal and in-range access points. Figure 6 present a detailed view of underwater projection technique, in which depth information can be employed by three anchor nodes ( , , ), ( , , ), and ( , , ). A projection is a mapping of the anchor nodes , , and to the horizontal plane containing node , then obtaining virtual anchors , , and . The projection is defined as nondegenerative if no two anchors have the same and . The task of localizing the sensor node in a 3D space can be reduced to localizing the node in a 2D space with a nondegenerative projection. In the projection plane, the arrival times of beacon signals from anchor nodes , and are measured by sensor node . starts transmission after receiving beacon signal; similarly starts transmission after receiving both and beacon signals. This whole procedure continuously repeated T/s. Since this projection is nondegenerative, the 3D underwater localization problem is transformed into a problem of localizing node in a horizontal plane with virtual anchors , , and as shown in Figure 6 . The distance between any anchor and node is represent by . Multiple localization measurements can be combined with triangulation to obtain position information with respect to a mobile node to be tracked. The commonly used localization techniques to obtain node information are network based, terminal based, network assisted, and terminal assisted. Beside this time calculation is also used by anchor or base station to estimate mobile node position. ToA is a packet forwarding by anchor node to other underwater mobile nodes; simply it is the amount of time a signal takes to propagate from transmitter to receiver. ToA packet consists of time; therefore perfect clock synchronization is needed in nodes. Similarly, TDoA is based on the mobile measurements of the relative arrival times of signals from different anchors or base stations in UWSNs. Figure 7 its location. For accurate localization, time synchronization of the different anchors/base stations is essential. This is obtained by a location measurement unit (LMU) at the concern anchors/base stations. Systems which use ToA generally require a complicated synchronization mechanism to maintain a reliable source of time for mobile sensors. The time synchronization difference between the two anchors/base stations is represented by real time difference in Figure 7 . Similarly, the observed time difference represents the time difference between the signal received by mobile node and transmitted from the anchor/base station. The propagation time difference between two base anchors/base stations is represented by geometric time difference.",
"role": "assistant"
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science.mslr2022_cochrane_multidoc_summarization | science.mslr2022_cochrane_multidoc_summarization.2146 | [
{
"content": "Review the provided collection of medical RCT summaries. Your objective is to distill the essential insights into a brief conclusion. Focus solely on the synthesis of findings without additional commentary. The RCT summaries are as follows:\n\n\n\nReport Title 1:\n[Efficacy of Pygeum africanum extract in the medical therapy of urination disorders due to benign prostatic hyperplasia: evaluation of objective and subjective parameters. A placebo-controlled double-blind multicenter study].\nReport Abstract 1:\nThe efficacy of an extract of Pygeum africanum in the treatment of micturitional disorders due to benign prostatic hyperplasia was tested in a multicentre double-blind trial versus placebo. Capsules containing 50 mg of Pygeum africanum extract or placebo were administered at a dosage of 1 capsule in the morning and 1 capsule in the evening over a period of 60 days. 263 patients were included in this study, which was carried out in 8 centres in Germany, France, and Austria. Evaluation was mainly based on quantitative parameters such as residual urine, uroflowmetry and the precise monitoring of diurnal and nocturnal pollakiuria. Treatment with the Pygeum africanum extract led to a marked clinical improvement: a comparison of the quantitative parameters showed a significant difference between the Pygeum africanum group and the placebo group with respect to therapeutic response. The characteristic subjective symptoms of micturitional disorders, which were evaluated by the patients in a qualitative manner, were also significantly improved by administration of Pygeum africanum extract. Overall assessment at the end of therapy, showed that micturition improved in 66% of the patients treated with Pygeum africanum extract, as compared with an improvement of 31% in the placebo group. The difference was significant at the statistical level of p less than 0.001. During therapy with Pygeum africanum extract, gastrointestinal side effects occurred in 5 patients. Treatment was discontinued in three of those cases.\n\n\nReport Title 2:\nComparison of once and twice daily dosage forms of Pygeum africanum extract in patients with benign prostatic hyperplasia: a randomized, double-blind study, with long-term open label extension.\nReport Abstract 2:\nTo compare the efficacy and safety of Pygeum africanum extract, 50 mg twice daily and 100 mg once daily.\n Patients with symptomatic benign prostatic hyperplasia (BPH) entered a 2-month randomized, parallel-group, double-blind, comparative phase (group A, 50 mg twice daily; group B, 100 mg once daily), followed by a 10-month, open phase (100 mg once daily). Main efficacy assessment parameters included International Prostate Symptom Score (IPSS), quality of life (QOL), and maximum urinary flow rate (Qmax).\n Two hundred nine patients completed the comparative phase in compliance with the protocol; 174 were included in the open phase. Both treatments had similar efficacy. IPSS (baseline 17 in both groups) improved by 38% in group A and 35% in group B. QOL improved by 28% in both groups. Qmax increased by 1.63 mL/s (16%) in group A and 2.02 mL/s (19%) in group B. After 12 months, the IPSS fell from 16 (baseline) to 9 (-46%). Half of the patients had an IPSS below 8. Mean Qmax increased by 1.65 mUs (15%). The safety profile was similar between groups and study phases.\n P. africanum extract at 50 mg twice daily and 100 mg once daily proved equally effective and safe at 2 months. Further improvements in efficacy with a satisfactory safety profile were documented after 12 months.\n\n\nReport Title 3:\nA clinical and urodynamic study of tadenan in the treatment of benign prostatic hypertrophy.\nReport Abstract 3:\n20 patients with benign prostatic hypertrophy were admitted to a double-blind noncrossover study for evaluation of the effect of Tadenan. Using either standard clinical criteria or urodynamic data obtained by the urinary drop spectrometer, no significant effect was found for the dosage and period of administration used.\n\n\nReport Title 4:\nUsefulness of Cernilton in the treatment of benign prostatic hyperplasia.\nReport Abstract 4:\nA total of 89 patients with benign prostatic hyperplasia (BPH) were treated pharmacologically for 4 months: 51 received Cernilton and 38 Tadenan (controls). Significant subjective improvement was found in 78% of the patients in the Cernilton group compared to only 55% of the Tadenan-treated patients. The obstructive and irritative symptoms responded best to the therapy. In the Cernilton-treated patients a significant improvement in the uroflow rate, decrease in residual urine and in prostate volume were found. This study shows that Cernilton is an effective therapy for patients with BPH.\n\n\nReport Title 5:\n[Standardized extract of Pygeum africanum in the treatment of benign prostatic hypertrophy. Controlled clinical study versus placebo].\nReport Abstract 5:\nnan\n\n\nReport Title 6:\n[Medical treatment of fibroadenomatous hypertrophy of the prostate with a new plant substance].\nReport Abstract 6:\nnan\n\n\nReport Title 7:\nCombined extracts of Urtica dioica and Pygeum africanum in the treatment of benign prostatic hyperplasia: double-blind comparison of two doses.\nReport Abstract 7:\nThe 134 patients (aged 53 to 84 years) with symptoms of benign prostatic hyperplasia were drawn from two medical centers in Warsaw. The patients were randomly assigned to receive two capsules of the standard dose of an urtica/pygeum preparation (300 mg of Urtica dioica root extract combined with 25 mg of Pygeum africanum bark extract) or two capsules containing half the standard dose twice daily for 8 weeks. After 28 days' treatment, urine flow, residual urine, and nycturia were significantly reduced in both treatment groups. After 56 days' treatment, further significant decreases were found in residual urine (half-dose group) and in nycturia (both groups). There were no between-group differences in these measures of efficacy. Five patients reported adverse effects of treatment; treatment was not discontinued in any patient because of side effects. It is concluded that half doses of the urtica/pygeum extract are as safe and effective as the recommended full doses.",
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"content": "A standardized preparation of Pygeum africanum may be a useful treatment option for men with lower urinary symptoms consistent with benign prostatic hyperplasia. However, the reviewed studies were small in size, were of short duration, used varied doses and preparations and rarely reported outcomes using standardized validated measures of efficacy. Additional placebo-controlled trials are needed as well as studies that compare Pygeum africanum to active controls that have been convincingly demonstrated to have beneficial effects on lower urinary tract symptoms related to BPH. These trials should be of sufficient size and duration to detect important differences in clinically relevant endpoints and use standardized urologic symptom scale scores.",
"role": "assistant"
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science.chemdner_ner | science.chemdner_ner.804 | [
{
"content": "Analyze the given text to identify specific entities. Focus on extracting relevant data.\n\nProvide your findings in JSON format. Each category should list the entities found.\n\nText:\n\nAntiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-α receptor activation in a genetic model of absence epilepsy. N-palmitoylethanolamine (PEA), an endogenous fatty acid ethanolamide, plays a key role in the regulation of the inflammatory response and pain through, among others, activation of nuclear peroxisome proliferator-activated receptors (PPAR-α). Endogenous cannabinoids play a protective role in several central nervous system (CNS) disorders, particularly those associated with neuronal hyperexcitability. We investigated the effects of PEA and the role of PPAR-α in absence epilepsy using the WAG/Rij rat model. PEA, anandamide (AEA), a PPAR-α antagonist (GW6471) and a synthetic CB1 receptor antagonist/inverse agonist (SR141716) were administered to WAG/Rij rats in order to evaluate the effects on epileptic spike-wave discharges (SWDs) on EEG recordings. We studied also the effects of PEA co-administration with SR141716 and GW6471 and compared these effects with those of AEA to evaluate PEA mechanism of action and focusing on CB1 receptors and PPAR-α. Both PEA and AEA administration significantly decreased SWDs parameters (absence seizures). In contrast, GW6471 was devoid of effects while SR141716 had pro-absence effects. The co-administration of SR141716 with PEA or AEA completely blocked the anti-absence effects of these compounds. GW6471 antagonized PEA's effects whereas it did not modify AEA's effects. Furthermore, we have also measured PEA, AEA and 2-AG (2-arachidonoylglycerol) brain levels identifying significant differences between epileptic and control rats such as decreased PEA levels in both thalamus and cortex that might contribute to absence epilepsy. Our data demonstrate that PEA has anti-absence properties in the WAG/Rij rat model and that such properties depend on PPAR-α and indirect activation of CB1 receptors. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'.",
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"content": "{\"Chemical\": [\"2-AG\", \"SR141716\", \"cannabinoids\", \"PEA\", \"anandamide\", \"GW6471\", \"N-palmitoylethanolamine\", \"2-arachidonoylglycerol\", \"fatty acid ethanolamide\", \"AEA\"]}",
"role": "assistant"
}
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.809 | [
{
"content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: A review of speech-based bimodal recognition \nChapter Title: B. General Fusion Hierarchy \n1. Abstract of Cited Paper (BIB001): Sensor fusion models have been characterized in the literature in a number of distinctly different ways: in terms of information levels at which the fusion is accomplished; the objectives of the fusion process, the application domain; the types of sensors employed, the sensor suite configuration and so on. The characterization most commonly encountered in the rapidly growing sensor fusion literature based on level of detail in the information is that of the now well known triplet: data level, feature level, and decision level. We consider here a generalized input-output (I/O) descriptor pair based characterization of the sensor fusion process that can be looked upon as a natural out growth of the trilevel characterization. The fusion system design philosophy expounded here is that an exhaustive exploitation of the sensor fusion potential should explore fusion under all of the different I/O-based fusion modes conceivable under such a characterization. Fusion system architectures designed to permit such exploitation offer the requisite flexibility for developing the most effective fusion system designs for a given application. A second facet of this exploitation is aimed at exploring the new concept of self-improving multisensor fusion system architectures wherein the central (fusion system) and focal (individual sensor subsystems) decision makers mutually enhance the other's performance by providing reinforced learning. A third facet is that of investigating fusion system architectures for environments wherein the different local decision makers may only be capable of narrower decisions that span only a subset of decision choices. The paper discusses these flexible fusion system architectures along with related issues and illustrates them with examples of their application to real-world scenarios. \n2. Abstract of Cited Paper (BIB002): Multisensor data fusion is an emerging technology applied to Department of Defense (DoD) areas such as automated target recognition, battlefield surveillance, and guidance and control of autonomous vehicles, and to non-DoD applications such as monitoring of complex machinery, medical diagnosis, and smart buildings. Techniques for multisensor data fusion are drawn from a wide range of areas including artificial intelligence, pattern recognition, statistical estimation and other areas. This paper provides a tutorial on data fusion, introducing data fusion applications, process models, and identification of applicable techniques. Comments are made on the state-of-the-art in data fusion. \n3. Abstract of Cited Paper (BIB003): We develop a common theoretical framework for combining classifiers which use distinct pattern representations and show that many existing schemes can be considered as special cases of compound classification where all the pattern representations are used jointly to make a decision. An experimental comparison of various classifier combination schemes demonstrates that the combination rule developed under the most restrictive assumptions-the sum rule-outperforms other classifier combinations schemes. A sensitivity analysis of the various schemes to estimation errors is carried out to show that this finding can be justified theoretically.\n\nReview Chapter:",
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"content": "Sensor fusion deals with the combination of information produced by several sources BIB002 , BIB003 . It has borrowed mathematical and heuristic techniques from a wide array of fields, such as statistics, artificial intelligence, decision theory, and digital signal processing. Theoretical frameworks for sensor fusion have also been proposed BIB004 . In pattern recognition, sensor fusion can be performed at the data level, feature level, or decision level (see Fig. 1 ); hybrid fusion methods are also available BIB001 . Low-level fusion can occur at the data level or feature level. Intermediate-level and high-level fusion typically involves the combination of recognition scores or labels produced as intermediate or final output of classifiers. Hall BIB001 argues that owing to the information loss, which occurs during the transformation of raw data into features and eventually into classifier outputs, classification accuracy is expected to be the lowest for decision fusion. However, it is also known that corruption of information due to noise is potentially highest and requirements for data registration most stringent, at the lower levels of the fusion hierarchy BIB002 , . In addition, low-level fusion is less robust to sensor failure than high-level fusion BIB002 . Moreover, low-level fusion generally requires more training data because it usually involves more free parameters than high-level fusion. It is also easier to upgrade a single-sensor system into a multisensor system based on decision fusion; sensors can be added, without having to retrain any legacy singlesensor classifiers. Additionally, the frequently-used simplifying assumption of independence between sensor-specific data holds better at the decision level, particularly if the classifiers are not of the same type. However, decision fusion might consequently fail to exploit the potentially beneficial correlation present at the lower levels.",
"role": "assistant"
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science.data_reco_mcq_sc | science.data_reco_mcq_sc.5415 | [
{
"content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: We present a method for automatically constructing an entity-video frame dataset from a collection of\n\nKeywords: image recognition visual grounding video\n\nDataset Information:\nHow2: The How2 dataset contains 13,500 videos, or 300 hours of speech, and is split into 185,187 training, 2022 development (dev), and 2361 test utterances. It has subtitles in English and crowdsourced Portuguese translations.\nUASOL: The UASOL an RGB-D stereo dataset, that contains 160902 frames, filmed at 33 different scenes, each with between 2 k and 10 k frames. The frames show different paths from the perspective of a pedestrian, including sidewalks, trails, roads, etc.\nImage and Video Advertisements: The Image and Video Advertisements collection consists of an image dataset of 64,832 image ads, and a video dataset of 3,477 ads. The data contains rich annotations encompassing the topic and sentiment of the ads, questions and answers describing what actions the viewer is prompted to take and the reasoning that the ad presents to persuade the viewer (\"What should I do according to this ad, and why should I do it?\nDeeperForensics-1.0: DeeperForensics-1.0 represents the largest face forgery detection dataset by far, with 60,000 videos constituted by a total of 17.6 million frames, 10 times larger than existing datasets of the same kind. The full dataset includes 48,475 source videos and 11,000 manipulated videos.\n\nAvailable Datasets: A: How2 B: UASOL C: Image and Video Advertisements D: DeeperForensics-1.0",
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{
"content": "How2",
"role": "assistant"
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science.craftchem_ner | science.craftchem_ner.4159 | [
{
"content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nGlucoseandInsulintolerancetestswereperformedasdescribed[35].",
"role": "user"
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{
"content": "[\"Glucose\", \"Insulin\"]",
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science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.2423 | [
{
"content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nNetwork models have been increasingly used in the past years to support summarization and analysis of narratives, such as famous TV series, books and news. Inspired by social network analysis, most of these models focus on the characters at play. The network model well captures all characters interactions, giving a broad picture of the narration’s content. A few works went beyond by introducing additional semantic elements, always captured in a single layer network. In contrast, we introduce in this work a multilayer network model to capture more elements of the narration of a movie from its script: people, locations, and other semantic elements. This model enables new measures and insights on movies. We demonstrate this model on two very popular movies.\n\nCited Works Summary:\n[1]: With the idea of social network analysis, we propose a novel way to analyze movie videos from the perspective of social relationships rather than audiovisual features. To appropriately describe role's relationships in movies, we devise a method to quantify relations and construct role's social networks, called RoleNet. Based on RoleNet, we are able to perform semantic analysis that goes beyond conventional feature-based approaches. In this work, social relations between roles are used to be the context information of video scenes, and leading roles and the corresponding communities can be automatically determined. The results of community identification provide new alternatives in media management and browsing. Moreover, by describing video scenes with role's context, social-relation-based story segmentation method is developed to pave a new way for this widely-studied topic. Experimental results show the effectiveness of leading role determination and community identification. We also demonstrate that the social-based story segmentation approach works much better than the conventional tempo-based method. Finally, we give extensive discussions and state that the proposed ideas provide insights into context-based video analysis.",
"role": "user"
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{
"content": "Some studies have been conducted to apply social network analysis (SNA) for movie story analysis. RoleNet [1] is an SNA-based approach that was proposed to analyze movie stories. It can identify automatically leading roles and corresponding communities by investigating the social interactions between characters using a weighted graph where nodes represent characters, and edges represent co-appearance relationships, two characters appear in the scene. Edge weight represents the number of co-appearances of two characters in the same scene. However, using only scenes to model the movie story is not enough: some scenes may be very long, and others are short. Using an additional source such as the dialog would be more adaptable than this assumption.",
"role": "assistant"
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science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.4816 | [
{
"content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nIn open set learning, a model must be able to generalize to novel classes when it encounters a sample that does not belong to any of the classes it has seen before. Open set learning poses a realistic learning scenario that is receiving growing attention. Existing studies on open set learning mainly focused on detecting novel classes, but few studies tried to model them for differentiating novel classes. In this paper, we recognize that novel classes should be different from each other, and propose distribution networks for open set learning that can model different novel classes based on probability distributions. We hypothesize that, through a certain mapping, samples from different classes with the same classification criterion should follow different probability distributions from the same distribution family. A deep neural network is learned to map the samples in the original feature space to a latent space where the distributions of known classes can be jointly learned with the network. We additionally propose a distribution parameter transfer and updating strategy for novel class modeling when a novel class is detected in the latent space. By novel class modeling, the detected novel classes can serve as known classes to the subsequent classification. Our experimental results on image datasets MNIST and CIFAR10 show that the distribution networks can detect novel classes accurately, and model them well for the subsequent classification tasks.\n\nCited Works Summary:\n[1]: For a training dataset with a nonexhaustive list of classes, i.e. some classes are not yet known and hence are not represented, the resulting learning problem is ill-defined. In this case a sample from a missing class is incorrectly classified to one of the existing classes. For some applications the cost of misclassifying a sample could be negligible. However, the significance of this problem can better be acknowledged when the potentially undesirable consequences of incorrectly classifying a food pathogen as a nonpathogen are considered. Our research is directed towards the real-time detection of food pathogens using optical-scattering technology. Bacterial colonies consisting of the progeny of a single parent cell scatter light at 635 nm to produce unique forward-scatter signatures. These spectral signatures contain descriptive characteristics of bacterial colonies, which can be used to identify bacteria cultures in real time. One bottleneck that remains to be addressed is the nonexhaustive nature of the training library. It is very difficult if not impractical to collect samples from all possible bacteria colonies and construct a digital library with an exhaustive set of scatter signatures. This study deals with the real-time detection of samples from a missing class and the associated problem of learning with a nonexhaustive training dataset. Our proposed method assumes a common prior for the set of all classes, known and missing. The parameters of the prior are estimated from the samples of the known classes. This prior is then used to generate a large number of samples to simulate the space of missing classes. Finally a Bayesian maximum likelihood classifier is implemented using samples from real as well as simulated classes. Experiments performed with samples collected for 28 bacteria subclasses favor the proposed approach over the state of the art.\n\n[2]: We present a framework for online inference in the presence of a nonexhaustively defined set of classes that incorporates supervised classification with class discovery and modeling. A Dirichlet process prior (DPP) model defined over class distributions ensures that both known and unknown class distributions originate according to a common base distribution. In an attempt to automatically discover potentially interesting class formations, the prior model is coupled with a suitably chosen data model, and sequential Monte Carlo sampling is used to perform online inference. Our research is driven by a biodetection application, where a new class of pathogen may suddenly appear, and the rapid increase in the number of samples originating from this class indicates the onset of an outbreak.\n\n[3]: Technologies for rapid detection of bacterial pathogens are crucial for securing the food supply. A light-scattering sensor recently developed for real-time identification of multiple colonies has shown great promise for distinguishing bacteria cultures. The classification approach currently used with this system relies on supervised learning. For accurate classification of bacterial pathogens, the training library should be exhaustive, i.e., should consist of samples of all possible pathogens. Yet, the sheer number of existing bacterial serovars and more importantly the effect of their high mutation rate would not allow for a practical and manageable training. In this study, we propose a Bayesian approach to learning with a nonexhaustive training dataset for automated detection of unknown bacterial serovars, i.e., serovars for which no samples exist in the training library. The main contribution of our work is the Wishart conjugate priors defined over class distributions. This allows us to employ the prior information obtained from known classes to make inferences about unknown classes as well. By this means, we identify new classes of informational value and dynamically update the training dataset with these classes to make it increasingly more representative of the sample population. This results in a classifier with improved predictive performance for future samples. We evaluated our approach on a 28-class bacteria dataset and also on the benchmark 26-class letter recognition dataset for further validation. The proposed approach is compared against state-of-the-art involving density-based approaches and support vector domain description, as well as a recently introduced Bayesian approach based on simulated classes. Copyright © 2010 Wiley Periodicals, Inc. Statistical Analysis and Data Mining 3: 289-301, 2010",
"role": "user"
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{
"content": "Non-exhaustive learning tries to learn from a non-exhaustive training set where some classes are missing. [1] proposed an empirical Bayesian approach to deal with non-exhaustive training datasets. [3] assumed Gaussian distributions for all classes (known and unknown) and dynamically updated class set based on the maximum likelihood detection of novelties. [2] defined a Dirichlet process prior model over class distributions to ensure that both known and unknown class distributions originate according to a common base distribution. However, these methods may have difficulties in high dimensional image data. DN proposed in this paper can deal with high dimensional or unstructured data naturally by learning a low-dimensional representation.",
"role": "assistant"
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science.mslr2022_cochrane_multidoc_summarization | science.mslr2022_cochrane_multidoc_summarization.3473 | [
{
"content": "Review the provided collection of medical RCT summaries. Your objective is to distill the essential insights into a brief conclusion. Focus solely on the synthesis of findings without additional commentary. The RCT summaries are as follows:\n\n\n\nReport Title 1:\nMaximizing immunization coverage through home visits: a controlled trial in an urban area of Ghana.\nReport Abstract 1:\nA strategy of home visits to maximize children's immunization coverage was implemented in three towns in Ghana. The strategy was tested in town 1 in a controlled trial where clusters of children were allocated to the intervention and control groups. A total of 200 mothers in the intervention group were visited at home by non-health workers and their children were referred to a routine under-fives' clinic. Subsequent home visits targeted at those who failed to complete immunization schedules were made by nurses. After 6 months, coverage had risen from 60% to 85%, which was 20% higher than in the town 1 control group of 219 age-matched children (P < 0.005). A similar home-visiting strategy in a neighbouring town resulted in a rise in coverage from 38% to 91% (n = 55), mainly through home immunizations. Children were more likely to complete the schedule if their fathers were interviewed and participated in the decision to send them to the clinic. Countries with national service programmes can use a home-visiting strategy to supplement and strengthen their routine immunization programmes. A wide range of other community-based primary health care interventions could also be tested and implemented using this methodology.\n\n\nReport Title 2:\nMonetary incentives in primary health care and effects on use and coverage of preventive health care interventions in rural Honduras: cluster randomised trial.\nReport Abstract 2:\nScaling-up of effective preventive interventions in child and maternal health is constrained in many developing countries by lack of demand. In Latin America, some governments have been trying to increase demand for health interventions by making direct payments to poor households contingent on them keeping up-to-date with preventive health services. We undertook a public health programme effectiveness trial in Honduras to assess this approach, contrasting it with a direct transfer of resources to local health teams.\n 70 municipalities were selected because they had the country's highest prevalence of malnutrition. They were allocated at random to four groups: money to households; resources to local health teams combined with a community-based nutrition intervention; both packages; and neither. Evaluation surveys of about 5600 households were undertaken at baseline and roughly 2 years later. Pregnant women and mothers of children younger than 3 years old were asked about use of health services (primary outcome) and coverage of interventions such as immunisation and growth monitoring (secondary outcome). Reports were supplemented with data from children's health cards and government service utilisation data. Analysis was by mixed effects regression, accounting for the municipality-level randomisation.\n The household-level intervention had a large impact (15-20 percentage points; p<0.01) on the reported coverage of antenatal care and well-child check-ups. Childhood immunisation series could thus be started more opportunely, and the coverage of growth monitoring was markedly increased (15-21 percentage points; p<0.01. Measles and tetanus toxoid immunisation were not affected. The transfer of resources to local health teams could not be implemented properly because of legal complications.\n Conditional payments to households increase the use and coverage of preventive health care interventions.\n\n\nReport Title 3:\nInforming resource-poor populations and the delivery of entitled health and social services in rural India: a cluster randomized controlled trial.\nReport Abstract 3:\nA lack of awareness about entitled health and social services may contribute to poor delivery of such services in developing countries, especially among individuals of low socioeconomic status.\n To determine the impact of informing resource-poor rural populations about entitled services.\n Community-based, cluster randomized controlled trial conducted from May 2004 to May 2005 in 105 randomly selected village clusters in Uttar Pradesh state in India. Households (548 intervention and 497 control) were selected by a systematic sampling design, including both low-caste and mid- to high-caste households.\n Four to 6 public meetings were held in each intervention village cluster to disseminate information on entitled health services, entitled education services, and village governance requirements. No intervention took place in control village clusters.\n Visits by nurse midwife; prenatal examinations, tetanus vaccinations, and prenatal supplements received by pregnant women; vaccinations received by infants; excess school fees charged; occurrence of village council meetings; and development work in villages.\n At baseline, there were no significant differences in self-reported delivery of health and social services. After 1 year, intervention villagers reported better delivery of several services compared with control villagers: in a multivariate analysis, 30% more prenatal examinations (95% confidence interval [CI], 17%-43%; P < .001), 27% more tetanus vaccinations (95% CI, 12%-41%; P < .001), 24% more prenatal supplements (95% CI, 8%-39%; P = .003), 25% more infant vaccinations (95% CI, 8%-42%; P = .004), and decreased excess school fees of 8 rupees (95% CI, 4-13 rupees; P < .001). In a difference-in-differences analysis, 21% more village council meetings were reported (95% CI, 5%-36%; P = .01). There were no improvements in visits by a nurse midwife or in development work in the villages. Both low-caste and mid- to high-caste intervention households reported significant improvements in service delivery.\n Informing resource-poor rural populations in India about entitled services enhanced the delivery of health and social services among both low- and mid- to high-caste households. Interventions that emphasize educating resource-poor populations about entitled services may improve the delivery of such services.\n clinicaltrials.gov Identifier: NCT00421291.\n\n\nReport Title 4:\nRedesigned immunization card and center-based education to reduce childhood immunization dropouts in urban Pakistan: a randomized controlled trial.\nReport Abstract 4:\nIn Pakistan during 2000-2004, about 11-13% of children who received the first dose of diphtheria-pertussis-tetanus (DPT1) failed to complete its third dose (DPT3). We assessed the effect of a redesigned immunization card and center-based education to mothers on DPT3 completion. We enrolled 1500 mother-child units at DPT1, randomized them to three intervention and one standard care groups, and recorded their DPT3 visits during a 90-day follow-up. In multivariable analysis, a significant increase of 31% (adjusted RR=1.31, 95% CI=1.18-1.46) in DPT3 completion was estimated in the group that received both redesigned card and center-based education compared with the standard care group.",
"role": "user"
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"content": "Home visits and health education may improve immunization coverage but the quality of evidence is low.",
"role": "assistant"
}
]
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science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.3730 | [
{
"content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nThe task of multiple people tracking in monocular videos is challenging because of the numerous difficulties involved: occlusions, varying environments, crowded scenes, camera parameters and motion. In the tracking-by-detection paradigm, most approaches adopt person re-identification techniques based on computing the pairwise similarity between detections. However, these techniques are less effective in handling long-term occlusions. By contrast, tracklet (a sequence of detections) re-identification can improve association accuracy since tracklets offer a richer set of visual appearance and spatio-temporal cues. In this paper, we propose a tracking framework that employs a hierarchical clustering mechanism for merging tracklets. To this end, tracklet re-identification is performed by utilizing a novel multi-stage deep network that can jointly reason about the visual appearance and spatio-temporal properties of a pair of tracklets, thereby providing a robust measure of affinity. Experimental results on the challenging MOT16 and MOT17 benchmarks show that our method significantly outperforms state-of-the-arts.\n\nCited Works Summary:\n[1]: Multi-Object Tracking (MOT) is a challenging task in the complex scene such as surveillance and autonomous driving. In this paper, we propose a novel tracklet processing method to cleave and re-connect tracklets on crowd or long-term occlusion by Siamese Bi-Gated Recurrent Unit (GRU). The tracklet generation utilizes object features extracted by CNN and RNN to create the high-confidence tracklet candidates in sparse scenario. Due to mis-tracking in the generation process, the tracklets from different objects are split into several sub-tracklets by a bidirectional GRU. After that, a Siamese GRU based tracklet re-connection method is applied to link the sub-tracklets which belong to the same object to form a whole trajectory. In addition, we extract the tracklet images from existing MOT datasets and propose a novel dataset to train our networks. The proposed dataset contains more than 95160 pedestrian images. It has 793 different persons in it. On average, there are 120 images for each person with positions and sizes. Experimental results demonstrate the advantages of our model over the state-of-the-art methods on MOT16.\n\n[2]: We present a multi-cue metric learning framework to tackle the popular yet unsolved Multi-Object Tracking (MOT) problem. One of the key challenges of tracking methods is to effectively compute a similarity score that models multiple cues from the past such as object appearance, motion, or even interactions. This is particularly challenging when objects get occluded or share similar appearance properties with surrounding objects. To address this challenge, we cast the problem as a metric learning task that jointly reasons on multiple cues across time. Our framework learns to encode long-term temporal dependencies across multiple cues with a hierarchical Recurrent Neural Network. We demonstrate the strength of our approach by tracking multiple objects using their appearance, motion, and interactions. Our method outperforms previous works by a large margin on multiple publicly available datasets including the challenging MOT benchmark.",
"role": "user"
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{
"content": "Recently, Ma [1] presented a framework that employs a three step process in which tracklets are first created, then cleaved, and then reconnected using a combination of Siamese-trained CNNs, Bi-Gated Recurrent Unit (GRU) and LSTM cells. By contrast, our approach utilizes a hierarchical clustering mechanism with a single multi-stage network to compute tracklet similarity, thereby minimizing false associations in the first step and mitigating the need for tracklet cleaving and reconnection. [2] , a multi-stage network was proposed to model the appearance, motion and interaction of targets. Their network design is similar to ours, but with the key difference that our model computes the similarity between two tracklets, rather than between a tracklet and a single detection.",
"role": "assistant"
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science.data_reco_mcq_sc | science.data_reco_mcq_sc.8836 | [
{
"content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: We present a fast and accurate stereo matching network to achieve efficient depth estimation.\n\nKeywords: stereo matching images\n\nDataset Information:\nKITTI-Depth: The KITTI-Depth dataset includes depth maps from projected LiDAR point clouds that were matched against the depth estimation from the stereo cameras. The depth images are highly sparse with only 5% of the pixels available and the rest is missing.\nMVSEC: The Multi Vehicle Stereo Event Camera (MVSEC) dataset is a collection of data designed for the development of novel 3D perception algorithms for event based cameras. Stereo event data is collected from car, motorbike, hexacopter and handheld data, and fused with lidar, IMU, motion capture and GPS to provide ground truth pose and depth images.\nDIML/CVl RGB-D Dataset: This dataset contains synchronized RGB-D frames from both Kinect v2 and Zed stereo camera. For the outdoor scene, the authors first generate disparity maps using an accurate stereo matching method and convert them using calibration parameters.\nKITTI: KITTI (Karlsruhe Institute of Technology and Toyota Technological Institute) is one of the most popular datasets for use in mobile robotics and autonomous driving. It consists of hours of traffic scenarios recorded with a variety of sensor modalities, including high-resolution RGB, grayscale stereo cameras, and a 3D laser scanner.\n\nAvailable Datasets: A: KITTI-Depth B: MVSEC C: DIML/CVl RGB-D Dataset D: KITTI",
"role": "user"
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{
"content": "KITTI",
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}
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science.medmentions_ner | science.medmentions_ner.1056 | [
{
"content": "Analyze the provided paragraph from a scientific document. Your goal is to identify and extract relevant entities.\n\nFormat your findings as a JSON object, where each key represents a category of entities, and the corresponding value is a list of entities identified in that category. If no entities are found for a category, return an empty list.\n\nFocus on precision and ensure that the output is strictly in JSON format.\n\nDocument:\n\nPhysiological and molecular responses of juvenile shortnose sturgeon (Acipenser brevirostrum) to thermal stress The shortnose sturgeon (Acipenser brevirostrum LeSueur, 1818) is a vulnerable species that is found along the eastern coast of North America. Little is known about temperature tolerance in this species and with a rapidly changing global climate, it becomes increasingly important to define the thermal tolerance of this species to better predict population distribution. Using a modified critical thermal maximum test (CTMax), the objectives of this study were to determine the impact of heating rate (0.1, 0.2 and 0.25°Cmin(-1)) on the thermal tolerance, associated hematological responses, and oxygen consumption in juvenile sturgeon. In addition, transcripts associated with physiological stress and heat shock (i.e., heat shock proteins) were also measured. Heating rate did not alter the CTMax values of shortnose sturgeon. Neither heating rate nor thermal stress affected plasma sodium and chloride levels, nor the expression of transcripts that included catalase, glucocorticoid receptor, heat shock protein70 (hsp70), heat shock protein 90α (hsp90α) and cytochrome P450 1a (cyp1a). However, regardless of heating rate, thermal stress increased both plasma potassium and lactate concentrations. Glucose levels were increased at heating rates of 0.2 and 0.25°Cmin(-1), but not at 0.1°Cmin(-1). Overall, oxygen consumption rates increased with thermal stress, but the response patterns were not affected by heating rate. These data support the hypothesis that shortnose sturgeon can tolerate acute heat stress, as many physiological and molecular parameters measured here were non-responsive to the thermal stress.",
"role": "user"
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"content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"expression\", \"physiological stress\", \"acute heat stress\", \"thermal stress\", \"heat shock\", \"thermal tolerance\", \"Physiological\", \"response\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"heat shock protein70\", \"heat shock proteins\", \"cyp1a\", \"cytochrome P450 1a\", \"hsp90\\u03b1\", \"catalase\", \"glucocorticoid receptor\", \"hsp70\", \"transcripts\", \"heat shock protein 90\\u03b1\"], \"ClinicalAttribute\": [\"oxygen consumption\"], \"Eukaryote\": [\"Acipenser brevirostrum\", \"shortnose sturgeon\", \"sturgeon\", \"LeSueur\"], \"Finding\": [\"temperature tolerance\", \"Glucose levels were increased\", \"hematological responses\", \"oxygen consumption rates increased\", \"increased both plasma potassium\", \"parameters\", \"CTMax values\", \"molecular responses\", \"lactate concentrations\"], \"Food\": [], \"HealthCareActivity\": [\"CTMax\", \"plasma sodium\", \"modified critical thermal maximum test\", \"chloride levels\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"species\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [], \"SpatialConcept\": [\"patterns\", \"population distribution\", \"eastern coast of North America\"], \"Virus\": []}",
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science.medmentions_ner | science.medmentions_ner.1619 | [
{
"content": "Analyze the provided paragraph from a scientific document. Your goal is to identify and extract relevant entities.\n\nFormat your findings as a JSON object, where each key represents a category of entities, and the corresponding value is a list of entities identified in that category. If no entities are found for a category, return an empty list.\n\nFocus on precision and ensure that the output is strictly in JSON format.\n\nDocument:\n\nModeling the ferrochelatase c.315-48C modifier mutation for erythropoietic protoporphyria (EPP) in mice Erythropoietic protoporphyria (EPP) is caused by deficiency of ferrochelatase (FECH), which incorporates iron into protoporphyrin IX (PPIX) to form heme. Excitation of accumulated PPIX by light generates oxygen radicals that evoke excessive pain and, after longer light exposure, cause ulcerations in exposed skin areas of individuals with EPP. Moreover, ∼5% of the patients develop a liver dysfunction as a result of PPIX accumulation. Most patients (∼97%) have a severe FECH mutation (Mut) in trans to an intronic polymorphism (c.315-48C), which reduces ferrochelatase synthesis by stimulating the use of an aberrant 3' splice site 63 nt upstream of the normal site for exon 4. In contrast, with the predominant c.315-48T allele, the correct splice site is mostly used, and individuals with a T/Mut genotype do not develop EPP symptoms. Thus, the C allele is a potential target for therapeutic approaches that modify this splicing decision. To provide a model for pre-clinical studies of such approaches, we engineered a mouse containing a partly humanized Fech gene with the c.315-48C polymorphism. F1 hybrids obtained by crossing these mice with another inbred line carrying a severe Fech mutation (named m1Pas) show a very strong EPP phenotype that includes elevated PPIX in the blood, enlargement of liver and spleen, anemia, as well as strong pain reactions and skin lesions after a short period of light exposure. In addition to the expected use of the aberrant splice site, the mice also show a strong skipping of the partly humanized exon 3. This will limit the use of this model for certain applications and illustrates that engineering of a hybrid gene may have unforeseeable consequences on its splicing.",
"role": "user"
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{
"content": "{\"AnatomicalStructure\": [\"ferrochelatase c.315-48C\", \"Fech\", \"C allele\", \"Fech gene\", \"m1Pas\", \"c.315-48T\", \"c.315-48C\", \"allele\", \"FECH\"], \"Bacterium\": [], \"BiologicFunction\": [\"liver dysfunction\", \"mutation\", \"3\\u0027 splice site\", \"T/Mut\", \"skin lesions\", \"ulcerations\", \"EPP\", \"anemia\", \"mutation (Mut) in trans to an intronic\", \"Erythropoietic protoporphyria\", \"erythropoietic protoporphyria\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [\"blood\"], \"BodySystem\": [\"skin\"], \"Chemical\": [\"protoporphyrin IX\", \"heme\", \"exon 4.\", \"FECH\", \"ferrochelatase\", \"exon 3\", \"PPIX\", \"iron\"], \"ClinicalAttribute\": [], \"Eukaryote\": [\"mice\", \"mouse\"], \"Finding\": [\"pain\", \"accumulation\", \"enlargement of liver and spleen\", \"symptoms\"], \"Food\": [], \"HealthCareActivity\": [\"therapeutic approaches\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"model\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [\"individuals\"], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"splicing\", \"Modeling\", \"pre-clinical studies\"], \"SpatialConcept\": [\"splice site\", \"63 nt upstream of the normal site\"], \"Virus\": []}",
"role": "assistant"
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.27627 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nUnusual biaryl torsional strain promotes reactivity in Cu-catalyzed Sommelet–Hauser rearrangement\n\nContent Extracts:\nIntroduction\n<p>Dearomatization is a robust method for the construction of polyfunctionalized cyclic compounds; it can generate quaternary carbon centers and multi-substituted C]C double bonds in one or two steps. Due to the high stabilization of aromaticity, dearomatization reactions are traditionally performed under harsh conditions, such as oxidation in the presence of hypervalent iodine, 1 Birch reduction, 2 enzymatic conditions, 3 or other conditions. 4 Dearomatization has recently been achieved using photochemistry and transition metal catalysis. In particular, catalytic asymmetric dearomatization (CADA) has attracted substantial attention, such as from the You group, for constructing optically pure molecules from arenes. 5 The Sommelet-Hauser reaction is an intramolecular rearrangement of benzyl ammonium salts to give ortho-substituted benzylamines (Scheme 1a, path A). 6-8 Sommelet-Hauser dearomatization can efficiently generate valuable three-dimensional compounds bearing quaternary carbon centers if the two ortho positions have non-hydrogen substituents (Scheme 1b). In a variation known as thio-Sommelet rearrangement, dearomatized compounds bearing thioether functionalities can be prepared by replacing the ammonium ylides with sulfur ylides. 9,10</p><p>A challenge to exploiting the Sommelet-Hauser reaction is preventing competitive Stevens rearrangement, 11,12 in which formal intramolecular nucleophilic attack at the benzylic position affords 2-phenylethanamine analogues (Scheme 1a, path B). Singleton has argued that these two types of rearrangements compete dynamically because they can occur via the same transition state. 13 Sommelet-Hauser rearrangement can be used to produce spiro-compounds from benzocyclic ammonium salts, but the reported reactions usually give low yields and wide product distribution. 14 For example, the reaction usually produces two regioisomers together with ring-enlarged products from Stevens rearrangement (Scheme 1c). Ring strain in seven-and eightmembered structures lowers the rearrangement rate, signicantly increasing the yields of desilylation by-products C. In addition, the requirement for pre-synthesized ammonium salts limits the substrate scope of the reaction. Third, the Sommelet-Hauser rearrangement appears incompatible with ammonium salts with fewer than seven members. As a result, the reaction cannot generate rings smaller than sixmembered N-heterocycles (Scheme 1c).</p><p>Herein we report the copper-catalyzed generation of nitrogen ylide intermediates capable of Sommelet-Hauser rearrangement, in which N-containing six-membered rings efficiently participate. We further report that molecular torsional strain in biaryl substrates increases their reactivity in this rearrangement.</p><p>We wondered whether we could adapt dearomatization via Sommelet-Hauser rearrangement to generate the important spirocyclohexaneindoline structural motif, found in several natural products including gelsemine, 15 21-oxogelsemine 16 and koumine (Fig. 1). 17 It also comprises the core structural unit of various biologically active molecules. 18</p>\n\nOptimization\n<p>We were unable to dearomatize biaryl compound 1a using diazo compound 2a in the presence of silver, rhodium or gold salts as catalysts, which are frequently used in reactions involving carbene (Table 1, entries 1-3). We were pleased to nd that 1a reacted with 2a in the presence of Cu(OTf) 0.5PhH at 90 C to give 27% of spiro product 3a as a single isomer, along with a small amount of 4a (entry 4). The reaction generated a spirostructure with adjacent quaternary and tertiary carbon centers in one step. Screening of copper salts showed Cu(acac) 2 to perform the best in terms of yield and reaction time (entries 5-9). Lowering the reaction temperature increased the selectivity for 3a over the Stevens rearrangement product 4a, improving the isolated yield of 3a to 72% (entry 10). Solvent screening identied methyl tert-butyl ether (MTBE) as the best (entries 11-13). The reaction proceeded smoothly with only 5 mol% of Cu(acac) 2 , albeit with a slightly lower yield (entry 14).</p>\n\nSubstrate scope\n<p>With the optimal conditions in hand, we tested the generality of this Cu(acac) 2 -catalyzed Sommelet-Hauser rearrangement. Diazo compounds with different ester groups, such as methyl, tert-butyl and substituted benzyl esters, reacted smoothly (3b- a Unless stated otherwise, the reaction was conducted with 1a (0.10 mmol), 2a (0.20 mmol), and a metal catalyst (10 mol%). b An unidentied product was formed. f). A diazo substrate with an electron-withdrawing group (CF 3 ) led to a slightly lower yield (3e). The reaction tolerated additional methyl groups, a uorine atom and methoxyl groups in the biaryl aniline skeleton (3g-3j, 3t). Naphthalene-based substrates and a binaphthalene derivative reacted uneventfully to give the spiro compounds in decent to excellent yields (3k-3r, 3t-3z and 3bb). Stereoinduction did not occur with the (R)-1-phenylethanol-derived diazo compound, such that a pair of diastereoisomers was isolated in a 1 : 1 ratio (3t). This rearrangement was compatible with ketones and amides, which afforded the desired products in decent to good yields (3u-3x). Introducing a methyl group adjacent to the C-N bond completely inhibited this transformation (3cc).</p><p>The reaction tolerated an aryl-Br bond. Scale-up also proved possible, with compound 3x isolated in 69% yield on the 1.0 mmol scale.</p><p>The two ortho-substituents (R 1 and R 2 in Table 2) strongly inuenced the efficiency of the Sommelet-Hauser reaction and selectivity for this type of rearrangement over Stevens rearrangement (Scheme 2). For example, under the standard conditions at 50-90 C, the conversions of 5 were less than 55%, while isolated yields of 6 were no more than 35%. Product 6 was much less stable during purication than products 3a-3bb.</p><p>Performing the reaction at higher temperature in toluene gave Stevens rearrangement product 7 as the major product, with 5 recovered at 55% yield.</p>\n\nSynthetic applications\n<p>Preliminary synthetic studies were performed to demonstrate the utility of this rearrangement. Under 1 atm H 2 , the diene compound 3k underwent chemoselective 1,4-hydrogenation in the presence of Pd/C to give 8k in 83% yield, whose structure was unambiguously conrmed by single-crystal X-ray diffraction analysis. The N-methyl group could be further modied via rhodium-catalyzed C-H functionalization to afford 9k. Finally, the ester functionality could be reduced to the corresponding alcohol using DIBAL-H at À78 C without eliminating the diene moiety. The diene was further cyclized in the presence of the MeNHOH$HCl catalyst to yield polycyclic compound 10k in 57% yield (Scheme 3).</p>\n\nMechanistic studies\n<p>In a plausible catalytic cycle (Scheme 4), the reaction begins when copper salt interacts with the diazo compound to give copper-carbene complex D, releasing one molecule of nitrogen gas. The subsequent reaction of the copper-carbene complex with amine 1 affords the ylide E. Intramolecular nucleophilic attack in E delivers the spiro product 3 either before or aer dissociation of the copper catalyst. To obtain structural information about ammonium salt E and explain the different reactivity between 1 and 5, two ammonium compounds F and G were synthesized and analyzed by single-crystal X-ray diffraction. The torsional angle (C5-C6/C7-C13) was around 41 in F and 29 in G. 19 Steric repulsion between the two ortho-substituents increased the distortion in the biaryl structure. We reasoned that the two ortho-substituents in E should distort its structure to a similar extent as in F. As a result, the relatively high-energy intermediate E undergoes a rapid intramolecular nucleophilic reaction to deliver spiro compounds. Alternatively, the increased torsion reduces the delocalization of the aniline lone-pair, which increases the basicity and accelerates the ammonium formation. Substituents on the substrates strongly inuence the ratio of the [2,3]-rearrangement product to the Stevens rearrangement product; 13 the latter rearrangement usually proceeds via a bi-radical pathway under thermal conditions. 20 These considerations imply that less distorted substrates such as 5 generate lower-energy ylide intermediates, which therefore must overcome a higher activation barrier to give spiro products. Consistent with this, compound 5 was associated with lower conversion rates under the similar conditions.</p>\n\nConclusions\n<p>We have reported a copper-catalyzed Sommelet-Hauser rearrangement to construct spiroindoline compounds bearing adjacent quaternary and tertiary carbon centers. Increasing the torsional strain in the biaryl substrate increases its reactivity in this transformation. This is, to our knowledge, the rst report in which Sommelet-Hauser rearrangement was used to generate spiro compounds bearing ve-membered N-heterocycles.</p>\n\nConflicts of interest\n<p>There are no conicts to declare.</p>",
"role": "user"
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{
"content": "A Cu-catalyzed Sommelet-Hauser dearomatization of dihydrophenanthridine and diazo compounds is reported for the synthesis of spiro-indolines. A spiro-structure with adjacent quaternary and tertiary carbon centers was constructed in one step as a single isomer. Increasing steric hindrance by introducing ortho-substituents dramatically improved substrate reactivity in this transformation.Scheme 1 The Sommelet-Hauser rearrangement.",
"role": "assistant"
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]
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science.scientific_papers_summarization_single_doc_pubmed | science.scientific_papers_summarization_single_doc_pubmed.1164 | [
{
"content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\nsulfonamides and sulfones \n serve both as useful intermediates in \n organic synthesis and as important target \n molecules in their own right . for example , enantioenriched \n secondary benzylic sulfonamides and sulfones display a range of biological \n activity ( e.g. , protein tyrosine phosphatase inhibitor , antisepsis agent , and -secretase inhibitor ) .\nhowever , to the best of our knowledge , there \n are no methods for the direct catalytic asymmetric synthesis of such \n sulfonamides , and just a few for such sulfones\n. one potential route to these compounds is the stereoconvergent \n coupling of a racemic -halosulfonamide / sulfone with an appropriate \n nucleophile ( eq 1 ) . during the past several \n years\n, we have described an array of nickel - catalyzed enantioselective \n cross - couplings of secondary alkyl electrophiles . whereas couplings \n of activated electrophiles ( a leaving group \n to a carbonyl , aryl , alkenyl , alkynyl , or cyano group ) proceed in \n good ee with a variety of nucleophiles ( alkyl- , aryl- , and alkenylmetal ) , reactions of unactivated electrophiles have been \n limited , with three exceptions , to alkylmetals , specifically alkyl-(9-bbn ) reagents.1 because -halosulfonyl \n compounds are generally poor substrates \n for sn2 reactions , and the sulfonyl group does not effectively \n stabilize an adjacent radical ( bond dissociation energy for a c h \n bond of dimethylsulfone : 99 kcal / mol ) , we view them as unactivated alkyl electrophiles .\nherein , we report \n the first examples of the stereoconvergent cross - coupling of unactivated \n alkyl electrophiles with nucleophiles other than organoboranes , as \n well as the first general method for their coupling with aryl- or \n alkenylmetal reagents ; in particular , we describe nickel / bis(oxazoline)-catalyzed \n cross - couplings of racemic -bromosulfonamides and -sulfones \n with organozinc and organozirconium reagents , thereby furnishing secondary \n benzylic and allylic sulfonamides and sulfones in good enantiomeric \n excess ( eq 2).2\nupon investigating a variety of reaction \n parameters , we determined \n that a nickel / bis(oxazoline ) catalyst \n can achieve the cross - coupling of an -bromosulfonamide with \n an arylzinc reagent in very good ee and yield at 20 c \n ( table 1 , entry 1 ) ; nicl2glyme \n and bis(oxazoline ) l1 ( ( r , r ) and ( s , s ) ) are commercially available . \n\nall previous reports of stereoconvergent negishi reactions of racemic \n electrophiles have employed activated coupling partners .\nthe yield was \n determined through \n gc analysis with the aid of a calibrated internal standard .\nessentially no cross - coupling \n is observed in the absence of nicl2glyme ( table 1 , entry 2 ) , and \n a low yield of the desired product is obtained if ligand l1 is omitted ( entry 3 ) . at room temperature , the coupling proceeds \n in good ee , but hydrodebromination predominates over c c bond \n formation .\nthe corresponding valine - derived bis(oxazoline ) ( l2 ) is nearly as effective as phenylglycine - derived l1 ( entries 1 and 5 ) , whereas removal of the gem - dimethyl \n substituents on the linker between the oxazolines of l1 leads to a substantial drop in efficiency ( entry 6 ) .\nalthough pybox \n ligands are often the ligand of choice for nickel - catalyzed stereoconvergent \n negishi reactions , pybox l4 is not effective for this particular cross - coupling , nor is a 1,2-diamine \n ligand ( entries 7 and 8) .\nthe use of phmgbr in \n place of phzni leads to a small loss in ee and a substantial loss \n in yield ( entry 9 ) . when the catalyst loading is reduced in half , \n no erosion in enantioselectivity\nis observed , although the yield falls \n by a modest amount ( entry 10 ) .\nthe process is somewhat oxygen - sensitive \n ( entry 11 ; 66% conversion ) but not particularly moisture - sensitive \n ( entry 12 ) . under these conditions\n, we can achieve stereoconvergent \n negishi \n cross - couplings of a variety of racemic -bromosulfonamides \n with phzni to generate highly enantioenriched benzylic sulfonamides \n ( table 2 ) .\nthe \n nitrogen of the sulfonamide can bear either an alkyl or an aryl substituent , \n with little impact on ee or yield ( entries 15 ) .\nfurthermore , \n the r side chain can include functional groups and can \n be either primary ( entries 68 ) or secondary ( entry 9 ) , although \n in the case of the latter a diminished yield is observed . on a gram \n scale , the cross - coupling illustrated in entry 2 proceeds in 92% ee \n and 98% yield .\nthe conditions \n that we developed for stereoconvergent negishi reactions \n of -bromosulfonamides ( table 2 ) can \n be applied without modification to the corresponding sulfones ( table 3 ) .\nthus , the r substituent can range in steric \n demand from methyl to t - butyl ( entries 14 ) , \n and it can be aromatic ( entry 5 ) . with respect to the r group , it may be linear or branched ( entries 15 ) .\nwe have examined \n the scope of arylzinc nucleophiles that participate \n in this method for the catalytic asymmetric synthesis of benzylic \n sulfonamides and sulfones ( table 4 ) .\nelectron - rich \n and electron - poor arylzinc reagents are suitable partners , as is a \n heteroarylzinc reagent , furnishing the desired product in very good \n ee .\nespecially noteworthy is our observation that o - substituted phenylzinc reagents can be employed with both sulfonamide- \n and sulfone - based electrophiles ( entries 57 and 911 ) ; \n in our previous studies of nickel - catalyzed enantioselective arylations , o - substituted nucleophiles have generally been poor coupling \n partners . all data are the average of two \n experiments .\namount of arzni : \n 2.0 equiv ; amount \n of catalyst : 20% nicl2glyme , 26% ( r , r)-l1 .\nnext , we sought to expand the scope of stereoconvergent \n cross - couplings \n of -bromosulfonamides and -sulfones to include a second family \n of nucleophiles , specifically , alkenylmetal reagents .\nwe determined \n that , whereas reactions of alkenylzinc reagents proceed \n in poor yield using the method described above , alkenylzirconium reagents serve as suitable nucleophiles under modified conditions \n ( table 5 ) .\nthus , an array \n of allylic sulfonamides and sulfones can \n be synthesized with good enantioselectivity in the presence of functional \n groups such as a thiophene and a primary alkyl chloride .\nwe have suggested that , for at least \n some nickel - catalyzed cross - couplings \n of alkyl electrophiles , an alkyl radical may be generated during the \n oxidative - addition step of the catalytic cycle . in the case of electrophiles that bear an appropriately positioned \n pendant olefin , we have observed complete cyclization of the putative \n radical onto the olefin in some instances , and no cyclization in another . in order to gain insight into the mechanism of the stereoconvergent \n arylations described herein , we investigated the negishi reaction \n of an -bromosulfonamide bearing a pendant olefin ( eq 3 ) . at 70%\nconversion \n of the electrophile , we observe a 38% yield of the direct ( uncyclized ) \n cross - coupling product ( 8) and a 17% combined yield of \n cyclized cross - coupling products ( 9).3 cyclopentane derivatives cis-9 and trans-9 are each an 1:1 \n mixture of \n diastereomers ( differing in the relative stereochemistry at the deuterium - bearing \n carbon ) , consistent with the expectation for cyclization of radical \n intermediate 10 ( but not for a simple organometallic \n pathway involving only -migratory insertion and then reductive \n elimination ) .\nour observation that uncyclized cross - coupling product 8 has deuterium only in the trans position suggests that , \n when intermediate 10 does cyclize , the process is irreversible .\nsimple 5-hexenyl radical cyclizations proceed with first - order \n rate constants of 10 s. although , to the best of our knowledge , the \n rate of cyclization of sulfonamide - substituted radical 10 has not been determined , it is very likely to be significantly slower \n than diffusion ( 10 s ) .\nour observation of cyclized , cross - coupled \n products ( 9 ) therefore represents evidence that a nickel - catalyzed \n asymmetric cross - coupling process may include a noncage radical pathway . \n\nconsistent with this suggestion , the ratio of uncyclized ( d)/cyclized ( c ) product changes as the concentration \n of catalyst changes ( figure 1 ) .\ndependence of the ratio of uncyclized ( d)/cyclized ( c ) \n product \n on the concentration of nickel .\nwe have developed methods for the enantioselective \n synthesis of \n secondary sulfonamides and sulfones , specifically , nickel - catalyzed \n negishi arylations and alkenylations of racemic -bromosulfonamides \n and -sulfones with readily available organozinc and organozirconium \n reagents ; with regard to stereoconvergent couplings of unactivated alkyl electrophiles , previous examples had been limited \n to organoboron nucleophiles and , with the exception of three isolated \n examples , to alkylation reactions . in terms of mechanism , \n a cyclization / stereochemical probe has provided evidence for a radical \n intermediate that has a sufficient lifetime to escape the solvent \n cage and cyclize irreversibly under the coupling conditions .\nadditional \n studies directed at elucidating the mechanisms of cross - coupling reactions \n of alkyl electrophiles , as well as expanding the scope of such processes , \n are underway .",
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"content": "the \n development of efficient methods for the generation of enantioenriched \n sulfonamides and sulfones is an important objective for fields such \n as organic synthesis and medicinal chemistry ; however , there have \n been relatively few reports of direct catalytic asymmetric approaches \n to controlling the stereochemistry of the sulfur - bearing carbon of \n such targets . in this report \n , we describe nickel - catalyzed stereoconvergent \n negishi arylations and alkenylations of racemic -bromosulfonamides \n and -sulfones that furnish the desired cross - coupling product in very \n good ee and yield for an array of reaction partners . \n mechanistic studies \n are consistent with the generation of a radical intermediate that \n has a sufficient lifetime to diffuse out of the solvent cage and to \n cyclize onto a pendant olefin .",
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science.scientific_papers_summarization_single_doc_pubmed | science.scientific_papers_summarization_single_doc_pubmed.1471 | [
{
"content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\nhamiltonian mapping demonstrates how the standard wham formalism can be modified and used to extrapolate information \n about a biased hamiltonian from the unmodified reference hamiltonian , h0(x ) , where x represents the molecular coordinates .\nwham is typically used along \n with umbrella sampling , in which a set \n of l additional restraining potentials , { v } = v1(x ) , \n ... , vl(x ) , are added to h0(x ) in order to enhance conformational sampling in rarely visited regions \n of phase space . in this case\n, the modified hamiltonian takes the form1where { } is the set \n of coupling parameters \n used for scaling individual biasing potentials , 0 = 1 , and h0(x ) = v0(x ) .\nthen , for r independent simulations , each performed at a temperature t = 1/kb ( where kb is the boltzmann constant ) and with differing \n { } , the bias is removed by solving the following pair of wham \n equations self - consistently2and3 t may be constant or vary \n across the r simulations .\n) is a particular \n value along a progress variable of interest , nm is the total number of configurations in \n the mth simulation , and nk({v}, ) is the histogram count \n of configurations with { v } and . finally , fm is related to the helmholtz \n free energy for the mth simulation .\nin contrast to standard wham , in the hamiltonian mapping framework , \n we proceed in the opposite direction ; we perform one or more simulations \n of the system under the original hamiltonian h0(x ) and then add a bias to the statistical \n averages computed from h0(x ) to examine thermodynamic behavior under a modified hamiltonian . \n for this scenario ,\neq 2 is recast as4essentially , \n the histogram counts nk now come from the sampling \n of h0(x ) , and the sum \n of the scaled restraining potentials in the denominator reduces to h0(x ) .\nbriefly , in \n this model , each residue is represented by a single bead centered \n at the c position and with the mass of the corresponding amino \n acid . an additive potential describes the bonded and non - bonded interactions \n between the beads .\nvirtual bonds and angles are defined by harmonic \n potentials with reference values determined by the c coordinates \n in the experimental structure . a potential for virtual dihedral angles \n\nis based upon backbone dihedral angle probability distributions from \n the protein data bank ( pdb ) for the 400 possible amino acid pairs \n and thus is independent of the specific topology of the system .\nresidue \n pairs separated by three or more bonds interact through the following \n potential5where rij is the distance between residues i and j , ij corresponds to \n the distance between the two residues at which vij is minimum , and ij is the interaction strength at ij .\nresidues located in close proximity in the experimental structure \n ( i.e. , forming a native contact ) interact favorably \n with ij values based on the statistical \n contact energies of miyazawa and jernigan , while residue pairs not in close proximity experience a slight repulsive \n interaction that takes the form of a typical 126 lennard - jones \n potential\n. further description of the go-like model and details \n of the simulation setup can be found in refs ( 25 ) and ( 8) , respectively .\nwe further \n consider the non - bonded interaction potential ( eq 5 ) for native contacts between the idp and the receptor in \n tuning the model to match the experimental kd .\nfor this set of intermolecular contacts , we scale the interaction \n strength , ij , by a factor \n so as to control the proportion of bound and unbound states throughout \n simulation . from the fraction of unbound states , pu ,\nthe kd is computed as6where [ protein ] is the concentration of protein \n in moles per liter ( 10 mol / l in the current study ) .\na configuration is considered unbound if zero intermolecular native \n contacts are formed and if the distance between the centers of mass \n of the idp and of the target protein is greater than the cutoff for \n calculating the non - bonded interactions ( 25 ) .\nwe also note \n that the strength of intramolecular contacts within the idp are tuned \n in a similar manner to reproduce the experimental estimate of residual \n helical structure in the unbound state .",
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"content": "molecular recognition by intrinsically \n disordered proteins ( idps ) \n plays a central role in many critical cellular processes . toward achieving \n detailed mechanistic understanding of idp target interactions , \n here \n we employ the hamiltonian mapping \n methodology , \n which is rooted in the weighted histogram analysis method ( wham ) , \n for the fast and efficient calibration of structure - based models in \n studies of idps . by performing reference simulations on a given hamiltonian \n , \n we illustrate for two model idps how this method can extrapolate thermodynamic \n behavior under a range of modified hamiltonians , in this case representing \n changes in the binding affinity ( kd ) of \n the system . given sufficient conformational sampling in a single trajectory , \n hamiltonian \n mapping accurately reproduces kd values from direct simulation . \n this method may be generally applied \n to systems beyond idps in force field optimization and in describing \n changes in thermodynamic behavior as a function of external conditions \n for connection with experiment .",
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science.data_reco_mcq_sc | science.data_reco_mcq_sc.13572 | [
{
"content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: A system for improving the training efficiency of neural architecture search by leveraging weight-sharing.\n\nKeywords: image classification images\n\nDataset Information:\nCIFAR-10: The CIFAR-10 dataset (Canadian Institute for Advanced Research, 10 classes) is a subset of the Tiny Images dataset and consists of 60000 32x32 color images. The images are labelled with one of 10 mutually exclusive classes: airplane, automobile (but not truck or pickup truck), bird, cat, deer, dog, frog, horse, ship, and truck (but not pickup truck).\nNAS-Bench-1Shot1: NAS-Bench-1Shot1 draws on the recent large-scale tabular benchmark NAS-Bench-101 for cheap anytime evaluations of one-shot NAS methods.\nNATS-Bench: A unified benchmark on searching for both topology and size, for (almost) any up-to-date NAS algorithm. NATS-Bench includes the search space of 15,625 neural cell candidates for architecture topology and 32,768 for architecture size on three datasets.\nCoNLL-2014 Shared Task: Grammatical Error Correction: CoNLL-2014 will continue the CoNLL tradition of having a high profile shared task in natural language processing. This year's shared task will be grammatical error correction, a continuation of the CoNLL shared task in 2013.\n\nAvailable Datasets: A: CIFAR-10 B: NAS-Bench-1Shot1 C: NATS-Bench D: CoNLL-2014 Shared Task: Grammatical Error Correction",
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"content": "CIFAR-10",
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science.chemprot_re | science.chemprot_re.73 | [
{
"content": "Examine the provided text and determine the interactions between chemical entities and genes. Focus on identifying any connections present.\n\nPresent your findings in a structured JSON format. Each relationship should be represented as an array entry. If no interactions are detected, return an empty array.\n\nText Content:\n\nDose-dependent effects of vitamin D on transdifferentiation of skeletal muscle cells to adipose cells. Fat infiltration within muscle is one of a number of features of vitamin D deficiency, which leads to a decline in muscle functionality. The origin of this fat is unclear, but one possibility is that it forms from myogenic precursor cells present in the muscle, which transdifferentiate into mature adipocytes. The current study examined the effect of the active form of vitamin D₃, 1,25-dihydroxyvitamin D₃ (1,25 (OH) ₂D₃), on the capacity of the C2C12 muscle cell line to differentiate towards the myogenic and adipogenic lineages. Cells were cultured in myogenic or adipogenic differentiation media containing increasing concentrations (0, 10⁻¹³, 10⁻¹¹, 10⁻⁹, 10⁻⁷ or 10⁻⁵ M) of 1,25 (OH) ₂D₃ for up to 6 days and markers of muscle and fat development measured. Mature myofibres were formed in both adipogenic and myogenic media, but fat droplets were only observed in adipogenic media. Relative to controls, low physiological concentrations (10⁻¹³ and 10⁻¹¹ M) of 1,25 (OH) ₂D3 increased fat droplet accumulation, whereas high physiological (10⁻⁹ M) and supraphysiological concentrations (≥10⁻⁷ M) inhibited fat accumulation. This increased accumulation of fat with low physiological concentrations (10⁻¹³ and 10⁻¹¹ M) was associated with a sequential up-regulation of PPARγ2 (PPARG) and FABP4 mRNA, indicating formation of adipocytes, whereas higher concentrations (≥10⁻⁹ M) reduced all these effects, and the highest concentration (10⁻⁵ M) appeared to have toxic effects. This is the first study to demonstrate dose-dependent effects of 1,25 (OH) ₂D₃ on the transdifferentiation of muscle cells into adipose cells. Low physiological concentrations (possibly mimicking a deficient state) induced adipogenesis, whereas higher (physiological and supraphysiological) concentrations attenuated this effect.",
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"content": "[]",
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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.14409 | [
{
"content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Dynamic Structure Formation of Peripheral Membrane Proteins\nContent:\nAbstract:\nUsing coarse-grained membrane simulations we show here that peripheral membrane proteins can form a multitude of higher-order structures due to membrane-mediated interactions. Peripheral membrane proteins characteristically perturb the lipid bilayer in their vicinity which supports the formation of protein assemblies not only within the same but surprisingly also across opposing leaflets of a bilayer. In addition, we also observed the formation of lipid-protein domains on heteregeneous membranes. The clustering ability of proteins, as quantified via the potential of mean force, is enhanced when radius and hydrophobic penetration depth of the proteins increases. Based on our data, we propose that membrane-mediated cluster formation of peripheral proteins supports protein assembly in vivo and hence may play a pivotal role in the formation of templates for signaling cascades and in the emergence of transport intermediates in the secretory pathway.\nIntroduction:\nIn recent years, our view on the organization of biomembranes has dramatically changed. The perception has shifted from the fluid mosaic paradigm with virtually no internal organisation[1] to a more inhomogeneous model in which biomembranes are more mosaic than fluid[2]. It is well accepted by now that membranes are not simple homogeneous two-dimensional fluids in which lipids and proteins are randomly dispersed. Rather, membranes are subdivided into( dynamic) domains that are composed of distinct lipids and proteins. In particular, the formulation of the ‘raft hypothesis’ by Simons and colleagues[3] has triggered numerous studies on the existence, composition, and dynamics of membrane microdomains. While the existence of lipid domains in artificial bilayers, i. e. regions with a distinct lipid composition, is by now well established[4], the existence of protein-lipid domains in vivo is much less clear and still a matter of debate. It is commonly appreciated, however, that the formation of( transient) higher-order structures on cellular membranes, e. g. during the formation of transport intermediates[5],[6] or in the context of signaling[7],[8], equips biomembranes with a distinct and dynamic substructure. While traditional biochemical approaches emphasize specific binding events of proteins to and within membranes via cognate motifs, work on membrane domains has also highlighted the role of lipids as mediators of( attractive) interactions. Theoretical and experimental studies have revealed, for example, that a mismatch between the hydrophobic thickness of a lipid bilayer and the length of the hydrophobic transmembrane domain of proteins can support oligomerization and protein sorting[9]–[14]. Indeed, protein assembly due to membrane-mediated interactions was predicted as early as 1984 by Mouritsen and Bloom[15]. Supporting experimental or simulation data, however, had remained ambiguous for a long time. Subsequently, attractive forces between transmembrane proteins due to elastic distortions of the lipid bilayer have been investigated in more detail with continuum models[16]–[18]. But also capillary forces[19], wetting effects[20], curvature[21],[22], membrane fluctuations[23]–[25], and lipid packing[26] have been implicated as a source for membrane-mediated attraction between transmembrane proteins. A plethora of membrane proteins, however, does not possess hydrophobic transmembrane domains but is only associated with one leaflet of the lipid bilayer. These are typically referred to as ‘integral monotopic proteins’ or ‘peripheral membrane proteins’( PMPs). Peripheral membrane proteins often contribute to vital cellular functions, e. g. in a multitude of important signaling cascades[27] or during the formation of transport intermediates in the early secretory pathway[28]. Moreover, PMPs frequently form higher-order structures and templates, sometimes even across opposing leaflets of a lipid bilayer. Given that membrane-mediated attraction fosters the assembly of transmembrane proteins, it is tempting to assume that also PMPs benefit from such a generic mechanism. As little theoretical and experimental data on this aspect are available, simulations lend themselves as a powerful tool to elucidate this question. Inspecting prominent examples of PMPs, e. g. prostaglandin H2 synthase, fatty acid amide hydrolase, but also members of the Ras family, Ras-like GTPases, and Wnt morphogens, it becomes clear that the size of the hydrophobic anchor of PMPs varies considerably( lengths from 3Å to 3 nm, surface area of up to). In many cases, its shape can be well approximated by an ellipsoid. Moreover, a recent simulation study showed that the hydrophobic moeity is buried in lipid bilayers to different extents which causes more or less severe deformations of the membrane[29]. It is hence tempting to model PMPs on a coarse-grained level to highlight generic geometrical effects that are not due to the presence of particular lipid species and/or amino acids. Here, we have used coarse-grained membrane simulations to study several aspects of the dynamics of peripheral membrane proteins. As compared to Molecular Dynamics( MD) approaches, the use of dissipative particle dynamics( DPD) allowed us to explore larger length and time scales for a variety of generic settings. The gain in computational efficiency of our approach comes at the expense of neglecting atomic details( and electrostatics) whereas hydrophobic and hydrodynamic interactions are preserved. Hence, geometric interactions that are due to the latter interactions, are highlighted in our approach. First, we have studied how PMPs with hydrophobic anchors of varying length and diameter perturb the host membrane locally. Second, we have determined the proteins' diffusion coefficients and relate these results to the well-known Saffman-Delbrück relation. Third, we have examined the tendency of PMPs to form clusters due to non-specific membrane-mediated interactions. As a result, we observed that different types of clusters form when PMPs are residing in the same and in opposite leaflets of a membrane. To explore the stability of these clusters, we have determined the potential of mean force, i. e. the attractive potential, for pairs of PMPs in the same and opposing leaflets of a bilayer. Based on our findings we discuss the relation between local membrane perturbations and the cluster formation ability of PMPs, and we also point out implications of our results on biological processes.\nDiscussion:\nIn conclusion, we have shown that peripheral membrane proteins can( transiently) form higher order structures due to membrane-mediated interactions. The clustering ability can be tuned via the penetration depth of the PMP's hydrophobic moiety and radius. To test our predictions experimentally, we propose the following approach: Using a set of well-characterized, fluorescently labeled PMPs that adsorb to the inner and/or outer leaflet of a liposome( e. g. a giant unilamellar vesicle, GUV), one may use fluorescence correlation spectroscopy( FCS) to quantify the degree of cluster formation. Using two PMP species with different fluorescent labels, say, a green and a red fluorophore, the formation of clusters can be detected on an almost single-molecule level by FCS via cross-correlating the red and green fluorescence signal[50]. Depending on the proximity of the fluorophores, also fluorescence resonance energy transfer( FRET) may be exploited to highlight clustering and even to determine the distance between PMPs. As both methods also work in vivo, assessing the clustering in living cells is also possible. Nevertheless, a cleaner and hence more quantitative setup with tunable properties of the bilayer, e. g. concerning lipid composition, is the GUV system. Clearly, the above experimental approach requires well characterized PMPs. Here, several possibilities may be envisaged. Synthetic peptides, for which radius and hydrophobic length can be designed at will, or purified peripheral membrane proteins from cells are interesting candidates. Besides those proteins that have mentioned already in the Introduction, a particularly interesting probe may be the cholera toxin B subunit which binds 5 gangliosides and hence forms an effective PMP with a fairly large radius. Also, functionalized nanobeads with controlled surface properties may be used as PMP-like particles. Moreover, mutagenesis of particular PMPs in signaling pathways, e. g. reggies/flotilins, or the formation of chimera proteins may provide a means to probe our predictions in vivo.",
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"content": "Eukaryotic cells are subdivided into a variety of compartments by membranes , i . e . by lipid bilayers into which a multitude of proteins are embedded . About 30% of all protein species in a cell are associated with membranes to perform vital functions , e . g . in signaling and transport pathways . A plethora of membrane-associated proteins , so-called peripheral membrane proteins , penetrate only one monolayer whereas transmembrane proteins span the entire thickness of a lipid bilayer . Despite the crucial role of peripheral membrane proteins in many cellular processes , little is known about the general principles of how they can form higher-order structures that eventually are biologically active units . Using a simulation approach we show and quantify here the influence of membrane-mediated interactions between peripheral membrane proteins . These interactions most likely play a pivotal role in forming higher-order structures in living cells . In particular , template formation in signaling cascades and coat assembly during the formation of transport intermediates may strongly benefit from the phenomena described here .",
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science.scicite_classification | science.scicite_classification.2715 | [
{
"content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\ndemonstrate high reliability in the current sample from ages 2 to 4 (range, α=0.84 to 0.94; Dishion et al. 2008).",
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"content": "Background",
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.1509 | [
{
"content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: A Review of Recent Techniques in Mixed-Criticality Systems \nChapter Title: Schedulability-Aware Techniques in MC Systems \n1. Abstract of Cited Paper (BIB001): SymTA/S is a system-level performance and timing analysis approach based on formal scheduling analysis techniques and symbolic simulation. The tool supports heterogeneous architectures, complex task dependencies and context aware analysis. It determines system-level performance data such as end-to-end latencies, bus and processor utilisation, and worst-case scheduling scenarios. SymTA/S furthermore combines optimisation algorithms with system sensitivity analysis for rapid design space exploration. The paper gives an overview of current research interests in the SymTA/S project. \n2. Abstract of Cited Paper (BIB002): Many safety-critical embedded systems are subject to certification requirements. However, only a subset of the functionality of the system may be safety-critical and hence subject to certification, the rest of the functionality is non safety-critical and does not need to be certified, or is certified to a lower level. The resulting mixed criticality system offers challenges both for static schedulability analysis and run-time monitoring. This paper considers a novel implementation scheme for fixed priority uniprocessor scheduling of mixed criticality systems. The scheme requires that jobs have their execution times monitored (as is usually the case in high integrity systems). An optimal priority assignment scheme is derived and sufficient response-time analysis is provided. The new scheme formally dominates those previously published. Evaluations illustrate the benefits of the scheme. \n3. Abstract of Cited Paper (BIB003): Systems in many safety-critical application domains are subject to certification requirements. For any given system, however, it may be the case that only a subset of its functionality is safety-critical and hence subject to certification, the rest of the functionality is non safety critical and does not need to be certified, or is certified to a lower level of assurance. An algorithm called EDF-VD (for Earliest Deadline First with Virtual Deadlines) is described for the scheduling of such mixed-criticality task systems. Analyses of EDF-VD significantly superior to previously-known ones are presented, based on metrics such as processor speedup factor (EDF-VD is proved to be optimal with respect to this metric) and utilization bounds. \n4. Abstract of Cited Paper (BIB004): A common trend in real-time safety-critical embedded systems is to integrate multiple applications on a single platform. Such systems are known as mixed-criticality (MC) systems as the applications are usually characterized by different criticality levels (CLs). Nowadays, multicore platforms are promoted due to cost and performance benefits. However, certification of multicore MC systems is challenging because concurrently executed applications with different CLs may block each other when accessing shared platform resources. Most of the existing research on multicore MC scheduling ignores the effects of resource sharing on the execution times of applications. This paper proposes a MC scheduling strategy which explicitly accounts for these effects. Applications are executed by a flexible time-triggered criticality-monotonic scheduling scheme. Schedulers on different cores are dynamically synchronized such that only a statically known subset of applications of the same CL can interfere on shared resources, e. g., memories, buses. Therefore, the timing effects of resource sharing are bounded and we quantify them at design time. We combine this scheduling strategy with a mapping optimization technique for achieving better resource utilization. The efficiency of the approach is demonstrated through extensive simulations as well as comparisons with traditional temporal partitioning and state-of-the-art scheduling algorithms. It is also validated on a real-world avionics system. \n5. Abstract of Cited Paper (BIB005): Synchronous languages are widely used to design safety-critical embedded systems. These languages are based on the synchrony hypothesis, asserting that all tasks must complete instantaneously at each logical time step. This assertion is, however, unsuitable for the design of mixed-criticality systems, where some tasks can tolerate missed deadlines. This paper proposes a novel extension to the synchronous approach for supporting three levels of task criticality: life, mission, and non-critical. We achieve this by relaxing the synchrony hypothesis to allow tasks that can tolerate bounded or unbounded deadline misses. We address the issue of task communication between multi-rate, mixed-criticality tasks, and propose a deterministic lossless communication model. To maximize system utilization, we present a hybrid static and dynamic scheduling approach that executes schedulable tasks during slack time. Extensive benchmarking shows that our approach can schedule up to 15% more task sets and achieve an average of 5.38% better system utilization than the Early-Release EDF (ER-EDF) approach. Tasks are scheduled fairer under our approach and achieve consistently higher execution frequencies, but require more preemptions. \n6. Abstract of Cited Paper (BIB006): Multicore systems are being increasingly used for embedded system deployments, even in safety-critical domains. Co-hosting applications of different criticality levels in the same platform requires sufficient isolation among them, which has given rise to the mixed-criticality scheduling problem and several recently proposed policies. Such policies typically employ runtime mechanisms to monitor task execution, detect exceptional events like task overruns, and react by switching scheduling mode. Implementing such mechanisms efficiently is crucial for any scheduler to detect runtime events and react in a timely manner, without compromising the system’s safety. This paper investigates implementation alternatives for these mechanisms and empirically evaluates the effect of their runtime overhead on the schedulability of mixed-criticality applications. Specifically, we implement in user-space two state-of-the-art scheduling policies: the flexible time-triggered FTTS [1] and the partitioned EDFVD [2], and measure their runtime overheads on a 60-core Intel R Xeon Phi and a 4-core Intel R Core i5 for the first time. Based on extensive executions of synthetic task sets and an industrial avionic application, we show that these overheads cannot be neglected, esp. on massively multicore architectures, where they can incur a schedulability loss up to 97%. Evaluating runtime mechanisms early in the design phase and integrating their overheads into schedulability analysis seem therefore inevitable steps in the design of mixed-criticality systems. The need for verifiably bounded overheads motivates the development of novel timing-predictable architectures and runtime environments specifically targeted for mixed-criticality applications. \n7. Abstract of Cited Paper (BIB007): Systems in many safety-critical application domains are subject to certification requirements. For any given system, however, it may be the case that only a subset of its functionality is safety-critical and hence subject to certification; the rest of the functionality is non-safety-critical and does not need to be certified, or is certified to lower levels of assurance. The certification-cognizant runtime scheduling of such mixed-criticality systems is considered. An algorithm called EDF-VD (for Earliest Deadline First with Virtual Deadlines) is presented: this algorithm can schedule systems for which any number of criticality levels are defined. Efficient implementations of EDF-VD, as well as associated schedulability tests for determining whether a task system can be correctly scheduled using EDF-VD, are presented. For up to 13 criticality levels, analyses of EDF-VD, based on metrics such as processor speedup factor and utilization bounds, are derived, and conditions under which EDF-VD is optimal with respect to these metrics are identified. Finally, two extensions of EDF-VD are discussed that enhance its applicability. The extensions are aimed at scheduling a wider range of task sets, while preserving the favorable worst-case resource usage guarantees of the basic algorithm. \n8. Abstract of Cited Paper (BIB008): We present a new graph-based real-time task model that can specify complex job arrival patterns and global state-based mode switching. The mode switching is of a mixed-criticality style, meaning that it allows immediate changes to the parameters of active jobs upon mode switches. The resulting task model generalizes previously proposed task graph models as well as mixed-criticality (sporadic) task models; the merging of these mutually incomparable modeling paradigms allows formulation of new types of tasks. A sufficient schedulability analysis for EDF on preemptive uniprocessors is developed for the proposed model. \n9. Abstract of Cited Paper (BIB009): The scheduling for mixed-criticality (MC) systems, where multiple activities have different certification requirements and thus different criticality on a shared hardware platform, has recently become an important research focus. In this work, considering that multicore processors have emerged as the de-facto platform for modern embedded systems, we propose a novel and efficient criticality-aware task partitioning algorithm (CA-TPA) for a set of periodic MC tasks running on multicore systems. We employ the state-of-the art EDF-VD scheduler on each core. Our work is based on the observation that the utilizations of MC tasks at different criticality levels can have quite large variations, hence when a task is allocated, its utilization contribution on different processors may vary by large margins and this can significantly affect the schedulability of tasks. During partitioning, CA-TPA sorts the tasks according to their utilization contributions on individual processors. Several heuristics are investigated to balance the workload on processors with the objective of improving the schedulability of tasks under CA-TPA. The simulation results show that our proposed CA-TPA scheme is effective, giving much higher schedulability ratios when compared to the classical partitioning schemes. \n10. Abstract of Cited Paper (BIB010): The integration of mixed-critical tasks into a platform is an increasingly important trend in the design of real-time systems due to its efficient resource usage. With a growing variety of activation patterns considered in real-time systems, some of them capture arbitrary activation patterns. As a consequence, the existing scheduling approaches in mixed-criticality systems (MCs), which assume the sporadic tasks with implicit deadlines, have sometimes become inapplicable or are ineffective. In this paper, we extend the sporadically activated task model to the arbitrarily activated task model in MCs with the preemptive fixed-task-priority schedule. By using the event arrival curve to model task activations, we present the necessary and sufficient schedulability tests that are based on the well-established results from Real-Time Calculus. We propose to use the busy-window analysis to do the sufficient test because it has been shown to be tighter than the sufficient test of using Real-Time Calculus. According...\n\nReview Chapter:",
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"content": "The tasks in MC system are divided into HC and LC task as mentioned above. Most papers assume that in MC systems, the worst case execution time (WCET) for HC tasks is low-level system assurance and high-level WCET is high-level system assurance, while LC tasks require only a low-level assurance, as they own a low-level WCET. During the operation, if any HC task exceeds its low-level WCET, all LC tasks will be abandoned for the system to leave su±cient system resources for satisfying the high-level assurance. If all tasks are executed within their deadline, and all tasks are performed at a low-level, and the HC tasks can satisfy their deadlines even when performing low-level WCET, the system is referred to as MC schedulable. Schedulability of tasks is the key of the MC system. To meet the schedulability of the system, most MC systems ensure the accurate operation of HC tasks, neglect or even abandon the performance of LC tasks. We will introduce the current research status below. Many researches have been devoted to use the EDF-VD scheduling algorithm for maintaining schedulability of MC systems. Baruah et al. 1 considered the scheduling of implicit-deadline sporadic task in MC systems on uniform multiprocessor platforms and introduced two policies: the MC scheduling algorithm earliest deadlinē rst-virtual deadlines (EDF-VD) BIB001 on uniprocessor, and the EDF-based global scheduling algorithm called fpEDF BIB004 on multiprocessor. Sigrist et al. BIB007 empirically assessed the in°uence of runtime overhead to schedulability of MC systems, and determined alternative solutions for the achievement of common MC mechanisms for multicores, and introduced two scheduling policies, one is the FTTS, BIB005 another is the partitioned EDF-VD. BIB001 Baruah 3 studied the scheduling of task in MC systems speci¯ed based on the three-parameter model of sporadic tasks on preemptive uniprocessor platforms and extended the EDF-VD scheduling algorithm BIB003 that schedules sporadic task in MC systems where multiple values are just used for the WCET parameter. Ramanathan and Easwaran 4 focused on the issue of MC scheduling on partitioned multiprocessor and used three di®erent scheduling approaches ECDF, BIB004 EDF-VD, BIB001 and Adaptive MC (AMC) BIB003 to decrease the maximum di®erence between the overall LC utilization and overall HC utilization assigned on each processor. However, from the conditions of schedulability of the EDF-VD scheduler, BIB008 utilizations of MC tasks at other criticality levels also play an important role besides maximizing utilization. Han et al. BIB010 used the EDF-VD algorithm BIB001 on each core and proposed a novel criticality-aware task partitioning algorithm for a group of periodic MC tasks operating on multicore systems. According to the synchrony hypothesis, synchronous languages asserted that all tasks must be accomplished immediately at each step of logical time. However, this assertion is improper for the design of MC systems, in which tasks like the LC tasks can endure missed deadlines. Yip et al. BIB006 proposed a new extension to the synchronous method for standing by three levels (life, noncritical and mission) of task criticality. They achieved this by relaxing the synchrony hypothesis to allow tasks that can tolerate unbounded or bounded deadline misses. But, the scheme that relaxes the synchrony hypothesis to allow MC goes against the communication synchronous model. To solve this, they used a common lossless bu®ering method with limited queue sizes. Then they proposed a lossless communication model to allow mission critical tasks and life to communicate at a certain frequency. To schedule life and mission critical tasks, they developed a static scheduling approach by using integer linear programming, which maximizes system utilization by assigning slack time across all tasks proportionally. To further increase runtime utilization, the tasks will be scheduled dynamically whenever possible during the slack. Extensive results showed that the proposed approach can schedule more task sets and achieve better system utilization compared to the ER-EDF 67 approach. Some researches used the¯xed priority (FP) scheduling algorithm to maintain schedulability of MC systems. Guan et al. proposed an e®ective algorithm named PLRS to schedule certi¯able MC sporadic tasks systems. PLRS applies FP-jobs scheduling methods, and allocates job priorities by balancing and exploring the asymmetric in°uences between the workload on distinct criticality levels. Chen et al. studied FP scheduling of MC systems on a uniprocessor platform in a more general way that uses di®erent priority sequences in di®erent stages of execution, and presented a novel priority assignment scheme called heuristic priority assignment (HPA) based on the popular optimal priority assignment (OPA) algorithm. BIB003 Hu et al. BIB011 analyzed the schedulability for dual-criticality (DC) systems with arbitrarily activated tasks. They extended the sporadic and activated task model to any activated task model in MC systems with the preemptive¯xed priority tasks schedule. By applying the arrival curve to express the upper limit of task activations, they integrated the perfect consequences from RTC BIB002 to analyze the schedulability of any activated tasks in MC systems. However, the scheduling and analysis of MC system using sporadic MC task models have been censured for its limited suitability to many real systems. To solve these problems, Ekberg and Yi BIB009 proposed a novel task model that calls the MS-DRT, which integrates arrival modes of jobs with global mode switching, and adopts a structured EDF-schedulability analysis approach where each mode of the system is relatively separated by abstracting the e®ects from other modes. However, in FP scheduling, unbounded priority inversion can be prevented by using priority inheritance protocols, but these protocols cannot work when zeroslack (ZS) schedulers are applied to schedule MC task-sets. Lakshmanan et al.",
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science.data_reco_mcq_sc | science.data_reco_mcq_sc.12783 | [
{
"content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: I want to train a generative adversarial network for person image synthesis.\n\nKeywords: person image synthesis\n\nDataset Information:\nISTD: The Image Shadow Triplets dataset (ISTD) is a dataset for shadow understanding that contains 1870 image triplets of shadow image, shadow mask, and shadow-free image.\nClothing1M: Clothing1M contains 1M clothing images in 14 classes. It is a dataset with noisy labels, since the data is collected from several online shopping websites and include many mislabelled samples.\nDeepFashion: DeepFashion is a dataset containing around 800K diverse fashion images with their rich annotations (46 categories, 1,000 descriptive attributes, bounding boxes and landmark information) ranging from well-posed product images to real-world-like consumer photos.\nFDF: A diverse dataset of human faces, including unconventional poses, occluded faces, and a vast variability in backgrounds.\n\nAvailable Datasets: A: ISTD B: Clothing1M C: DeepFashion D: FDF",
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{
"content": "DeepFashion",
"role": "assistant"
}
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science.scientific_papers_summarization_single_doc_pubmed | science.scientific_papers_summarization_single_doc_pubmed.8761 | [
{
"content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\none of the few well - understood features of intensive care unit ( icu ) delirium is its association with poor patient outcome .\nrisk factor stratification is essential to the understanding , prevention and treatment of any disorder , and is a cornerstone of scientific endeavor in clinical research .\nthe largest study on icu delirium risk factors to date is published in the previous issue of critical care .\ndelirium in the critical care setting is said to occur in 22% to over 80% of patients .\nsuch broad variations in delirium incidence may be partly attributable to differences in predisposing risk factors , which may differ between icus .\nco - morbidities present prior to icu admission have particularly seldom been considered in icu delirium studies ; several of them are discussed in the paper by van rompaey and colleagues .\nphysicians hold opinions on the risks and benefits of environmental factors ( for example , physical restraints ) affecting the patient once in the icu ; however , little is known about these factors .\nhuman interaction , such as the effect visitors may have on delirium , remains unexplored in the critically ill patient .\nthese environmental features , discussed in van rompaey and colleagues ' paper , are important not only because they are inexpensive but also perhaps because they less likely to harm patients than poorly studied pharmacological interventions .\nthe patients described in the study were no longer intubated and thus were perhaps less ill ; in addition , not all centers collected all risk factor data . van rompaey and\ncolleagues nevertheless provide confirmation that several previously identified risk factors remain significant in this multicenter study , challenge other risk factors , and add several risk factors not previously described .\nalcohol use is not screened for routinely , validated alcohol withdrawal scales remain under - used , and intervention for withdrawal is seldom incorporated into treatment plans .\nthis knowledge is all the more surprising because the relevant studies identify alcohol abuse as a significant risk factor for developing delirium .\nwhether alternatives to routine care ( that is , benzodiazepines titrated to symptoms , rather than antipsychotics ) in these high - risk patients are of any benefit is unknown .\nage has been considered a risk factor for delirium in non - icu populations and by some icu investigators .\nwhen van rompaey and colleagues consider pre - existing cognitive dysfunction , tobacco use and alcohol , age does not appear to confer an additional risk for delirium .\nif dementia is a risk factor but age is not and studies considering pre - icu admission co - morbidities would indicate this is true prevention or prophylaxis of this common and morbid disorder in the icu should consider different interventions than , say , similar initiatives on the wards .\nseveral previously described predisposing factors ( psychoactive drugs , sedatives and opiates ) are revisited and their relative contribution to the risk of icu delirium is tempered by the case mix , and the addition of other variables .\nthe most novel elements in this study , however , are the environmental risks for icu delirium .\nvisible daylight , visitors and not being physically restrained seem to result in a lower incidence of delirium .\nit is refreshing to know that in the high - tech environment of icus , someone still asks the question ' which inexpensive and nonmorbid approach is useful ? '\ncombinations of pharmacotherapy and nonpharmacologic interventions such as psychotherapy are used in a broad range of psychiatric disorders . in some situations ,\nmental health is purportedly based on the ' functioning of a high - order nervous system in constant and complex relation with the personal and social environment ' .\nseveral of the points raised by the authors ( such as the benefit of company ) offer simple venues for nonpharmacologic intervention .\nthe rise in odd ratios for delirium in physically restrained patients yet make sense when one considers how fearful delirious patients are .\nother reports have recently corroborated that nonpharmacologic interventions may impact on delirium ; early physiotherapy and ambulation appears to be associated with a decrease in delirium days in a recently conducted randomized , controlled study .\nall recommended or clinically used antipsychotic drugs have been validated for the treatment of schizophrenia in young populations over short periods of time .\nthe potential for harm with these drugs is all the more worrisome given that their effectiveness and side effect profiles in older or critically ill populations are largely unknown .\nthere is an urgent need for carefully conducted studies differentiating cognitively intact patients from those with subsyndromal delirium or frank delirium , which will integrate stratification based on risk factors such as those described by the authors .\nonly then can we move forward with the disorder , which arguably causes patients , their families and their caregivers the most distress during critical illness .",
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"content": "icu delirium is associated with poor patient outcome . \n risk factor stratification is essential to the understanding , prevention and treatment of this disorder . \n alcohol consumption , smoking and prior cognitive impairment appear strongly correlated with delirium risk . \n several potentially modifiable associations deserve prospective study : these include administration of sedatives and opiates ; multiple catheters ; as well as minimizing physical restraints and enabling visitors .",
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science.pico_ner | science.pico_ner.2992 | [
{
"content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nA randomized , double-blind comparison of atomoxetine and placebo on response inhibition and interference control in children and adolescents with autism spectrum disorder and comorbid attention-deficit/hyperactivity disorder symptoms .",
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"content": "{\"Intervention\": [\"placebo\", \"atomoxetine\"], \"Outcome\": [], \"Participant\": [\"autism spectrum disorder and comorbid attention-deficit/hyperactivity disorder symptoms\", \"children\", \"adolescents\"]}",
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science.bioasq_factoid_qa | science.bioasq_factoid_qa.286 | [
{
"content": "Given the following biomedical passages, answer the question succinctly. Ensure your response is precise and limited to the answer only.\n\nQuestion: Which is the neurodevelopmental disorder associated to mutations in the X- linked gene mecp2?\n\nPassages: Rett syndrome is caused by mutations in the gene coding for methyl CpG-binding protein 2 (MeCP2).\nRett syndrome is one of the most common causes of complex disability in girls. It is characterized by early neurological regression that severely affects motor, cognitive and communication skills, by autonomic dysfunction and often a seizure disorder. It is a monogenic X-linked dominant neurodevelopmental disorder related to mutation in MECP2, which encodes the methyl-CpG-binding protein MeCP2.\nRecently, this syndrome has been associated with mutations of the MECP2 gene, a transcriptional repressor of still unknown target genes. Here we report a detailed mutational analysis of 62 patients from UK and Italian archives, representing the first comparative study among different populations and one of the largest number of cases so far analyzed.\nOut of the 365 cases, 315 had MECP2 gene mutations and 3 had de novo CDKL5 gene mutations. No patients had FOXG1 mutation.\nMutations were detected in ≈ 70% of classic and ≈ 21% of variant RTT, respectively. Amongst MR cases, 2.1% carried MECP2 mutations.\nMutations in the MECP2 gene were detected in 13 of the 20 (65 percent) RS patients.\nThis multicenter investigation into the phenotypic correlates of MECP2 mutations in Rett syndrome has provided a greater depth of understanding than hitherto available about the specific phenotypic characteristics associated with commonly occurring mutations\nMutation screening revealed 31 different mutations in 68 patients and 12 non-pathogenic polymorphisms.\nIn this study, the MECP2 sequences in 121 unrelated Chinese patients with classical or atypical RTT were screened for deletions and mutations. In all, we identified 45 different MECP2 mutations in 102 of these RTT patients.\nMutations in MECP2 were found in about 55%\nWe identified mutations in the MECP2 gene and documented the clinical manifestations in 65 Rett syndrome patients to characterize the genotype-phenotype spectrum.\nWe searched for mutations by sequencing the MECP2 coding region in 45 sporadic cases (35 with classic RTT, eight with variant forms and two males) and in seven families with two or more affected females. Following our previous report of mutations in two families and eight sporadic cases, we here present 18 additional mutations.\nThe responsible gene, encoding methyl-CpG binding protein 2 (MeCP2), was recently discovered. Here we explore the spectrum of phenotypes resulting from MECP2 mutations. Both nonsense (R168X and R255X) and missense (R106W and R306C) mutations have been found, with multiple recurrences.\nMutations were identified in 44/55 (80%) unrelated classical sporadic and familial RTT patients, but only 1/5 (20%) sporadic cases with suggestive but non-diagnostic features of RTT\nCollectively, we tested 228 unrelated female patients with a diagnosis of possible (209) or classic (19) RTT and found MECP2 mutations in 83 (40%) of 209 and 16 (84%) of 19 of the patients, respectively. Thirty-two different mutations were identified (8 missense, 9 nonsense, 1 splice site, and 14 frameshifts), of which 12 are novel and 9 recurrent in unrelated patients.\nMutations in MECP2 were identified from most of the patients with classical and variant RTT (25 of 27 cases)\nIn our series, 19 different de novo MECP2 mutations, eight of which were previously unreported, were found in 35 out of 50 Rett girls (70%)\nCausative mutations in the MeCP2 gene were identified in 63% of patients, representing a total of 30 different mutations. Mutations were identified in 72% of patients with classical RTT and one third of atypical cases studied (8 of 25).\nWe have identified 15 different MECP2 mutations in 26 of 30 Danish RTT patients.",
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"content": "Rett syndrome",
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.5663 | [
{
"content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: A Survey of Automated Deduction \nChapter Title: Resolution Theorem Proving \n1. Abstract of Cited Paper (BIB001): This book explains what automated reasoning is and what it can do and then demonstrates how to use it to solve complex problems with applications in logic circuit design, circuit validation, real-time system design and expert systems. A diskette containing the automated reasoning program \"Otter\" is included. It is available for the first time to PCs and workstations. The book has input files, commentary, examples in \"Otter\" notation and a user's manual that enables readers to experiment with the material presented as well as with ideas of their own. Other features include: various challenge problems that allow readers to test, compare and evaluate new ideas and techniques; techniques for answering open questions and finding shorter proofs; methods for finding such proofs; examples and puzzles to aid in the understanding of parallel versions of an automated reasoning program; and problems. \n2. Abstract of Cited Paper (BIB002): We describe a parallel theorem prover based on the Argonne theorem-proving system OTTER. The parallel system, called Roo, runs on shared-memory multiprocessors such as the Sequent Symmetry. We explain the parallel algorithm used and give performance results that demonstrate near-linear speedups on large problems. \n3. Abstract of Cited Paper (BIB003): We present various refutationally complete calculi for first-order clauses with equality that allow for arbitrary selection of negative atoms in clauses. Refutation completeness is established via the use of well-founded orderings on clauses for defining a Herbrand model for a consistent set of clauses. We also formulate an abstract notion of redundancy and show that the deletion of redundant clauses during the theorem proving process preserves refutation completeness. It is often possible to compute the closure of nontrivial sets of clauses under application of non-redundant inferences. The refutation of goals for such complete sets of clauses is simpler than for arbitrary sets of clauses, in particular one can restrict attention to proofs that have support from the goals without compromising refutation completeness. Additional syntactic properties allow to restrict the search space even further, as we demonstrate for so-called quasiHorn clauses. The results in this paper contain as special cases or generalize many known results about Knuth-Bendix-like completion procedures (for equations, Horn clauses, and Horn clauses over built-in Booleans), completion of first-order clauses by clausal rewriting, and inductive theorem proving for Horn clauses. \n4. Abstract of Cited Paper (BIB004): This paper provides a detailed description of the CNF part of the TPTP Problem Library for automated theorem-proving systems. The library is available via the Internet and forms a common basis for development and experimentation with automated theorem provers. This paper explains the motivations and reasoning behind the development of the TPTP (thus implicitly explaining the design decisions made) and describes the TPTP contents and organization. It also provides guidelines for obtaining and using the library, summary statistics about release v1.2.1, and an overview of the tptp2X utility program. References for all the sources of TPTP problems are provided. \n5. Abstract of Cited Paper (BIB005): This paper documents the design, competing systems, results, and conclusions of the CADE-14 ATP System Competition (CASC-14).\n\nReview Chapter:",
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"content": "In the late 60s and early 70s most work in automated deduction went into finding resolution refinements. Variants of resolution with exotic names: hyper-resolution, model elimination, semantic resolution, RUE, etc, abounded, BIB002 . There was also a technique called paramodulation for equational reasoning, which can be viewed as a generalisation of term rewriting, BIB001 . Most of this refinement activity has now died down. The major exception is work on superposition, BIB004 , which seeks to apply work on orderings from termination research 3 to refine resolution. Most work on resolution now focuses on efficient implementation methods. The goal is to enable resolution-based provers to generate millions of intermediate clauses in a brute force search for a proof, running for hours or days. 4 . Clever indexing techniques are used to enable required clauses to be retrieved quickly from a database containing millions of candidates, . Parallelism is exploited to divide the task between many processors, BIB003 . Technology for precompiling unification and sharing storage is borrowed back from logic programming -so called, Prolog technology theorem proving, . Algorithms are refined for detecting and removing redundant clauses. Resolution-based provers are currently evaluated on empirical grounds. Comparisons between provers are mostly based on success rates and run times on standard corpora of problems. The main corpus is the TPTP (Thousands of Problems for Theorem Provers) library, BIB005 . This is also used as the basis for an annual competition between provers run in conjunction with the CADE conferences, BIB006 ]. There is also a lot of interest in tackling open conjectures in mathematics. Conjectures best suited to this approach are combinatorial problems in new areas of mathematics, where human intuitions are less well developed, . The Robbins Algebra conjecture is a good example. Brute force search through all the various possibilities is often an appropriate approach to such problems -and machines are much better suited to brute force solutions than humans. Resolution is a refutation-based procedure; it proves a conjecture when it derives a contradiction in the form of the empty clause. When the conjecture is false the search for a contradiction may terminate with failure or the search may continue unsuccessfully forever. In the case of terminating failure a counterexample can be constructed from the finite search space. This potential can be exploited to build models of formulae from unsuccessful attempts to find proofs of their negations. There has been a lot of interest in exploiting this potential recently; several model constructing programs have been built and successful applications developed, . There is even a category in the CADE theorem prover competition for such model constructing programs.",
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science.craftchem_ner | science.craftchem_ner.4701 | [
{
"content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nTheirroleinthisprocessisnotknown.",
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"content": "[]",
"role": "assistant"
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science.data_reco_mcq_sc | science.data_reco_mcq_sc.9587 | [
{
"content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: We introduce a new learning framework, CASED, that facilitates the optimization of deep learning models\n\nKeywords: lung nodule detection chest\n\nDataset Information:\nMNIST-1D: A minimalist, low-memory, and low-compute alternative to classic deep learning benchmarks. The training examples are 20 times smaller than MNIST examples yet they differentiate more clearly between linear, nonlinear, and convolutional models which attain 32, 68, and 94% accuracy respectively (these models obtain 94, 99+, and 99+% on MNIST).\nNYU-VP: NYU-VP is a new dataset for multi-model fitting, vanishing point (VP) estimation in this case. Each image is annotated with up to eight vanishing points, and pre-extracted line segments are provided which act as data points for a robust estimator.\nLUNA: The LUNA challenges provide datasets for automatic nodule detection algorithms using the largest publicly available reference database of chest CT scans, the LIDC-IDRI data set. In LUNA16, participants develop their algorithm and upload their predictions on 888 CT scans in one of the two tracks: 1) the complete nodule detection track where a complete CAD system should be developed, or 2) the false positive reduction track where a provided set of nodule candidates should be classified.\nAMASS: AMASS is a large database of human motion unifying different optical marker-based motion capture datasets by representing them within a common framework and parameterization. AMASS is readily useful for animation, visualization, and generating training data for deep learning.\n\nAvailable Datasets: A: MNIST-1D B: NYU-VP C: LUNA D: AMASS",
"role": "user"
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{
"content": "LUNA",
"role": "assistant"
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.12131 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nA new cascade halosulfonylation of 1,7-enynes toward 3,4-dihydroquinolin-2(1H)-ones via sulfonyl radical-triggered addition/6-exo-dig cyclization\n\nContent Extracts:\n\n<p>Organosulfones represent a highly valuable class of compounds and serve as \"privileged motifs\" in the field of agrochemistry and pharmaceutical chemistry owing to their significant biological activities such as anticancer, anti-HIV, and antibacterial.1 They are also extensively utilized as the key precursors in numerous total syntheses2 as the sulfone functionality can be removed readily by various desulfonylation methods.3 Therefore, considerable efforts have been made toward the formation of sulfones.4 Traditional methods for sulfone preparation involved S-nucleophilic substitution between carbon electrophiles and sodium sulfinates or thiophenols followed by oxidation (Scheme 1a).5 These methods suffer from multistep sequences to preinstall a leaving group and incompatibility with many functional groups. Most recently, the addition of sulfonyl radicals to unsaturated systems such as alkenes and alkynes which offers a straightforward approach for the synthesis of sulfone compounds has been extensively explored.6 Various in-situ generated sulfonyl radicals, from sulfonyl halides,7 sodium sulfinate,8 arylsulfinic acids,9 cyanide10 and azide11 by treatment of radical initiators or photolysis, have been successfully applied in these radical additions (Scheme 1b). Alternatively, easily available arylsulfonyl hydrazides also behave as a sulfonyl radical source in the presence of a stoichiometric amount of oxidants,12 which have been specially developed in addition-cyclization toward sulfonylated indolin-2-ones (Scheme 1c).13 Recently, we reported the addition of a variety of C-center radicals to the double bond of N-tethered 1,7-enynes 1. In these transformations, regioselective radical addition cascades were postulated involving the participation of a vinyl intermediate, followed by hydrogen abstraction and radical coupling to give spiro-substituted cyclopenta[c]quinolones (Scheme 1d).14 We reasoned that under suitable oxidative conditions, the sulfonyl radicals could be engaged in additional bond-forming events with N-tethered 1,7-enynes 1 to form the vinyl intermediates, which would be trapped by adequate radicals partners through radical coupling, thus expanding the synthetic utility of these processes. Herein we report the successful realization of this concepts via a novel cascade 1,7-enyne-cyclization trapped by two different radicals, which enabled the one-pot synthesis of densely functionalized 3,4-dihydroquinolin-2(1H)-ones with unprecedented substitution patterns through halosulfonylation of 1,7-enynes (Scheme 1e).</p><p>We first investigated the reaction between 1,7-enynes 1a and tosylhydrazide (2a) in the presence of different iodine sources and oxidants to identify the optimal reaction conditions and the results are summarized in Table 1. Using tetrabutylammonium iodide (TBAI, 1.0 equiv.) as an iodine source and t-butyl hydroperoxide (TBHP, 2.0 equiv.) as an oxidant in CH3CN (acetonitrile) at 60 °C, the expected 3,4-dihydroquinolin-2(1H)-ones 3a was obtained in 60% yield (Table 1, entry 1). A slightly lower yield (58%) was afforded in the presence of 1.0 equivalent of I2 (entry 2). In another case of NIS, the reaction work more efficiently and delivered a higher 69% yield (entry 3). However, use of KI completely compressed the reaction process (entry 4). Screening followed by other oxidants revealed that tert-butyl peroxybenzoate (TBPB), benzoyl peroxide (BPO) and di-tert-butyl peroxide (DTBP) all met little success in this radical addition-cyclization (entries 5–7). Subsequently, taking the combination of TBHP with NIS, we utilized 1,4-dioxane, DMF, DMSO, DCE or toluene as the solvent in this reaction to examine the solvent effects and found that DCE was the best choice, which provided 3a in 76% yield (entries 8–12). To our delight, the yield of 3a could be improved to 84% when the dosage of NIS was increased to 1.2 equivalents in DCE at 60 °C (entry 13). Further increasing load of NIS or TBHP did not facilitate reaction process (entries 14–16). It was also found that the reaction temperature impacted an important influence on the reaction efficiency. The lower conversion was observed with reaction temperature being at either 40 °C or 80 °C (entry 13 vs entries 17 and 18). Some control reactions showed that the transformation did not take place in the absence of either NIS or TBHP (entries 19 and 20).</p><p>Having the optimized conditions in hand, we turned to evaluate the generality of the halosulfonylation using a variety of N-tethered 1,7-enynes 1 and arylsulfonyl hydrazides. Satisfyingly, a wide range of highly substituted 3,4-dihydroquinolin-2(1H)-ones 3b–3y were obtained in a highly selective and functional-group-compatible manner using NIS as the stoichiometric halogen source (Scheme 2). Substrates 1 with different substitution patterns on the aromatic rings of both the alkynyl (R2) and sulfonyl (Ar) moieties can be efficiently transformed into the corresponding poly-functionalized 3,4-dihydroquinolin-2(1H)-ones 3 in good to excellent yields. Similarly, arylsulfonoyl hydrazides possessing various electron-deficient or electron-rich substituents at different positions of aromatic ring were well-tolerated. Additionally, 2-naphthalenyl (2-Np) counterpart was an adaptable substrate in this transformation, allowing the radical-initiated addition-cyclization to the corresponding 3,4-dihydroquinolin-2(1H)-ones 3w in 71% yield. The reaction can be extended to different functional group such as methyl, fluoro, and chloro on N-phenyl moiety, with the realization of domino iodosulfonylation of 1,7-enynes. Unluckily, replacing aryl group with n-butyl group on the alkynyl unit, 1,7-enynes 1s was not an adaptable substrate for this reaction (Scheme 2, 3aa), which may be ascribed to the relative instability of the vinyl radical intermediate B, generated in situ from sulfonyl radical-triggered addition/6-exo-dig cyclization. On the basis of our success with domino iodosulfonylation of 1,7-enynes, we turned our attention to probing the feasibility of domino bromosulfonylation of 1,7-enynes by exchanging NIS for N-bromosuccinimide (NBS). As expected, this protocol tolerates various 1,7-enynes, leading to a highly stereoselective synthesis of structurally diverse 3,4-dihydroquinolin-2(1H)-ones 4a-4d in generally good yields (Scheme 2). The halogen atom was introduced into the exocyclic vinyl unit in this process (products 3 and 4), offering an opportunity for further elaboration. Unfortunately, N-chlorosuccinimide (NCS) did not work in this halosulfonylation of 1,7-enynes.</p><p>The resultant densely functionalized 3,4-dihydroquinolin-2(1H)-ones 3 and 4 were fully characterized by their NMR spectroscopy and HRMS. Furthermore, in the case of compound 3y (Figure 1), its structure was unambiguously determined by X-ray diffraction (see the Supporting Information).</p><p>To gain the mechanistic insights of this reaction, several control experiments were conducted. 1,7-Enynes 1a was subjected to reaction with 2.0 equiv of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) or butylhydroxytoluene (BHT) (Scheme 3a), but without observation of desired product 3a, which indicates the possible radical process. Next, without arylsulfonyl hydrazides, the reaction between 1a and 2.2 equiv. of NIS under standard conditions failed to yield diiodinated 3,4-dihydroquinolin-2(1H)-ones 5 (Scheme 3b), confirming that arylsulfonyl radical, generated in situ from aryl sulfonoylhydrazide, triggered α,β--conjugated addition/6-exo-dig cyclization to form vinyl radical intermediate, which was captured by iodine radical. Therefore, sulfonylation occurred prior to iodination step. Unfortunately, exchanging methyl group for hydrogen on the terminal olefin unit, 1,7-conjugated enynes 5 failed to give product 6 under the standard conditions (scheme 3c), showing that the methyl group located in terminal olefin unit plays a key role in the success of this reaction.</p><p>A plausible mechanism is depicted in Scheme 4 on the basis of control experiments mentioned above and the previously reported literature. The first step is to form the sulfonyl radical from sulfonyl hydrazides under the oxidative conditions (Schemes 4a and 4b) with the release of N2 (Scheme 4c).15 The intermolecular α,β-conjugated addition of the resulting sulfonyl radical onto 1,7-conjugated enynes 1, followed by 6-exo-dig cyclization gives vinyl radical intermediate B.14 In the presence of iodine radical, B is converted into highly substituted 3,4-dihydroquinolin-2(1H)-ones 3 (Scheme 4d). The formation of products 4 is similar to this mechanism. Although sulfonyl radicals triggered addition-cyclization reaction has been achieved well,12 the halosulfonylation of 1,7-enynes toward densely functionalized 3,4-dihydroquinolin-2(1H)-ones via a three-component radical addition/6-exo-dig cyclization is very rare in organic chemistry as mentioned earlier.</p><p>In summary, we have developed a new metal-free arylsulfonyl radical-triggered 1,7-enyne-cyclization that offers efficient construction of densely functionalized 3,4-dihydroquinolin-2(1H)-ones via three-component domino halosulfonylation. This reaction enables sequential arylsulfonyl radical addition/6-exo-dig cyclization/radical coupling process, allowing the formation of successive C–S, C–C, and C-I (or C-Br) bonds. The method provides a direct and practical access to important functional N-sulfonylated quinolin-2(1H)-one derivatives for potential applications in organic and medicinal chemistry.</p>",
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"content": "A new cascade three-component halosulfonylation of 1,7-enynes for efficient synthesis of densely functionalized 3,4-dihydroquinolin-2(1H)-ones has been established from readily accessible arylsulfonyl hydrazides and NIS (or NBS). The reaction pathway involves in situ-generated sulfonyl radical-triggered \\xce\\xb1,\\xce\\xb2-conjugated addition/6-exo-dig cyclization/radical coupling sequence, resulting in continuous multiple bond-forming events including C\\xe2\\x80\\x93S, C-C and C-I (or C-Br) bonds to rapidly build up molecular complexity.",
"role": "assistant"
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science.bc7_litcovid_topic_classification | science.bc7_litcovid_topic_classification.4377 | [
{
"content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nBACKGROUND: Widespread access to the internet has boosted the emergence of online hospitals. A new outpatient service called \"internet hospital plus drug delivery\" (IHDD) has been developed in China, but little is known about this platform. OBJECTIVE: The aim of this study is to investigate the characteristics, acceptance, and initial impact of IHDD during the outbreak of COVID-19 in a tertiary hospital in South China. METHODS: The total number of and detailed information on online prescriptions during the first 2 months after work resumption were obtained. Patients' gender, age, residence, associated prescription department, time of prescription, payment, and drug delivery region were included in the analysis. RESULTS: A total of 1380 prescriptions were picked up or delivered between March 2 and April 20, 2020. The largest group of patients were 36-59 years old (n=680, 49.3%), followed by the 18-35 years age category (n=573, 41.5%). In total, 39.4% (n=544) of the patients chose to get their medicine by self-pickup, while 60.6% (n=836) preferred to receive their medicine via drug delivery service. The top five online prescription departments were infectious diseases (n=572, 41.4%), nephrology (n=264, 19.1%), endocrinology (n=145, 10.5%), angiocardiopathy (n=107, 7.8%), and neurology (n=42, 3%). Of the 836 delivered prescriptions, 440 (52.6%) were sent to Guangdong Province (including 363 [43.4%] to Shenzhen), and 396 (47.4%) were sent to other provinces in China. CONCLUSIONS: The IHDD platform is efficient and convenient for various types of patients during the COVID-19 crisis. Although offline visits are essential for patients with severe conditions, IHDD can help to relieve pressure on hospitals by reducing an influx of patients with mild symptoms. Further efforts need to be made to improve the quality and acceptance of IHDD, as well as to regulate and standardize the management of this novel service.",
"role": "user"
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{
"content": "[\"Prevention\"]",
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science.chemdner_ner | science.chemdner_ner.561 | [
{
"content": "Analyze the given text to identify specific entities. Focus on extracting relevant data.\n\nProvide your findings in JSON format. Each category should list the entities found.\n\nText:\n\nLongitudinal in vivo imaging of bone formation and resorption using fluorescence molecular tomography. Bone research often focuses on anatomical imaging of the bone microstructure, but in order to gain better understanding in how bone remodeling is modulated through interventions also bone formation and resorption processes should be investigated. With this in mind, the purpose of this study was to establish a longitudinal in vivo imaging approach of bone formation and resorption using fluorescence molecular tomography (FMT). In this study the reproducibility, accuracy and sensitivity of FMT for bone imaging were assessed by performing longitudinal measurements with FMT and comparing it to in vivo micro-computed tomography on a set of control mice, and mice in which load-adaptation was induced in the sixth caudal vertebra. The precision error for FMT measurements, expressed as coefficient of variation, was smaller than 16%, indicating acceptable reproducibility. A correlation was found between bone resorption measured with FMT and bone resorption rate measured with in vivo micro-computed tomography only over the first 14days (R=0.81, p<0.01), but not between bone formation measured with FMT and bone formation rate measured with in vivo micro-CT. Bone formation measured by FMT was 89-109% greater (p<0.05) for mice subjected to mechanical loading than control mice. Bone resorption was 5-8% lower, but did not reach a significant difference between groups, indicating moderate sensitivity for FMT. In conclusion, in vivo FMT in mouse tail bones is feasible but needs to be optimized for monitoring load adaptation in living mice.",
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"content": "{\"Chemical\": []}",
"role": "assistant"
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.4801 | [
{
"content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: Emerging NUI-Based Methods for User Authentication: A New Taxonomy and Survey \nChapter Title: D. Avenues for Research \n1. Abstract of Cited Paper (BIB001): In this paper we present an approach to close the gap between text-dependent and text-independent speaker verification performance. Text-constrained GMM-UBM systems are created using word segmentations produced by a LVCSR system on conversational speech allowing the system to focus on speaker differences over a constrained set of acoustic units. Results on the 2001 NIST extended data task show this approach can be used to produce an equal error rate of < 1 %. \n2. Abstract of Cited Paper (BIB002): This paper examines a novel security model for voice biometrics that decomposes the overall problem into bits of “biometric identity security,” bits of “knowledge security,” and bits of “traditional encryption security.” This is the first paper to examine balancing security gained from text-dependent and text-independent voice biometrics under this model. Our formulation allows for text-dependent voice biometrics to address both what you know and who you are. A text-independent component is added to defeat replay attacks. Further, we experimentally examine an extension of the recently introduced Vaulted Voice Verification protocol and the security tradeoffs of adding these elements. We show that by mixing text-dependent with text-independent voice verification and by expanding the challenge-response protocol, Vaulted Voice Verification can preserve privacy while addressing the problematic issues of voice as a remote/mobile biometric identifier. The resulting model supports both authentication and key release with the matching taking place client side, where a mobile device may be used. This novel security model addresses a real and crucial problem: that of security on a mobile device.\n\nReview Chapter:",
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"content": "Apart from resolving security and usability issues that exist in both text-independent and text-dependent approaches, one interesting direction for future work is to use a hybrid of these two approaches in order to simultaneously: 1) improve the authentication performance of text-independent systems when only a limited number of training samples from a user are available, thereby enhancing security and usability of the system in terms of effectiveness, and 2) enhance the security against replay attacks (physical observation) in relation to replay attacks of text-dependent systems. This concept was introduced in a system called \"text-constrained\" speaker recognition BIB002 . Another example of this is to use a challengeresponse based authentication protocol where the model is created based on a limited number of short-phrases BIB003 . In whisper authentication, one important question to address is its usability: is it convenient and non-intrusive to use? Also, as many acoustic properties of whisper signals can vary drastically from one's normal voice BIB001 , it would be interesting to develop an effective recognition algorithm that can verify whisper signals using enrolled normal speaking signals. Such an algorithm would allow users to authenticate in the situation when speaking in a normal voice is not appropriate. In addition, as demonstrated by ear-bone conduction authentication, it is possible for a microphone to be used as a sensor to acquire other physiological biometrics, e.g., body fluid and skeleton properties, when embedded in wearable devices that are attached to other parts of the body.",
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science.chemdner_ner | science.chemdner_ner.3234 | [
{
"content": "Analyze the given text to identify specific entities. Focus on extracting relevant data.\n\nProvide your findings in JSON format. Each category should list the entities found.\n\nText:\n\nHow to measure hazards/risks following exposures to nanoscale or pigment-grade titanium dioxide particles. Due to its multifunctional applications, titanium dioxide particles have widespread use in commerce. The particle-types function as sources of pigment color, in food products, anti-bacterial components, ultraviolet radiation scavengers, catalysts, as well as in cosmetics. Because of its inherent properties in a diverse number of products, exposures may occur via any of the major point-of-entry routes, i.e., inhalation, oral or dermal. Although the majority of TiO2 applications are known to exist in the pigment-grade form, nanoscale forms of TiO2 are also common components in several products. This brief review is designed to identify relevant toxicology and risk-related issues which inform health effects assessments on the various forms of titanium dioxide particles. While there has been an abundance of hazard data generated on titanium dioxide particulates, many of the published reports have limited informational value for assessing health effects due, in large part, to shortcomings in experimental design issues, such as: (1) inadequate material characterization of test samples; (2) questionable relevance of experimental systems employed to simulate human exposures; (3) applications of generally high doses, exclusive focus on acute toxicity endpoints, and a lack of reference benchmark control materials, to afford interpretation of measured results; and/or (4) failure to recognize fundamental differences between hazard and risk concepts. Accordingly, a number of important toxicology issues are identified and integrated herein to provide a more comprehensive assessment of the health risks of different forms of pigment-grade and nanoscale titanium dioxide particles. It is important to note that particle-types of different TiO2 compositions may have variable toxicity potencies, depending upon crystal structure, particle size, particle surface characteristics and surface coatings. In order to develop a more robust health risk evaluation of TiO2 particle exposures, this review focuses on the following issues: A comprehensive evaluation of the existing animal and human health data is a necessary prerequisite for facilitating accurate assessments of human health risks to TiO2 exposures.",
"role": "user"
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"content": "{\"Chemical\": [\"titanium dioxide\", \"TiO2\"]}",
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science.chemdner_ner | science.chemdner_ner.2019 | [
{
"content": "Analyze the given text to identify specific entities. Focus on extracting relevant data.\n\nProvide your findings in JSON format. Each category should list the entities found.\n\nText:\n\nA review of mouse critical size defect models in weight bearing bones. Current and future advances in orthopedic treatment are aimed at altering biological interactions to enhance bone healing. Currently, several clinical scenarios exist for which there is no definitive treatment, specifically segmental bone loss from high-energy trauma or surgical resection - and it is here that many are aiming to find effective solutions. To test experimental interventions and better understand bone healing, researchers employ critical size defect (CSD) models in animal studies. Here, an overview of CSDs is given that includes the specifications of varying models, a discussion of current scaffold and bone graft designs, and current outcome measures used to determine the extent of bone healing. Many promising graft designs have been discovered along with promising adjunctive treatments, yet a graft that offers biomechanical support while allowing for neovascularization with eventual complete resorption and remodeling remains to be developed. An overview of this important topic is needed to highlight current advances and provide a clear understanding of the ultimate goal in CSD research - develop a graft for clinical use that effectively treats the orthopedic conundrum of segmental bone loss.",
"role": "user"
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"content": "{\"Chemical\": []}",
"role": "assistant"
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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.9706 | [
{
"content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Identification of an elaborate NK-specific system regulating HLA-C expression\nContent:\nAbstract:\nThe HLA-C gene appears to have evolved in higher primates to serve as a dominant source of ligands for the KIR2D family of inhibitory MHC class I receptors. The expression of NK cell-intrinsic MHC class I has been shown to regulate the murine Ly49 family of MHC class I receptors due to the interaction of these receptors with NK cell MHC in cis. However, cis interactions have not been demonstrated for the human KIR and HLA proteins. We report the discovery of an elaborate NK cell-specific system regulating HLA-C expression, indicating an important role for HLA-C in the development and function of NK cells. A large array of alternative transcripts with differences in intron/exon content are generated from an upstream NK-specific HLA-C promoter, and exon content varies between HLA-C alleles due to SNPs in splice donor/acceptor sites. Skipping of the first coding exon of HLA-C generates a subset of untranslatable mRNAs, and the proportion of untranslatable HLA-C mRNA decreases as NK cells mature, correlating with increased protein expression by mature NK cells. Polymorphism in a key Ets-binding site of the NK promoter has generated HLA-C alleles that lack significant promoter activity, resulting in reduced HLA-C expression and increased functional activity. The NK-intrinsic regulation of HLA-C thus represents a novel mechanism controlling the lytic activity of NK cells during development.\nIntroduction:\nNatural Killer( NK) cells use two major receptor systems to detect alterations in the expression of MHC class I on potential target cells: the CD94:NKG2A receptor recognizing non-classical HLA-E, and the MHC class I receptors represented by Ly49 in the mouse and KIR in humans[1]. The recognition of HLA-E by NKG2A is dependent on the presentation of the MHC class I leader peptide, and thus surveys cells for the presence or absence of MHC class I expression in general. In contrast, each Ly49 or KIR is specific for a subset of MHC class I molecules, providing a more precise detection of alterations in the expression of individual MHC class I genes. Several studies have demonstrated a switch from NKG2A expression to Ly49/KIR expression as NK cells mature[2–4]. The measurement of HLA expression levels by mass spectroscopy of peripheral blood lymphocytes revealed that HLA-A/B/C levels are at least 25 times higher than that of HLA-E[5], suggesting that the level of inhibitory signaling by MHC class I receptors may increase as NK cells mature and switch from NKG2A recognition of HLA-E to KIR-mediated HLA binding. The education of NK cells by MHC class I is currently an area of intensive research[6–8]. The interaction of inhibitory MHC class I receptors with their ligands has been shown to augment NK cell potential, leading to higher lytic activity and cytokine secretion. The dynamic nature of NK cell education has been revealed by transfer of NK cells into a novel MHC environment, leading to a change in their responsiveness[9–11]. A recent study of human NK cell education has indicated a role for NK cell-intrinsic expression of HLA in the tuning of NK cell activity, as silencing of HLA expression in primary NK cells reduced their function[12]. The role of the human HLA-C gene in NK cell education is of particular interest, as it appears to have developed primarily as a ligand for the KIR2D family of receptors[13, 14]. Whereas only small subsets of HLA-A and HLA-B alleles possess KIR ligands, all HLA-C alleles are recognized. Furthermore, HLA-A or HLA-B cell surface expression levels are 13–18 times higher than HLA-C[5], consistent with a primary role of HLA-C in tuning NK cell responsiveness rather than presenting antigen to T cells. Evolutionary selection for an optimal level of KIR:HLA interaction is implied by the observed allelic variation of KIR cell surface expression levels and differences in ligand affinity of KIR alleles for HLA molecules[15]. Recent studies have also revealed variability in the level of cell surface expression of HLA-C alleles, indicating that variation in ligand levels may also be involved in the tuning of NK responsiveness[16, 17]. In order to gain insight into the mechanisms underlying allele-specific differences in HLA-C expression, we conducted a detailed analysis of polymorphisms in predicted transcription factor( TF) binding sites in the 1. 5 kb region upstream of the HLA-C coding region. Several TF sites were identified that possessed a disruptive single nucleotide polymorphism( SNP) associated with reduced promoter activity[18]. However, a SNP that disrupted a consensus Ets-binding site located approximately 1. 3 kb upstream of the HLA-C start codon was not associated with altered promoter activity in the panel of cell lines studied. The detailed analysis of this region described in the current study reveals that the upstream Ets site is contained within an NK-specific promoter that produces translatable full-length HLA-C transcripts. The presence of these transcripts is associated with a higher level of HLA-C expression on NK cells. Disruption of the Ets site by a SNP in the HLA-C*02/*05/*07/*08 alleles results in the loss of NK-specific transcripts and decreased HLA-C expression. The analysis of NK cells from individuals homozygous for the Ets-disrupting SNP revealed that the loss of NK-specific HLA-C transcripts is associated with higher functional activity. The presence of NK-specific control elements in the HLA-C gene supports a central role for this gene in the development and regulation of NK cells.\nDiscussion:\nThe presence of an NK-specific promoter coupled with an elaborate alternative splicing mechanism to control the translatability of HLA-C mRNA implies an important role for endogenous NK cell HLA-C protein in the development and/or function of NK cells. The increased NK activity we have observed in individuals unable to upregulate HLA-C levels on mature NK cells suggests that endogenous HLA-C plays a role in the tuning of NK cell function. These results are consistent with the evolution of the HLA-C gene to function as a ligand for the KIR family of MHC class I receptors expressed by human NK cells. The change in RNA splicing patterns and the increase in HLA-C expression levels as NK cells mature provides additional evidence for a role of HLA-C in controlling human NK cell function. It is remarkable that alternative RNA splicing generates both on/off( intron retention and exon skipping) and rheostat-like( variation in 5´-UTR length) control of HLA-C expression in NK cells, consistent with endogenous HLA-C levels playing an important role in NK function or differentiation. There is a considerable body of evidence demonstrating an association of increased NK cell activity with the presence of KIR that recognize self HLA( NK education). However, this correlation has been attributed to the recognition of HLA on target cells. MHC class I on the NK cell surface has been shown to control NK activity in mouse NK cells, and this is explained by the ability of Ly49 to recognize class I MHC in cis due to the presence of a flexible stalk in the Ly49 proteins. Although cis interactions with MHC have been demonstrated for the Ly49 receptors[24], and cis interaction is required for murine NK cell licensing[25], there has been no direct evidence of cis interaction of KIR with HLA. Since KIR do not have a flexible stalk, it is believed that cis interaction of KIR with HLA on the cell surface does not occur. It may be possible, however, for inhibitory signaling to occur in endosomes if both KIR and HLA are present. Vesicles containing target cell HLA-C have been observed in KIR2DL1-expressing NK cells, indicating acquisition and internalization of ligand by KIR[26]. It is therefore possible that high levels of endogenous NK cell HLA-C may contribute to inhibitory signaling in these endosomes. The results presented here, together with the previous observation that modulation of HLA expression in NK cells suppresses their activity[12], strongly suggests that KIR:HLA interactions are occurring in human NK cells. The maturation of NK cells from a CD56bright to a CD56dim phenotype is associated with the acquisition of lytic activity[27]. HLA-C levels increase in CD56dim NK cells as well as mature CD57-positive NK cells, and this upregulation is associated with higher levels of translatable NK-Pro HLA-C transcripts due to increased inclusion of exon 1. Therefore, it appears that HLA-C levels increase when the NK cell acquires lytic activity, or alternatively the acquisition of lytic activity is triggered by increased HLA-C levels. At first glance, the increased functional activity of NK cells with reduced HLA-C due to the lack of NK-Pro transcripts seems to be at odds with the observed increase in HLA-C levels on NK cells as they become more mature and functionally active. However, these results are consistent with a model wherein the upregulation of HLA-C in mature NK cells occurs to regulate their function rather than having a direct effect on education. KIR gene expression is activated by a stochastic mechanism in developing NK cells, and there is sequential receptor acquisition until a sufficient inhibitory signal is achieved, which results in a fully functional, educated NK cell[28]. The observed increase in HLA-C expression that occurs with increasing numbers of expressed KIR genes in an NK cell suggests that increased HLA-C levels are a result of NK cell education, rather than driving it. In order for upregulated levels of NK cell HLA-C to play a role in NK education, it would have to occur in the uneducated NK population. Furthermore, it has been shown that differing levels of HLA-C have no effect on the licensing/education of NK cells[29]. The higher levels of HLA-C observed on educated versus uneducated NK cells, further supports upregulation of HLA-C on NK cells as a product of NK education rather than a cause. Fig 8 shows a schematic detailing the changes in NK-Pro mRNA structure and HLA-C expression as NK cells differentiate. The immature CD56bright, NKG2A+ve, KIR-ve cells have low levels of HLA-C produced primarily from proximal promoter transcripts, since NK-Pro cDNAs in immature cells are largely untranslatable. At the intermediate stage of differentiation, KIR expression is stochastically activated in CD56dim cells, and the presence of a ligand for the expressed KIR produces an educated NK cell. This leads to upregulated HLA-C in the mature NK cell due to an increase in the level of translatable HLA-C NK-Pro mRNAs. Increased levels of HLA-C in the mature NK cell are predicted to control lytic activity due to cis inhibitory signaling. The tissue-specific differences in mRNA splicing of the NK-Pro transcript and the differences in HLA-C protein expression on NK cells from various tissues that we have observed could represent a tuning mechanism that regulates the responsiveness of NK cells in certain tissues. It will therefore be of interest to examine if the observed differences in HLA-C levels on NK cells from different tissues correlates with their ability to recognize and lyse targets with reduced HLA-C expression. The increased activity of NK cells with low HLA-C expression due to the presence of an inactivating SNP in NK-Pro suggests that the threshold of NK cell activation is lower, which might also produce a state of decreased lytic potential over time due to more frequent degranulation. Conversely, an increased accumulation of granules, and thus lytic potential would be predicted to occur in NK cells with a high level of HLA-C. Testing the serial-killing activity of high versus low HLA-C expressing NK cells could address this possibility. Allele-specific differences in 5´-UTR exon content also imply selection for an optimal level of HLA-C expression in NK cells, perhaps in conjunction with allelic differences in KIR-binding affinity, in order to achieve an appropriate level of inhibitory signaling. A detailed examination of NK cell HLA-C levels in individuals that are homozygous for HLA-C alleles with distinct splicing patterns and comparing expression levels with the affinity of the allele for the corresponding KIR would be required to investigate this. The existence of HLA-C alleles of both C1( C*07/C*08) and C2( C*02/C*05) supratypes with an inactivated NK-specific promoter suggests that there may be circumstances wherein the absence of upregulated expression of NK cell HLA-C would be beneficial. It will be of interest to determine whether there are any associations of NK-Pro deficient HLA-C alleles with clinical outcomes in infectious disease or bone marrow transplantation.",
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"content": "It has been proposed that the human HLA-C gene evolved in higher primates to serve as a ligand for the KIR family of inhibitory receptors for MHC class I that are expressed by natural killer ( NK ) cells and regulate their activity . NK cell potential is determined by the level of MHC class I on surrounding cells and on the NK cell itself . We have uncovered a highly complex system regulating HLA-C expression in NK cells . A NK-specific promoter produces a large array of differentially-spliced transcripts that vary in their ability to be translated into HLA-C protein . As NK cells differentiate and become more cytotoxic , the level of HLA-C expression increases , and this correlates with an increased abundance of translatable HLA-C mRNAs . A subset of HLA-C alleles have a promoter polymorphism that abrogates its activity , resulting in NK cells that are unable to upregulate HLA-C levels , and consequently , possess increased functional activity . Overall , our findings provide insight into the mechanisms of NK cell development , as well as a method to identify individuals with high NK activity , that may provide superior outcomes in hematopoietic stem cell transfer .",
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science.covid_deepset_qa | science.covid_deepset_qa.671 | [
{
"content": "Analyze the following excerpt from a biomedical text. Identify the relevant information needed to respond to the inquiry. Provide only the necessary details in your answer.\n\nContext: The glycoproteins are the known or presumed ligands for at least two distinct cellular receptors, the 3 integrin chain and decay accelerating factor, or DAF [30, 31] ; with gC1qR/p32 also identified as another potential entry receptor [32] . Comparisons with the tick-borne encephalitis virus E protein, led Tischler et al. to consider the Gc glycoprotein as a potential class II fusion protein, perhaps imparting fusion activity to the virion, and this hypothesis has gained support in other studies [33, 34] . Additional activities have been identified with, or claimed to be related to, Gn. For many of these studies, an underlying premise has held that there are differences between the glycoproteins of -pathogenic‖ hantaviruses relative to viruses in the genus that are dubbed to be -non-pathogenic‖. While it is true that it has not yet been possible to link Prospect Hill virus (PHV) to human disease, the absence of evidence for its pathogenicity should perhaps not be equated with the evidence of its absence. One might only consider that the level of disease (e.g., lethargy, fever, proteinuria, and azotemia) associated with infection of nonhuman primates by PHV is not significantly different from that recorded for nonhuman primate models using the known-pathogen Puumala virus (PUUV) [35, 36] . For the purpose of this discussion we will presume that apathogenic hantaviruses are indeed apathogenic. While some studies have suggested that Gn glycoproteins are directed more rapidly into the ubiquitin-proteosome pathway than are apathogenic forms, others have interpreted differences in the handling of Gn glycoproteins across hantavirus species by the ubiquitin-proteosomal system as independent of pathogenicity [37] [38] [39] . Some investigators have directed their efforts toward identifying a differential capacity, either kinetic or in absolute magnitude, in the ability of pathogenic and apathogenic hantaviruses to elicit an interferon response in cells. One premise that emerges is that apathogenic forms would tend to induce an earlier innate response that would render it more likely that the virus would be quickly cleared or rendered less competent in its replication so as to blunt any pathological response in the host [40] [41] [42] . The anti-hantavirus innate response can in some cases be attributed to viral interaction as a ligand of TLR-3, but not in others, and in endothelial cells, it appears not to require more than the viral particle itself, even when introduced in replication-incompetent form [43, 44] . Proteins and mRNAs prominently induced by hantaviruses include MxA and IFIT-1 (ISG-56) and others including some with known or suspected anti-viral activity. Those hantaviruses, often highly pathogenic strains, that fail to induce a potent antiviral response, are suspected or presumed to have a (more) potent interferon-pathway antagonism mechanism relative to other viruses, a mechanism that acts positively to prevent an effective innate response from forming, at least early in infection [42, 45] . Yet some instances are reported wherein highly pathogenic hantaviruses, such as SNV, are also able to induce expression of interferon-stimulated gene mRNAs, even very early in infection, with ISG proteins, as expected, taking longer to appear in the cell [44] . Anti-interferon activities have also been attributed to the NSs protein that may be elaborated in cells infected by serotypes that encode this protein [46] . Other investigators have examined the activities of hantavirus glycoproteins and other proteins that might themselves directly affect some aspects of the pathogenic progression associated with hantavirus infection of humans, such as vascular permeability changes. While early attempts to directly cause increases in permeability of endothelial monolayers with viral particles or viral infection were largely disappointing, hantaviruses have been identified as adversely affecting endothelial migration over substrata and in potentiating VEG-F-induced endothelial permeability [47, 48] . The shorter (50-kD) nucleocapsid or N protein is a structural component of the viral nucleocapsid, along with the genomic viral RNA segments. As an RNA-binding protein that engages the hairpin termini of the genomic segments with high affinity [49, 50] , it limits the access of the RNA to host nucleases and helps to render viral replication a closed process within the cytoplasm. It also acts as a peripheral membrane protein, as does the L protein [51] , an activity that could play a role in its presumed, but not yet demonstrated function as matrix [52] . Until recently, it had not been appreciated that N has a wide variety of other activities, some of which can be linked, not only to fundamental requirements of replication, but also to the interference with an array of the intracellular processes of the normal cell. Thus, an interaction between the amino terminus of the hantavirus N protein and the cellular protein Daxx has been proposed, with the suggestion of potential pro-apoptotic consequences [51] . N is also reported to interact with actin microfilaments, and the SUMO-1 protein [53, 54] . Using reporter-gene based assays, Connie Schmaljohn and her colleagues have reported that Hantaan virus' nucleocapsid protein has an inhibitory role in inflammatory responses mediated by NF kappa B (NF-B). The effects on NF-B expression appeared to be confined to prevention of its nuclear translocation after its attempted activation with lipopolysaccharide, LPS [55] . In the cytoplasm of infected cells, N protein can be found in cellular P bodies where it sequesters and protects 5' caps. It may locate the caps through its interaction with DCP1, a key constituent of P bodies. During hantavirus infection, the viral RNAs become concentrated in P bodies, through their interaction with N and DCP1. The N protein demonstrates preferential protection of mRNAs engineered to prematurely terminate their encoded protein in comparison to native mRNAs [56] . N protein has been increasingly linked to viral replication and translation, sometimes in previously unanticipated ways. It is among a growing family of diverse viral proteins that can serve as a nonspecific -RNA chaperone‖, an activity that should facilitate the L polymerase's access to vRNA for transcription and replication, in that it can transiently dissociate misfolded RNA structures [57] . Some of N protein's effects on translation might not immediately be recognized to be adaptive in nature. It can replace the entire EIF4F translational initiation complex, simultaneously presenting the ribosome with a replacement for the cap-binding activity of eIF 4E, binding to the 43S pre-initiation complex as does eIF 4G, while replacing the helicase activity of eIF 4A, which is presumed to be needed to dissociate higher-order RNA structure [56, 58] . These three factors normally work together to achieve translational initiation. In P bodies, N protein's ability to bind at high affinity to capped native cellular oligoribonucleotides, along with its activity in protecting capped RNAs from degradation likely facilitates the access of capped oligonucleotides for use in transcriptional initiation by L polymerase (-cap snatching‖). Trafficking of N for viral assembly: Classically, N protein in infected cells appears to be clustered or particulate in nature, with a heavy concentration at a single perinuclear location, widely considered to be the Golgi [27] . The N proteins of hantaviruses are found in association with particulate fractions, and confocal microscopy and biochemical-inhibitor studies have shown that N tracks along microtubules but not with actin filaments [52] . The ultimate destination for N, for its assembly into viral particles is the Golgi, and it traffics there via the endoplasmic reticulum-Golgi intermediate complex (ERGIC), also known as vesicular-tubular cluster [52] . A dominant negative inhibitor, dynamitin, associated with dynein-mediated transport, reduced N's accumulation in the Golgi. Later studies suggested that the specific dependence on microtubular transport is specific to Old World hantaviruses such as HTNV, but that the New World hantavirus ANDV is instead associated with actin filaments [59] . However, recent data indicates that microtubular transport is indeed utilized for the New World hantavirus SNV [60] . Hantavirus diseases of man have long been suspected of having an immunopathogenic basis in part because of their relatively long incubation period of 2-3 weeks and the observed temporal association between immunologic derangements and the first appearance of signs and symptoms of hantavirus illness. HFRS and HCPS share many clinical features, leading many investigators to consider them to be, in essence, different manifestations of a similar pathogenic process, differing mainly in the primary target organs of disease expression ( Table 2 ). The pathogenesis of hantavirus infections is the topic of a continuously-updated review in the series UpToDate [61] . By the time symptoms appear in HCPS, both strong antiviral responses, and, for the more virulent viral genotypes, viral RNA can be detected in blood plasma or nucleated blood cells respectively [63, 64] . At least three studies have correlated plasma viral RNA with disease severity for HCPS and HFRS, suggesting that the replication of the virus plays an ongoing and real-time role in viral pathogenesis [65] [66] [67] . Several hallmark pathologic changes have been identified that occur in both HFRS and HCPS. A critical feature of both is a transient (~ 1-5 days) capillary leak involving the kidney and retroperitoneal space in HFRS and the lungs in HCPS. The resulting leakage is exudative in character, with chemical composition high in protein and resembling plasma. The continued experience indicating the strong tissue tropism for endothelial cells, specifically, is among the several factors that make β3 integrin an especially attractive candidate as an important in vivo receptor for hantaviruses. It is likely that hantaviruses arrive at their target tissues through uptake by regional lymph nodes, perhaps with or within an escorting lung histiocyte. The virus seeds local endothelium, where the first few infected cells give rise, ultimately, to a primary viremia, a process that appears to take a long time for hantavirus infections [62, 63] . By the time that secondary viremia emerges, the agents of the more severe forms of HFRS and HCPS have begun to achieve sufficient mass as to induce, through PAMP-PRR interactions and other means, the expression of proinflammatory cytokines [64] . For HCPS, that expression favors the pulmonary bed and lymphoid organs, yet, for unknown reasons, spares the retroperitoneum and, in general, the kidney. In HFRS the situation is reversed, and yet it is often not appreciated that the expected preferential tissue tropism of HFRS-associated viruses and their HCPS-associated counterparts for the renal and pulmonary beds, respectively, is not as one would predict through the manifestations of the two diseases. Local elaboration of inflammatory and chemotactic mediators is considered to be a requirement for the development of systemic disease symptoms, with those abnormalities sometimes culminating in shock and death. Yet it is not hypoxemia, due to the prominent pulmonary edema, that leads to death in most fatal cases of HCPS, but rather intoxication of the heart by as-yet-undefined mediators that leads to the low cardiac output state and the associated shock syndrome [64, 65] . It is tempting to speculate that mediators produced in the lung in connection with the inflammatory infiltrate can percolate through the coronary circulation with minimal dilution in HCPS, a disadvantageous consequence of the close anatomic juxtaposition of the two organs. Thus, at least three classes of potential mechanisms, some overlapping and all certainly nonexclusive of the others, could be presumed to underlie the pathogenesis of HCPS. These include:\n\n(1) Innate immune mechanisms. The nature of interactions between hantavirus pathogen-associated molecular patterns (PAMP) with the pattern recognition receptors (PRR) of susceptible endothelial cells are beginning to be clarified. The prototypical HTNV appears to be recognized by TLR-3 [43] . Such an infection has consequences such as increased expression of HLA-DR in dendritic cells [66] and differentiation of monocytes toward dendritic cells [67] . (2) Direct viral effects. The observed correlation between viral load and disease severity leaves the possibility open that hantavirus particles or RNA can themselves have toxic effects on cells or on signaling. Some investigators have favored direct viral toxicity, acting through the inhibition of endothelial cell barrier function, as an explanation for much of the capillary leak, although there is widespread agreement that multiple mechanisms that mediate pathogenesis likely operate simultaneously in the affected patient [68] . A potentially important clue toward the mechanism by which hantavirus infections deplete blood platelets and, in some cases cause hemorrhagic manifestations, was advanced by the recent discovery that pathogenic hantaviruses are able to recruit platelets to adhere to endothelial cell surfaces, with β3 integrin used as a critical binding element [69] . (3) Pathogenic effects caused by the activities of specific viral macromolecules. We have reviewed some of the activities associated with the Gn, Gc and N, virally-encoded polypeptides in previous sections. Testing models of pathogenesis can be done more effectively when there is an animal model that mimics key aspects of the disease. There is no such model that closely mimics HFRS, but animal models exist for both the asymptomatic carriage of PUUV and SNV by their native carrier rodents, the bank vole Myodes glareolus and the deer mouse P. maniculatus; as well as a Syrian hamster model using ANDV or the related Maporal virus from Venezuela, for which an HCPS-mimetic disease is observed [70] [71] [72] [73] . The ANDV-Syrian hamster model has a number of features in common with the human disease, as well as some differences. Unlike the neurologic diseases that have been possible to elicit with HTNV, the hamster model for HCPS appears to be caused by capillary leak that results in pulmonary edema and the production of a pleural effusion with exudative characteristics. Typically the hamsters die between 11 and 14-d post-inoculation, reflecting a slightly accelerated incubation period in comparison to human infections. As with human HCPS, the microscopic examination of the lung reveals abundant fibrin deposition, thickened alveolar septa, and viral antigen expressed abundantly in the microvascular endothelium. ANDV-infected hamsters fitted with physiologic monitoring devices exhibited diminished pulse pressures, tachycardia, and hypotension that appear to closely mimic the shock that is believed to be the proximate cause of demise in patients who succumb to HCPS [65, 74] .\n\nInquiry: Which two distinct cellular receptors the glycoproteins are the known or presumed ligands for?",
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"content": "the 3 integrin chain and decay accelerating factor, or DAF",
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science.scientific_lay_summarisation_elife_single_doc_summ | science.scientific_lay_summarisation_elife_single_doc_summ.2353 | [
{
"content": "Transform the provided sections of a biomedical research paper into a digestible summary for a general audience. Focus on simplifying complex ideas while retaining key scientific insights.\n\nResearch Title: Integration of two RAB5 groups during endosomal transport in plants\nContent Overview:\nAbstract:\nRAB5 is a key regulator of endosomal functions in eukaryotic cells. Plants possess two different RAB5 groups, canonical and plant-unique types, which act via unknown counteracting mechanisms. Here, we identified an effector molecule of the plant-unique RAB5 in Arabidopsis thaliana, ARA6, which we designated PLANT-UNIQUE RAB5 EFFECTOR 2( PUF2). Preferential colocalization with canonical RAB5 on endosomes and genetic interaction analysis indicated that PUF2 coordinates vacuolar transport with canonical RAB5, although PUF2 was identified as an effector of ARA6. Competitive binding of PUF2 with GTP-bound ARA6 and GDP-bound canonical RAB5, together interacting with the shared activating factor VPS9a, showed that ARA6 negatively regulates canonical RAB5-mediated vacuolar transport by titrating PUF2 and VPS9a. These results suggest a unique and unprecedented function for a RAB effector involving the integration of two RAB groups to orchestrate endosomal trafficking in plant cells.\nIntroduction:\nEukaryotic cells contain various single-membrane-bound organelles, each of which possesses distinctive constituents and functions. For an organelle to maintain a specific identity and function, the protein and lipid content must be strictly regulated; however, organelles are actively interconnected, exchanging various substances to fulfill complex and diverse cellular activities. The inter-organelle trafficking system mediated by vesicular and/or tubular trafficking intermediates plays an integral role in ensuring proper organelle function. A single round of membrane trafficking involves several sequential steps: budding of vesicles/tubules from a donor organelle, delivery of the transport vesicles, and tethering and fusion of the vesicles with the target membrane. RAB GTPase is an evolutionarily conserved key regulator of the targeting/tethering step and is also responsible for other cellular activities, such as organelle movement and inter- and intracellular signaling( Saito and Ueda, 2009; Stenmark, 2009). These functions of RAB GTPases are fulfilled through nucleotide state-dependent binding with specific sets of proteins, collectively called effector proteins. To ensure the organized and specialized functions of each RAB GTPase, interactions with effectors should be temporally, spatially, and combinatorially regulated for each trafficking event( Grosshans et al., 2006; Zerial and McBride, 2001). The early endosome acts as a communication platform between the intracellular environment and the cell surface and/or extracellular space. RAB5 is a key regulator of a wide spectrum of early endosomal functions in animal cells, including homotypic fusion between early endosomes, endosomal motility, regulation of lipid metabolism at the endosomal membrane, and signal transduction via the early endosome( Grosshans et al., 2006; Miaczynska et al., 2004; Zerial and McBride, 2001). RAB5 is also conserved in a broad range of eukaryotic systems, suggesting its ancient origin in the evolution of eukaryotes( Brighouse et al., 2010; Dacks and Field, 2007; Elias, 2010; Pereira-Leal and Seabra, 2001). Endocytic trafficking pathways demonstrate surprising diversity among lineages, representing uniquely acquired endosomal and endocytic functions in each lineage. The endocytic pathway in plant cells provides a striking example: internalized proteins are initially delivered to the trans-Golgi network( Dettmer et al., 2006), some parts of which mature into multivesiculated late endosomes that acquire RAB5( Scheuring et al., 2011). Conversely, in animal cells, sequestered proteins are initially delivered to RAB5-positive early endosomes, which mature into RAB7-positive late endosomes, mediated by a RAB5 effector complex comprising SAND1/Mon1 and CCZ1( Kinchen and Ravichandran, 2010). This complex, which is also conserved in plants, distinctly regulates endosomal transport from animal and yeast systems( Ebine et al., 2014; Singh et al., 2014; Takemoto et al., 2018). Plants are equipped with multiple vacuolar trafficking pathways that involve RAB5 and RAB7 in unique ways( Bottanelli et al., 2012; Ebine et al., 2014; Singh et al., 2014), further underpinning the diversification of endosomal trafficking systems between plant and animal systems. However, the mechanisms underlying diversified endosomal trafficking systems involving evolutionarily conserved RAB5 remain unresolved. The presence of the plant-unique RAB5 group, ARA6/RABF1 group, is a remarkable feature of plant endosomal trafficking. Arabidopsis thaliana has three RAB5 members: two canonical RAB5 members, ARA7( aka RABF2b) and RHA1( aka RABF2a), which act in vacuolar and endocytic transport( Dhonukshe et al., 2006; Ebine et al., 2011; Kotzer et al., 2004; Sohn et al., 2003), and plant-unique ARA6( aka RABF1)( Ueda et al., 2001). In lieu of cysteine residues that are isoprenylated at the C-terminus, which are essential for membrane binding and functions of canonical RAB GTPases( Seabra, 1998), ARA6 harbors an extra stretch in the N-terminus, where this protein is N-myristoylated and palmitoylated to target a distinct subpopulation of endosomes from canonical RAB5 with substantial overlap( Haas et al., 2007; Ueda et al., 2001). ARA6 promotes formation of the SNARE complex, which contains plant-specific R-SNARE VAMP727 at the plasma membrane( Ebine et al., 2011), and an endosomal function has also been described; overexpression of the nucleotide-free mutant form of ARA6 results in impaired vacuolar trafficking( Bolte et al., 2004; Bottanelli et al., 2012). Despite their distinct functions, ARA6 and canonical RAB5 share the common activating factor, VPS9a( Goh et al., 2007). Intriguingly, loss-of-function mutations of ARA6 and canonical RAB5 confer counteracting effects in a vps9a mutant, further highlighting the distinct functions of these two plant RAB5 groups( Ebine et al., 2011), although the molecular mechanism integrating these two groups in endosomal trafficking remains unexplored. In the present study, we identified and characterized the first effector molecule of ARA6, PLANT-UNIQUE RAB5 EFFECTOR 2( PUF2). Based on these results, PUF2 is a key integrator of the two RAB5 groups in the unique endosomal trafficking system of plants.\nDiscussion:\nThe existence of two RAB5 groups with distinct functions, specifically the canonical and plant-unique RAB5 groups, is a unique characteristic of the plant membrane trafficking system. These RAB5 groups share the upstream regulator VPS9a, containing the VPS9 domain, which is also conserved in activating factors for RAB5 in animal systems( Carney et al., 2006; Goh et al., 2007; Ishida et al., 2016). In animal cells, several VPS9 domain-containing proteins with distinct domain structures regulate Rab5 activity in different endocytic trafficking processes. In plant cells, by contrast, the single activating factor VPS9a coordinates two plant RAB5 groups during vacuolar and endosomal transport, whose molecular mechanisms remain unknown. In the present study, we identified a novel ARA6 effector, PUF2, which acts as a keystone to integrate the functions of two plant RAB5 groups together with VPS9a on the endosomal membrane. PUF2 captures inactive canonical RAB5 and VPS9a on the endosomal membrane, leading to efficient activation of canonical RAB5 and the enhancement of vacuolar transport from endosomes to the vacuole. ARA6, the plant-unique RAB5 in Arabidopsis, diminishes this process by competitively binding to PUF2 in its GTP-bound state against GDP-bound canonical RAB5, thus balancing the distinct canonical RAB5- and ARA6-mediated endosomal transport pathways in plant cells( Figure 7E). No striking homologs of PUF2 have been observed in sequence databases of non-plant systems, suggesting that PUF2 was uniquely acquired by the plant lineage. However, PUF2 shares several characteristics with the animal Rab5 effector protein Rabaptin-5/RABEP1, and both proteins contain four coiled-coil regions. Furthermore, both PUF2 and Rabaptin-5/RABEP1 interact with GTP-bound Rab5 members at one of the coiled-coil regions and also interact with their activating factors at another coiled-coil region( Horiuchi et al., 1997). Rabaptin-5 directly binds to the active form of another Rab GTPase, Rab4, at a distinct coiled-coil region from Rab5, suggesting coordination of the two endosomal Rab GTPase functions by this molecule. Although these data suggest functional similarities between PUF2 and Rabaptin-5, PUF2 appears to preferentially interact with inactive canonical RAB5, and GTP-bound active ARA6 represses the action of canonical RAB5 via competitive binding to PUF2. Furthermore, PUF2 interacts with ARA6 and VPS9a at its C-terminal and N-terminal coiled-coil regions, respectively, whereas Rabaptin-5 interacts with Rab5 and Rabex-5 at its fourth and third coiled-coil regions, respectively( Mattera et al., 2006; Vitale et al., 1998). Rabaptin-5 promotes Rab5 activation by alleviating the autoinhibition of Rabex-5( Delprato and Lambright, 2007; Lippé et al., 2001), resulting in additional Rab5 activation to form an active RAB5 domain on the endosomal membrane. Thus, the mechanisms utilized by PUF2 and Rabaptin-5 are completely different. The downregulation of a Rab GTPase by another Rab GTPase via competitive binding with an effector and a common GEF has not previously been reported. These findings demonstrate that plants have developed specific mechanisms to regulate RAB5 GTPases by acquiring two plant-unique machinery components, ARA6 and PUF2, to participate in the underlying mechanism of endocytic pathway regulation in plants. Although efficient recruitment of VPS9a to the endosome requires PUF2, it is not yet clear how PUF2 is targeted to the endosomal membrane. In the case of Rabaptin-5, Rabaptin-5 interacts with several proteins in addition to Rab5, Rab4, and Rabex-5, including Rabphillin-3( a Rab3 effector: Ohya et al., 1998), γ-adaptin, and GGA( Golgi-localizing, γ-adaptin ear homology domain, ARF-binding proteins)( Mattera et al., 2003). The similarity between PUF2 and Rabaptin-5 at the amino acid sequence level is low, and their modes of actions are divergent, but PUF2 may also have other interacting partners because proteins with multiple coiled-coil regions frequently interact with multiple proteins. In the future, it would be interesting to isolate molecules responsible for the upstream regulation of plant RAB5 groups by recruiting PUF2 onto the endosomal membrane. Further screening and characterization of other binding partners of PUF2 is needed. We recently observed an effector of canonical RAB5 in Arabidopsis, EREX, which appears to act only during embryogenesis and early developmental stages( Sakurai et al., 2016), suggesting canonical RAB5 utilizes several distinct effector proteins at different developmental stages. ARA6 may also exert its function by interacting with multiple effector proteins, and the identification and analysis of other ARA6 effectors will allow us to understand the precise molecular mechanisms underlying ARA6 functioning. Such approaches will reveal how plants have pioneered plant-specific endosomal trafficking pathways and provide valuable information regarding the general mechanisms involved in membrane trafficking system diversification during the evolution of eukaryotic organisms.",
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"content": "Living cells often contain compartments that pass proteins , fats and other biological molecules to one another via a process called membrane trafficking . Endosomes are one of the key platforms of membrane trafficking . These structures accumulate molecules from the outside of the cell , sort them , and then redirect them back to the cell surface or send them to other compartments within the cell where they can be broken down . Proteins known as RAB5s regulate many of the activities of endosomes . Some are found in a wide range of organisms , including animals , fungi , and plants , and are referred to as the “canonical” RAB5 group . Another group of RAB5 proteins are unique to land plants and some green algae . The existence of two RAB5 groups ( i . e . canonical and plant-unique ) is a distinctive feature of plant cells . In 2011 , researchers showed that a plant-unique RAB5 could interfere with and counteract the activities of a canonical RAB5 . However , it remained ambiguous how these proteins could do this . To resolve this question , Ito et al . – who include several researchers from the 2011 study – set out to find proteins that interact with a plant-unique RAB5 from Arabidopsis thaliana . The experiments identified one partner of a plant-unique RAB5 , which was named PUF2 . Unexpectedly , further experiments revealed that PUF2 also regulates canonical RAB5 . PUF2 was found on the surface of the endosome together with RAB5s and a protein that activates RAB5s . Notably , PUF2 also interacted with the activating factor and the inactive form of canonical RAB5 . Based on these findings , Ito et al . propose that PUF2 acts as a landmark to bring inactive canonical RAB5 close to its activating factor , which helps to activate canonical RAB5 . They suggest that the plant-unique RAB5 also competitively binds to the landmark and blocks the canonical RAB5 . Membrane trafficking is a universal system for all living organisms , yet the system seems to be customized among different organisms . These new findings provide further evidence that land plants have evolved a unique mechanism to regulate the activities of their endosomes . The next step is to reconstruct how this system evolved and unravel its relevance to the evolution of plant-specific traits .",
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