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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.14453 | [
{
"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, Morphotype-Specific Candida albicans β-Glucan Exposure during Infection and Drug Treatment\nContent:\nAbstract:\nCandida albicans, a clinically important dimorphic fungal pathogen that can evade immune attack by masking its cell wall β-glucan from immune recognition, mutes protective host responses mediated by the Dectin-1 β-glucan receptor on innate immune cells. Although the ability of C. albicans to switch between a yeast- or hyphal-form is a key virulence determinant, the role of each morphotype in β-glucan masking during infection and treatment has not been addressed. Here, we show that during infection of mice, the C. albicans β-glucan is masked initially but becomes exposed later in several organs. At all measured stages of infection, there is no difference in β-glucan exposure between yeast-form and hyphal cells. We have previously shown that sub-inhibitory doses of the anti-fungal drug caspofungin can expose β-glucan in vitro, suggesting that the drug may enhance immune activity during therapy. This report shows that caspofungin also mediates β-glucan unmasking in vivo. Surprisingly, caspofungin preferentially unmasks filamentous cells, as opposed to yeast form cells, both in vivo and in vitro. The fungicidal activity of caspofungin in vitro is also filament-biased, as corroborated using yeast-locked and hyphal-locked mutants. The uncloaking of filaments is not a general effect of anti-fungal drugs, as another anti-fungal agent does not have this effect. These results highlight the advantage of studying host–pathogen interaction in vivo and suggest new avenues for drug development.\nIntroduction:\nCandida albicans, a common commensal organism of humans, has emerged as an important fungal pathogen clinically due to the immunocompromised status of many patients as well as the ineffectiveness of current anti-fungal drugs[1]. The immune system has many pathways for recognizing and responding to C. albicans, including innate immune Toll-like receptors, lectin receptors, antibody, complement, and mannose binding lectin[2]. A major innate immune receptor for C. albicans is Dectin-1, a lectin that can recognize β-glucan, a unique component of the fungal cell wall. In vitro analysis shows that Dectin-1 recognizes fungal β-glucan( comprising glucan polymers with mixed β1, 3- and β1, 6- linkages), and signals through unique pathways to induce phagocytosis, up-regulation of immune killing mechanisms, and production of pro-inflammatory cytokines[3]. The mechanism of β-glucan signaling through Dectin-1 is unclear because this signature molecule on Candida and other fungi is enveloped by a cell wall mannoprotein layer that masks almost all of the β-glucan from immune recognition and mutes the host immune response[4],[5],[6],[7],[8]. On one hand, the β-glucan masking observed in vitro runs contrary to an active role for Dectin-1 recognition of β-glucan during infection[8],[9],[10]. On the other hand, in vitro Dectin-1 is clearly able to mediate protective responses to fungi and zymosan, a treated fungal particle with exposed β-glucan[9],[11],[12],[13],[14]. In addition, work in knock-out mice suggests at least a conditional requirement for Dectin-1 in resistance to the SC5314 strain of C. albicans, which may be dependent on mouse strain and/or C. albicans strain[13],[14]. An additional complexity at the Candida-host interface is that C. albicans has several developmental cell types including yeast, pseudohyphae, and hyphae, each with different modes of interaction with innate immune cells[15],[16]. The ability of C. albicans to switch between the yeast and filamentous forms is strongly associated with virulence. Filaments are distinct from yeast-form cells in cell wall structure, cell wall proteins and transcriptional programs. In addition, the hyphal form of the fungus has been shown to cause more tissue damage than the yeast-form fungus in ex vivo models of candidiasis[17],[18],[19]. Furthermore, immune recognition of yeast provokes a different immune response compared to recognition of hyphae[15],[20]. Intriguing recent work has suggested that only yeast-form cells possess exposed β-glucan at a few sites[9], but this has yet to be shown in vivo. Although β-glucan can be an important signal for innate immune cells in vitro, and the β-glucan receptor Dectin-1 protects against fungal disease in mice, we still understand little of the dynamics of β-glucan-Dectin-1 interaction during infection or drug treatment. We have developed a new technique to directly measure morphotype-specific β-glucan exposure in mouse tissue during infection and anti-fungal treatment. We find unexpected dynamics of β-glucan exposure during infection and during treatment with the cell wall-directed drug caspofungin. Caspofungin treatment, either in vitro or in vivo, causes dramatic, hyphal-biased exposure of β-glucan. By contrast, although in the absence of the drug there is progressive unmasking of β-glucan during infection, there is no difference between yeast form and hyphal cells. Our results support a role for Dectin-1 in recognition of C. albicans during infection and drug therapy and demonstrate a novel morphotype bias in the action of the anti-fungal caspofungin, highlighting new avenues for drug development.\nDiscussion:\nA critical goal in understanding both host-pathogen interaction and drug action is to probe their dynamics during infection. In vivo experiments show that cell wall β-glucan is a key fungal signature molecule used by the innate immune system to clear fungal infection, yet in vitro experiments suggest that Candida albicans masks β-glucan from immune recognition. To resolve this apparent paradox, we developed and exploited an ex vivo fluorescence( EVF) technology to measure the changes in exposure of β-glucan in live cells during infection. This procedure showed that in the normal course of infection β-glucan is initially masked but subsequently exposed on the surface of C. albicans. This reconciles in vitro data that C. albicans β-glucan is masked by mannoprotein[8],[9] with in vivo infection data suggesting a potential role for Dectin-1 in immunity to C. albicans. In vivo data with knockout mice is inconsistent– clearance of the SC5314 strain of C. albicans, used in this study, from mice in the mixed BL/6×129/Sv background, is dependent on Dectin-1[14], whereas clearance of a different strain of C. albicans from mice in the BL/6 background does not require Dectin-1 for efficient clearance[13]. Taken together, these data suggest that the Dectin-1 β-glucan receptor plays a role in resistance to C. albicans in conditions most similar to those used in our study[14]. Although it is not known how this unmasking occurs during the course of the infection, it is possible that, with time, immune cells accumulate in sufficient numbers to directly damage the cell wall and expose β-glucan. Infiltrating immune cells may also create an environment that induces physiological defenses in the fungus, resulting in altered cell wall signaling and increased exposure of β-glucan. Innate immune cells with the capacity to damage Candida are recruited to the site of infection in the first several days of infection, favoring these models[21],[27],[28]. Alternatively, there may be a novel pathogen-intrinsic pathway late in infection which is programmed to alter architectural changes independent of immune function. EVF also permits unambiguous identification of cellular morphotype, allowing a rigorous analysis of β-glucan exposure in yeast vs. hyphal cells. In the absence of drug there is no difference in exposure of β-glucan between yeast-form and hyphal cells: both are effectively masked from the immune system early during infection and both are unmasked later. This provides evidence that during systemic infection of tissues, filamentous growth does not allow the fungus to evade recognition by the Dectin-1 β-glucan receptor. Previous work with in vitro-grown C. albicans using different media to promote morphotype-specific growth had suggested that hyphal cells are uniquely immune from Dectin-1-mediated recognition[9]. However, our in vivo results show clearly that during infection there is no morphotype-specific masking or unmasking of β-glucan. This contrast highlights the critical advantage of looking at the host-pathogen interaction during infection rather than in vitro. Treatment of mice with CF during disseminated infection unmasks C. albicans β-glucan and makes it available for immune recognition by the Dectin-1 β-glucan receptor. Although unmasking during the normal course of infection shows no morphotype specificity, CF-mediated unmasking is filament-biased and both β-glucan unmasking and fungicidal activities of CF are directed more at filaments than yeast-form cells. The bias may be due to intrinsic compositional differences between hyphal and yeast wall[29],[30],[31],[32] or due to differences in transcription of cell wall regulators sensitive to caspofungin[33]. Filament bias may contribute to the clinical efficacy of CF by selecting for yeast-form growth which is less invasive, more easily cleared and stimulates a more protective immune response[15],[20]. The finding that a particularly effective anti-fungal drug has morphotype bias opens the possibility of new anti-fungals designed for increased effectiveness against the filamentous, invasive form of C. albicans. The morphotype bias also highlights the potential shortcomings of using a single growth condition to determine in vitro drug effectiveness, which can favor one morphotype over another and fail to reveal such biases. Our findings draw attention to a relatively unexplored avenue for drug development—the identification of drugs that do not affect the growth or viability of the pathogen per se but render the pathogen more susceptible to the host immune system. It is likely that clinical use of CF also causes increased recognition through the β-glucan receptor, making hyphal cells more susceptible to immune attack and contributing to the success of the drug. Recent work shows that caspofungin causes unmasking in other fungal species and makes them more susceptible to immune attack, underlining the broad-spectrum robustness of this drug's activity to expose β-glucan even in the absence of classical fungicidal activity[4],[6]. Development of new anti-fungal drugs that specifically cause β-glucan unmasking may reveal novel classes of drugs that target a non-essential process, provide broad-spectrum clinical protection, and do not select for resistance in the absence of immune pressure.",
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"content": "Candida is a common human commensal but disseminated candidiasis is a serious clinical problem , especially among immunocompromised patients . The innate immune system controls Candida infection , in part through the germline-encoded β-glucan receptor Dectin-1 . However , during in vitro growth , Candida albicans mutes Dectin-1 recognition by cloaking its β-glucan underneath a layer of mannan . Bridging these two seemingly contradictory observations , we demonstrate that C . albicans masks β-glucan early during infection , but it becomes exposed later , allowing Dectin-1 to recognize the fungi and mediate immunity . Remarkably , treatment of mice with sub-therapeutic doses of the antifungal drug caspofungin causes exposure of β-glucan on C . albicans even when it would not be exposed naturally . We introduce a new technique for monitoring of epitope exposure during infection , which can be used to monitor the availability of any epitope for immune recognition . This technique allowed us to show that natural unmasking of β-glucan is not morphotype-specific , but drug-mediated unmasking is biased towards the invasive filamentous form of C . albicans . These results highlight the unexplored area of dynamic epitope exposure during infection and therapy , which might be targetable to enhance immune recognition and fungal clearance .",
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science.scicite_classification | science.scicite_classification.1847 | [
{
"content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nThe particles, or signals, are well known [2, 3, 6, 10, 12] in cellular automata (CAs) where iterated parallel processing of strings occurs.",
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"content": "Background",
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science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.693 | [
{
"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:\nBy expanding the connection of objects to the Internet and their entry to human life, the issue of security and privacy has become important. In order to enhance security and privacy on the Internet, many security protocols have been developed. Unfortunately, the security analyzes that have been carried out on these protocols show that they are vulnerable to one or few attacks, which eliminates the use of these protocols. Therefore, the need for a security protocol on the Internet of Things (IoT) has not yet been resolved. Recently, Khor and Sidorov cryptanalyzed the protocol and presented an improved version of it. In this paper, at first, we show that this protocol also does not have sufficient security and so it is not recommended to be used in any application. More precisely, we present a full secret disclosure attack against this protocol, which extracted the whole secrets of the protocol by two communication with the target tag. In addition, recently proposed an ultralightweight mutual authentication RFID protocol for blockchain enabled supply chains, supported by formal and informal security proofs. However, we present a full secret disclosure attack against this protocol as well.\n\nCited Works Summary:\n[1]: Within the next few years, billions of IoT devices will densely populate our cities. In this paper we describe a new type of threat in which adjacent IoT devices will infect each other with a worm that will rapidly spread over large areas, provided that the density of compatible IoT devices exceeds a certain critical mass. In particular, we developed and verified such an infection using the popular Philips Hue smart lamps as a platform. The worm spreads by jumping directly from one lamp to its neighbors, using only their built-in ZigBee wireless connectivity and their physical proximity. The attack can start by plugging in a single infected bulb anywhere in the city, and then catastrophically spread everywhere within minutes. It enables the attacker to turn all the city lights on or off, to permanently brick them, or to exploit them in a massive DDOS attack. To demonstrate the risks involved, we use results from percolation theory to estimate the critical mass of installed devices for a typical city such as Paris whose area is about 105 square kilometers: The chain reaction will fizzle if there are fewer than about 15,000 randomly located smart lamps in the whole city, but will spread everywhere when the number exceeds this critical mass (which had almost certainly been surpassed already). To make such an attack possible, we had to find a way to remotely yank already installed lamps from their current networks, and to perform over-the-air firmware updates. We overcame the first problem by discovering and exploiting a major bug in the implementation of the Touchlink part of the ZigBee Light Link protocol, which is supposed to stop such attempts with a proximity test. To solve the second problem, we developed a new version of a side channel attack to extract the global AES-CCM key (for each device type) that Philips uses to encrypt and authenticate new firmware. We used only readily available equipment costing a few hundred dollars, and managed to find this key without seeing any actual updates. This demonstrates once again how difficult it is to get security right even for a large company that uses standard cryptographic techniques to protect a major product.",
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"content": "A factor that can help expand the IoT is to create confidence for users of this technology in terms of maintaining their privacy and security, because if there is no proper security in its infrastructure, damage to IoT-based equipment, the possibility of losing personal information, the loss of privacy, and even the disclosure of economic and other data, are highly likely, and this may lead to the inability to use it in critical applications. Ronen and Shamir in [1] pointed out that if security is not taken into account in the IoT-based infrastructure, the technology will threaten the future of the world as a nuclear bomb.",
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science.scicite_classification | science.scicite_classification.4642 | [
{
"content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nWhile the prevalence of hyperechogenicity is only *9 % in healthy adults (Berg et al. 1999a), the statistical power was appropriate for detecting significant differences between groups (e.g. grip force group-by-trial interaction = 0.87).",
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{
"content": "Background",
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}
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science.scientific_lay_summarisation_elife_single_doc_summ | science.scientific_lay_summarisation_elife_single_doc_summ.445 | [
{
"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: Genetic basis of sRNA quantitative variation analyzed using an experimental population derived from an elite rice hybrid\nContent Overview:\nAbstract:\nWe performed a genetic analysis of sRNA abundance in flag leaf from an immortalized F2( IMF2) population in rice. We identified 53, 613, 739 unique sRNAs and 165, 797 sRNA expression traits( s-traits). A total of 66, 649 s-traits mapped 40, 049 local-sQTLs and 30, 809 distant-sQTLs. By defining 80, 362 sRNA clusters, 22, 263 sRNA cluster QTLs( scQTLs) were recovered for 20, 249 of all the 50, 139 sRNA cluster expression traits( sc-traits). The expression levels for most of s-traits from the same genes or the same sRNA clusters were slightly positively correlated. While genetic co-regulation between sRNAs from the same mother genes and between sRNAs and their mother genes was observed for a portion of the sRNAs, most of the sRNAs and their mother genes showed little co-regulation. Some sRNA biogenesis genes were located in distant-sQTL hotspots and showed correspondence with specific length classes of sRNAs suggesting their important roles in the regulation and biogenesis of the sRNAs.\nIntroduction:\nSmall RNAs( sRNAs) are non-coding RNAs mainly 18–30 nt in length that regulate a wide range of biological processes in eukaryotic organisms( Carthew and Sontheimer, 2009; Axtell, 2013). According to their origin, sRNAs can be grouped into two major types: hpRNAs that are derived from single-stranded precursors with a hairpin structure( such as microRNAs[miRNAs]) and short interfering RNA( siRNAs) that are derived from double-stranded RNA precursors such as heterochromatic small interfering RNAs( hc-siRNA) and trans-acting siRNAs( ta-siRNA). There has been an explosion of interest in recent years in studies of miRNAs and siRNAs on their identification, biogenesis, and functioning in diverse biological processes. In plants, sRNAs function in regulating growth, development( Juarez et al., 2004; Zhu and Helliwell, 2011), architecture( Jiao et al., 2010; Miura et al., 2010), yield( Zhang et al., 2013), and response to biotic and abiotic stresses( Lu et al., 2008; Shukla et al., 2008). Such regulations are usually achieved by mediating endogenous mRNA cleavage and decay, DNA methylation of source and target loci, and chromatin modification and transcriptional silencing( Arikit et al., 2013). Although the sRNAs differ in length, sequences, and functions, the pathways for their biogenesis and functioning from precursor transcription, processing, maturation, and action are relatively conserved, which involve the activities of a number of enzymes including RNA polymerase II( Pol II), RNA-dependent RNA polymerases( RDRs), Dicer-like proteins( DCLs), and Argonautes( AGOs)( Chen, 2009; Ghildiyal and Zamore, 2009). It is also known that the abundance of sRNA species can be highly variable among individuals within a species, and the possible regulatory role of such quantitative difference has been assumed( He et al., 2010; Groszmann et al., 2011b). It is not known whether the quantitative variation of sRNA species between genotypes is related to the biological machinery, as quantitative variation of sRNAs has not been assayed at the population level and their genetic control has yet to be elucidated. The recently developed expression quantitative trait locus( eQTL) analysis has provided an approach for determining the genetic control of the expression level of a gene, including cis- and trans-eQTLs, as well as epistatic effects( Becker et al., 2012). This approach can also be applied to the genetic analysis of quantitative variation of sRNAs by regarding the abundance of the sRNAs in the population as quantitative traits. Once the QTLs are identified, subsequent studies can be pursued very much the same way as the analysis of genes and regulatory networks underpinning phenotypic QTLs( Xing and Zhang, 2010). There have been several studies focusing on the genetic regulation of known and validated miRNAs and small nucleolar RNAs in specific tissues/cells from samples of the human population( Borel et al., 2011; Gamazon et al., 2012; Parts et al., 2012; Civelek et al., 2013; Jin and Lee, 2013; Siddle et al., 2014). These studies detected a number of cis- and trans-miQTLs that could also influence the expression of the mRNA targets, which may be associated with phenotype difference. Here, we performed a whole genome QTL analysis of the entire sRNA kingdom consisted of 18-nt to 26-nt sRNAs from flag leaf of rice using an experimental genetic population. The analysis revealed features of the genetic controls of sRNA abundance showing both commonality and distinction with their precursor transcripts. It was also shown that the abundance of sRNAs is probably related to proteins constituting the machinery for sRNA biogenesis and functioning.\nDiscussion:\nThe variation of sRNA abundance in a population depends on a range of factors: the levels of transcription of the precursors that is influenced by local elements mostly residing in the promoter regions of the sRNA itself; the mother gene or long non-coding RNAs where the sRNA is produced; polymorphisms in sequence influencing their biogenesis; and variation in distant regulatory factors located distantly from where the sRNA is generated. Our results indicated that almost one third of the detected local-sQTLs exhibited much larger effects than distant-sQTLs, consistent with the studies for eQTL of mRNA expression( Kliebenstein, 2009), suggesting that local elements are a major regulatory factor for sRNA variation. Local-QTLs regulating the expression of large numbers of traits were observed for s-traits but not for e-traits, resulting from the enrichment of s-traits in the region produced by the extensive and consecutive overlapping transcripts from the mother genes. Hotspots were found for both distant-QTLs of mRNA e-traits and sRNA s-traits, both of which could influence the expression variations of a large number of traits. Our results showed that quantitative variation for a large portion of sRNAs transcribed from genic regions did not share the genetic control of the expression with the corresponding mother genes, although by common sense those sRNAs have to be transcribed along and regulated by the promoters of the mother genes. Similar results were reported in previous studies of miRNAs and their host genes, which were regulated or processed independently from their respective regulatory elements( Siddle et al., 2014). The results of Monteys et al.( 2010) and Ozsolak et al.( 2008) suggested that the transcription of sRNAs may also be regulated by their own promoters, independent of the mother genes. The widespread occurrence of such independent genetic controls between the sRNAs and the mother genes suggested that independent transcription of the sRNAs might be a common phenomenon, rather than only special circumstances. Moreover, the large number of distant-sQTLs that were not collocated with the distant-eQTLs for the corresponding mother genes supported the independent regulatory basis of the transcription of the sRNAs. Our results showed that some of the sRNA biogenesis genes such as DCLs, AGOs, and RDRs were probably responsible for the quantitative variation of a large number of sRNAs. OsRDR2 was found in a region of consecutive distant-sQTL hotspots explaining the expression variation of many sRNAs, most of which were 24 nt. This was also a region of consecutive distant-scQTL hotspots with the highest number of distant-scQTLs. OsDCL2b was also found in consecutive distant-sQTL hotspots regulating the expression of sRNAs, most of which were 22 and 24 nt. Although OsDCL2a and OsDCL1c were not in distant-sQTL hotspots due to lack of local recombination in that region, they were also in bins regulating the expression of a large number of s-traits. This is in accordance with the reports that RDRs function on the upstream of DCLs in the process of sRNA biogenesis( Chapman and Carrington, 2007). Studies in sRNA pathways in Arabidopsis showed that DCL2 is responsible for the synthesis of 22 nt or 24 nt siRNAs, while RDR2 functions in the production of endogenous 24 nt siRNAs and the conversion of ssRNA template into dsRNAs that serve as substrates for DCLs( Arikit et al., 2013), which is in good agreement with the sQTLs found in this study. However, it should also be noted that these genes were associated with s-QTLs for only a small portions of the s-traits, while the quantitative variation of the sRNA abundance for majority of the s-traits was independent of the sRNA biogenesis genes. One of the most interesting finding perhaps concerns the sRNAs from the two loci, LOC_Os03g01360 and LOC_Os07g01240, and their regulation patterns. Although both loci produced thousands of sRNAs, which were the most numerous in the genome, they showed sharp contrast in where the sRNAs were generated and the regulatory mechanisms with which the sRNAs were produced. sRNAs from LOC_Os03g01360 mostly originated from the 2-kb upstream and genic regions and were tightly co-regulated with each other and also with the mother gene. By contrast, sRNAs from LOC_Os07g01240 were mostly produced in the intronic region and loosely co-regulated with each other and not co-regulated with the mother gene; in fact, the s-trait variation and sQTLs were detected even without the expression variation of the mother gene. Since neither of the genes has been previously identified as related to the production and function of sRNAs, their roles in sRNA biogenesis warrant further investigation. Another noticeable finding is the widespread negative dominance of sRNA levels detected in the IMF2 population such that heterozygotes had lower level of the sRNAs than the means of the two homozygotes( negative partial dominance) or the lower homozygote( negative overdominance). Such negative dominance was also observed in comparative sRNA profiling of hybrids relative to the parents in crosses of rice and Arabidopsis( Groszmann et al., 2011b, 2013; He et al., 2013), revealing a predominant-negative regulation of siRNA expression in hybrids( He et al., 2010; Chodavarapu et al., 2012). Our genetic analysis revealed that the sQTLs showing negative dominance of the sRNA levels are mostly distant-sQTLs, indicating regulation by distant elements likely at the transcriptional level. Studies of transcript levels of genes( mRNAs) in the hybrid against the parents in the same rice cross also revealed more negative dominance than positive dominance, also indicating down-regulation in the hybrid relative to the parents( Huang et al., 2006). How the down-regulation of these two classes of transcripts was related to each other and how the two classes of down-regulation are related to the hybrid performance present great challenges for future studies.",
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"content": "Genes within the DNA of a plant or animal contain instructions to make molecules called RNAs . Some RNA molecules can be decoded to make proteins , whereas others have different roles . A single gene often contains the instructions to make both protein-coding RNAs and non-coding RNAs . Molecules called small RNAs ( or sRNAs ) do not code for proteins . Instead , sRNAs can control protein-coding RNA molecules or chemically alter the DNA itself; this allows them to perform many different roles in living organisms . In plants , for example , these molecules affect how the plant grows , the shapes and structures it forms , and how likely it is to survive challenges such as drought and diseases . Often different plants of the same species have different amounts of sRNAs , but the reasons for this remain unclear . Now , Wang , Yao et al . have made use of a technique called ‘expression quantitative locus’ analysis to look at how sRNAs in rice plants are controlled by additional information encoded within DNA . The analysis identified over 53 million sRNA molecules from a population of rice plants . Many of these sRNAs varied in their abundance between different plants within the population . Wang , Yao et al . also found many thousands of individual instructions within the DNA of the rice that can either increase or reduce the abundance of their associated sRNA . Some of the abundant sRNAs were influenced by instructions within their own genes; some were influenced by instructions from other genes; and some were influenced by both . Wang , Yao et al . also found that the control of protein-coding RNAs was not necessarily related to the control of sRNAs encoded by the same gene . Further work is now needed to identify which specific DNA sequences regulate the abundance of sRNA molecules in plants and other organisms .",
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science.scicite_classification | science.scicite_classification.3457 | [
{
"content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nAdult, 12–14 week-old male C57/Bl6 mice (n = 12/group) underwent constriction of the pulmonary artery or thoracic aorta as previously described to generate models of acute primary and progressive secondary RVPO respectively [14,19].",
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},
{
"content": "Method",
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}
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.451 | [
{
"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: Progress in Outlier Detection Techniques: A Survey \nChapter Title: C. DISTANCE-BASED APPROACHES \n1. Abstract of Cited Paper (BIB001): This paper deals with finding outliers (exceptions) in large, multidimensional datasets. The identification of outliers can lead to the discovery of truly unexpected knowledge in areas such as electronic commerce, credit card fraud, and even the analysis of performance statistics of professional athletes. Existing methods that we have seen for finding outliers can only deal efficiently with two dimensions/attributes of a dataset. In this paper, we study the notion of DB (distance-based) outliers. Specifically, we show that (i) outlier detection can be done efficiently for large datasets, and for k-dimensional datasets with large values of k (e.g., $k \\ge 5$); and (ii), outlier detection is a meaningful and important knowledge discovery task.First, we present two simple algorithms, both having a complexity of $O(k \\: N^2)$, k being the dimensionality and N being the number of objects in the dataset. These algorithms readily support datasets with many more than two attributes. Second, we present an optimized cell-based algorithm that has a complexity that is linear with respect to N, but exponential with respect to k. We provide experimental results indicating that this algorithm significantly outperforms the two simple algorithms for $k \\leq 4$. Third, for datasets that are mainly disk-resident, we present another version of the cell-based algorithm that guarantees at most three passes over a dataset. Again, experimental results show that this algorithm is by far the best for $k \\leq 4$. Finally, we discuss our work on three real-life applications, including one on spatio-temporal data (e.g., a video surveillance application), in order to confirm the relevance and broad applicability of DB outliers. \n2. Abstract of Cited Paper (BIB002): A distance-based outlier detection method that finds the top outliers in an unlabeled data set and provides a subset of it, called outlier detection solving set, that can be used to predict the outlierness of new unseen objects, is proposed. The solving set includes a sufficient number of points that permits the detection of the top outliers by considering only a subset of all the pairwise distances from the data set. The properties of the solving set are investigated, and algorithms for computing it, with subquadratic time requirements, are proposed. Experiments on synthetic and real data sets to evaluate the effectiveness of the approach are presented. A scaling analysis of the solving set size is performed, and the false positive rate, that is, the fraction of new objects misclassified as outliers using the solving set instead of the overall data set, is shown to be negligible. Finally, to investigate the accuracy in separating outliers from inliers, ROC analysis of the method is accomplished. Results obtained show that using the solving set instead of the data set guarantees a comparable quality of the prediction, but at a lower computational cost. \n3. Abstract of Cited Paper (BIB003): This paper presents a k-nearest neighbors (kNN) method to detect outliers in large-scale traffic data collected daily in every modern city. Outliers include hardware and data errors as well as abnormal traffic behaviors. The proposed kNN method detects outliers by exploiting the relationship among neighborhoods in data points. The farther a data point is beyond its neighbors, the more possible the data is an outlier. Traffic data here was recorded in a video format, and converted to spatial-temporal (ST) traffic signals by statistics. The ST signals are then transformed to a two-dimensional (2D) (x, y) -coordinate plane by Principal Component Analysis (PCA) for dimension reduction. The distance-based kNN method is evaluated by unsupervised and semi-supervised approaches. The semi-supervised approach reaches 96.19% accuracy.\n\nReview Chapter:",
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{
"content": "Distance-based methods detect outliers by computing the distances between points. A data point that is at a far distance from its nearest neighbor is regarded as an outlier. The most commonly used distance-based outlier detection definition is centered on the concept of the local neighborhood, k-nearest neighbor (KNN) BIB004 , and the traditional distance threshold. One of the earliest studies of computing distancebased outliers by Knorr and Ng BIB001 defined distance-based outliers as: Definition: In a dataset T, an object O is a DB (p, D)-outlier if minute fraction p of the objects in the dataset lies beyond the distance D from O. Other well-known definitions of distance-based outliers given the distance measure of feature space, define outliers as: i. Points with less than p different samples within the distance d BIB002 . ii. The top n examples whose distance to thekth nearest neighbor are the greatest . iii. The top n examples whose average distance to the k nearest neighbors are the greatest BIB003 . The abbreviation DB(p,D) is the Distance-Based outlier detected using the parameters p and D. DB outlier detection methods are moderate non-parametric approaches that scale well for large data sets with a medium to high dimensionality. In comparison with statistical techniques, they tend to have a more robust foundation and are more flexible and computationally efficient. In our subsequent section, we classify the distance-based methods into the following groups -distance-based computation method using k-nearest neighbor computation, pruning techniques, and data stream related works. Some of the most commonly used distance-based approaches to detect outliers are as follows:",
"role": "assistant"
}
]
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science.bioasq_factoid_qa | science.bioasq_factoid_qa.802 | [
{
"content": "Given the following biomedical passages, answer the question succinctly. Ensure your response is precise and limited to the answer only.\n\nQuestion: In which phase of clinical trials was sutezolid in 2018?\n\nPassages: After decades of quiescence in the development of antituberculosis medications, bedaquiline and delamanid have been conditionally approved for the treatment of drug-resistant tuberculosis, while several other novel compounds (AZD5847, PA-824, SQ109 and sutezolid) have been evaluated in phase II clinical trials.",
"role": "user"
},
{
"content": "phase II",
"role": "assistant"
}
]
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science.ddi_ner | science.ddi_ner.613 | [
{
"content": "Examine the provided biomedical abstract. Identify and list entities based on the specified categories: [\"Brand\", \"Drug\", \"DrugGroup\", \"UnapprovedDrug\"].\n\nFormat your findings as a JSON object: {\"Brand\": [\"Aspirin\", ...], \"DrugGroup\": [\"Salicylate\", ...], \"Drug\": [\"Phenobarbital\", ...], \"UnapprovedDrug\": [\"Heroin\", ...]}. Each key represents an entity type, and the corresponding value is a list of entities. If no entities are found for a type, use an empty list [].\n\nFocus solely on producing the JSON object.\n\nSource Text:\n\nConcomitant use of calcium supplements and L-lysine may increase calcium absorption",
"role": "user"
},
{
"content": "{\"Brand\": [], \"Drug\": [\"L-lysine\", \"calcium\"], \"DrugGroup\": [], \"UnapprovedDrug\": []}",
"role": "assistant"
}
]
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science.scicite_classification | science.scicite_classification.1495 | [
{
"content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nThe Division I players from the current study were older than the Division II players, however, all were within the typical range of collegiate soccer players documented in the literature [3,5,28,29,40,49].",
"role": "user"
},
{
"content": "Background",
"role": "assistant"
}
]
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science.scierc_re | science.scierc_re.208 | [
{
"content": "Examine the provided abstract from a computer science paper. Your objective is to identify and extract relationships between entities. Present these relationships in a structured JSON format.\n\nInput Text:\n\nRecent years have seen increasing research on extracting and using temporal information in natural language applications. However most of the works found in the literature have focused on identifying and understanding temporal expressions in newswire texts. In this paper we report our work on anchoring temporal expressions in a novel genre, emails. The highly under-specified nature of these expressions fits well with our constraint-based representation of time, Time Calculus for Natural Language (TCNL). We have developed and evaluated a Temporal Expression Anchoror (TEA), and the result shows that it performs significantly better than the baseline, and compares favorably with some of the closely related work.",
"role": "user"
},
{
"content": "[[\"emails\", \"temporal expressions\", \"FEATURE-OF\"], [\"Time Calculus for Natural Language (TCNL)\", \"constraint-based representation of time\", \"HYPONYM-OF\"], [\"Temporal Expression Anchoror (TEA)\", \"baseline\", \"COMPARE\"], [\"newswire texts\", \"temporal expressions\", \"FEATURE-OF\"]]",
"role": "assistant"
}
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science.healthver_entailment | science.healthver_entailment.4065 | [
{
"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: a vaccine exists for the novel covid-19\n\nResearch Abstract:\nThe recent emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 is a major burden for health care systems worldwide.\nIt is important to address if the current infection control instructions based on active ingredients are sufficient.\nWe therefore determined the virucidal activity of two alcohol-based hand rub solutions for hand disinfection recommended by the World Health Organization (WHO), as well as commercially available alcohols.\nEfficient SARS-CoV-2 inactivation was demonstrated for all tested alcohol-based disinfectants.\nThese findings show the successful inactivation of SARS-CoV-2 for the first time and provide confidence in its use for the control of COVID-19.\nImportance The current COVID-19 outbreak puts a huge burden on the world’s health care systems.\nWithout effective therapeutics or vaccines being available, effective hygiene measure are of utmost importance to prevent viral spreading.\nIt is therefore crucial to evaluate current infection control strategies against SARS-CoV-2.\nWe show the inactivation of the novel coronavirus for the first time and endorse the importance of disinfectant-based hand hygiene to reduce SARS-CoV-2 transmission.",
"role": "user"
},
{
"content": "{\"verdict\": \"NEI\", \"evidence\": []}",
"role": "assistant"
}
]
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science.healthver_entailment | science.healthver_entailment.1734 | [
{
"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: If you are considered high risk, you may show rarer and more severe symptoms.\n\nResearch Abstract:\nINTRODUCTION: Neurological manifestations can occur during coronavirus disease 19 (COVID-19).\nSeveral pathogenic mechanisms have been hypothesized, without conclusive results.\nIn this study, we evaluated the most frequent neurological symptoms in a cohort of hospitalized COVID-19 patients, and also investigated the possible relationship between plasmatic inflammatory indices and olfactory disorders (ODs) and between muscle pain and creatine kinase (CK).\nMETHODS: We consecutively enrolled hospitalized COVID-19 patients.\nA structured questionnaire concerning typical and neurological symptoms, focusing on headache, dizziness, ODs, taste disorders (TDs), and muscle pain, was administrated by telephone interviews.\nRESULTS: Common neurological symptoms were reported in the early phase of the disease, with a median onset ranging from 1 to 3 days.\nHeadache showed tension-type features and was more frequently associated with a history of headache.\nPatients with ODs less frequently needed oxygen therapy.\nInflammatory indices did not significantly differ between patients with and without ODs.\nMuscle pain did not show any association with CK level but was more frequently associated with arthralgia and headache.\nCONCLUSION: In our cohort, ODs were an early symptom of COVID-19, more frequently reported by patients with milder forms of disease.\nHeadache in association with arthralgia and muscle pain seems to reflect the common symptoms of the flu-like syndrome, and not COVID-19 infection-specific.",
"role": "user"
},
{
"content": "{\"verdict\": \"NEI\", \"evidence\": []}",
"role": "assistant"
}
]
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science.healthver_entailment | science.healthver_entailment.2708 | [
{
"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: Social Distancing Key to Lowering COVID-19 Disease Risk\n\nResearch Abstract:\nThe infectious diseases are spreading due to human interactions enabled by various social networks.\nTherefore, when a new pathogen such as SARS-CoV-2 causes an outbreak, the non-pharmaceutical isolation strategies (e.g., social distancing) are the only possible response to disrupt its spreading.\nTo this end, we introduce the new epidemic model (SICARS) and compare the centralized (C), decentralized (D), and combined (C+D) social distancing strategies, and analyze their efficiency to control the dynamics of COVID-19 on heterogeneous complex networks.\nOur analysis shows that the centralized social distancing is necessary to minimize the pandemic spreading.\nThe decentralized strategy is insufficient when used alone, but offers the best results when combined with the centralized one.\nIndeed, the (C+D) is the most efficient isolation strategy at mitigating the network superspreaders and reducing the highest node degrees to less than 10% of their initial values.\nOur results also indicate that stronger social distancing, e.g., cutting 75% of social ties, can reduce the outbreak by 75% for the C isolation, by 33% for the D isolation, and by 87% for the (C+D) isolation strategy.\nFinally, we study the impact of proactive versus reactive isolation strategies, as well as their delayed enforcement.\nWe find that the reactive response to the pandemic is less efficient, and delaying the adoption of isolation measures by over one month (since the outbreak onset in a region) can have alarming effects; thus, our study contributes to an understanding of the COVID-19 pandemic both in space and time.\nWe believe our investigations have a high social relevance as they provide insights into understanding how different degrees of social distancing can reduce the peak infection ratio substantially; this can make the COVID-19 pandemic easier to understand and control over an extended period of time.",
"role": "user"
},
{
"content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"Our analysis shows that the centralized social distancing is necessary to minimize the pandemic spreading.\", \"The decentralized strategy is insufficient when used alone, but offers the best results when combined with the centralized one.\", \"Indeed, the (C+D) is the most efficient isolation strategy at mitigating the network superspreaders and reducing the highest node degrees to less than 10% of their initial values.\", \"Our results also indicate that stronger social distancing, e.g., cutting 75% of social ties, can reduce the outbreak by 75% for the C isolation, by 33% for the D isolation, and by 87% for the (C+D) isolation strategy.\"]}",
"role": "assistant"
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science.scientific_papers_summarization_single_doc_arxiv | science.scientific_papers_summarization_single_doc_arxiv.153686 | [
{
"content": "Given the full text of a scientific research paper, write an abstract section for the paper. Your response should contain only the abstract without any other text.\n\nArticle text:\nthe shape of the free surface of a ferrofluid in a static magnetic field is one of the prominent examples for a non - trivial interplay between magnetic and hydrodynamic degrees of freedom in ferrohydrodynamics : on the one hand the magnetic stresses contribute to the force balance determining the surface profile whereas on the other hand the local magnetic field depends on this profile due to the magnetic boundary conditions at the surface of the magnetically permeable material @xcite .\na particularily popular setup is the conical meniscus of a ferrofluid surrounding a vertical current - conducting wire @xcite , see fig .\n1 . neglecting surface tension the conical shape can be determined analytically from the balance between gravitational and magnetic force @xcite . in the present note\nwe investigate theoretically the influence of surface tension on the shape of the conical meniscus .\nalthough surface tension is known to modify free surface profiles in ferrohydrodynamics and its influence has been studied , e.g. , for small gaps @xcite and capillaries @xcite to our knowledge no systematic investigation has been done so far for the conical meniscus problem . clearly , surface tension is present in all experiments in ferrohydrodynamics and a full understanding of its impact on a basic experiment in the field is hence desirable . as expected no analytical expression for the free surface profile can be derived when surface tension is included .\nthe numerical determination can be reduced to a singular boundary value problem for an ordinary differential equation which is , however , not completely straightforward to solve . still , using an appropriate transformation ,\naccurate solutions can be obtained .\nthe numerical effort is much smaller than in alternative procedures such as finite difference , galerkin , or collocation methods which is for example used from commercial software like ansys or comsol multiphysics @xcite the paper is organized as follows . in section\nii we collect the basic equations describing the system .\nsection iii contains the analysis of a somewhat idealized situation . in section\niv we discuss the modification of the results if the idealizations of section iii are removed .\nfinally section v provides some conclusions .\nthe setup to be investigated is sketched in fig . 1 . an infinitely long , straight wire of radius @xmath1 oriented along the @xmath2-axis of a cylindrical coordinate system @xmath3 carries an electric current @xmath4 .\nthe wire is surrounded by two superimposed liquids .\nthe lower one with density @xmath5 is a ferrofluid with a given magnetization law @xmath6 .\nthe upper one has density @xmath7 and is a non - magnetic fluid .\nthe interface between the two fluids is characterized by an interface tension @xmath8 .\nfor @xmath9 there is no magnetic field and the flat interface between the two fluids is taken as the @xmath10plane of the coordinate system . for @xmath11\na magnetic field @xmath12 builds up which induces a force density in the lower fluid .\nthis gives rise to an axis - symmetric conical interface parametrized by a function @xmath0 the determination of which is the central aim .\nnote that the magnetic field ( [ h(r ) ] ) is everywhere tangential to the surface and is therefore independent of the detailed shape of the surface which makes the analysis of this case particularily transparent . of the ferrofluid is axis - symmetric .\n, width=321 ] one way to determine @xmath0 is by minimizing the total energy @xmath13 of the system .\nit is convenient then to use the energy of the flat interface configuration as reference state and hence to minimize the energy difference between states with a non - trivial @xmath0 and @xmath14 .\nequivalently one may start with the ferrohydrodynamic bernoulli equation @xcite .\nthe total energy difference @xmath13 is the sum of three parts , the gravitational , the surface , and the magnetic energy , @xmath15 the different parts are given , respectively , by @xmath16 and @xcite @xmath17 here @xmath18 denotes that part of the volume occupied by the ferrofluid for which @xmath19 , @xmath20 is the area of the interface between the two fluids and @xmath21 is the permeability of free space .\nnote that in the last equality of ( [ e_m ] ) we have assumed that the magnetization @xmath22 and the magnetic field @xmath23 are parallel as is the case in ferrofluids .\nnote also that @xmath24 is given by ( [ h(r ) ] ) .\nthe euler - lagrange equation @xmath25 corresponding to the minimization of @xmath26 $ ] is a nonlinear ordinary differential equation for the desired interface profile @xmath0 . for a unique solution this equation has to be complemented by appropriate boundary conditions\n. these are @xmath27 and @xmath28 where the prime denotes differentiation with respect to @xmath29 .\nthe second boundary condition results from the young equation @xcite @xmath30 for the contact angle @xmath31 of the fluids at the wire and the fact that @xmath32 ( cf . fig\nwe first analyse a somewhat simplified version of the boundary value problem derived in the last section .\nthe simplifications are the following .\nwe assume that the non - magnetic fluid is absent , @xmath33 , that the magnetization law of the ferrofluid is linear , @xmath34 where @xmath35 denotes the magnetic susceptibility , and that the diameter of the wire is negligible , @xmath36 .\nsince the magnetic field @xmath24 diverges for @xmath37 so does the magnetic force density . in order to get a stable interface profile\nthe magnetic force has to be counterbalanced by gravitation and surface tension which is possible only if @xmath38 this equation replaces the boundary condition ( [ boundaryr ] ) in the present case .\nconsequently @xmath39 and @xmath40 are irrelevant and only @xmath8 remains which will be denoted simply by @xmath41 in the present section .\nusing the simplifying assumptions we find for the magnetic energy ( [ e_m ] ) the expression @xmath42 which allows to explicitly perform the variation in eq.([eleq ] ) . as a result\nwe get the following differential equation for @xmath0 @xmath43 it is convenient to introduce dimensionless quantities by measuring both @xmath29 and @xmath44 in units of @xmath45{\\frac{\\mu_0\\chi i^2}{8 \\pi^2 g \\varrho_1}}\\ ] ] and @xmath41 in units of @xmath46 .\n( [ euler ] ) then acquires the form @xmath47 this equation is easily solved for @xmath48 yielding the well - known hyperbola @xmath49 @xcite .\na perturbative solution for @xmath50 by expanding @xmath0 in powers of @xmath41 was found to yield satisfactory results only for values of @xmath41 much smaller than those relevant in experiments .\nwe therefore turned to a numerical solution .\n( [ dimlesseuler ] ) together with the boundary conditions ( [ boundaryinf ] ) and ( [ bc3 ] ) represents a singular boundary value problem of second kind ( see , e.g. , @xcite ) .\nthe main problem that makes a straightforward numerical solution inexpedient are the infinite intervals for @xmath29 and @xmath44 .\nwe therefore transform both quantities according to ( cf . also fig .\n1 ) @xmath51 and describe the interface profile by @xmath52 .\nthe boundary conditions ( [ boundaryinf ] ) and ( [ bc3 ] ) then transform into @xmath53 respectively which are much more convenient for the subsequent numerical solution . substituting the derivatives in ( [ dimlesseuler ] ) according to @xmath54 we find as differential equation for @xmath55 @xmath56 rewriting this equation in the form @xmath57 the boundary value problem ( [ euler2 ] ) , ( [ boundary2 ] ) can now easily be solved numerically using , e. g. , the nonlinear finite - difference method described in @xcite . as initial\nguess for the solution which is needed in this procedure the transformation of the analytical solution @xmath58 for @xmath48 given by @xmath59{\\tan(\\varphi)}$ ] may be used .\nfig.[figrequal0 ] shows the resulting interface profile for parameter values corresponding to the ferrofluid emg909 of ferrotec @xcite . for comparison the shape for @xmath48 is also shown .\nit is clearly seen that the free surface profile is markedly modified by the influence of the surface tension .\nas expected the inclusion of surface tension makes the profile narrower since an additional force pointing radially inward builds up . as determined numerically for @xmath36 and @xmath60a for the ferrofluid emg909 with parameters @xmath61kgm@xmath62 , @xmath63nm@xmath64 , and @xmath65 ( full line ) .\nalso shown is the result for @xmath48 and otherwise identical parameters ( dashed line ) .\n( b ) same profiles as in ( a ) in terms of the transformed function @xmath55.,width=321 ]\nthe above solution of the idealized problem forms a convenient starting point for the discussion of the influence of those feature in the original setup that were neglected in the previous section .\na simple modification is the case in which the ferrofluid is superimposed by a non - magnetic liquid .\nthen the density @xmath5 has to substituted by the density difference @xmath66 and the surface tension @xmath41 is to be replaced by the interface tension @xmath8 . the gravitational contribution to the total energy\ngets reduced and consequently larger displacements from the flat interface are to be expected .\nthe situation can be analyzed quantitatively without further effort by mapping it to the case analyzed in the previous section .\nin fact the interface profile is again determined by eq .\n( [ dimlesseuler ] ) with only the dimensionless units and the value of @xmath41 being modified . as an explicit example we show in fig.[figcorrections](a ) how the interface profile of fig .\n[ figrequal0 ] gets modified for @xmath67kgm@xmath62 and @xmath68 .\ndeviations form the linear magnetization law which become relevant in particular for small values of @xmath29 where the magnetic field gets strong can also be dealt with .\nan improved approximation is provided by the langevin relation @xcite , @xmath69 with the saturation magnetization of the fluid @xmath70 , the magnetic moment @xmath71 of a single ferromagnetic particle , the boltzmann - constant @xmath72 and the temperature @xmath73 .\nthe zero - field susceptibility is then given by @xmath74 .\nthe density of the magnetic energy can again be determined analytically @xmath75 this expression gives rise to a somewhat more complicated equation for @xmath0 , however , the overall procedure of section iii remains valid .\nas shown in fig .\n[ figcorrections](a ) the modification of the result for linear magnetization law is usually small in accordance with the fact that the fraction of the ferrofluid volume for which the field is large is rather small . finally , to elucidate the influence of a non - zero radius of the wire we consider the problem for @xmath76 but with @xmath33 and a linear magnetization law .\nthe main qualitative difference is that instead of ( [ bc3 ] ) we have to use ( [ boundaryr ] ) as boundary condition for small @xmath29 .\nthis implies that @xmath0 is not singular at the lower boundary .\nhence already the simple transformation @xmath77 is sufficient to get a numerically tractable boundary value problem for the function @xmath78 . as initial\nguess a linear dependence @xmath79 may be used .\nnote that @xmath80 fixes the value of @xmath0 at @xmath81 whereas the boundary condition ( [ boundaryr ] ) involves the derivative @xmath82 at @xmath81 .\ntherefore @xmath80 or equivalently @xmath83 has to be modified until the required value for @xmath84 is obtained .\nthis procedure leads to a monotonic relation between the prescribed contact angle @xmath31 and @xmath83 , cf .\n[ figcorrections](c ) . with the help this value for @xmath83 the complete surface profile @xmath0\ncan then be determined .\n[ figcorrections](b ) shows a collection of surface profiles with different @xmath83 and corresoponding contact angles @xmath31 . in the limiting case @xmath85 ,\nthe surface profile is independent of the contact angle @xmath31 as demonstrated in fig .\n[ figcorrections](d ) for a sequence of profiles with different values of @xmath1 and a fixed contact angle @xmath86 .\nin the present investigation we have determined the free surface profile of a magnetic fluid surrounding a vertical current carrying wire with special emphasis on the effects of interface and surface tension respectively .\nwe have found that for experimentally relevant parameter values there is a strong influence of the surface tension giving rise to a more slender profile as compared to the well - studied case without surface tension @xcite .\na more general magnetization law including saturation as well as the prescription of the contact angle at the wire changes the profile only in the vicinity of the wire .\na superimposed non - magnetic liquid changes the overall scale of the profile due to the reduction of the gravitational energy .",
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{
"content": "we study the influence of surface tension on the shape of the conical miniscus built up by a magnetic fluid surrounding a current - carrying wire . \n minimization of the total energy of the system leads to a singular second order boundary value problem for the function @xmath0 describing the axially symmetric shape of the free surface . \n an appropriate transformation regularizes the problem and allows a straightforward numerical solution . \n we also study the effects a superimposed second liquid , a nonlinear magnetization law of the magnetic fluid , and the influence of the diameter of the wire on the free surface profile .",
"role": "assistant"
}
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science.craftchem_ner | science.craftchem_ner.2839 | [
{
"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:\nBrainandcelllineRT-PCRreactionproductshadidenticalbandpatternsonethidium-bromidestainedagarosegels.",
"role": "user"
},
{
"content": "[\"ethidium - bromide\", \"agarose\"]",
"role": "assistant"
}
]
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science.bioasq_general_qa | science.bioasq_general_qa.465 | [
{
"content": "Review the provided biomedical excerpts and respond to the question concisely. Ensure your answer is derived solely from the given context and avoid adding any extraneous information.\n\nQuestion: What is known about saponins in crops and human consumption?\n\nExcerpts: Saponins are readily soluble in water and are approved by the US FDA for inclusion in beverages intended for human consumption. The addition of saponins to existing water supplies offers a new form of intervention into the cycle of rotavirus infection. We believe that saponins will 'coat' the epithelium of the host's small intestine and prevent attachment of rotavirus.\nThe levels of antinutrients in meal from the raw seeds were: trypsin inhibitor activity (14.6-28.7 mg trypsin inhibited/g), lectin (25.6-52.2 unit; one unit is the reverse of minimum amount of mg meal/ml assay which produced haemagglutination), saponins (1.9-2.3% as diosgenin equivalent) and phytate (8.4-10%).\nQuinoa cultivars currently grown in North America and Europe require removal of bitter-tasting saponins from the grain prior to human consumption.\nAntinutrients, including phytate, glycoside, saponin and tannin, were screened and quantified. Phytate (112.82 ± 0.1 mg/100 g), glycoside (2.33 ± 0.00 mg/100 g), saponin (1.31 ± 0.00 mg/100g) and tannin (0.21 ± 0.00 mg/100 g) were present in the fruit but phlobatanin and glycosides with steroidal rings were not found.\nantinutritional factors (phytic acid, trypsin inhibitor activity (TIA) and saponins)",
"role": "user"
},
{
"content": "Saponins are considered antinutrients for humans and have a bitter taste. They should be removed from the crops before consumption.",
"role": "assistant"
}
]
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science.chemdner_ner | science.chemdner_ner.3475 | [
{
"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\nSustained resistance to acute MPTP toxicity by hypothalamic dopamine neurons following chronic neurotoxicant exposure is associated with sustained up-regulation of parkin protein. Hypothalamic tuberoinfundibular dopamine (TIDA) neurons remain unaffected in Parkinson disease (PD) while there is significant degeneration of midbrain nigrostriatal dopamine (NSDA) neurons. A similar pattern of susceptibility is observed following acute exposure to the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and the resistance of TIDA neurons to MPTP is associated with increased expression of parkin and ubiquitin carboxy-terminal hydrolase L-1 (UCHL- 1). In the present study, the response of TIDA and NSDA neurons to acute MPTP administration following chronic MPTP exposure was examined. Mice were treated with ten injections of either MPTP (20 mg/kg; s.c.; every 3.5 days) or saline vehicle (10 ml/kg; s.c.; every 3.5 days). Following a 21 day recovery period, chronic saline- and MPTP-treated mice received an additional injection of either saline (10 ml/kg; s.c.) or MPTP (20 mg/kg; s.c.) and were sacrificed 24 h later. NSDA neurons displayed significant axon terminal degeneration (as indexed by decreases in DA, tyrosine hydroxylase (TH) and DA transporter concentrations in the striatum) as well as loss of TH-immunoreactive (IR) neurons in the substantia nigra (SN) following MPTP, whereas TIDA neurons revealed no overt axon terminal pathology or loss of TH-IR cell bodies. NSDA neuronal pathology was associated with transient decreases in concentrations of parkin and UCHL-1 protein in the SN, which returned to normal levels by 21 days following cessation of chronic neurotoxicant exposure. Resistance of TIDA neurons to MPTP toxicity was correlated with a transient increase in UCHL-1 and a sustained elevation in parkin in the arcuate nucleus. TIDA neurons represent a DA neuron population with a unique and inherent ability to adapt to acute and chronic toxicant administration with a sustained elevation of the neuroprotective protein parkin. The correlation between the ability to increase parkin and UCHL-1 expression and the resistance of DA neurons to neurotoxicant exposure is consistent with a functional link between these features and an underlying differential susceptibility to toxicant-associated neurodegeneration.",
"role": "user"
},
{
"content": "{\"Chemical\": [\"1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine\", \"carboxy\", \"tyrosine\", \"MPTP\", \"dopamine\"]}",
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}
]
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science.ncbi_ner | science.ncbi_ner.392 | [
{
"content": "Examine the text below and extract disease-related entities. Present your findings in a structured JSON format.\n\nYour response should be a JSON object with keys as entity types and values as lists of entities. If no entities are found, return an empty list for that type.\n\nContent:\n\nDetermination of the mutations responsible for the Lesch-Nyhan syndrome in 17 subjects. Hypoxanthine--guanine phosphoribosyltransferase (HPRT) is a purine salvage enzyme that catalyzes the conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate. Previous studies of mutant HPRT proteins analyzed at the molecular level have shown a significant heterogeneity. This investigation further verifies this heterogeneity and identifies insertions, deletions, and point mutations. The direct sequencing of the polymerase chain reaction-amplified product of reverse-transcribed HPRT mRNA enabled the rapid identification of the mutations found in 17 previously uncharacterized cell lines derived from patients with the Lesch-Nyhan syndrome..",
"role": "user"
},
{
"content": "{\"Disease\": [\"Lesch-Nyhan syndrome\"]}",
"role": "assistant"
}
]
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.5092 | [
{
"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: Software Updating in Wireless Sensor Networks: A Survey and Lacunae \nChapter Title: Lacunae \n1. Abstract of Cited Paper (BIB001): Trigger signals both at horizontal and vertical line frequency required for an oscilloscope are derived from the horizontal synchronization output stage of a television receiver without any direct electrical connection to the receiver. A pick-up coil or tuned pick-up circuit is positioned in the vicinity of the receiver. The signals induced in the coil or circuit are applied to a comparator. The output of the comparator is at the required TTL level to provide the horizontal trigger to the oscilloscope. If a vertical trigger is also required, the comparator output is applied to a frequency doubler circuit. The output of the frequency doubler circuit is divided by 525, the so-divided output constituting vertical trigger circuits for the oscilloscope. A monitoring circuit for horizontal sync signals is connected to the comparator output and indicates the presence of horizontal sync signals by activation of a light emitting diode.\n\nReview Chapter:",
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{
"content": "Autonomic behavior has been identified as a valuable, if not essential, feature for Wireless Sensor Networks in general BIB001 . In BIB002 , the conclusion is that autonomous behavior is required for over-the-air updates in a Wireless Sensor Network. Reviewing a large number of research results, with regard to this requirement, identifies the following lacunae:",
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]
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science.mslr2022_cochrane_multidoc_summarization | science.mslr2022_cochrane_multidoc_summarization.3184 | [
{
"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:\nInduction of pre-ovulatory gonadotrophin surge with gonadotrophin-releasing hormone agonist compared to pre-ovulatory injection of human chorionic gonadotrophins for ovulation induction in intrauterine insemination treatment cycles.\nReport Abstract 1:\nThe clinical outcome of intrauterine insemination (IUI) treatment cycles employing a gonadotrophin-releasing hormone agonist [GnRHa, triptorelin (Decapeptyl)] or human chorionic gonadotrophin (HCG) for ovulation induction was compared. A group of 48 patients presenting with amenorrhoea, oligomenorrhoea or unexplained infertility were all treated with human menopausal gonadotrophins (HMG) from day 5 of the cycle, on an individualized schedule. They were then randomly divided into two groups to receive either a single s.c. injection of 0.1 mg triptorelin or a single i.m. injection of 10,000 IU HCG after follicular maturation. IUI was performed approximately 24 and 48 h following the injection. A transitory increase in serum luteinizing hormone and follicle stimulating hormone concentrations was achieved following injection of GnRHa. A total of 24 patients received 72 treatment cycles with GnRHa, producing 11 conceptions (15.3%) and two abortions (18.2%), resulting in a term pregnancy rate of 13.6%. There were four cases of grade 3-4 ovarian hyperstimulation syndrome (OHSS), two of which were conception cycles. In all, 24 patients underwent 68 cycles treated with HCG, producing 18 conceptions (26.5%) and six abortions (33.3%), resulting in a term pregnancy rate of 19.0%. There were eight cycles of grade 3-4 OHSS, two of which were conception cycles. These results show that an s.c. injection of a relatively low dose of GnRHa can be as effective as HCG in producing pregnancy in IUI treatment cycles.\n\n\nReport Title 2:\nTiming intrauterine insemination either 33 or 39 hours after administration of human chorionic gonadotropin yields the same pregnancy rates as after superovulation therapy.\nReport Abstract 2:\nTo compare a short and long interval between hCG administration and IUI after superovulation for the treatment of infertility.\n Prospective, randomized clinical trial.\n University hospital-based fertility clinic.\n Patients planning superovulation and IUI for the treatment of infertility.\n Patients with >or=2 years of infertility enrolled for superovulation and IUI treatment were randomized to IUI after a short (32-34-hour) or long (38-40-hour) interval after hCG injection. Superovulation was accomplished with hMG or recombinant FSH, with dose adjustment until the maturation of two to five follicles, at which time hCG was given. Sperm was prepared with a gradient centrifugation technique, with IUI performed high up in the uterine fundus.\n Pregnancy rates.\n Of the 348 patient cycles randomized, 270 treatment cycles were initiated. Eighty-one initiated cycles were canceled, leaving 189 completed randomized cycles from 75 patients for analysis. Pregnancy rates were not significantly different between groups. There were pregnancies in 20 of the 96 short hCG-IUI interval cycles (21%) and in 14 of the 93 long hCG-IUI interval cycles (15%) (odds ratio = 0.673, 95% confidence interval 0.297-1.518).\n Pregnancy rates are the same after superovulation therapy whether IUI is done after a short or a long interval after hCG injection.\n\n\nReport Title 3:\nIntrauterine insemination with recombinant or urinary human chorionic gonadotropin: A prospective randomized trial.\nReport Abstract 3:\nOur aim was to compare the efficacy and safety of recombinant and urinary human chorionic gonadotropin (rhCG and uhCG, respectively) for the induction of follicle maturation in women undergoing intrauterine insemination (IUI).\n Patients were randomized to receive rhCG or uhCG. IUI was carried out 24 h (day 1) and 48 h (day 2) after hCG administration, except for all cases in which ovulation occurred after 24 h.\n The two treatments were comparable in terms of progesterone levels on day 7 and day 12. Pregnancy rates were comparable between the treatment groups. Of the 64 women who received rhCG, 29.7% became pregnant; there were 16.7% clinical pregnancies and 3.1% biochemical pregnancies per started cycle, and an ongoing pregnancy rate of 93.7% was reported. Of the 61 patients who received uhCG, 24.6% became pregnant; there were 15.9% clinical pregnancies and 1.1% biochemical pregnancies per started cycle, and ongoing pregnancy rate was 92.9%. No adverse effects were noted in either group.\n The recombinant products can be effectively used instead of urinary products; moreover, apart from the equivalent efficacy in ovulation induction and safety described in this study, it is necessary to consider the advantages provided by the recombinant form.\n\n\nReport Title 4:\nPregnancy rates after timed intercourse or intrauterine insemination after human menopausal gonadotropin stimulation of normal ovulatory cycles: a controlled study.\nReport Abstract 4:\nForty-eight patients with male (n = 16) or idiopathic (n = 32) infertility were stimulated with human menopausal gonadotropin. Intrauterine insemination (IUI) or natural intercourse were performed after either human chorionic gonadotropin (hCG)-induced or spontaneous, urinary luteinizing hormone (LH) surge-monitored ovulation. A total of 148 cycles were analyzed. In 40 cycles treated with hCG-induced ovulation and IUI, 3 (7.5%) patients conceived, whereas 37 women accomplished natural intercourse after hCG-induced ovulation and 2 (5.5%) became pregnant. When inseminated after a spontaneous LH surge, 3 (8.8%) of 34 patients achieved a pregnancy; no conception occurred in 37 spontaneously ovulatory cycles combined with timed intercourse. Pregnancy rates did not substantially differ between the treatment modalities or between mono-ovulatory and polyovulatory cycles. The cycle characteristics between spontaneous ovulatory and hCG-induced cycles significantly did differ.\n\n\nReport Title 5:\nComparison of leuprolide acetate and human chorionic gonadotropin for the induction of ovulation in clomiphene citrate-stimulated cycles.\nReport Abstract 5:\nTo examine the relative efficacies of leuprolide acetate (LA) and hCG in inducing ovulation and a normal luteal phase during clomiphene citrate (CC)-stimulated superovulation cycles.\n Prospective, randomized, blinded, and cross-controlled in consecutive cycles.\n Large military tertiary care center.\n Twenty-one ovulatory patients undergoing superovulation with CC and IUIs for the treatment of unexplained or male factor infertility.\n Clomiphene citrate (100 mg/d) on cycle days 5 through 9 in both of the study cycles. Administration of 2 mg SC LA in one cycle and 10,000 IU IM hCG in another cycle for induction of the midcycle surge.\n Serum LH, FSH, E2, and P levels every 12 hours for 36 hours after administration of either LA or hCG to characterize the midcycle hormonal dynamics. Luteal phase duration and serum P levels during the midluteal phase were used to estimate the adequacy of the luteal phase. Serial ultrasounds also were done to determine the incidence of luteinized unruptured follicle syndrome.\n Serum FSH levels in the periovulatory interval were significantly higher after the administration of LA. There were no differences in the periovulatory E2 or P levels or the incidence of sonographic evidence of ovulation after administration of either LA or hCG. Although midluteal serum P levels were higher in the cycles in which hCG was administered, all 42 treatment cycles had adequate luteal phases as assessed by luteal phase duration and three midluteal P levels. Ongoing pregnancies occurred after both LA- and hCG-stimulated cycles.\n Leuprolide acetate and hCG were equivalent in their abilities to induce ovulation. Further evaluation of the adequacy of the luteal phase and the ensuing pregnancy rates after LA induction of an endogenous gonadotropin surge are indicated.\n\n\nReport Title 6:\nA controlled study of human chorionic gonadotrophin induced ovulation versus urinary luteinizing hormone surge for timing of intrauterine insemination.\nReport Abstract 6:\nForty-eight patients in a programme of intrauterine insemination (IUI) were randomized in a cross-over study. All were stimulated with clomiphene citrate (CC) and inseminated either after follicular rupture induced by human chorionic gonadotrophin (HCG) or after a spontaneous urinary luteinizing hormone (LH) surge. The HCG was administered when follicles of 18-22 mm in diameter were observed on ultrasound and IUI was performed 37-40 h thereafter. The monitoring of a urinary LH peak was carried out using a rapid urinary LH test. IUI took place approximately 22 h after detection of the LH surge. Overall, the pregnancy rates were 9.3% (4/43) after HCG induced ovulation and 20.5% (9/44) after spontaneous ovulation (P = 0.12). Analysis of mid-cycle events showed that following sonographic criteria, the HCG injection was performed significantly earlier in the cycle compared with the spontaneous LH surge. In addition, the mean diameter of the preovulatory follicles was significantly smaller and insemination was substantially earlier in the HCG induced cycles. These findings suggest that a beneficial effect arises from allowing the natural process of final follicular maturation to occur.\n\n\nReport Title 7:\nComparison of urinary and recombinant human chorionic gonadotropin during ovulation induction in intrauterine insemination cycles: a prospective randomized clinical trial.\nReport Abstract 7:\nTo compare the in vivo effectiveness of recombinant (r) hCG with urinary (u) hCG during controlled ovarian hyperstimulation and intrauterine insemination (COH-IUI) cycles.\n Prospective controlled clinical study.\n Private IVF center.\n Two hundred eighty-four subjects undergoing COH-IUI cycles.\n Women were randomized into receiving r-hCG or u-hCG for final maturation and induction of ovulation.\n Clinical pregnancy rate and outcome of pregnancy.\n Background characteristics were similar in the two groups studied except for a slight difference in the mean duration of infertility (3.0 vs. 2.3). There was no significant difference in the number of follicles > or =16 mm, mean peak E(2), or mean 1-week P levels between the two groups. The clinical pregnancy rate was 27.1% in the recombinant group compared with 28.5% in the urinary group. The outcome of pregnancy was similar in both groups.\n Recombinant hCG was found to be as effective as u-hCG in achieving pregnancy during COH-IUI cycles. This is in agreement with earlier studies on the effectiveness of r-hCG in IVF cycles.\n\n\nReport Title 8:\nProspective, randomized, crossover study to evaluate the benefit of human chorionic gonadotropin-timed versus urinary luteinizing hormone-timed intrauterine inseminations in clomiphene citrate-stimulated treatment cycles.\nReport Abstract 8:\nTo compare two methods of timing IUI, urinary LH monitoring and transvaginal ultrasonography/ hCG timing of ovulation, in patients receiving clomiphene citrate.\n Prospective, randomized, crossover study.\n Yale University Reproductive Medicine Center.\n Infertile couples undergoing IUI because of unexplained infertility, anovulation, or male factor infertility.\n Patients received clomiphene citrate on days 3-7 of the menstrual cycle and were randomized initially to one of two monitoring protocols. In protocol A, urinary LH monitoring was used to time IUI. Urinary LH levels were determined daily with the use of commercial kits, starting on day 10 of the cycle. When urinary LH was detected, IUIs were performed daily for the next 2 days. In protocol B, ultrasound monitoring of folliculogenesis was performed until a leading follicle of > or = 18 mm was noted, at which time hCG (10,000 IU) was given intramuscularly and IUIs were performed daily for the next 2 days. If no pregnancy occurred, the couple crossed over to the alternate protocol for the next cycle and continued this alternating therapy for a total of four cycles.\n Pregnancy rate per cycle.\n One hundred forty-one cycles were completed. In these cycles, six pregnancies occurred, for an overall pregnancy rate of 4.26% per cycle. The pregnancy rate with LH-timed IUI was 4.29% (3/70) and that with hCG-induced ovulation was 4.23% (3/71); the difference was not statistically significant.\n Timing IUI with the use of a relatively expensive and time-consuming method such as ultrasound monitoring of folliculogenesis and hCG induction of ovulation does not appear to produce an increased pregnancy rate over urinary LH monitoring of ovulation.\n\n\nReport Title 9:\nClomiphene citrate monitoring for intrauterine insemination timing: a randomized trial.\nReport Abstract 9:\nTo compare pregnancy rates with two different methods of intrauterine insemination (IUI) timing in patients treated with clomiphene citrate (CC).\n Prospective, randomized trial.\n Academic medical center.\n One hundred fifty ovulatory, infertile women.\n Patients were randomized into a luteinizing hormone (LH) surge group or a follicle monitoring/human chorionic gonadotropin (hCG) group. All patients underwent baseline ultrasound, and took clomiphene citrate, during days 5-9. Patients in the LH surge group underwent IUI on the day after a home test for the LH surge was positive, whereas those in the hCG group received hCG according to ultrasound parameters and underwent insemination 33-40 hours later. Patients remained in the same study group for up to three cycles.\n Pregnancy rates per cycle and per patient.\n No significant differences were found between groups in pregnancy rates per patient or per cycle. The LH surge group underwent IUI significantly later than the hCG group. Cancellation rates were significantly higher for the LH surge group (31% vs. 11%) and attributable mainly to failure to detect an LH surge. The majority of pregnancies in both treatment groups occurred in the first cycle.\n The decision to use hCG for IUI timing should be influenced by factors other than pregnancy rates.",
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"content": "There is no evidence to advise one particular treatment option over another. The choice should be based on hospital facilities, convenience for the patient, medical staff, costs and drop-out levels. Since different time intervals between hCG and IUI did not result in different pregnancy rates, a more flexible approach might be allowed.",
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science.scientific_lay_summarisation_elife_single_doc_summ | science.scientific_lay_summarisation_elife_single_doc_summ.1459 | [
{
"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: Regenerating hair cells in vestibular sensory epithelia from humans\nContent Overview:\nAbstract:\nHuman vestibular sensory epithelia in explant culture were incubated in gentamicin to ablate hair cells. Subsequent transduction of supporting cells with ATOH1 using an Ad-2 viral vector resulted in generation of highly significant numbers of cells expressing the hair cell marker protein myosin VIIa. Cells expressing myosin VIIa were also generated after blocking the Notch signalling pathway with TAPI-1 but less efficiently. Transcriptomic analysis following ATOH1 transduction confirmed up-regulation of 335 putative hair cell marker genes, including several downstream targets of ATOH1. Morphological analysis revealed numerous cells bearing dense clusters of microvilli at the apical surfaces which showed some hair cell-like characteristics confirming a degree of conversion of supporting cells. However, no cells bore organised hair bundles and several expected hair cell markers genes were not expressed suggesting incomplete differentiation. Nevertheless, the results show a potential to induce conversion of supporting cells in the vestibular sensory tissues of humans.\nIntroduction:\nLoss of the sensory ‘hair’ cells from the cochlea, the mammalian hearing organ, as a consequence of exposure to ototoxic drugs, excessive noise or through ageing, results in permanent hearing loss. More than 40% of those aged over 50% and 70% of those over 70 have a clinically significant hearing loss( Action on Hearing Loss; www. actiononhearingloss. org. uk/your-hearing/about-deafness-and-hearing-loss/statistics. aspx). Hearing loss has also been reported as a risk factor for dementia( Livingston et al., 2017). Loss of hair cells from the vestibular epithelia of the inner ear, results in balance dysfunction causing dizziness and vertigo, significantly under-appreciated disabling conditions. As with hearing loss, the prevalence of vestibular dysfunction increases with age. Dizziness is the most common reason for visits to the GP in those over 75% and 80% of unexplained falls in the elderly are attributable to vestibular dysfunction( Agrawal et al., 2009; Baloh et al., 2001; Department of Health, 1999; Herdman et al., 2000; Pothula et al., 2004). Regeneration of hair cells could potentially offer a therapeutic approach to amelioriate these conditions. In the sensory epithelia of the inner ear in all vertebrates each hair cell is surrounded and separated from its neighbours by intervening supporting cells. Hair cells derive their name from the organised bundle of projections from the apical poles. They are mechanotransducers that convert motion into electrical signals. Supporting cells play a role in maintaining the physiological environment necessary for hair cell function and survival, and also repair the lesions in the epithelium when hair cells die. In non-mammalian vertebrates, hair cells lost from the auditory or vestibular sensory epithelia are replaced spontaneously by new ones( Collado et al., 2008; Rubel et al., 2013). These nascent hair cells are derived from supporting cells. Initially, new hair cells arise from direct, non-mitotic transdifferentiation( phenotypic conversion) of supporting cells into hair cells( Cafaro et al., 2007; Taylor and Forge, 2005). Other supporting cells re-enter the cell cycle, the daughter cells giving rise to hair and supporting cells( Burns and Stone, 2017; Cafaro et al., 2007; Collado et al., 2008; Rubel et al., 2013). There is no regeneration in the adult mammalian auditory system. However, there is a limited capacity to regenerate hair cells in vivo in the mammalian vestibular system( Forge et al., 1993; 1998; Lopez et al., 1997; Kawamoto et al., 2009). These hair cells arise by direct phenotypic conversion of supporting cells( Li and Forge, 1997; Lin et al., 2011). We recently reported the presence of cells bearing immature hair bundles in the vestibular system of elderly people( Taylor et al., 2015). This suggests that a capacity to regenerate hair cells may exist at a very low level throughout life in humans. During development, supporting cells and hair cells are derived from the same homogeneous population of precursor cells following a terminal mitotic event( Kelley, 2006). The mosaic patterning of hair and supporting cells develops by lateral inhibition mediated by the Notch signalling pathway( Kiernan, 2013). In cells differentiating as hair cells the basic helix-loop-helix transcription factor Atonal homolog 1( Atoh1) is transiently expressed and has been shown to be necessary for sensory precursors to differentiate into hair cells( Bermingham et al., 1999; Kelley, 2006; Woods et al., 2004). The nascent hair cells express the Notch ligand Delta1 on their surface which activates the Notch receptor, a transmembrane protein, in adjacent neighbouring cells. The inhibitory activity of Notch prevents the adjacent cell following the same fate, so this cell will not become a hair cell but instead will be a supporting cell. Ligand binding to the Notch receptor triggers the extracellular cleavage of Notch by tumour necrosis factor alpha converting enzyme( TACE)( Kopan and Ilagan, 2009) and intracellular cleavage by γ-secretase( Kiernan, 2013). This releases the Notch intracellular domain which enters the nucleus interacting with several transcription factors to suppress Atoh1 expression thereby inhibiting differentiation as a hair cell and promoting HES/HEY expression, propelling those cells to become supporting cells. Atoh1 is expressed during hair cell regeneration in chick and zebrafish and several studies have shown that ectopic overexpression of Atoh1 in the organ of Corti or vestibular sensory epithelia of mammals is sufficient to induce generation of cells that express hair cell marker proteins( Zheng and Gao, 2000). These arise by direct transdifferentiation without an intervening mitotic event. Overexpressing Atoh1 or using γ- secretase inhibitors, potentially offer means to induce supporting cells to become hair cells. Both these approaches have been applied to murine vestibular epithelia depleted of hair cells( Lin et al., 2011; Staecker et al., 2007). We have established a consortium of surgeons throughout the UK to harvest human vestibular epithelia from translabyrinthine operations for the removal of acoustic neuromas( vestibular schwannomas)( Taylor et al., 2015). Here we use the vestibular epithelium collected from such surgeries to examine the capacity of supporting cells to generate new hair cells in adult human inner ear tissue. We have used an adenoviral vector to deliver ATOH1( adV2- ATOH) to transduce cells in human sensory epithelia from which hair cells have been ablated with the ototoxic agent, gentamicin. We find that significant numbers of cells expressing hair cell markers can be generated. We have also exposed tissue to the γ- secretase inhibitor TAPI1( TNFα protease inhibitor 1), a TACE inhibitor. Cells expressing hair cell marker proteins are also generated but in fewer numbers that with ATOH1 transduction. However, neither protocol resulted in fully differentiated hair cells. Studies of gene expression following ATOH1 transduction by RNA sequencing confirmed that a significant cascade of downstream effectors is induced by this treatment. However, this induction falls short of complete hair cell conversion but highlights components that may be necessary in completing the conversion events.\nDiscussion:\nHere we demonstrate the plasticity of the human vestibular epithelia via manipulation of developmental pathways using a viral vector to transduce supporting cells. The capacity of this vector to incorporate ATOH1 into sufficient supporting cells and subsequently yield large numbers of myosin VIIa+ cells supports our contention that it is possible to regenerate damaged epithelium and offers a therapeutic intervention to balance disorders caused by hair cell loss.",
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"content": "The inner ear contains our balance system ( the vestibular system ) and our hearing organ ( the cochlea ) . Their sensing units , the hair cells , detect movement or sound waves . A loss of hair cells is a major cause of inner ear disorders , such as dizziness , imbalance and deafness . When hair cells die , supporting cells that surround them close the ‘wound’ to repair the tissue . In fish , amphibians , reptiles and birds , the supporting cells can replace lost hair cells , but in mammals – including humans – hair cells are unable to regenerate in the cochlea , so hearing loss is permanent . However , previous research has shown that in certain mammals , spontaneous replacement of lost hair cells in the vestibular system can occur , but not enough to lead to a full recovery . Scientists have been able to convert supporting cells in the vestibular system of mice into hair cells by using either certain chemicals , or by introducing a specific gene into the supporting cells . In the mouse embryo , this gene , called Atoh1 , switches on a signalling pathway in the inner ear , through which a non-specialised precursor cell becomes a hair cell . Inducing hair cell regeneration could be a therapy for inner ear disorders . Therefore , Taylor et al . wanted to find out if such procedures would work in inner ear tissue from humans . The researchers collected intact tissue samples from the vestibular system of patients who had undergone surgery to have a tumour removed , which would normally destroy the inner ear . All existing hair cells were removed so that mainly supporting cells remained . Then , the tissue was either treated with chemicals that increased the production of hair cells or received the gene ATOH1 . The results showed that the cells containing the gene were able to develop many features characteristic of hair cells . And a smaller number of hair cells treated with the chemicals also started to develop hair cell-like features . A gene analysis after the ATOH1 transfer revealed a number of active genes known to be markers of hair cells , but also several inactive ones . This suggests that additional factors are necessary for generating fully functional hair cells . Dizziness and balance disorders present a major health care burden , particularly in the elderly population . Yet , they are often disregarded and overlooked . This study suggests that hair cell regeneration could be a feasible therapy for some forms of balance disorders linked to loss of vestibular hair cells . More research is needed to identify the other factors at play to test if hair cell regeneration in the cochlea could be used to treat hearing impairment .",
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science.scicite_classification | science.scicite_classification.3868 | [
{
"content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\n…it should also be noted that coral mucus contains very high concentrations of organic and inorganic matter, leading to typically rare, r-selected (i.e. fast growing and nutrient sensitive) bacteria in seawater recruiting to the mucus matrix and increasing rapidly in abundance (Allers et al. 2008).",
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"content": "Background",
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science.medmentions_ner | science.medmentions_ner.2014 | [
{
"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\nCD169 is a marker for highly pathogenic phagocytes in multiple sclerosis Phagocytes, such as macrophages and microglia, are key effector cells in the pathophysiology of multiple sclerosis (MS). It is widely accepted that they instigate and promote neuroinflammatory and neurodegenerative events in MS. An increasing amount of studies indicate that Siglec-1, also known CD169, is a marker for activated phagocytes in inflammatory disorders. In this study, we set out to define how CD169(+) phagocytes contribute to neuroinflammation in MS. CD169 - diphtheria toxin receptor (DTR) mice, which express human DTR under control of the CD169 promoter, were used to define the impact of CD169(+) cells on neuroinflammation. Flow cytometry and immunohistochemistry were utilized to determine the expression and distribution of CD169. We show that CD169 is highly expressed by lesional and circulating phagocytes in MS and experimental autoimmune encephalomyelitis (EAE). Our data further indicate that CD169 represents a selective marker for early activated microglia in MS and EAE lesions. Depletion of CD169(+) cells markedly reduced neuroinflammation and ameliorated disease symptoms in EAE - affected mice. Our findings indicate that CD169(+) cells promote neuroinflammation. Furthermore, they suggest that CD169(+) phagocytes play a key role in the pathophysiology of MS. Hence, targeting CD169(+) phagocytes may hold therapeutic value for MS.",
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"content": "{\"AnatomicalStructure\": [\"activated microglia\", \"phagocytes\", \"microglia\", \"Phagocytes\", \"cells\", \"macrophages\", \"effector cells\", \"CD169\"], \"Bacterium\": [], \"BiologicFunction\": [\"neurodegenerative\", \"circulating\", \"experimental autoimmune encephalomyelitis\", \"MS\", \"inflammatory disorders\", \"EAE\", \"disease\", \"multiple sclerosis\", \"neuroinflammation\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"CD169(+)\", \"promoter\", \"DTR\", \"Siglec-1\", \"diphtheria toxin receptor\", \"CD169\"], \"ClinicalAttribute\": [\"marker\"], \"Eukaryote\": [\"mice\", \"human\"], \"Finding\": [\"findings\", \"lesional\", \"symptoms\", \"play\", \"lesions\"], \"Food\": [], \"HealthCareActivity\": [\"immunohistochemistry\", \"Flow cytometry\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"study\", \"studies\"], \"SpatialConcept\": [], \"Virus\": []}",
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science.healthver_entailment | science.healthver_entailment.1690 | [
{
"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: Hydroxychloroquine, on the other hand, completely lacks antiviral activity, thus providing no scientific basis for its further use in COVID-19 patients.\n\nResearch Abstract:\nSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative representative of a severe respiratory illness resulted in widespread human infections and deaths in nearly all of the countries since late 2019.\nThere is no therapeutic FDA-approved drug against SARS-CoV-2 infection, although a combination of anti-viral drugs is directly being practiced in some countries.\nA broad-spectrum of antiviral agents are being currently evaluated in clinical trials, and in this review, we specifically focus on the application of Remdesivir (RVD) as a potential anti-viral compound against Middle East respiratory syndrome (MERS) -CoV, SARS-CoV and SARS-CoV-2.\nFirst, we overview the general information about SARS-CoV-2, followed by application of RDV as a nucleotide analogue which can potentially inhibits RNA-dependent RNA polymerase of COVs.\nAfterwards, we discussed the kinetics of SARS- or MERS-CoV proliferation in animal models which is significantly different compared to that in humans.\nFinally, some ongoing challenges and future perspective on the application of RDV either alone or in combination with other anti-viral agents against CoVs infection were surveyed to determine the efficiency of RDV in preclinical trials.\nAs a result, this paper provides crucial evidence of the potency of RDV to prevent SARS-CoV-2 infections.\nCommunicated by Ramaswamy H. Sarma.",
"role": "user"
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{
"content": "{\"verdict\": \"NEI\", \"evidence\": []}",
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science.healthver_entailment | science.healthver_entailment.578 | [
{
"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: COVID-19 disease, caused by SARS-CoV-2, is known to have three phases of the disease, that of early infection, the lung phase, and the severe hyperinflammatory phase. However, SARS-CoV-2 is not only a lung-tropic virus but also infects the gut cells and vascular endothelium. \n\nResearch Abstract:\nThe outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has posed the world at a pandemic risk.\nCoronavirus-19 disease (COVID-19) is an infectious disease caused by SARS-CoV-2, which causes pneumonia, requires intensive care unit hospitalization in about 10% of cases and can lead to a fatal outcome.\nSeveral efforts are currently made to find a treatment for COVID-19 patients.\nSo far, several anti-viral and immunosuppressive or immunomodulating drugs have demonstrated some efficacy on COVID-19 both in vitro and in animal models as well as in cases series.\nIn COVID-19 patients a pro-inflammatory status with high levels of interleukin (IL)-1B, IL-1 receptor (R)A and tumor necrosis factor (TNF)-α has been demonstrated.\nMoreover, high levels of IL-6 and TNF-α have been observed in patients requiring intensive-care-unit hospitalization.\nThis provided rationale for the use of anti-rheumatic drugs as potential treatments for this severe viral infection.\nOther agents, such as hydroxychloroquine and chloroquine might have a direct anti-viral effect.\nThe anti-viral aspect of immunosuppressants towards a variety of viruses has been known since long time and it is herein discussed in the view of searching for a potential treatment for SARS-CoV-2 infection.",
"role": "user"
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{
"content": "{\"verdict\": \"NEI\", \"evidence\": []}",
"role": "assistant"
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science.healthver_entailment | science.healthver_entailment.4170 | [
{
"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: cold weather and snow prevent the coronavirus disease\n\nResearch Abstract:\nThe novel coronavirus, since its first outbreak in December, has, up till now, affected approximately 114,542 people across 115 countries.\nMany international agencies are devoting efforts to enhance the understanding of the evolving COVID-19 outbreak on an international level, its influences, and preparedness.\nAt present, COVID-19 appears to affect individuals through person-to-person means, like other commonly found cold or influenza viruses.\nIt is widely known and acknowledged that viruses causing influenza peak during cold temperatures and gradually subside in the warmer temperature, owing to their seasonality.\nThus, COVID-19, due to its regular flu-like symptoms, is also expected to show similar seasonality and subside as the global temperatures rise in the northern hemisphere with the onset of spring.\nDespite these speculations, however, the systematic analysis in the global perspective of the relation between COVID-19 spread and meteorological parameters is unavailable.\nHere, by analyzing the region- and city-specific affected global data and corresponding meteorological parameters, we show that there is an optimum range of temperature and UV index strongly affecting the spread and survival of the virus, whereas precipitation, relative humidity, cloud cover, etc. have no effect on the virus.\nUnavailability of pharmaceutical interventions would require greater preparedness and alert for the effective control of COVID-19.\nUnder these conditions, the information provided here could be very helpful for the global community struggling to fight this global crisis.\nIt is, however, important to note that the information presented here clearly lacks any physiological evidences, which may merit further investigation.\nThus, any attempt for management, implementation, and evaluation strategies responding to the crisis arising due to the COVID-19 outbreak must not consider the evaluation presented here as the foremost factor.",
"role": "user"
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"content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"Thus, COVID-19, due to its regular flu-like symptoms, is also expected to show similar seasonality and subside as the global temperatures rise in the northern hemisphere with the onset of spring.\"]}",
"role": "assistant"
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]
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science.data_reco_mcq_mc | science.data_reco_mcq_mc.2382 | [
{
"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: I'm trying to improve my trilinear interaction model in VQA.\n\nKey Terms: visual question answering images text\n\nDataset Summaries:\nTDIUC: Task Directed Image Understanding Challenge (TDIUC) dataset is a Visual Question Answering dataset which consists of 1.6M questions and 170K images sourced from MS COCO and the Visual Genome Dataset. The image-question pairs are split into 12 categories and 4 additional evaluation matrices which help evaluate models’ robustness against answer imbalance and its ability to answer questions that require higher reasoning capability.\nVisual7W: Visual7W is a large-scale visual question answering (QA) dataset, with object-level groundings and multimodal answers. Each question starts with one of the seven Ws, what, where, when, who, why, how and which.\nKnowIT VQA: KnowIT VQA is a video dataset with 24,282 human-generated question-answer pairs about The Big Bang Theory. The dataset combines visual, textual and temporal coherence reasoning together with knowledge-based questions, which need of the experience obtained from the viewing of the series to be answered.\nVizWiz: The VizWiz-VQA dataset originates from a natural visual question answering setting where blind people each took an image and recorded a spoken question about it, together with 10 crowdsourced answers per visual question. The proposed challenge addresses the following two tasks for this dataset: predict the answer to a visual question and (2) predict whether a visual question cannot be answered.\nVQA-CP: The VQA-CP dataset was constructed by reorganizing VQA v2 such that the correlation between the question type and correct answer differs in the training and test splits. For example, the most common answer to questions starting with What sport… is tennis in the training set, but skiing in the test set.\nVQA-HAT: VQA-HAT (Human ATtention) is a dataset to evaluate the informative regions of an image depending on the question being asked about it. The dataset consists of human visual attention maps over the images in the original VQA dataset.\nVQA-E: VQA-E is a dataset for Visual Question Answering with Explanation, where the models are required to generate and explanation with the predicted answer. The VQA-E dataset is automatically derived from the VQA v2 dataset by synthesizing a textual explanation for each image-question-answer triple.\n\nDataset Options: A: TDIUC B: Visual7W C: KnowIT VQA D: VizWiz E: VQA-CP F: VQA-HAT G: VQA-E",
"role": "user"
},
{
"content": "[\"TDIUC\", \"Visual7W\"]",
"role": "assistant"
}
]
|
science.ncbi_ner | science.ncbi_ner.538 | [
{
"content": "Examine the text below and extract disease-related entities. Present your findings in a structured JSON format.\n\nYour response should be a JSON object with keys as entity types and values as lists of entities. If no entities are found, return an empty list for that type.\n\nContent:\n\nDeficiency of the fifth component of complement in human subjects. Clinical, genetic and immunologic studies in a large kindred. The discovery of a large kindred with a heritable deficiency of the fifth component of complement (C5) has permitted the accumulation of new clinical, genetic and immunologic data concerning the role of C5 in human subjects. The proband, who has had nine episodes of disseminated gonococcal infection, has a hemolytic C5 level of approximately 0. 5 per cent of normal. No C5 protein was detectable, but low levels of functional C5 activity could be found using a sensitive bactericidal assay. The probands twin as well as another sister also had extremely low levels of hemolytic C5 (approximately 0. 5 per cent normal), but both these subjects have been healthy. Hemolytic complement and bacteriolytic activity could be restored by the addition of purified C5. No chemotactic activity for polymorphonuclear leukocytes could be generated in the C5-deficient serums upon activation of either the classic or alternative pathways, again demonstrating the importance of C5 in human subjects for the production of chemotactic factors. The chemotactic responsiveness of the patients polymorphonuclear leukocytes and monocytes to preformed chemotactic factors was not depressed. Twenty-two of 32 other family members from three generations had depressed whole hemolytic complement levels. In 19 of 30 family members, levels of hemolytic C5 ranged from 13 to 64 per cent of normal. No linkage for C5 deficiency and the A or B loci of the major histocompatibility complex could be found. These data suggest an autosomal codominant mode of inheritance of C5 deficiency. Deficiency of C5 is compatible with good health, but it can be associated with repeated disseminated gonococcal infection",
"role": "user"
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{
"content": "{\"Disease\": [\"deficiency of the fifth component of complement\", \"C5 deficiency\", \"Deficiency of the fifth component of complement\", \"gonococcal infection\", \"C5-deficient\", \"Deficiency of C5\"]}",
"role": "assistant"
}
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science.healthver_entailment | science.healthver_entailment.2548 | [
{
"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: SARS-CoV-2's rapid spread is likely due to the movements of people with no or very mild symptoms - namely, those who are unaware that they even have the virus. That is why social distancing is such an important containment measure, they explain.\n\nResearch Abstract:\nSocial distancing measures, with varying degrees of restriction, have been imposed around the world in order to stem the spread of COVID-19.\nIn this work we analyze the effect of current social distancing measures in the United States.\nWe quantify the reduction in doubling rate, by state, that is associated with social distancing.\nWe find that social distancing is associated with a statistically-significant reduction in the doubling rate for all but three states.\nAt the same time, we do not find significant evidence that social distancing has resulted in a reduction in the number of daily confirmed cases.\nInstead, social distancing has merely stabilized the spread of the disease.\nWe provide an illustration of our findings for each state, including point estimates of the effective reproduction number, R, both with and without social distancing.\nWe also discuss the policy implications of our findings.",
"role": "user"
},
{
"content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"We find that social distancing is associated with a statistically-significant reduction in the doubling rate for all but three states.\"]}",
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}
]
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science.scitldr_aic | science.scitldr_aic.1334 | [
{
"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\nWe propose a framework for extreme learned image compression based on Generative Adversarial Networks (GANs), obtaining visually pleasing images at significantly lower bitrates than previous methods.\nThis is made possible through our GAN formulation of learned compression combined with a generator/decoder which operates on the full-resolution image and is trained in combination with a multi-scale discriminator.\nAdditionally, if a semantic label map of the original image is available, our method can fully synthesize unimportant regions in the decoded image such as streets and trees from the label map, therefore only requiring the storage of the preserved region and the semantic label map.\nA user study confirms that for low bitrates, our approach is preferred to state-of-the-art methods, even when they use more than double the bits.\nImage compression systems based on deep neural networks (DNNs), or deep compression systems for short, have become an active area of research recently.\nThese systems (e.g. BID6 BID33 ) are often competitive with modern engineered codecs such as WebP (WebP), JPEG2000 BID37 ) and even BPG (Bellard) (the state-of-the-art engineered codec).\nBesides achieving competitive compression rates on natural images, they can be easily adapted to specific target domains such as stereo or medical images, and promise efficient processing and indexing directly from compressed representations BID41 .\nHowever, deep compression systems are typically optimized for traditional distortion metrics such as peak signal-to-noise ratio (PSNR) or multi-scale structural similarity (MS-SSIM) BID44 .\nFor very low bitrates (below 0.1 bits per pixel (bpp)), where preserving the full image content becomes impossible, these distortion metrics lose significance as they favor pixel-wise preservation of local (high-entropy) structure over preserving texture and global structure.\nTo further advance deep image compression it is therefore of great importance to develop new training objectives beyond PSNR and MS-SSIM.\nA promising candidate towards this goal are adversarial losses BID13 which were shown recently to capture global semantic information and local texture, yielding powerful generators that produce visually appealing high-resolution images from semantic label maps BID43 .In\nthis paper, we propose and study a generative adversarial network (GAN)-based framework for extreme image compression, targeting bitrates below 0.1 bpp. We\nrely on a principled GAN formulation for deep image compression that allows for different degrees of content generation. In\ncontrast to prior works on deep image compression which applied adversarial losses to image patches for artifact suppression BID33 BID12 , generation of texture details BID25 , or representation learning for thumbnail images BID35 , our generator/decoder operates on the full-resolution image and is trained with a multi-scale discriminator BID43 .We\nconsider two modes of operation (corresponding to unconditional and conditional GANs BID13 BID31 ), namely• generative compression (GC), preserving the overall image content while generating structure of different scales such as leaves of trees or windows in the facade of buildings, and • selective generative compression (SC), completely generating parts of the image from a semantic label map while preserving user-defined regions with a high degree of detail.We emphasize that GC does not require semantic label maps (neither for training, nor for deployment). A\ntypical use case for GC are bandwidth constrained scenarios, where one wants to preserve the full image as well as possible, while falling back to synthesized content instead of blocky/blurry blobs for regions for which not sufficient bits are available to store the original pixels. SC\ncould be applied in a video call scenario where one wants to fully preserve people in the video stream, but a visually pleasing synthesized background serves the purpose as well as the true background.In the GC operation mode the image is transformed into a bitstream and encoded using arithmetic coding. SC\nrequires a semantic/instance label map of the original image which can be obtained using off-the-shelf semantic/instance segmentation networks, e.g., PSPNet and Mask R-CNN BID18 , and which is stored as a vector graphic. This\namounts to a small, image dimension-independent overhead in terms of coding cost. On the\nother hand, the size of the compressed image is reduced proportionally to the area which is generated from the semantic label map, typically leading to a significant overall reduction in storage cost.For GC, a comprehensive user study shows that our compression system yields visually considerably more appealing results than BPG (Bellard) (the current state-of-the-art engineered compression algorithm) and the recently proposed autoencoder-based deep compression (AEDC) system . In particular\n, our GC models trained for compression of general natural images are preferred to BPG when BPG uses up to 95% and 124% more bits than those produced by our models on the Kodak (Kodak) and RAISE1K BID11 data set, respectively. When constraining\nthe target domain to the street scene images of the Cityscapes data set BID9 , the reconstructions of our GC models are preferred to BPG even when the latter uses up to 181% more bits. To the best of our\nknowledge, these are the first results showing that a deep compression method outperforms BPG on the Kodak data set in a user study-and by large margins. In the SC operation\nmode, our system seamlessly combines preserved image content with synthesized content, even for regions that cross multiple object boundaries, while faithfully preserving the image semantics. By partially generating\nimage content we achieve bitrate reductions of over 50% without notably degrading image quality.\nThe GC models produce images with much finer detail than BPG, which suffers from smoothed patches and blocking artifacts.\nIn particular, the GC models convincingly reconstruct texture in natural objects such as trees, water, and sky, and is most challenged with scenes involving humans.\nAEDC and the MSE baseline both produce blurry images.We see that the gains of our models are maximal at extreme bitrates, with BPG needing 95-181% more bits for the C = 2, 4 models on the three datasets.\nFor C = 8 gains are smaller but still very large (BPG needing 21-49% more bits).\nThis is expected, since as the bitrate increases the classical compression measures (PSNR/MS-SSIM) become more meaningful-and our system does not employ the full complexity of current state-of-the-art systems, as discussed next.State-of-the-art on Kodak: We give an overview of relevant recent learned compression methods and their differences to our GC method and BPG in Table 1 in the Appendix.\nBID33 also used GANs (albeit a different formulation) and were state-of-the-art in MS-SSIM in 2017, while the concurrent work of is the current state-of-the-art in image compression in terms of classical metrics (PSNR and MS-SSIM) when measured on the Kodak dataset (Kodak).\nNotably, all methods except ours (BPG, Rippel et al., and Minnen et al.) employ adaptive arithmetic coding using context models for improved compression performance.\nSuch models could also be implemented for our system, and have led to additional savings of 10% in .\nSince Rippel et al. and Minnen et al. have only released a selection of their decoded images (for 3 and 4, respectively, out of the 24 Kodak images), and at significantly higher bitrates, a comparison with a user study is not meaningful.\nInstead, we try to qualitatively put our results into context with theirs.In Figs. 12-14 in the Appendix, we compare qualitatively to BID33 .\nWe can observe that even though BID33 use 29-179% more bits, our models produce images of comparable or better quality.\nIn FIG1 , we show a qualitative comparison of our results to the images provided by the concurrent work of , as well as to BPG (Bellard) on those images.\nFirst, we see that BPG is still visually competitive with the current state-of-the-art, which is consistent with moderate 8.41% bitrate savings being reported by in terms of PSNR.\nSecond, even though we use much fewer bits compared to the example images available from , for some of them (Figs. 15 and 16) our method can still produce images of comparable visual quality.Given the dramatic bitrate savings we achieve according to the user study (BPG needing 21-181% more bits), and the competitiveness of BPG to the most recent state-of-the-art , we conclude that our proposed system presents a significant step forward for visually pleasing compression at extreme bitrates.Sampling the compressed representations: In FIG1 we explore the representation learned by our GC models (with C = 4), by sampling the (discrete) latent space ofŵ.\nWhen we sample uniformly, and decode with our GC model into images, we obtain a \"soup of image patches\" which reflects the domain the models were trained on (e.g. street sign and building patches on Cityscapes).\nNote that we should not expect these outputs to look like normal images, since nothing forces the encoder outputŵ to be uniformly distributed over the discrete latent space.However, given the low dimensionality ofŵ (32 × 64 × 4 for 512 × 1024px Cityscape images), it would be interesting to try to learn the true distribution.\nTo this end, we perform a simple experiment and train an improved Wasserstein GAN (WGAN-GP) BID14 onŵ extracted from Cityscapes, using default parameters and a ResNet architecture.\n4 By feeding our GC model with samples from the WGAN-GP generator, we easily obtain a powerful generative model, which generates sharp 1024 × 512px images from scratch.\nWe think this could be a promising direction for building high-resolution generative models.\nIn FIG5 in the Appendix, we show more samples, and samples obtained by feeding the MSE baseline with uniform and learned code samples.\nThe latter yields noisier \"patch soups\" and much blurrier image samples than our GC network.\nFigure 6 : Mean IoU as a function of bpp on the Cityscapes validation set for our GC and SC networks, and for the MSE baseline.\nWe show both SC modes: RI (inst.), RB (box).\nD + annotates models where instance semantic label maps are fed to the discriminator (only during training); EDG + indicates that semantic label maps are used both for training and deployment.\nThe pix2pixHD baseline BID43 was trained from scratch for 50 epochs, using the same downsampled 1024 × 512px training images as for our method.\nThe heatmaps in the lower left corners show the synthesized parts in gray.\nWe show the bpp of each image as well as the relative savings due to the selective generation.In FIG2 we present example Cityscapes validation images produced by the SC network trained in the RI mode with C = 8, where different semantic classes are preserved.\nMore visual results for the SC networks trained on Cityscapes can be found in Appendix F.7, including results obtained for the RB operation mode and by using semantic label maps estimated from the input image via PSPNet .Discussion\n: The quantitative evaluation of the semantic preservation capacity (Fig. 6 ) reveals that the SC networks preserve the semantics somewhat better than pix2pixHD, indicating that the SC networks faithfully generate texture from the label maps and plausibly combine generated with preserved image content. The mIoU\nof BPG, AEDC, and the MSE baseline is considerably lower than that obtained by our SC and GC models, which can arguably be attributed to blurring and blocking artifacts. However,\nit is not surprising as these baseline methods do not use label maps during training and prediction.In the SC operation mode, our networks manage to seamlessly merge preserved and generated image content both when preserving object instances and boxes crossing object boundaries (see Appendix F.7). Further,\nour networks lead to reductions in bpp of 50% and more compared to the same networks without synthesis, while leaving the visual quality essentially unimpaired, when objects with repetitive structure are synthesized (such as trees, streets, and sky). In some\ncases, the visual quality is even better than that of BPG at the same bitrate. The visual\nquality of more complex synthesized objects (e.g. buildings, people) is worse. However, this\nis a limitation of current GAN technology rather than our approach. As the visual\nquality of GANs improves further, SC networks will as well. Notably, the\nSC networks can generate entire images from the semantic label map only.Finally, the semantic label map, which requires 0.036 bpp on average for the downscaled 1024 × 512px Cityscapes images, represents a relatively large overhead compared to the storage cost of the preserved image parts. This cost vanishes\nas the image size increases, since the semantic mask can be stored as an image dimension-independent vector graphic.\nWe proposed and evaluated a GAN-based framework for learned compression that significantly outperforms prior works for low bitrates in terms of visual quality, for compression of natural images.\nFurthermore, we demonstrated that constraining the application domain to street scene images leads to additional storage savings, and we explored combining synthesized with preserved image content with the potential to achieve even larger savings.\nInteresting directions for future work are to develop a mechanism for controlling spatial allocation of bits for GC (e.g. to achieve better preservation of faces; possibly using semantic label maps), and to combine SC with saliency information to determine what regions to preserve.\nIn addition, the sampling experiments presented in Sec. 6.1 indicate that combining our GC compression approach with GANs to (unconditionally) generate compressed representations is a promising avenue to learn high-resolution generative models.",
"role": "user"
},
{
"content": "GAN-based extreme image compression method using less than half the bits of the SOTA engineered codec while preserving visual quality",
"role": "assistant"
}
]
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science.drug_combo_extraction_re | science.drug_combo_extraction_re.446 | [
{
"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: Additive effect of the combination of griseofulvin and ketoconazole against Microsporum canis in vitro . The susceptibility of 28 strains of Microsporum canis to griseofulvin, to ketoconazole and to a combination of both antifungal drugs was determined. griseofulvin proved to be more active than ketoconazole. The combination of both antifungal agents was found to exert an additive effect.\n\nTarget Sentence: Additive effect of the combination of griseofulvin and ketoconazole against Microsporum canis in vitro .",
"role": "user"
},
{
"content": "[[\"griseofulvin\", \"ketoconazole\", \"POS\"]]",
"role": "assistant"
}
]
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science.genia_ner | science.genia_ner.1136 | [
{
"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\nThrombin generation by apoptotic vascular smooth muscle cells. Thrombin activation requires assembly of a prothrombinase complex of activated coagulation factors on an anionic phospholipid surface, classically provided by activated platelets. We have previously shown that anionic phosphatidylserine is exposed by rat vascular smooth muscle cells (VSMCs) undergoing apoptosis after serum withdrawal. In this study, using a chromogenic assay, we have shown thrombin generation by apoptotic VSMCs expressing c-myc (VSMC-myc) with an area under the thrombin-generation curve (AUC) of 305 + /-17 nmol x min / L and a peak thrombin (PT) of 154 + /-9 nmol / L. The thrombin-generating potential of the apoptotic VSMC-myc cells was greater than that of unactivated platelets (P =. 003 for AUC; P =. 0002 for PT) and similar to calcium-ionophore activated platelets (AUC of 332 + /-15 nmol x min / L, P =. 3; PT of 172 + /-8 nmol / L, P =. 2). Thrombin activation was also seen with apoptotic human VSMCs (AUC of 211 + /-8 nmol x min / L; PT of 103 + /-4 nmol / L) and was inhibited by annexin V (P <. 0001 for AUC and PT). VSMC-myc cells maintained in serum generated less thrombin than after serum withdrawal (P =. 0002 for AUC and PT). VSMCs derived from human coronary atherosclerotic plaques that apoptose even in serum also generated thrombin (AUC of 260 + /-2 nmol x min / L; PT of 128 + /-4 nmol / L). We conclude that apoptotic VSMCs possess a significant thrombin-generating capacity secondary to phosphatidylserine exposure. Apoptotic cells within atherosclerotic plaques may allow local thrombin activation, thereby contributing to disease progression.",
"role": "user"
},
{
"content": "{\"CellLine\": [\"apoptotic VSMC - myc cells\", \"VSMC - myc cells\", \"VSMC - myc\"], \"CellType\": [\"unactivated platelets\", \"the apoptotic VSMC - myc cells\", \"VSMC - myc cells\", \"apoptotic VSMCs\", \"activated platelets\", \"VSMCs\", \"apoptotic human VSMCs\", \"apoptotic vascular smooth muscle cells\", \"rat vascular smooth muscle cells\"], \"DNA\": [], \"Protein\": [\"coagulation factors\", \"c - myc\", \"thrombin\", \"Thrombin\", \"prothrombinase complex\"], \"RNA\": []}",
"role": "assistant"
}
]
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science.pico_ner | science.pico_ner.2002 | [
{
"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\nEffect of pravastatin on kidney function and urinary protein excretion in autosomal dominant polycystic kidney disease . OBJECTIVE Autosomal dominant polycystic kidney disease ( ADPKD ) is progressive , resulting in end-stage kidney failure in most patients . Experimental and clinical studies have suggested that statins may slow the progression of chronic kidney disease in general and ADPKD specifically . MATERIAL AND METHODS This randomized open-label clinical trial was conducted to assess the effect of pravastatin 20 mg on kidney function and urinary protein excretion in patients with ADPKD . Sixty patients were initially recruited but 49 of these received either pravastatin 20 mg or no treatment for 2 years . Trial visits were conducted every 3 months , assessing kidney function by estimated glomerular filtration rate and 24 h urine creatinine clearance and urinary protein excretion . RESULTS There were no significant ( p > 0.05 ) changes in markers of kidney function or urinary protein excretion between groups over the 2 years despite a significant fall in total serum cholesterol in pravastatin-treated patients ( p = 0.029 ) . CONCLUSION This trial found that taking 20 mg pravastatin for 2 years had no significant effect on kidney function or urinary protein excretion in patients with ADPKD . The lack of statistical power limits the external validity of these findings . A larger , longer duration study using a higher dose of a more potent statin is required .",
"role": "user"
},
{
"content": "{\"Intervention\": [\"statins\", \"no treatment\", \"pravastatin-treated\", \"pravastatin\"], \"Outcome\": [\"urinary protein excretion\", \"glomerular filtration rate\", \"24 h urine creatinine clearance\", \"progression\", \"chronic kidney disease\", \"kidney function\", \"changes\", \"markers of kidney function\"], \"Participant\": [\"end-stage kidney failure in most patients .\", \"Autosomal dominant polycystic kidney disease ( ADPKD )\", \"patients with ADPKD .\", \"49\", \"autosomal dominant polycystic kidney disease .\", \"Sixty patients\"]}",
"role": "assistant"
}
]
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.12748 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nA Heterocyclic Molecule with Significant Activity Against Dengue Virus\n\nContent Extracts:\n\n<p>The etiological agents of dengue fever (DF) and dengue hemorrhagic fever (DHF) are four closely related dengue viruses, which are antigenically similar but immunologically distinct serotypes of the family called Flavivirus.1–3 The major vector for these viruses is the mosquito, Aedes aegypti. Estimates make the number of cases of dengue fever as high as 100 million annually, which makes this arthropod-borne viral infection a serious global health problem.4 Dengue virus genome is a single, positive-stranded RNA of about 11 kD with a 5′-cap but without a polyadenylated terminus. After fusion and entry, translation of genomic RNA occurs in infected cells.1,3 Processing of the viral polyprotein is apparently catalyzed by both viral and cellular enzymes. NS proteins are involved in the replication cycle. For example, the NS3 viral protease protein is essential for viral replication.5 The NS5 conserved protein has a methyltransferase motif in the N-terminal domain and an RNA-dependent RNA polymerase in the C-terminal domain. The transferase and polymerase are possible viral targets in antiviral strategies.5–7 However, there are no specific approved drugs or vaccines for the treatment or prevention of DF and DHF. This communication reports on the synthesis and antiviral activity of a novel, uracil-based multifunctional compound, 1, which is a potent inhibitor of the replication of dengue virus. In contrast, its deaza analog, 2, was inactive against this flavivirus (Figure 1).</p>\n\nSynthesis\n<p>Synthesis of the target compound was achieved using the Gould-Jacobs reaction8,9 as the key step (Scheme 1, see footnote 11 for details). Thus, condensation of 6-amino-1,3-dibenzyluracil (5), prepared through the coupling of 3 and 4,10 and diethyl ethoxymethylenemalonate under basic conditions, provided the aminomethylenemalonate 6 (42%). Intermediate 6 was heated in Dowtherm A (heat transfer fluid), which resulted in intramolecular cyclization to produce the pyridopyrimidine ester 7 (74%). Hydrolysis of ester 7 under acidic conditions afforded the target compound 1 as a crystalline solid in 67% yield. The structure of 1 was established by UV, 1H and 13C NMR and HRMS data.11 Compound 2 was synthesized by a related methodology.12</p>\n\nAntiviral Activity and Mechanism\n<p>Compound 1 exhibited relatively strong activity against dengue virus type 2 (New Guinea C) with an EC50 of 5.7μg/ml [visual inspection of cytopathic effect (CPE) inhibition] and 6.3μg/ml (neutral red uptake assay) and CC50 of >100 μg/ml producing a TI (therapeutic index) of >18 and >16, respectively, in Vero cells.13 Confirmatory virus yield reduction (VYR) assay gave an EC90 value of 3.8 μg/ml and a CC50 of >100 μg/ml, resulting in a TI of >26. The activity appears to be specific for this compound as the related synthesized compound, 2, that is without the endocyclic nitrogen in the second ring, does not exhibit significant activity against this virus family. Compound 1 represents one of the few compounds that has strong antiviral activity against dengue virus. Interestingly, this compound is moderately active by neutral red assay and highly active (TI > 63) in the virus yield reduction (VYR) assay against yellow fever virus (17D strain), another virus within the Flavivirus genus.</p><p>The mechanism of the antiviral activity of compound 1 is likely associated with its ability to inhibit the enzyme, inosine monophosphate dehydrogenase (IMPDH; EC 1.1.1.205). IMPDH catalyses the oxidative conversion of inosine 5′-monophosphate (IMP) to xanthosine 5′-monophosphate (XMP) with the involvement of the coenzyme, nicotinamide adenine dinucleotide (NAD+).14–16 IMPDH is an important target enzyme in drug discovery. Consistent with this suggestion is the observation that some nucleosides, which are inhibitors of IMPDH as their monophosphates, have been found to have anticancer, antiviral and immunosuppressive activity.17–22 Inhibition of IMPDH results in the reduction of the GTP pool and linear correlations do exist between GTP inhibition and antiviral activity against RNA viruses.23 The mechanism of the antiviral activity of compound 1 may be associated with its inherent ability to inhibit IMPDH through interference of the formation of ternary complex normally formed between the enzyme, the substrate IMP and the cofactor, NAD+.</p><p>In order to investigate the binding of inhibitor 1 with IMPDH in the presence of IMP, extensive molecular modeling studies were carried out using SYBYL 7.2 and GOLD 3.2. Figure 2 shows the preferred docking pose of inhibitor 1 in the active site region of IMPDH.</p><p>The binding allows for favorable stacking interactions between the hypoxanthine base of substrate IMP and the fused heterocyclic ring of the inhibitor. Additionally, the pyridine ring nitrogen of the inhibitor is appropriately situated to form hydrogen bonds with Thr333 and Gln441. This is a key interaction with the enzyme as the absence of this nitrogen (as in compound 2) results in significantly lower RNA antiviral activity. The carboxylate moiety of 1 is positioned to form hydrogen bonds with Asn303 and Gly326. In addition, the \"phenolic\" OH and the adjacent amide carbonyl may form a hydrogen bonding network with Asp 274 via a water molecule. The two phenyl rings may have stacking or other interactions, one with His 93 and the other with the carbonyl of Gln 441. Our molecular modeling studies confirm the ability of inhibitor 1 to bind in the active site region of the inhibitor. This binding would interfere with the interaction of the cofactor, NAD+, and IMPDH in the formation of the ternary complex with the substrate, which is required for hydration of the hypoxanthine ring.15 Support for our molecular modeling data and interpretation comes from the X-ray crystal structure of the complex of IMPDH, IMP and mycophenolic acid (MPA) together with the mutagenesis and kinetic data for the mechanism of the non-competitive inhibition of IMPDH by MPA.24 It is also of relevance to note that MPA exhibits antiviral activity against dengue,25 yellow fever virus26 and West Nile virus.27 Further validation that the mechanism of the antiviral activity of compound 1 is connected with its ability to inhibit IMPDH came from the observation that addition of guanosine to the cell culture assay medium reversed the antiviral activity, presumably by replenishing the levels of the GTP pool.</p><p>In conclusion, we have synthesized a new heterocyclic compound, 1, that shows relatively strong in vitro antiviral activity against dengue virus. This compound is also highly active against another virus of the genus, Flavivirus, the yellow fever virus. In addition, the compound exhibits antiviral activity, albeit low, against other RNA viruses. The mechanism of the antiviral activity is likely associated with inhibition of the enzyme, IMPDH and this is supported by the observation that addition of guanosine to the cell culture medium reverses the antiviral activity. Molecular docking data point to specific hydrogen bonding interactions with a number of amino acids in the active site of IMPDH and to a stacking interaction with the bound natural substrate, IMP. Inhibitor 1 represents one of the few compounds that exhibit significant activity against dengue virus.</p>\n\n\n<p>Structures of target compounds</p><p>Molecular modeling (SYBYL 7.2, GOLD 3.3) of IMPDH complexed with inhibitor 1 (shown in green) and substrate IMP. The inhibitor interferes with the binding of NAD+ with the enzyme.</p><p>Synthesis of antiviral compound 1.</p>",
"role": "user"
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"content": "There are no specific approved drugs or vaccines for the treatment or prevention of infectious dengue virus and there are very few compounds known that inhibit the replication of this virus. This communication describes the concise synthesis of two uracil-based multifunctional compounds. One of these compounds (1) has strong activity against dengue virus. It also exhibits low activity against a few other RNA viruses, but is highly active against yellow fever virus, a related flavivirus. It is likely that the mechanism of action of the antiviral activity of this compound is through its inhibition of the enzyme, inosine monophosphate dehydrogenase (IMPDH). Molecular modeling studies reveal that the compound can have specific hydrogen bonding interactions with a number of amino acids in the active site of IMPDH, a stacking interaction with the bound natural substrate, IMP, and the ability to interfere with the binding of NAD+ with IMPDH, prior to the hydration step.",
"role": "assistant"
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science.acl_arc_intent_classification | science.acl_arc_intent_classification.1482 | [
{
"content": "Examine the given text from a research paper in the field of NLP. Your task is to identify the role of the citation within the context provided. Focus on understanding the intent behind the citation and classify it accordingly.\n\nSection Title:\nNone\n\nText Before Citation:\nWe employ the idea of ultraconservative update (Crammer and Singer, 2003; Crammer et al., 2006) to propose two incremental methods for local training in Algorithm 2 as follows. Unlike the global method which performs tuning on the whole development set Dev + Di as in Algorithm 1, Wi can be incrementally learned by optimizing on Di based on Wb. Our goal is to find an optimal weight, denoted by Wi, which is a local weight and used for decoding the sentence ti.\n\nCitation Text:\nWe employ the idea of ultraconservative update ( Crammer and Singer , 2003 ; Crammer et al. , 2006 ) to propose two incremental methods for local training in Algorithm 2 as follows .\n\nText After Citation:\nUltraconservative update is an efficient way to consider the trade-off between the progress made on development set Dev and the progress made on Di. It desires that the optimal weight Wi is not only close to the baseline weight Wb, but also achieves the low loss over the retrieved examples Di. The idea of ultraconservative update can be formalized as follows: where d(W, Wb) is a distance metric over a pair of weights W and Wb.",
"role": "user"
},
{
"content": "Uses",
"role": "assistant"
}
]
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science.chemdner_ner | science.chemdner_ner.1286 | [
{
"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\nAdvancements in the field of intravaginal siRNA delivery. The vaginal tract is a suitable site for the administration of both local and systemic acting drugs. There are numerous vaginal products on the market such as those approved for contraception, treatment of yeast infection, hormonal replacement therapy, and feminine hygiene. Despite the potential in drug delivery, the vagina is a complex and dynamic organ that requires greater understanding. The recent discovery that injections of double stranded RNA (dsRNA) in Caenorhabditis elegans (C. elegans) results in potent gene specific silencing, was a major scientific revolution. This phenomenon known as RNA interference (RNAi), is believed to protect host genome against invasion by mobile genetic elements such as transposons and viruses. Gene silencing or RNAi has opened new potential opportunities to study the function of a gene in an organism. Furthermore, its therapeutic potential is being investigated in the field of sexually transmitted infections such as human immunodeficiency virus (HIV) and other diseases such as age-related macular degeneration (AMD), diabetes, hypercholesterolemia, respiratory disease, and cancer. This review will focus on the therapeutic potential of siRNA for the treatment and/or prevention of infectious diseases such as HIV, HPV, and HSV within the vaginal tract. Specifically, formulation design parameters to improve siRNA stability and therapeutic efficacy in the vaginal tract will be discussed along with challenges, advancements, and future directions of the field.",
"role": "user"
},
{
"content": "{\"Chemical\": []}",
"role": "assistant"
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science.pubmedqa_qa | science.pubmedqa_qa.144 | [
{
"content": "Analyze the given text and respond to the inquiry. Choose from: \"YES\", \"NO\", or \"MAYBE\".\n\nText:\n(BACKGROUND) The aim of this study is to explore whether availability of sports facilities, parks, and neighbourhood social capital (NSC) and their interaction are associated with leisure time sports participation among Dutch adolescents.\n(METHODS) Cross-sectional analyses were conducted on complete data from the last wave of the YouRAction evaluation trial. Adolescents (n = 852) completed a questionnaire asking for sports participation, perceived NSC and demographics. Ecometric methods were used to aggregate perceived NSC to zip code level. Availability of sports facilities and parks was assessed by means of geographic information systems within the zip-code area and within a 1600 meter buffer. Multilevel logistic regression analyses, with neighborhood and individual as levels, were conducted to examine associations between physical and social environmental factors and leisure time sports participation. Simple slopes analysis was conducted to decompose interaction effects.\n(RESULTS) NSC was significantly associated with sports participation (OR: 3.51 (95%CI: 1.18;10.41)) after adjustment for potential confounders. Availability of sports facilities and availability of parks were not associated with sports participation. A significant interaction between NSC and density of parks within the neighbourhood area (OR: 1.22 (90%CI: 1.01;1.34)) was found. Decomposition of the interaction term showed that adolescents were most likely to engage in leisure time sports when both availability of parks and NSC were highest.\n\nInquiry:\nAre neighbourhood social capital and availability of sports facilities related to sports participation among Dutch adolescents?\n\nResponse:",
"role": "user"
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{
"content": "MAYBE",
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}
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science.medmentions_ner | science.medmentions_ner.924 | [
{
"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\nShape oscillations of particle - coated bubbles and directional particle expulsion Bubbles stabilised by colloidal particles can find applications in advanced materials, catalysis and drug delivery. For applications in controlled release, it is desirable to remove the particles from the interface in a programmable fashion. We have previously shown that ultrasound waves excite volumetric oscillations of particle - coated bubbles, resulting in precisely timed particle expulsion due to interface compression on a ultrafast timescale [Poulichet et al., Proc. Natl. Acad. Sci. U. S. A., 2015, 112, 5932]. We also observed shape oscillations, which were found to drive directional particle expulsion from the antinodes of the non-spherical deformation. In this paper we investigate the mechanisms leading to directional particle expulsion during shape oscillations of particle - coated bubbles driven by ultrasound at 40 kHz. We perform high-speed visualisation of the interface shape and of the particle distribution during ultrafast deformation at a rate of up to 10(4) s(-1). The mode of shape oscillations is found to not depend on the bubble size, in contrast with what has been reported for uncoated bubbles. A decomposition of the non-spherical shape in spatial Fourier modes reveals that the interplay of different modes determines the locations of particle expulsion. The n-fold symmetry of the dominant mode does not always lead to desorption from all 2n antinodes, but only those where there is favourable alignment with the sub-dominant modes. Desorption from the antinodes of the shape oscillations is due to different, concurrent mechanisms. The radial acceleration of the interface at the antinodes can be up to 10(5)-10(6) ms(-2), hence there is a contribution from the inertia of the particles localised at the antinodes. In addition, we found that particles migrate to the antinodes of the shape oscillation, thereby enhancing the contribution from the surface pressure in the monolayer.",
"role": "user"
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{
"content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"materials\", \"particles\", \"particle\"], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"oscillations\", \"inertia\"], \"Food\": [], \"HealthCareActivity\": [], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [], \"MedicalDevice\": [\"drug delivery\"], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [], \"SpatialConcept\": [\"shape\", \"Shape\", \"locations\", \"volumetric\", \"directional\", \"n-fold symmetry\", \"non-spherical\"], \"Virus\": []}",
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science.scicite_classification | science.scicite_classification.65 | [
{
"content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nConsequently, the findings of our study suggest that increased PWV noted in new onset diabetes after kidney transplantation [48,49] may already, at least in part, be present before the transplantation and a result of pre-diabetes or insulin resistance in the uraemic patients awaiting a kidney transplant.",
"role": "user"
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{
"content": "Background",
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science.healthver_entailment | science.healthver_entailment.3583 | [
{
"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: UV light kill the new coronavirus\n\nResearch Abstract:\nObjective: To evaluate the hypothesis that light could reduce the lethality of COVID-19.\nMethods: Most models for projections of the spread and lethality of COVID-19 take into account the ambient temperature, neglecting light.\nRecent advances in understanding the mechanism of action of COVID-19 have shown that it causes a systemic infection that significantly affects the hematopoietic system and hemostasis, factors extremely dependent of light, mainly in the region of visible and infrared radiation.\nResults: In the COVID-19 patients hemoglobin is decreasing and protoporphyrin is increasing, generating an extremely harmful accumulation of iron ions in the bloodstream, which are able to induce an intense inflammatory process in the body with a consequent increase in C-reactive protein and albumin.\nObserving the unsaturation characteristics of the cyclic porphyrin ring allows it to absorb and emit radiation mainly in the visible region.\nThis characteristic can represent an important differential to change this process in the event of an imbalance in this system, through the photobiomodulation to increase the production of adenosine triphosphate (ATP) using red and near-infrared radiation (R-NIR) and vitamin D using ultraviolet B (UVB) radiation.\nThese two compounds have the primary role of activating the defense mechanisms of the immune system, enabling greater resistance of the individual against the attack by the virus.\nAccording to the theory of electron excitation in photosensitive molecules, similar to hemoglobin heme, after the photon absorption there would be an increase in the stability of the iron ion bond with the center of the pyrrole ring, preventing the losses of heme function oxygen transport (HbO2).\nThe light is also absorbed by cytochrome c oxidase in the R-NIR region, with a consequent increase in electron transport, regulating enzyme activity and resulting in a significant increase of oxygen rate consumption by mitochondria, increasing ATP production.\nConclusions: The most favorable range of optical radiation to operate in this system is between R-NIR region, in which cytochrome c oxidase and porphyrin present absorption peaks centered at 640 nm and HbO2 with absorption peak centered at 900 nm.\nBased on the mechanisms described earlier, our hypothesis is that light could reduce the lethality of COVID-19.",
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{
"content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"Based on the mechanisms described earlier, our hypothesis is that light could reduce the lethality of COVID-19.\"]}",
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science.scitldr_aic | science.scitldr_aic.1161 | [
{
"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\nWe review three limitations of BLEU and ROUGE – the most popular metrics\n\nused to assess reference summaries against hypothesis summaries, come up with\n\ncriteria for what a good metric should behave like and propose concrete ways to\n\nassess the performance of a metric in detail and show the potential of Transformers-based Language Models to assess reference summaries against hypothesis summaries.\nEvaluation metrics play a central role in the machine learning community.\nThey direct the efforts of the research community and are used to define the state of the art models.\nIn machine translation and summarization, the two most common metrics used for evaluating similarity between candidate and reference texts are BLEU [Papineni et al., 2002] and ROUGE [Lin, 2004] .\nBoth approaches rely on counting the matching n-grams in the candidates summary to n-grams in the reference text.\nBLEU is precision focused while ROUGE is recall focused.\nThese metrics have posed serious limitations and have already been criticized by the academic community [Reiter, 2018] [Callison-Burch et al., 2006] [Sulem et al., 2018] [Novikova et al., 2017] .\nIn this work, we formulate an empirical criticism of BLEU and ROUGE, establish a criteria that a sound evaluation metric should have and propose concrete ways to test any metric towards these criteria.\nWe also use recent advances in NLP to design a data-driven metric addressing the weaknesses found in BLEU and ROUGE and scoring high on the criteria for a sound evaluation metric.\n2 Related Work 2.1 BLEU, ROUGE and n-gram matching approaches BLEU (Bilingual Evaluation Understudy) [Papineni et al., 2002] and ROUGE (Recall-Oriented Understudy for Gisting Evaluation) [Lin, 2004] have been used to evaluate many NLP tasks for almost two decades.\nThe general acceptance of these methods depend on many factors including their simplicity and the intuitive interpretability.\nYet the main factor is the claim that they highly correlate with human judgement [Papineni et al., 2002] .\nThis has been criticised extensively by the literature and the shortcomings of these methods have been widely studied.\nReiter [Reiter, 2018] , in his structured review of BLEU, finds a low correlation between BLEU and human judgment.\nCallison et al [Callison-Burch et al., 2006] examines BLEU in the context of machine translation and find that BLEU does neither correlate with human judgment on adequacy(whether the hypothesis sentence adequately captures the meaning of the reference sentence) nor fluency(the quality of language in a sentence).\nSulem et al [Sulem et al., 2018] examines BLEU in the context of text simplification on grammaticality, meaning preservation and simplicity and report BLEU has very low or in some cases negative correlation with human judgment.\nIn this work, we have established a framework to assess metrics comparing the quality of reference and hypothesis summary/translations.\nBased on these criteria, we compare evaluators using recent Transformers to BLEU and ROUGE and highlight their potential to replace BLEU and ROUGE.",
"role": "user"
},
{
"content": "New method for assessing the quaility of similarity evaluators and showing potential of Transformer-based language models in replacing BLEU and ROUGE.",
"role": "assistant"
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science.mslr2022_ms2_multidoc_summarization | science.mslr2022_ms2_multidoc_summarization.4093 | [
{
"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: Sex differences in stress responses: social rejection versus achievement stress\nSummary: BACKGROUND Sex differences in stress responses may be one mechanism underlying gender differences in depression . We hypothesized that men and women would show different adrenocortical responses to different stressors . In particular , we predicted that women would show greater responses to social rejection stressors , whereas men would demonstrate greater responses to achievement stressors . METHODS Following a rest session in which they habituated to the laboratory , 50 healthy volunteers ( 24 men and 26 women , mean age 19.1 , SD = 1.13 ) were r and omly assigned to achievement or rejection stress conditions . The achievement condition involved a mathematical and a verbal challenge ; the rejection condition involved two social interaction challenges . Self-reported affect and salivary cortisol were measured throughout each stress session ( baseline , stress , and poststress periods ) . RESULTS There were no sex differences in mood ratings following the stressors ; however , cortisol responses showed the predicted gender by condition by time interaction . Men showed significantly greater cortisol responses to the achievement challenges , but women showed greater cortisol responses to the social rejection challenges . CONCLUSIONS Women appear more physiologically reactive to social rejection challenges , but men react more to achievement challenges . Women 's greater reactivity to rejection stress may contribute to the increased rates of affective disorders in women\n\n\nReport 2:\nTitle: Gender differences in testosterone and cortisol response to competition\nSummary: This study examined intra-individual change in testosterone , cortisol , and hormone-behavior relationships in response to a rowing ergometer competition . Forty-six members ( 23 females ) of a university crew team provided saliva sample s before , 20- and 40-min post-competition , as well as baselines on a non-competition day . Behavioral assessment s included measures of previous rowing experience , dominance , competitiveness , bonding with teammates , pre- and post-competition mental state and performance . Men 's and women 's endocrine responses to this competitive setting were more different than alike and varied by level of competitive experience , the specific phase of the competitive event , and the particular hormone measured . Inter-individual differences in testosterone and cortisol were differentially associated with social affiliation with teammates but rarely with dominance or competitiveness . Theoretically , the findings support the integration of features of the ' tend and befriend ' model with the biosocial model of status , and suggest future research directions that may lead to clarification and refinement of those ideas\n\n\nReport 3:\nTitle: Effect of Exercise at Three Exercise Intensities on Salivary Cortisol\nSummary: Changes in cortisol concentration in response to exercise at 3 different intensities were quantified . Ten apparently healthy , recreationally active males participated . On 4 separate occasions , subjects were assigned a r and om order of 1-hour cycle ergometer bouts of exercise at 44.5 ± 5.5 % , 62.3 ± 3.8 % , and 76.0 ± 6.0 % ( mean ± SD ) of Vo2peak and a resting control session . Saliva sample s were collected before exercise at 10 , 20 , 40 , and 59 minutes of exercise and at 20 minutes of recovery . Differences in cortisol concentration were assessed via multivariate analysis of variance ( α= 0.05 ) Tukey post hoc analysis when indicated . During the highest-intensity exercise session , cortisol was significantly higher at 59 minutes of exercise ( p = 0.004 ) and at 20 minutes of recovery ( p = 0.016 ) than at those same time points during the resting control session . No significant differences in cortisol concentration were noted among resting , low- , and moderate-intensity exercise . Exercise < 40 minutes in duration elicited no significant differences at any intensity . These data indicate that only exercise of high intensity and long duration results in significant elevations of salivary cortisol\n\n\nReport 4:\nTitle: Anticipatory cortisol, testosterone and psychological responses to judo competition in young men\nSummary: This study compares the anticipatory hormonal and psychological responses of 17 male judo players to an official competition with the data obtained during eight resting sessions carried out at the same time of day , throughout an entire sports season . Testosterone ( T ) and cortisol ( C ) levels were determined 1 h and 30 min before competition , and mood , anxiety and expectancies were also evaluated . C levels and anxiety scores were concurrently higher before the contest than in resting conditions ; however , non-significant correlations between them were found . The anticipatory T response was not significant for the whole group . However , one group of subjects did display T increases , higher C levels , and higher motivation to win scores than the other group . Furthermore , this group also obtained a better outcome . Thus , this hormonal pattern and its relationships with psychological variables suggest an adaptive psychobiological response to a competition . Results are discussed in the context that neuroendocrine response to competition is associated with cognitive appraisal\n\n\nReport 5:\nTitle: Systematic review automation technologies\nSummary: Systematic review s , a cornerstone of evidence -based medicine , are not produced quickly enough to support clinical practice . The cost of production , availability of the requisite expertise and timeliness are often quoted as major contributors for the delay . This detailed survey of the state of the art of information systems design ed to support or automate individual tasks in the systematic review , and in particular systematic review s of r and omized controlled clinical trials , reveals trends that see the convergence of several parallel research projects . We surveyed literature describing informatics systems that support or automate the processes of systematic review or each of the tasks of the systematic review . Several projects focus on automating , simplifying and /or streamlining specific tasks of the systematic review . Some tasks are already fully automated while others are still largely manual . In this review , we describe each task and the effect that its automation would have on the entire systematic review process , summarize the existing information system support for each task , and highlight where further research is needed for realizing automation for the task . Integration of the systems that automate systematic review tasks may lead to a revised systematic review workflow . We envisage the optimized workflow will lead to system in which each systematic review is described as a computer program that automatically retrieves relevant trials , appraises them , extracts and synthesizes data , evaluates the risk of bias , performs meta- analysis calculations , and produces a report in real time\n\n\nReport 6:\nTitle: Sex-Specific Effects of Social Support on Cortisol and Subjective Responses to Acute Psychological Stress\nSummary: The effects of short-term social support on cortisol levels and subjective responses to acute psychological stress were investigated in healthy adults ( total N = 66 ) . In anticipation of a public-speaking task in front of an audience , subjects received either no social support ( \" no support \" ) or social support from an opposite-sex stranger ( \" stranger \" ) or from their boyfriend or girlfriend ( \" partner \" ) . Support providers were instructed to enact both instrumental and emotional support during the 10-minute anticipation period . The results obtained suggest sex-specific effects of social support . Although men in the partner support condition showed significant attenuation of cortisol responses compared with unsupported and stranger-supported men , women showed no response decrement under stranger support . In contrast to men , women showed a tendency toward increased cortisol responses when supported by their boyfriends . The endocrine response differences between male and female subjects were unrelated to question naire-derived psychological variables . No sex and group differences in perceived stress , mood changes , or social desirability were observed . Although the overall level of subjective well-being throughout the experiment was elevated in the partner support condition , no sex or group differences were observed in perceived stress , well-being changes , and social desirability . Opposite to their cortisol responses , women rated both stranger and partner support attempts more favorably than did men . No significant correlations were observed between the perceived stressfulness of the situation , mood changes , and cortisol responses . These results provide preliminary evidence for sex-specific patterns of social support efficacy to acute psychological stress with respect to adrenocortical responses\n\n\nReport 7:\nTitle: Habituation of cortisol responses to repeated psychosocial stress—further characterization and impact of genetic factors\nSummary: Although a rapid response habituation to repeated stress exposure is a key characteristic of the hypothalamus-pituitary-adrenal ( HPA ) axis , several studies document a substantial inter-individual variability of such HPA response patterns . In order to further investigate the individual differences in the habituation of this important neuroendocrine system to psychosocial stress , 54 male twin pairs were exposed to moderate psychosocial stress on three occasions , each exposure separated by a 1-week interval . Additionally , an ACTH(1 - 24 ) stimulation test ( 1 microg ) and a dexamethasone suppression test ( 0.5 mg ) were performed . Although on average the expected decrease of mean cortisol and ACTH responses across stress exposures was observed , only 52 % of the subjects showed this well-documented general decline and almost 16 % of the participants even showed a response sensitization across sessions . Furthermore , a weak habituation was related to low cortisol responses to both the first stress exposure as well as the ACTH challenge . Moreover , genetic analyses did not reveal any evidence for a substantial heritability of the individual cortisol response habituation or an association between this habituation and two common polymorphisms in the glucocorticoid receptor gene\n\n\nReport 8:\nTitle: Women's intercollegiate volleyball and tennis: Effects of warm-up, competition, and practice on saliva levels of cortisol and testosterone\nSummary: In virtually all sports , participants \" warm-up \" prior to formal competition . Women athletes from a highly ranked varsity college volleyball team and , in a second study , a highly ranked varsity college tennis team gave saliva sample s before warm-up , at mid-warm-up ( volleyball ) or after warm-up ( tennis ) , and immediately after intercollegiate competition . For volleyball and tennis , warm-up was associated with a substantial elevation in saliva levels of testosterone which was carried over through the period of actual competition . Cortisol levels were relatively unchanged during warm-up , but typically rose during competition . Thus , as women prepare for athletic competition by warming up , testosterone levels rise in apparent anticipation of the coming contest and then remain high through the period of play . In volleyball and tennis , after- practice testosterone level was significantly higher than before- practice level , and practice session increases in testosterone ( but not cortisol ) were positively correlated with increases in testosterone during intercollegiate competition . When practice and competitive play share as yet undetermined key elements , individual differences in this endocrine response to \" competition \" appear stable across practice and intercollegiate competition",
"role": "user"
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"content": "Summary / conclusion The anticipatory cortisol response before sport competition reflects moderate cortisol reactivity that prepares athletes optimally for the dem and s of sport competition via the influence on cognitive processes and attentional control .\nHowever , both female athletes and international competitors did not demonstrate a significant anticipatory cortisol response , possibly due to differences in appraisal of the stress of sport competition",
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science.mslr2022_cochrane_multidoc_summarization | science.mslr2022_cochrane_multidoc_summarization.3434 | [
{
"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:\nAntioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial.\nReport Abstract 1:\nTo evaluate the efficacy of antioxidant supplementation in preventing kwashiorkor in a population of Malawian children at high risk of developing kwashiorkor.\n Prospective, double blind, placebo controlled trial randomised by household.\n 8 villages in rural southern Malawi.\n 2372 children in 2156 households aged 1-4 years were enrolled; 2332 completed the trial.\n Daily supplementation with an antioxidant powder containing riboflavin, vitamin E, selenium, and N-acetylcysteine in a dose that provided about three times the recommended dietary allowance of each nutrient or placebo for 20 weeks.\n The primary outcome was the incidence of oedema. Secondary outcomes were the rates of change for weight and length and the number of days of infectious symptoms.\n 62 children developed kwashiorkor (defined by the presence of oedema); 39/1184 (3.3%) were in the antioxidant group and 23/1188 (1.9%) were in the placebo group (relative risk 1.70, 95% confidence interval 0.98 to 2.42). The two groups did not differ in rates of weight or height gain. Children who received antioxidant supplementation did not experience less fever, cough, or diarrhoea.\n Antioxidant supplementation at the dose provided did not prevent the onset of kwashiorkor. This finding does not support the hypothesis that depletion of vitamin E, selenium, cysteine, or riboflavin has a role in the development of kwashiorkor.",
"role": "user"
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"content": "Based on the one available trial, we could draw no firm conclusion for the effectiveness of supplementary antioxidant micronutrients for the prevention of kwashiorkor in pre-school children.",
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science.scitldr_aic | science.scitldr_aic.1305 | [
{
"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\nNeural networks can converge faster with help from a smarter batch selection strategy.\nIn this regard, we propose Ada-Boundary, a novel adaptive-batch selection algorithm that constructs an effective mini-batch according to the learning progress of the model.Our key idea is to present confusing samples what the true label is.\nThus, the samples near the current decision boundary are considered as the most effective to expedite convergence.\nTaking advantage of our design, Ada-Boundary maintains its dominance in various degrees of training difficulty.\nWe demonstrate the advantage of Ada-Boundary by extensive experiments using two convolutional neural networks for three benchmark data sets.\nThe experiment results show that Ada-Boundary improves the training time by up to 31.7% compared with the state-of-the-art strategy and by up to 33.5% compared with the baseline strategy.\nDeep neural networks (DNNs) have achieved remarkable performance in many fields, especially, in computer vision and natural language processing BID13 BID5 .\nNevertheless, as the size of data grows very rapidly, the training step via stochastic gradient descent (SGD) based on mini-batches suffers from extremely high computational cost, which is mainly due to slow convergence.\nThe common approaches for expediting convergence include some SGD variants BID28 BID11 that maintain individual learning rates for parameters and batch normalization BID9 that stabilizes gradient variance.Recently, in favor of the fact that not all samples have an equal impact on training, many studies have attempted to design sampling schemes based on the sample importance BID25 BID3 (1) at the training accuracy of 60%.\nAn easy data set (MNIST) does not have \"too hard\" sample but \"moderately hard\" samples colored in gray, whereas a relatively hard data set (CIFAR-10) has many \"too hard\" samples colored in black.\n(b) shows the result of SGD on a hard batch.\nThe moderately hard samples are informative to update a model, but the too hard samples make the model overfit to themselves.\net al., 2017; BID10 .\nCurriculum learning BID0 ) inspired by human's learning is one of the representative methods to speed up the training step by gradually increasing the difficulty level of training samples.\nIn contrast, deep learning studies focus on giving higher weights to harder samples during the entire training process.\nWhen the model requires a lot of epochs for convergence, it is known to converge faster with the batches of hard samples rather than randomly selected batches BID21 BID17 BID4 .\nThere are various criteria for judging the hardness of a sample, e.g., the rank of the loss computed from previous epochs BID17 .Here\n, a natural question arises: Does the \"hard\" batch selection always speed up DNN training? Our\nanswer is partially yes: it is helpful only when training an easy data set. According\nto our indepth analysis, as demonstrated in FIG1 (a), the\nhardest samples in a hard data set (e.g., CIFAR-10) were too hard to learn. They are\nhighly likely to make the decision boundary bias towards themselves, as shown in FIG1 (b) . On\nthe other\nhand, in an easy data set (e.g., MNIST), the hardest samples, though they are just moderately hard, provide useful information for training. In practice,\nit was reported that hard batch selection succeeded to speed up only when training the easy MNIST data set BID17 BID4 , and our experiments in Section 4.4 also confirmed the previous findings. This limitation\ncalls for a new sampling scheme that supports both easy and hard data sets.In this paper, we propose a novel adaptive batch selection strategy, called Ada-Boundary, that accelerates training and is better generalized to hard data sets. As opposed to existing\nhard batch selection, Ada-Boundary picks up the samples with the most appropriate difficulty, considering the learning progress of the model. The samples near the current\ndecision boundary are selected with high probability, as shown in FIG3 (a). Intuitively speaking, the\nsamples\nfar from the decision boundary are not that helpful since they are either too hard or too easy: those on the incorrect (or correct) side are too hard (or easy). This is the reason why we regard\nthe samples around the decision boundary, which are moderately hard, as having the appropriate difficulty at the moment. Overall, the key idea of Ada-Boundary\nis to use the distance of a sample to the decision boundary for the hardness of the sample. The beauty of this design is not to require\nhuman intervention. The current decision boundary should be directly\ninfluenced by the learning progress of the model. The decision boundary of a DNN moves towards eliminating\nthe incorrect samples as the training step progresses, so the difficulty of the samples near the decision boundary gradually increases as the model is learned. Then, the decision boundary keeps updated to identify the\nconfusing samples in the middle of SGD, as illustrated in FIG3 (b) . This approach is able to accelerate the convergence\nspeed\nby providing the samples suited to the model at every SGD iteration, while it is less prone to incur an overfitting issue.We have conducted extensive experiments to demonstrate the superiority of Ada-Boundary. Two popular convolutional neural network (CNN) 1 models are\ntrained using three benchmark data sets. Compared to random batch selection, Ada-Boundary significantly\nreduces the execution time by 14.0-33.5%. At the same time, it provides a relative improvement of test error\nby 7.34-14.8% in the final epoch. Moreover, compared to the state-of-the-art hard batch selection BID17\n, Ada-Boundary achieves the execution time smaller by 18.0% and the test error smaller by 13.7% in the CIFAR-10 data set.2 Ada-Boundary COMPONENTS The main challenge for Ada-Boundary is to evaluate\nhow close a sample is to the decision boundary. In this section, we introduce a novel distance measure and present a method\nof computing the sampling probability based on the measure.\nIn this paper, we proposed a novel adaptive batch selection algorithm, Ada-Boundary, that presents the most appropriate samples according to the learning progress of the model.\nToward this goal, we defined the distance from a sample to the decision boundary and introduced a quantization method for selecting the samples near the boundary with high probability.\nWe performed extensive experiments using two CNN models for three benchmark data sets.\nThe results showed that Ada-Boundary significantly accelerated the training process as well as was better generalized in hard data sets.\nWhen training an easy data set, Ada-Boundary showed a fast convergence comparable to that of the state-of-the-art algorithm; when training relatively hard data sets, only Ada-Boundary converged significantly faster than random batch selection.The most exciting benefit of Ada-Boundary is to save the time needed for the training of a DNN.\nIt becomes more important as the size and complexity of data becomes higher, and can be boosted with recent advance of hardware technologies.\nOur immediate future work is to apply Ada-Boundary to other types of DNNs such as the recurrent neural networks (RNN) BID18 and the long short-term memory (LSTM) BID7 , which have a neural structure completely different from the CNN.\nIn addition, we plan to investigate the relationship between the power of a DNN and the improvement of Ada-Boundary.",
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"content": "We suggest a smart batch selection technique called Ada-Boundary.",
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science.craftchem_ner | science.craftchem_ner.3486 | [
{
"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:\nRT-PCRwasthenusedwith(+)orwithout(-)reversetranscriptase(RT)andwithprimersetsspecificforSnailandGAPDHmRNAs.",
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"content": "[\"mRNAs\"]",
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.21994 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nMicro-/Nano-Structures Fabricated by Laser Technologies for Optoelectronic Devices\n\nContent Extracts:\nIntroduction\n<p>There are many animals and plants using unique micro-/nano-structures to improve their environmental adaptability (Han et al., 2016; Han et al., 2020a; Cao et al., 2020). For example, micro-/nano-structures on a lotus leaf and taro surface exhibit superhydrophobic properties (Zhang et al., 2012b; Wang et al., 2021b; Lv et al., 2021). Grating-like structures on butterfly wings trap light, leading to the colorful butterfly wing (Wang et al., 2012; Jiang et al., 2016; Zou et al., 2020). Learning from nature, micro-/nano-structures have been adopted in the various functional devices for broad applications (Han et al., 2019; Zhang et al., 2019; Zhang et al., 2021). Therefore, many researchers have focused on the fabrication and application of micro-nano structures (Zhang et al., 2012a; Han et al., 2015; Liu et al., 2021). Mainly, due to unique optical and electrical properties, micro-/nano-structures have become an essential part of optoelectronic devices.</p><p>Laser fabrication technologies show high efficiency, high precision, and low thermal effect (Li et al., 2020a; Fu et al., 2020; Ma et al., 2020; You et al., 2020; Fu et al., 2021). Laser technologies can be used to fabricate micro-/nano-structures by the interaction between laser and materials (Liu et al., 2019; Han et al., 2020b; Liu et al., 2020; Wang et al., 2021a). Especially, ultrafast lasers can fabricate broadband, transparent anti-reflection surfaces, which promote the performance of optoelectronic devices by enhancing the light absorption or introducing surface plasmon-polariton (Zhang et al., 2010; Liapis et al., 2017; Jia et al., 2020).</p><p>In this review, we summarize recent progress on micro-/nano-structures fabricated by laser technologies. Typical light trapping mechanism and surface plasmon-polariton of the micro-nano structure are discussed. Then, we outlined the typical applications, including photodetectors, photovoltaic cells, organic light-emitting devices, etc. Finally, the challenges and prospects are discussed.</p>\n\nMechanism\n<p>Introducing micro-/nano-structures inside or outside the devices can improve optoelectronic devices' performance (Ma and Cui, 2020; Na and Chew, 2020; Chen et al., 2021). Inspired by the moth-eye structure, the reflectivity is reduced by introducing micro-/nano-structures. Mainly, the light will be internally reflected many times inside the structure to form a \"light trap\" (Zhang et al., 2020a; Otte and Denz, 2020; Yang et al., 2021). As a result, the existence of micro-/nano-structures can improve the light absorption capacity of the optoelectronic device. Moreover, the efficiency of optoelectronic devices can be enhanced by surface plasmon-polariton (Eaton et al., 2016; Li et al., 2020b; Zhang et al., 2020b).</p>\n\nPhotodetector\n<p>Silicon material plays an important role in silicon-based optoelectronic integrated devices preparation. Take photodetectors as an example, the bandgap of silicon material is around 1.1–1.3 eV, limiting silicon material for infrared radiation (IR) photodetection. Therefore, many efforts, such as ion implantation or structural defects, have been developed to extend the absorption band of silicon. As a pioneer, Zhao's group (Li et al., 2017; Yu et al., 2017; Li et al., 2018) fabricated supersaturated silicon material with nitrogen, sulfur, and Au by femtosecond laser ablation (Figure 1A). After the femtosecond laser ablation in nitrogen (N2) atmosphere, the surface silicon material evolved into a bead-like micro-/nano-structures with a height of 3∼4 μm and a distance of 3∼4 μm (Li et al., 2018). Micro-/nano-structures are beneficial for a stronger light trapping effect. Compared with the initial silicon material, laser-treated N-doped silicon material has a broader absorption (0.25–2.5 μm) and higher absorptivity (Figure 1B). The inset of Figure 1C is the device structure of the laser-treated silicon-based IR photodetector. The photo responsivity is 5.3 mA/W (V = 10 V).</p>\n\n\n<p>Micro-/nano-structures fabricated by laser technologies for optoelectronic devices. (A) Femtosecond laser manufacturing system. Reproduced from (Yu et al., 2017) with permission of IEEE. (B) The corresponding absorptivity of nitrogen-doped silicon substrate. (C) Infrared photodetection performance. Reproduced from (Li et al., 2018) with permission of IEEE. (D) The preparation process of PDMS convex PMLA film. (E) Simulated absorption spectra of films. (F) Solar cell performance. Reproduced from (Fang et al., 2018) with permission of American Chemical Society. (G) Schematic diagram of laser two-beam interferes processing. Reproduced from (Bi et al., 2013; Jiang et al., 2014) with permission of WILEY-VCH. (H) Absorption spectra for WOLEDs. (I) Performance of WOLED. Reproduced from (Bi et al., 2013) with permission of WILEY-VCH.</p>\n\nPhotovoltaic Cell\n<p>Photovoltaic cells convert sunlight to electric energy. Usually, light utilization efficiency is very low due to the reflection loss. To solve this problem, various anti-reflection structures have been designed. For example, Fang et al. proposed a 100% relative packing density film for enhancing photovoltaic cells performance (Fang et al., 2018). As shown in Figure 1D, direct-write ultraviolet (UV) laser photolithography system was employed to fabricate a paraboloidal concave photoresist pattern (master mold). Then polydimethylsiloxane (PDMS) was spin-coated onto the master mold. After thermally cured, structured PDMS was separated from the master mold for further use. Figure 1E is the simulated absorption spectra of films. Si substrate with paraboloidal microlens array (PMLA) film shows the highest absorption due to the suppressing reflection. It is worth noting that PMLA antireflective (AR) film indicates superhydrophobicity and self-cleaning ability. Finally, the short-circuit current density increases from 35.6 to 37.2 mA/cm2 after integrating the PMLA AR film (Figure 1F). Instead of integrating the AR film on the photovoltaic cells surface, structured photoelectrodes or active layers have been fabricated by femtosecond laser ablation, interference, or laser-induced periodic surface structures for photocurrent enhancement (Zhang et al., 2015; Cui et al., 2016; Soldera et al., 2016).</p>\n\nLight-Emitting Diode\n<p>Bi et al. (2013) demonstrated white organic light-emitting diodes (WOLEDs) with broadband excitation by introducing two-dimensional gratings. As shown in Figure 1G, the grating structures were prepared by two-beam laser interference (Guo et al., 2012; Jiang et al., 2014; Yan et al., 2015). Introducing dual-period corrugations into the WOLED metal electrodes achieves broadband absorption (Figure 1H). In addition, broadband SPP modes lead to broadband light extraction. Significantly, broadband light extraction deeply affects the WOLEDs performance (Figure 1I). Compared with traditional planar devices, the current efficiency is increased by 37%, and the external quantum efficiency is increased by 48%. Recently, combining laser interference lithography and reactive ion etching, Ju et al. proposed flexible OLEDs with light extraction structure for optical efficiency improvement (Lee et al., 2019; Kim et al., 2020).</p>\n\nConclusion and Outlook\n<p>This minireview summarizes recent progress on micro-/nano-structures fabricated by laser technologies for optoelectronic devices. The existence of micro-/nano-structures can improve the light absorption capacity and the efficiency of optoelectronic devices. Typical optoelectronic devices have been successfully designed and demonstrated the critical role of micro-/nano-structures. Significantly, new photoelectric applications, such as photoelectric dichroism, have been proposed and fabricated by laser technology based on various materials (Drevinskas et al., 2015; Jiang et al., 2020; Kuroiwa and Tatsuma, 2020; Zou et al., 2021a; Zou et al., 2021b; Xuan et al., 2021). Although successful works have demonstrated the distinguish characters, the efficiency of laser processing materials needs to improve, which benefits device preparation efficiency. With the rapid development of nanofabrication technology, advanced fundamental theories, new structural design, micro-/nano-structures will improve devices performances.</p>\n\nAuthor Contributions\n<p>All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.</p>\n\nFunding\n<p>This research was funded by the Strategic Priority Research Program of CAS (Grant No. XDC07030303), the National Natural Science Foundation of China (61905087), and Fundamental Research Funds for the Central Universities (2020-JCXK-18).</p>\n\nConflict of Interest\n<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>\n\nPublisher’s Note\n<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>",
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"content": "Due to unique optical and electrical properties, micro-/nano-structures have become an essential part of optoelectronic devices. Here, we summarize the recent developments in micro-/nano-structures fabricated by laser technologies for optoelectronic devices. The fabrication of micro-/nano-structures by various laser technologies is reviewed. Micro-/nano-structures in optoelectronic devices for performance improvement are reviewed. In addition, typical optoelectronic devices with micro-nano structures are also summarized. Finally, the challenges and prospects are discussed.",
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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.2146 | [
{
"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: Hemodynamic Traveling Waves in Human Visual Cortex\nContent:\nAbstract:\nFunctional MRI( fMRI) experiments rely on precise characterization of the blood oxygen level dependent( BOLD) signal. As the spatial resolution of fMRI reaches the sub-millimeter range, the need for quantitative modelling of spatiotemporal properties of this hemodynamic signal has become pressing. Here, we find that a detailed physiologically-based model of spatiotemporal BOLD responses predicts traveling waves with velocities and spatial ranges in empirically observable ranges. Two measurable parameters, related to physiology, characterize these waves: wave velocity and damping rate. To test these predictions, high-resolution fMRI data are acquired from subjects viewing discrete visual stimuli. Predictions and experiment show strong agreement, in particular confirming BOLD waves propagating for at least 5–10 mm across the cortical surface at speeds of 2–12 mm s-1. These observations enable fundamentally new approaches to fMRI analysis, crucial for fMRI data acquired at high spatial resolution.\nIntroduction:\nFunctional magnetic resonance imaging( fMRI) experiments have substantially advanced our understanding of the structure and function of the human brain[1]. Hemodynamic responses to neuronal activity are observed experimentally in fMRI data via the blood oxygenation dependent( BOLD) signal, which provides a noninvasive measure of neuronal activity. Understanding the mechanisms that drive this BOLD response, combined with detailed characterization of its spatial and temporal properties, is fundamental for accurately inferring the underlying neuronal activity[2]. Such an understanding has clear benefits for many areas of neuroscience, particularly those concerned with detailed functional mapping of the cortex[3], those using multivariate classifiers that implicitly incorporate the spatial distribution of BOLD[4],[5], and those that focus on understanding and modeling spatiotemporal cortical activity[6]–[10]. The temporal properties of the hemodynamic BOLD response have been well characterized by existing physiologically based models, such as the balloon model[11]–[14]. Although the spatial response of BOLD has been characterized experimentally via hemodynamic point spread functions[15]–[18], it is commonly agreed that the spatial and spatiotemporal properties are relatively poorly understood[19],[20]. Many studies work from the premise that the hemodynamic BOLD response is space-time separable, i. e. is the product of a temporal HRF and a simple Gaussian spatial kernel. The latter assumed as a simple ansatz or ascribed to diffusive effects, for example[21]. This approach raises the following concerns:( i) since the temporal dynamics of the HRF is the focus of most theoretical analyses, e. g. the balloon model, this precludes dynamics that couple space and time, dismissing whole classes of dynamics, such as waves;( ii) in practice, employing a static spatial filter then convolving with a temporal HRF on a voxel-wise basis neglects non-separable interactions between neighboring voxels; and( iii) calculating temporal correlations between voxels then assumes that the hemodynamic processes responsible for the signal occur on scales smaller than the resolution of the measurements. In summary, neglecting spatial effects such as voxel-voxel interactions and boundary conditions( e. g., blood outflow from one voxel must enter neighboring ones) ignores important phenomena and physical constraints that could be used to increase signal to noise ratios and to improve inferences of neural activity and its spatial structure. These constraints are becoming increasingly relevant, as advances in hardware and software improve the spatial resolution of fMRI by reducing voxel sizes. While treating spatial hemodynamics as a Gaussian is a reasonable first approximation[15]–[20],[22], this requires spatiotemporal BOLD dynamics, such as spatially delayed activity to be attributed solely to the underlying neuronal activity, without hemodynamic effects from neighboring tissue, an assumption that may not be valid. In this limit, BOLD measurements would simply impose a spatial low-pass filter of neuronal activity[20]. Several studies have already presented results that challenge this assumption, most strikingly by demonstrating reliable classification of neuronal structures such as ocular dominance or orientation columns[4],[5] on scales significantly smaller than the resolution of the fMRI protocols used[4],[5],[19],[23],[24]. Although there are suggestions that the organization of orientation columns may have low spatial frequency components, hemodynamics may also contribute to this effect. Going in the opposite direction, as voxels decrease in size, they must eventually become smaller in linear extent than the hemodynamic response, and thus become highly interdependent. Recent studies[20],[25]–[27], have highlighted how BOLD responses involve active changes in cortical vasculature, and hence reflect their mechanical and other spatiotemporal response properties, with spatial scales that are at least partly distinct from the scales of the underlying neuronal activity[20]. Given the above points, the mapping between neuronal activity and the spatially extended BOLD response cannot be assumed to be a spatially local temporal convolution[20], but should rather be treated in a comprehensive framework that accounts for both spatial and temporal properties and their interactions. A recent theoretical approach[25] treats cortical vessels as pores penetrating the cortical tissue and draws on a rich framework of methods developed in geophysics[28] to derive a physiologically based approximation of the hemodynamics. This model is expressed in terms of a closed set of dynamical equations that reduces to the familiar balloon model[25] in the appropriate limit where spatial effects are averaged over each voxel. It analyzes the spatiotemporal hemodynamic response by modeling the coupled changes in blood flow, pressure, volume, and oxygenation levels that occur in response to neural activity. The objective of the present work is to make and empirically test novel predictions of the model, focusing particularly on spatiotemporal dynamics. We first predict the quantitative spatiotemporal hemodynamic response function( stHRF) for physiologically plausible parameters. We find that the model predicts a local response and damped traveling waves, whose speed and range are potentially observable with current high resolution fMRI. Second, we acquire and characterize such high resolution fMRI data from subjects viewing a visual stimulus designed to excite spatially localized neuronal activity in primary visual cortex. We observe hemodynamic waves in these experimental data, whose characteristics confirm our theoretical predictions of wave ranges, damping rates, and speeds, and constrain the physiological parameters of the model.\nDiscussion:\nThe increasing resolution of functional MRI and the development of analysis methods that depend on spatial patterns in these data underline the need for a systematic, quantitative approach to the spatial and temporal properties of the BOLD signal that is based on the properties of the underlying tissue and vasculature. Here we apply a recent physiologically based theory of hemodynamics in cortical tissue and vasculature to derive the linear spatiotemporal hemodynamic response function( stHRF), which is the response to a spatiotemporally localized stimulus of moderate amplitude. High resolution fMRI data are then used to test the predicted BOLD response to localized neuronal modulation in early visual cortex. Just two extra measurable parameters – vβ and Γ- suffice to characterize the spatial properties of the response. The theory used is the first to make a mean-field approximation to cortical vasculature and goes beyond spatially point-like multicompartment models[12],[36],[37] as it allows calculation of spatiotemporal hemodynamic responses to general stimuli. It predicts, and the data demonstrate, that the hemodynamic response to a spatially highly localized neuronal drive exhibits traveling waves that propagate over a few mm of cortical tissue. Moreover, the velocity, damping and characteristic range of the observed waves are well within the range of theoretical predictions. These traveling waves have not been previously predicted or reported in human cortex. The central part of the response is non-propagating and has a temporal profile consistent with the standard balloon model[11]–[14],[38]. A further key implication of the spatial effects in our data is that fMRI voxels should only be treated independently if each voxel is larger than the stHRF scale. For interpreting fMRI acquired at sufficiently high spatial resolution the spatiotemporal properties of the stHRF must also be taken into account. Moreover, when voxels are small, we speculate that propagation of hemodynamic waves beyond their boundaries may underlie the observation that some experiments can be sensitive to structures at scales below the voxel size, including ocular dominance and orientation preference columns[4],[5],[24]. The combination of modeling and data allows us to estimate key physiological parameters of the model from observations of individual subjects. This lays the basis for replacing fMRI analysis procedures that rely on purely empirical analysis by ones that relate to the underlying physiology. We have shown how characterization of the spatiotemporal properties of fMRI data allows properties of the cortical tissue and vasculature to be inferred, hence accounting for differences between subjects and, potentially, brain regions. For example, relatively low blood viscosity and/or high tissue stiffness are predicted to lead to longer-range wave propagation. Specific experimental manipulations, such as the use of blood-thinning agents, could be employed to test the predicted changes in wave speed and spatial range. Similarly, the reduction in tissue elasticity that typically occurs with ageing[39], should be able to be probed noninvasively via its effects on wave velocity, and thereby taken into account when making inferences about neuronal activity in cohorts where age may be a confound. Likewise, regionally specific vascular properties have recently been highlighted as an important potential confound in studies of effective connectivity[40],[41], thereby underlining the need for a careful measurement and allowance for hemodynamic effects. It is worth asking why hemodynamic waves have not been previously observed in fMRI. Some reasons are:( i) If voxel dimensions are large and sampled over a long time period, the hemodynamic response is not sufficiently resolved to detect propagating waves( ii) If the BOLD signal is spatially smoothed, then the spatiotemporal structure of the measured BOLD signal will be averaged out;( iii) Wave propagation is confined to occur within the cortical sheet and will be only be readily apparent in surface-based data reconstruction;( iv) Hemodynamic waves from a point source( e. g., a localized activation in a typical study) in two spatial dimensions decay more rapidly with distance than from the line source our experiment, where net decay can occur only in the direction perpendicular to the cortical locus of our one-dimensional stimulus. Despite these points, as high resolution protocols and surface-rendered data analysis techniques gain widespread use, the need for quantitative spatial analysis will likewise grow. An important consequence of having hemodynamic traveling waves is that the spatial dynamics of BOLD are not independent of their temporal dynamics. The conventional factorization into spatial and temporal convolution operators is thus not valid in general. A greater understanding of the BOLD response, and brain mapping in general, would come from understanding the spatiotemporal hemodynamic response[20]. The present spatiotemporal HRF provides a solution to this problem, starting from a theory of spatiotemporal hemodynamics. Several other issues arise from having hemodynamic traveling waves.( i) The existence of hemodynamic waves mean that spatiotemporal hemodynamics, induced by nearby sources, can interact in a nontrivial way, a property that occurs in the temporal domain, concerning the nonlinear interaction between temporally proximate responses[13],[38].( ii) These findings cast further doubt on those measures of effective connectivity, such as Granger causality, unless they include a careful treatment of hemodynamic effects[40],[42],[43].( iii) On the other hand, experimental designs could exploit the wave properties of hemodynamics by using stimuli that induce resonant properties of cortical tissue- akin to the temporal domain[14]- enhancing detection of the evoked signal. Traveling waves of neuronal or glial origin have been described throughout the brain, including in visual cortex[43]–[46], raising the question of whether these waves might be responsible for the hemodynamic traveling waves seen in our data. However, several considerations argue against this:( i) The close match between the theoretically predicted values and the observed data strongly supports the conclusion that the waves in our data are of hemodynamic origin.( ii) Previous studies[45],[47],[48] that reported propagating neuronal waves in V1 of similar spatial extent to those seen here demonstrated that these waves are 1–2 orders of magnitude faster( approximately 200 mm s−1 in cats[47], 100–250 mm s−1 in primates[45] and 50–70 mm s−1 in rats[48]), and waves in cortical white matter travel even faster[43]. Likewise, although the spatial scales may be similar to those presently reported, the diffusion of nitrous oxide- which mediates the coupling between neuronal activity and vasodilation- occurs too rapidly to explain our results[21].( iii) Another possible source of propagating signal of possible relevance are calcium waves traveling via astrocytes because these mediate the neuronal signal in vasodilation. However, these calcium waves travel at ∼10 µm s−1[49], which is 2 orders of magnitude slower that the waves reported here. Although hemodynamic waves have not been characterized, detected, or previously modeled, existing work has detailed some spatiotemporal properties of the BOLD response. Previous studies have demonstrated hemodynamic contributions to spatiotemporal BOLD response, including: the effect of draining veins[50],[51] which induces a latent BOLD signal due to these veins; effects across vascular layers[52],[53] that induce layer dependent delays of the BOLD response; and general effects of the vascular network[43] that cause delayed BOLD responses across extensive brain regions. Studies have also implemented ways to minimize such effects to improve spatial specificity of functional activations[43],[50]. The hemodynamic waves are different from the mentioned phenomena in that they exhibit propagation across the cortical surface. As the waves pass through they induce changes in arterioles, capillaries, and venules – not reliant on overall drainage by large veins. The possible interplay of these effects will be subject to future modeling and experimental work. In summary, with advances in imaging technology and data analysis, intervoxel effects will become more pronounced, demanding spatiotemporal analyses based on the underlying brain structure and hemodynamics. By verifying a model that enables such analysis, the present paper opens the way to new fMRI probes of brain activity. These new possibilities include experiments using spatial deconvolution to discriminate between neural and hemodynamic contributions to the spatiotemporal BOLD response evoked by complex sensory stimuli. An important potential application would be to disentangle negative components of the BOLD response from surround inhibition in the visual cortex. Our analysis also affords novel insights and physiological information on neurovasculature, a subject of particular significance to ageing and vascular health. Finally, the combination of the present stHRF with spatially embedded neural field models[8] would allow a systematic and integrated computational framework for inferring dynamic activity in underlying neuronal populations from fMRI data.",
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"content": "Functional magnetic resonance imaging ( fMRI ) experiments have advanced our understanding of the structure and function of the human brain . Dynamic changes in the flow and concentration of oxygen in blood are observed experimentally in fMRI data via the blood oxygen level dependent ( BOLD ) signal . Since neuronal activity induces this hemodynamic response , the BOLD signal provides a noninvasive measure of neuronal activity . Understanding the mechanisms that drive this BOLD response is fundamental for accurately inferring the underlying neuronal activity . The goal of this study is to systematically predict spatiotemporal hemodynamics from a biophysical model , then test these in a high resolution fMRI study of the visual cortex . Using this theory , we predict and empirically confirm the existence of hemodynamic waves in cortex – a striking and novel finding .",
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science.data_reco_mcq_sc | science.data_reco_mcq_sc.2991 | [
{
"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 estimate disparity from stereo images.\n\nKeywords: stereo matching images\n\nDataset Information:\nMPI Sintel: MPI (Max Planck Institute) Sintel is a dataset for optical flow evaluation that has 1064 synthesized stereo images and ground truth data for disparity. Sintel is derived from open-source 3D animated short film Sintel.\nMiddlebury: The Middlebury Stereo dataset consists of high-resolution stereo sequences with complex geometry and pixel-accurate ground-truth disparity data. The ground-truth disparities are acquired using a novel technique that employs structured lighting and does not require the calibration of the light projectors.\nDAVANet: A large-scale multi-scene dataset for stereo deblurring, containing 20,637 blurry-sharp stereo image pairs from 135 diverse sequences and their corresponding bidirectional disparities.\nMiddlebury 2014: The Middlebury 2014 dataset contains a set of 23 high resolution stereo pairs for which known camera calibration parameters and ground truth disparity maps obtained with a structured light scanner are available. The images in the Middlebury dataset all show static indoor scenes with varying difficulties including repetitive structures, occlusions, wiry objects as well as untextured areas.\n\nAvailable Datasets: A: MPI Sintel B: Middlebury C: DAVANet D: Middlebury 2014",
"role": "user"
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"content": "Middlebury",
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science.craftchem_ner | science.craftchem_ner.1654 | [
{
"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:\nTable1",
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"content": "[]",
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science.craftchem_ner | science.craftchem_ner.3605 | [
{
"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:\nConnectingcilium1(arrowhead1)demonstratedsevenmicrotubledoublets,whilecilium2andcilium3exhibitednine.",
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science.scientific_papers_summarization_single_doc_pubmed | science.scientific_papers_summarization_single_doc_pubmed.10587 | [
{
"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:\ninverted nipple may cause various cosmetic , psychological , breast feeding and hygienic problems . providing a symmetrical nipple shape and position with permanent projection\nnonsurgical treatments include breast shells , breast pumps and syringe techniques . however , the beneficial and permanent effects of these treatments are controversial . in the teimourian technique which is the one of the most commonly used surgical technique ,\nall the lactiferous ducts are cut and the dermal flaps are used as supportive bulk under the nipple for correcting moderate and severe nipple inversion . in the present study , we aimed to make a new modification of the teimourian method .\nafter the release of the nipples , the flaps were tunnelised beneath the nipple and the tip of each flap was fixed to the nipple base in reverse s - shaped design .\nthe modified design of the traditional triangular dermal flap procedure provides much more suspension effect as well as filling dead space under the nipple .\nit represents simple and reliable surgical technique to avoid the recurrence of inversion and to provide satisfying shape and projection of the nipple with minimal scar .\nthree nipples of two female patients treated with the reverse s - shaped fixation method are presented . according to the criteria of han and hong , the nipples were classified as grades 2 and 3 [ figure 1 ] .\n( b ) preoperative view of the unilateral case the operation was performed under local anaesthesia .\ntwo opposite linear incisions at 3 and 9 oclock on the two sides of the everted nipple were made within the range of the areola .\nafterwards , the areolar skin was dissected and the epidermis was separated from the dermis over the planned flap area .\nthe base width of the flaps was determined as equal to radius of the nipple .\non the two sides of the triangles with no epithelium , the incisions were deepened into the subcutaneous fatty tissue .\non the two sides of the triangles with no epithelium , two conic shape areolar dermal flaps were created the retracting ducts and fibrous bands beneath the nipple were released with blunt dissection .\nif the nipple was still not free after these dissections , all the retracting ducts were transected so as not to restrict the nipple .\nthe conic shape triangular flaps on both sides of the inverted nipple were turned down and advanced through the tunnel beneath the nipple as the filling tissue for the dead space [ figure 3 ] .\nthe tip of each flap was sutured to the nipple base where any incision was not made at 6 and 12 oclock , also next to the base itself in reverse s shape [ figure 4 ] . because the length of the flap is shorter than the diameter of the areolar external circle , the fixations of the flaps provided a strongly suspending effect and the flaps was completely able to fill out the dead space beneath the nipple .\nany complication was not observed and the patients recovered uneventfully during the follow - up period .\nthe conic - shape triangular flaps on both sides of the inverted nipple were turned down and advanced through the tunnel beneath the nipple as the filling tissue for the dead space the tip of each flap was sutured to the nipple base where any incision was not made at 6 and 12 oclock , also next to the base itself in reverse s shape early postoperative view of the patient\nthree nipples of two female patients treated with the reverse s - shaped fixation method are presented . according to the criteria of han and hong , the nipples were classified as grades 2 and 3 [ figure 1 ] .\n( b ) preoperative view of the unilateral case the operation was performed under local anaesthesia .\ntwo opposite linear incisions at 3 and 9 oclock on the two sides of the everted nipple were made within the range of the areola .\nafterwards , the areolar skin was dissected and the epidermis was separated from the dermis over the planned flap area .\nthe base width of the flaps was determined as equal to radius of the nipple .\non the two sides of the triangles with no epithelium , the incisions were deepened into the subcutaneous fatty tissue . two conic shape areolar dermal flaps\non the two sides of the triangles with no epithelium , two conic shape areolar dermal flaps were created the retracting ducts and fibrous bands beneath the nipple were released with blunt dissection .\nif the nipple was still not free after these dissections , all the retracting ducts were transected so as not to restrict the nipple .\nthe conic shape triangular flaps on both sides of the inverted nipple were turned down and advanced through the tunnel beneath the nipple as the filling tissue for the dead space [ figure 3 ] .\nthe tip of each flap was sutured to the nipple base where any incision was not made at 6 and 12 oclock , also next to the base itself in reverse s shape [ figure 4 ] . because the length of the flap is shorter than the diameter of the areolar external circle , the fixations of the flaps provided a strongly suspending effect and the flaps was completely able to fill out the dead space beneath the nipple .\nany complication was not observed and the patients recovered uneventfully during the follow - up period .\nthe conic - shape triangular flaps on both sides of the inverted nipple were turned down and advanced through the tunnel beneath the nipple as the filling tissue for the dead space the tip of each flap was sutured to the nipple base where any incision was not made at 6 and 12 oclock , also next to the base itself in reverse s shape early postoperative view of the patient\nduring the postoperative follow - up period , surgical complications such as traction pain , infection , haematoma , permanent numbness , or skin necrosis were not observed .\nfollow - up examinations were performed at 3 to 9 months ( average , 6 months ) and revealed no evidence of recurring inversion .\ninverted nipple can simply be defined as nipples that lie on a lower plane than the areola due to shortened lactiferous ducts embedded in short fibrous bands .\nthe grading system by han and hong is commonly used to determine the grade of deformation . according to the grading system , in grade 2 cases , the nipples can be pulled out but can not maintain projection and have strongly tendency to go back again .\nblunt dissection for surgical release should be performed until the inversion does not recur without traction .\nthe lactiferous ducts are mildly retracted and do not need to be cut for the release of fibrosis in the majority of the patients . a temporary traction suture with a suitable dressing is generally preferred after surgery for 2 weeks . in grade 3\ncases , the nipple can hardly be pulled out manually due to the severe fibrosis . for correcting grade 3 cases ,\ntwo or three deepithelialised dermal flaps should be used to make up for soft tissue deficiency after the release of fibrotic bands and a traction suture is also applied postoperatively .\nthere are numerous surgical and nonsurgical techniques introduced in the literature and among these , the incision - release and local flap methods are generally used in the treatment of grades 2 and 3 nipple inversion cases .\nmany of the flap descriptions over the last two decades are designed on the teimourian technique . in these techniques , two or three\ntriangular flaps tunnelled and approximated below the nipple are used to fill the dead space and achieve eversion .\nthe presented method can also be suggested as a modification of the teimourian method and the technique presented by kim et al . in this study , we introduced a new nipple suspension technique using nipple - based dermal flaps for correcting moderately and severely inverted nipples .\nthe most significant difference of the recommended method is in its geometrical design as compared to similar surgical methods using dermal triangular flaps . in our procedure , because two triangular dermal nipple - based areolar flaps are fixed on the opposite side of the nipple base , their geometrically design was called reverse s shape . as a consequence of this design ,\nthe reverse s - shaped fixation of triangular flaps provides more traction effect to keep the nipples in protruded position after they are released .\nthe other advantages and differences of our technique is as follows : \n linear incision is used to create the triangular flaps on the areola , thus the scar is more uneventful and minimal;the operation time is relatively shorter because the flaps are raised without deepithelialisation;the triangular dermal flaps provide enough bulk beneath the inverted nipple;the size of the triangular flap is slightly shorter than the diameter of the areola , the flaps cause an efficiently suspending effect under the released nipple ; andthe lactiferous ducts can be preserved in grade 2 cases or if the women particularly hope to breast feeding . \n \nlinear incision is used to create the triangular flaps on the areola , thus the scar is more uneventful and minimal ; the operation time is relatively shorter because the flaps are raised without deepithelialisation ; the triangular dermal flaps provide enough bulk beneath the inverted nipple ; the size of the triangular flap is slightly shorter than the diameter of the areola , the flaps cause an efficiently suspending effect under the released nipple ; and the lactiferous ducts can be preserved in grade 2 cases or if the women particularly hope to breast feeding . the technique introduced is not to be able to preserve the lactiferous tubules .\nhowever it is well - known that these functional units beneath the nipple areolar complex may already be absent in grade 2 and especially grade 3 inverted nipple cases .\noptimal surgical procedure in the treatment of the moderate or severe nipple inversion cases should provide a satisfying shape , sufficient projection and preserve ductal function when required . in conclusion , as an alternative nipple suspending method , the reverse s - shaped fixation method of triangular flaps is recommended to be used in any kind of nipple inversion with satisfying results and minimal scar .",
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"content": "the primary aim in the treatment of inverted nipple is to achieve a satisfactory and permanent projection of the nipple . \n the drawbacks of reported techniques include sensory disturbance of the nipple , marked scarring of the nipple and areola , destruction of breast function and incomplete correction . in the present study , \n the authors introduced a new modification of using two opposite nipple - based areolar dermal flap in the treatment of grades 2 and 3 inverted nipple cases . \n nipple - based areolar flaps designed at 3 oclock and 9 oclock were raised by two linear incisions and the tip of each flap was sutured on the base of the nipple close to the base itself in a reverse s shape at 6 and 12 oclock . \n successful outcome was obtained due to a strongly suspending effect of the design of the flaps . \n the mean follow - up period was 6 months . \n the patients were satisfied with the result and the scars were minimal . \n the authors recommend the use of the technique that is a simple , reliable and with minimal scars for correcting grades 2 and 3 inverted nipples .",
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science.scientific_papers_summarization_single_doc_pubmed | science.scientific_papers_summarization_single_doc_pubmed.1448 | [
{
"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:\nurinary stones are rarely seen in the urethra and are usually encountered in men with urethral stricture or diverticulum .\nurethral diverticula can present in many ways , including recurrent urinary tract infections ( utis ) , dysuria , increased urinary frequency , urgency , and hematuria .\nin addition to causing the symptoms above , diverticula also can be complicated with stones or malignancy , both of which can lead to bladder outlet or urethral obstruction . stone formation has been reported to occur in 1% to 10% of patients with urethral diverticula .\nurinary stasis and chronic infection have been identified as the causes of calculi formation within urethral diverticula .\nthe case of a woman with a giant calculus in a urethral diverticulum is reported .\na 62-year - old woman was first seen in the urology clinic complaining of a 1-year history of constant lower abdominal pain , dysuria , and dyspareunia .\nshe also noted an increase in the volume of the vaginal wall that coincided with an increase of pain in this area .\nwritten informed consent was obtained from the patient for the publication of this case report and any accompanying images .\nthe general patient examination was normal , but a focused genital examination revealed a large mass of approximately 4 cm near the urethra .\nwhen compressing the urethra , leakage of purulent discharge from the meatal orifice was noted . a kidney , ureter , bladder x - ray showed a giant calculi ( figure 1 ) , and cystoscopy revealed an extrusion of the posterolateral distal urethra . on admission , vital signs were all normal and laboratory tests demonstrated microscopic pyuria ( 2030/high power field ) .\nthe diverticulum was punctured by electrocautery and dissected with periurethral tissue , which allowed total removal of the calculi ( figure 2 ) . a tagged 3 - 0 with silk suture\nthe foley catheter was kept in place for 7 days . oral antibiotic therapy with ciprofloxacin\nthe estimated prevalence of urethral diverticula in adult women is between 0.6% and 6% , and associated stone formation is reported in 1.5% to 10% of cases .\nthe cause of diverticula remains largely unknown and ranges from congenital to traumatic ( instrumentation , childbirth ) to infectious causes .\nthe formation of abscesses and these may rupture into the urethral lumen , forming the diverticula . the quality of life of patients who have a diverticulum ( especially with calculi ) may be significantly disturbed because of complications such as dysuria , dyspareunia , uti , and postvoid dribbling .\nany patient with lower urinary tract symptoms that have proved to be unresponsive to traditional treatment should be suspected of having a urethral diverticulum . in patients with urethral diverticula\nother ways to confirm a diagnosis of urethral diverticula are voiding cystourethrogram , intravenous pyelography , and ultrasonography .\npresumably , a stone should also be visualized within the diverticula by one of these diagnostic modalities .\nthe issues that remain focus on determining symptomatic relief by conservative therapy , assessing satisfactory long - term treatment of diverticulum , and determining the possible benefit from surgical excision . however , the confirmation of number , site , and size of the diverticulum is important before operation to prevent complications such as urethral stricture , urethro - vaginal fistula and incontinence due to injury of sphincter .\ndiagnosis of a complicated diverticulum can be easily achieved if one possesses a high degree of clinical suspicion .\nthus , this diagnosis should be considered in the case of recurrent utis , hematuria , and dysuria , as well as in patients with masses felt on pelvic examination . surgical approach with litholapaxy followed by diverticulectomy",
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"content": "abstracturethral diverticula with calculi have a low incidence as reported in the literature . \n diverticulum of female urethra is rare , often discovered due to associated complications . \n we report a case of diverticulum of the female urethra containing giant calculi in a 62-year - old multiparous woman . \n she consulted with our office due to dysuria and a hard , painful periurethral mass in the anterior vagina wall . \n the diverticulum was approached surgically by a vaginal route , and local extraction of the calculi and subsequent diverticulectomy successfully treated the condition.diagnosis of a complicated diverticulum can be easily achieved if one possesses a high degree of clinical symptoms .",
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science.scitldr_aic | science.scitldr_aic.1258 | [
{
"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\nGenerative adversarial networks (GANs) are a class of deep generative models which aim to learn a target distribution in an unsupervised fashion.\nWhile they were successfully applied to many problems, training a GAN is a notoriously challenging task and requires a significant amount of hyperparameter tuning, neural architecture engineering, and a non-trivial amount of ``tricks\".\nThe success in many practical applications coupled with the lack of a measure to quantify the failure modes of GANs resulted in a plethora of proposed losses, regularization and normalization schemes, and neural architectures.\nIn this work we take a sober view of the current state of GANs from a practical perspective.\nWe reproduce the current state of the art and go beyond fairly exploring the GAN landscape.\nWe discuss common pitfalls and reproducibility issues, open-source our code on Github, and provide pre-trained models on TensorFlow Hub.\nDeep generative models are a powerful class of unsupervised machine learning models.\nThe power of these models was recently harnessed in a variety of applications, including image generation, learned compression, and domain transfer BID13 Radford et al., 2016; BID0 BID0 .\nGenerative adversarial networks BID8 are one of the main approaches to learning such models in a fully unsupervised fashion.\nThe GAN framework can be viewed as a two-player game where the first player, the generator, is learning to transform some simple input distribution (usually a standard multivariate Normal or uniform) to a distribution on the space of images, such that the second player, the discriminator, cannot tell whether the samples belong to the true distribution or were synthesized.\nBoth players aim to minimize their own loss and the solution to the game is the Nash equilibrium where neither player can improve their loss unilaterally.\nThis powerful framework can also be derived by minimizing a divergence between the model distribution and the true distribution BID20 .Training\nGANs involves solving a minimax problem over the parameters of the generator and the discriminator which are usually parameterized as deep convolutional neural networks. Consequently\n, this minimax problem is notoriously hard to solve in practice. As a result\n, a plethora of loss functions, regularization and normalization schemes, coupled with neural architecture choices, have been proposed BID8 Salimans et al., 2016; BID19 BID9 BID18 .Our contributions\n. In this work we\nprovide a thorough empirical analysis of these competing approaches, and help the researchers and practitioners navigate this space. We first define\nthe GAN landscape -the set of loss functions, normalization and regularization schemes, and the most commonly used architectures. We explore this\nsearch space on several modern large-scale data sets by means of hyperparameter optimization, considering both \"good\" sets of hyperparameters reported in the literature, as well as ones obtained by Gaussian Process regression. By analyzing the\nimpact of the loss function, we conclude that the non-saturating loss is sufficiently stable across data sets, architectures and hyperparameters. We then proceed\nto decompose the effect of various normalization and regularization schemes, as well as varying architectures. We show that both\ngradient penalty BID9 as well as spectral normalization BID19 are useful in the context of high-capacity architectures. Finally, we discuss\nsome common pitfalls, reproducibility issues, and practical considerations. We provide reference\nimplementations, including training and evaluation code on Github 1 and provide pre-trained models on TensorFlow Hub. 2 2 THE GAN LANDSCAPE\nGiven that there are 4 major components (loss, architecture, regularization, normalization) to analyze for each data set, it is infeasible to explore the whole landscape.\nHence, we opt for a more pragmatic solution -we keep some dimensions fixed, and vary the others.\nFor each experiment we highlight three aspects: (1) FID distribution of the top 5% of the trained models, (2) the corresponding sample diversity score, and (3) the tradeoff between the computational budget (i.e. number of models to train) and model quality in terms of FID.\nEach model was retrained 5 times with a different random seed and we report the median score.\nThe variance for models obtained by Gaussian Process regression is handled implicitly so we train each model once.\nIn this work we study the GAN landscape: losses, regularization and normalization schemes, and neural architectures, and their impact on the on the quality of generated samples which we assess by recently introduced quantitative metrics.\nOur fair and thorough empirical evaluation suggests that one should consider non-saturating GAN loss and spectral normalization as default choices when applying GANs to a new data set.\nGiven additional computational budget, we suggest adding the gradient penalty from BID9 and train the model until convergence.\nFurthermore, additional marginal gains can be obtained by combining normalization and regularization empirically confirming the importance of the Lipschitz constant of the discriminator.\nFurthermore, both types of architectures proposed up-to this point perform reasonably well.\nA separate ablation study uncovered that most of the tricks applied in the ResNet style architectures lead to marginal changes in the quality and should be avoided due to the high computational cost.\nAs a result of this large-scale study we identify the common pitfalls standing in the way of accurate and fair comparison and propose concrete actions to demystify the future results -issues with metrics, data set preprocessing, non-determinism, and missing implementation details are particularly striking.\nWe hope that this work, together with the open-sourced reference implementations and trained models, will serve as a solid baseline for future GAN research.\nWe present an empirical study with SNDCGAN and ResNet CIFAR architectures on CIFAR10 in figure 5 and figure 6 .\nIn addition to Section 3.1, we evaluate one more kind of loss on CIFAR10.\nHere HG, NS and WGAN stand for hinge loss, non saturating loss and Wasserstein loss respectively.\nWe observe that hinge loss performs very similar to non-saturating loss.\nDISPLAYFORM0",
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"content": "A sober view on the current state of GANs from a practical perspective",
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science.bioasq_factoid_qa | science.bioasq_factoid_qa.31 | [
{
"content": "Given the following biomedical passages, answer the question succinctly. Ensure your response is precise and limited to the answer only.\n\nQuestion: How many clinical trials for off-label drugs in neonates are cited in the literature.\n\nPassages: Of the 17 Paediatric Investigation Plans submitted, 14 have resulted in an EMA Decision, 3 were withdrawn by the applicants, 8 were granted a full waiver from development, and 1 resulted in a negative opinion. Decisions as issued included 15 clinical trials, with at least 1,282 children to be recruited into studies across five different products. Neonates were included in four of the products. CONCLUSIONS: The small number of submissions indicates a lack of new drugs being developed for the management of pain. Ethical concerns that too many vulnerable children will be recruited into clinical trials must be balanced against limiting the number of off-label prescribing and obtaining age-appropriate information on paediatric use.\nPaediatric Investigations Plans (PIPs) submitted with a Decision (outcome) reached between September 2007 and March 2010 were included in the analysis.",
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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.16067 | [
{
"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: Unmet needs for analyzing biological big data: A survey of 704 NSF principal investigators\nContent:\nAbstract:\nIn a 2016 survey of 704 National Science Foundation( NSF) Biological Sciences Directorate principal investigators( BIO PIs), nearly 90% indicated they are currently or will soon be analyzing large data sets. BIO PIs considered a range of computational needs important to their work, including high performance computing( HPC), bioinformatics support, multistep workflows, updated analysis software, and the ability to store, share, and publish data. Previous studies in the United States and Canada emphasized infrastructure needs. However, BIO PIs said the most pressing unmet needs are training in data integration, data management, and scaling analyses for HPC—acknowledging that data science skills will be required to build a deeper understanding of life. This portends a growing data knowledge gap in biology and challenges institutions and funding agencies to redouble their support for computational training in biology.\nIntroduction:\nGenotypic data based on DNA and RNA sequences have been the major driver of biology’s evolution into a data science. The current Illumina HiSeq X sequencing platform can generate 900 billion nucleotides of raw DNA sequence in under 3 days—4 times the number of annotated nucleotides currently stored in GenBank, the United States “reference library” of DNA sequences[1, 2]. In the last decade, a 50, 000-fold reduction in the cost of DNA sequencing[3] has led to an accumulation of 9. 3 quadrillion( million billion) nucleotides of raw sequence data in the National Center for Biotechnology Information( NCBI) Sequence Read Archive( SRA). The amount of sequence in the SRA doubled on average every 6–8 months from 2007–2016[4, 5]. It is estimated that by 2025, the storage of human genomes alone will require 2–40 exabytes[5]( an exabyte of storage would hold 100, 000 times the printed materials of the U. S. Library of Congress[6]). Beyond genotypic data, big data are flooding biology from all quarters—phenotypic data from agricultural field trials, patient medical records, and clinical trials; image data from microscopy, medical scanning, and museum specimens; interaction data from biochemical, cellular, physiological, and ecological systems; as well as an influx of data from translational fields such as bioengineering, materials science, and biogeography. A 2003 report of a National Science Foundation( NSF) blue-ribbon panel, headed by Daniel Atkins, popularized the term cyberinfrastructure to describe systems of data storage, software, high performance computing( HPC), and people who can solve scientific problems of the size and scope presented by big data[7]. The report was the impetus for several cyberinfrastructure projects in the biological sciences, including the NSF’s CyVerse, the Department of Energy’s KBase, and the European Grid Infrastructure and the European Life Sciences Infrastructure for Biological Information( ELIXIR)[8]. The Atkins Report described cyberinfrastructure as the means to harness the data revolution and to develop a “knowledge economy. ” Although people were acknowledged as active elements of cyberinfrastructure, few published studies have assessed how well their computational and cyberinfrastructure needs are being met. In 2006, EDUCAUSE surveyed 328 information technology( IT) professionals, primarily chief information officers, at institutions in the US and Canada[9]. When asked about preferences for funding allocation, respondents rated training and consulting( 20%) a distant second to infrastructure and storage( 46%). This suggested that “training and consulting get short shrift when bumped against the realities of running an IT operation”[9]. Similarly, infrastructure and training emerged as important needs in a study done as part of the 2015 University of Illinois’s “Year of Cyberinfrastructure”[10]. Faculty and graduate students responding to a survey( n = 327) said they needed better access to data storage( 36%), data visualization( 29%), and HPC( 19%). Training was not addressed in the initial survey, suggesting that it was not viewed as integral to discussions of cyberinfrastructure. However, it emerged as a major need in follow-up focus groups( n = 200). Over the last 4 years, CyVerse has taken the computational pulse of the biological sciences by surveying attendees at major professional meetings. Consistently and across different conference audiences, 94% of students, faculty, and researchers said that they currently use large data sets in their research or think they will in the near future( n = 1, 097). Even so, 47% rated their bioinformatics skill level as “beginner, ” 35% rated themselves “intermediate, ” and 6% said they have never used bioinformatics tools; only 12% rate themselves “advanced”( n = 608); 58% felt their institutions do not provide all the computational resources needed for their research( n = 1, 024). These studies suggest a scenario of big data inundating unprepared biologists.\nDiscussion:\nThis study fills a gap in the published literature on the computational needs of biological science researchers. Respondents had all been awarded at least 1 peer-reviewed grant from NSF BIO and thus represent competitive researchers across a range of biological disciplines. Even so, a majority of this diverse group of successful biologists did not feel that their institutions are meeting their needs for tackling large data sets. This study stands in stark contrast to previous studies that identified infrastructure and data storage as the most pressing computational needs[9, 10]. BIO PIs ranked availability of data storage and HPC lowest on their list of unmet needs. This provides strong evidence that the NSF and individual universities have succeeded in developing a broadly available infrastructure to support data-driven biology. Hardware is not the issue. The problem is the growing gap between the accumulation of many kinds of data—and researchers’ knowledge about how to use them effectively. The biologists in this study see training as the most important factor limiting their ability to best use the big data generated by their research. Closing this growing data knowledge gap in biology demands a concerted effort by individual biologists, by institutions, and by funding agencies. We need to be creative in scaling up computational training to reach large numbers of biologists at all phases of their education and careers and in measuring the impact of our educational investments. Metrics for a supercomputer are readily described in terms of petaflops and CPUs, and we can facilely measure training attendance and “satisfaction. ” However, answering unmet training needs will require a better understanding of how institutions are attempting to meet these needs—and how we can best assess their outcomes[11]. Some solutions already exist. For example, data sets available at the SRA provide almost unlimited entry points for course-based undergraduate research experiences( CUREs), which scale up discovery research in the context of for-credit courses. Participation in CUREs significantly improves student graduation rates and retention in science—effects that persist across racial and socioeconomic status[12, 13]. However, many biologists acquire skills for big data analysis on their own, in the midst of their careers. Software Carpentry and Data Carpentry[14] are volunteer-driven organizations that provide a cost-effective, disseminated model for reaching biologists outside of an academic classroom. Reflected in the top 2 unmet needs of BIO PIs is the looming problem of integrating data from different kinds of experiments and computational platforms. This will be required for a deeper understanding of “the rules of life”[15, 16]—notably, genotype-environment-phenotype interactions that are essential to predicting how agricultural plants and animals can adapt to changing climates. Such integration demands new standards of data management and attention to metadata about how these data are collected. The BIO PIs in this study are anticipating a new world of pervasive data and the training they will need to become data scientists. Likewise, funding agencies need to recognize that significant new investments in training are now required to make the best use of the biological data infrastructures they have helped establish over the last decade.",
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"content": "Our computational needs assessment of 704 principal investigators ( PIs ) with grants from the National Science Foundation ( NSF ) Biological Sciences Directorate ( BIO ) confirmed that biology is awash with big data . Nearly 90% of BIO PIs said they are currently or will soon be analyzing large data sets . They considered a range of computational needs important to their work , including high performance computing ( HPC ) , bioinformatics support , multistep workflows , updated analysis software , and the ability to store , share , and publish data . However , a majority of PIs—across bioinformatics and other disciplines , large and small research groups , and 4 NSF BIO programs—said their institutions are not meeting 9 of 13 needs . Training on integration of multiple data types ( 89% ) , on data management and metadata ( 78% ) , and on scaling analysis to cloud/HPC ( 71% ) were the 3 greatest unmet needs . Hardware is not the problem; data storage and HPC ranked lowest on their list of unmet needs . The problem is the growing gap between the accumulation of big data—and researchers’ knowledge about how to use it effectively .",
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science.craftchem_ner | science.craftchem_ner.2977 | [
{
"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:\nGeneration,maintenanceanddifferentiationofCbCln3cerebellarneuronalprecursorlines",
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.35277 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nCHEMICAL SENSING BASED ON CATALYTIC NANOMOTORS: MOTION-BASED DETECTION OF TRACE SILVER\n\nContent Extracts:\n\n<p>Considerable recent efforts have been devoted to the development of artificial nanomotors.1 In particular, fuel-driven bisegment Au-Pt nanowires exhibit autonomous self-propulsion due to electrocatalytic decomposition of hydrogen peroxide fuel.1,2 Such autonomous motion of catalytic nanowire motors holds great promise for exciting applications ranging from drug-delivery, nanoscale assembly and transport, or motion-based biosensing.1</p><p>This Communication reports on the first example of using catalytic nanomotors for motion-based chemical sensing, and particularly for specific detection of trace silver ions. During recent experiments in our laboratory involving electrochemically-triggered motion of catalytic nanowire motors3 we observed unusual speed acceleration associated with silver ions generated at a pseudo silver-wire reference electrode placed in the vicinity of the nanowire motors. Such unexpected specific silver effect upon the speed of catalytic nanomotors has been exploited in the present work for designing a new motion-based silver sensing protocol. The new protocol relies on the use of an optical microscope for tracking the speed of nanowire motors and offers highly selective, sensitive and simple measurements of trace silver based on direct visualization.</p><p>Figure 1A displays traces of Au-Pt nanomotors (over a 3 second period), taken from videos of the nanowires in the presence of eleven different cations (100 µM each), along with the peroxide fuel. Ten of these cations caused a significant speed reduction, including a Brownian motion or a slower non-Brownian motion (with speeds ranging from 0.3 to 7.1 µm s−1). Such slow speed (compared to a actual speed of ~10 µm s−1 observed without these salts) is consistent with the self-electrophoresis mechanism for the propulsion of catalytic nanomotors,4 where the speed decreases linearly with the solution conductivity.5 In contrast, the nanomotors move over a dramatically longer path in the presence of silver (shown in the middle), displaying an average speed of 52 µm s−1. Also shown in Figure 1 (B) is the histogram depicting the average speed of the nanomotors in the presence of the different cations tested. These data, along with the corresponding video (shown in the SI; Video 1), clearly illustrate the remarkably selective acceleration in the presence of silver. Adding other cations (e.g., Pb2+ or K+ up to 5 µM) had only slight reductions in the speed signal in the presence of the silver analyte. Apparently, the presence of a silver ion can greatly minimize the ionic-strength limitation of catalytic nanomotors. High speed of ~20 µm s−1 was maintained in the presence of 0.1 mM K+ (compared to a slow motion of 7 µm s−1 observed for K+ without the silver). Higher (>mM) salt concentrations, however, led to the expected conductivity-induced speed diminution.</p><p>The highly selective motion-based response is characterized also with a defined concentration dependence, with the speed (or distance) providing the quantitative information. Figure 2 (A–D) displays track lines of the catalytic nanomotors (over a 2 second period) obtained in the presence of different silver concentrations (0, 1, 10 and 100 µM; A–D). These traces indicate clearly that the nanomotors travel longer distances (ranging from 19–104 µm) upon increasing the silver concentration. Such paths correspond to speeds ranging from 9.6 µm s−1 (without silver) to 52 µm s−1 (at 100 µM silver). Also shown in Figure 2E is a calibration plot of the speed vs. silver concentration over the 10−9 to 10−4 M range. Such plot displays a defined concentration dependence over the 0.5 to 100 µM range, along with a negligible concentration effect at lower Ag(I) levels. The well-defined concentration dependence is clearly illustrated from the corresponding videos (shown in SI Video 2). Note that the behavior observed in Figure 2 is conflicting to what commonly expected upon increasing the salt concentration.5</p><p>Several possible mechanisms have been considered to explain the unusual acceleration of Au-Pt nanomotors in the presence of silver ions. The most promising explanation relies on the underpotential deposition (UPD) of silver on the Au-Pt nanowires. With the addition of silver ions, these ions adsorb over the nanowire surface and are then reduced in the presence of hydrogen peroxide. Energy dispersive X-ray spectroscopy (EDX) measurements confirmed the presence of metallic silver over the Pt and Au segments of the nanowires (at 13 and 0.4 Ag atomic %, respectively), following a 0.5 hour exposure to the silver-nitrate/hydrogen-peroxide solution. A clear change of the color of the Pt segment was observed from analogous SEM experiments. No such compositional or color changes were observed in the presence of silver alone (without hydrogen peroxide). As will be illustrated below, a similar silver deposition was observed on platinum and gold nanorods. In addition, nanomotors exposed to a 100 µM Ag(I)/5% H2O2 solution for 0.5 and 24 hours, followed by an thorough wash with nanopure water, displayed high speeds of 20 and 35 µm s−1, respectively, in a fresh silver-free 5% H2O2 solution. These data confirm that the deposited Ag(0), rather than the dissolved Ag(I), is responsible for the accelerated motion. The possibility of depositing Ag(0) by UPD onto gold nanorods and platinum surfaces was discussed by several groups.6</p><p>Such silver deposition onto catalytic nanowires can lead to differences in the surface and catalytic properties (and hence to a faster the axial speed). Deposition of silver onto the Au segment increases the mixed potential difference (ΔE) between the anodic and cathodic segments, leading to an accelerated nanomotor motion in a manner similar to that reported recently for high-speed alloy nanomotors.7 Similarly, the silver deposition onto the Pt segment may make it a more catalytically active. The accelerated electrocatalytic decomposition of hydrogen peroxide was indicated also from the sharp decline of the motor speed following a 10 min exposure to the silver ion (compared to a longer ~30 min period observed without silver). The fast speed was then restored upon restoring the initial fuel level.</p><p>To isolate the role of the individual segments upon the speed acceleration, the motility of monocomponent Pt and Au nanorods was examined in the presence of silver nitrate. Surprisingly, monocomponent Pt rods displayed a dramatic acceleration from 3.5 to 22.6 µm s−1 in the presence of 10 µM silver ion (Video 3 SI). Monocomponent Au nanorods, in contrast, display a Brownian motion in the presence and absence of Ag(I). The EDX data of Figure 1 SI confirm the presence of silver on monocomponent Pt and Au nanowires, with Ag(0) values of up to 18 and 10 (Ag atomic %), respectively. Apparently, the Ag(0) deposition onto monocomponent platinum nanowires leads to the asymmetry (bimetal character) essential to induce the electrocatalytic propulsion. This is in agreement with a recent hydrogen-peroxide based fuel cell study where a Pt-Ag (anodecathode) combination exhibits the highest current density compared to other anode–cathode combinations, including Au-Ag one.8 Similarly, it was reported that Au-Ag bimetallic nanowire motors have a very slow speed of 6 µm s−1.4 The self-diffusiophoresis mechanism9 may also be considered for explaining the silver effect. Here, the deposition of silver over the nanomotors increases the localized gradient of reaction products around the nanomotors, leading to a diffusiophoretic movement of nanomotor.9 Such ionic gradient around the nanomotors results in a net electric field in solution that facilitates the increased speed.</p><p>In summary, we have described the first example of motion-based chemical sensing involving fuel-driven nanomotors. Effective measurements of trace Ag(I) have been accomplished based on the dramatic and specific acceleration of bimetal nanowire motors in the presence of this ion. While these initial data clearly demonstrate the utility of catalytic nanomotors for measuring micromolar concentrations of silver, additional work is required towards a better understanding of the unusual silver effect or the defined concentration dependence and for adapting the new concept for practical real-life applications. The presence of silver also facilitates the operation of catalytic nanomotors in conducting media that were not accessible earlier to catalytic nanomotors. While the new concept of motion-based sensing has been illustrated for trace measurements of Ag(I), we anticipate that it would lead to a wide range of novel sensing protocols. Current efforts in our laboratory examine new bioaffinity displacement assays based the ability of a target biomolecule to trigger the movement of an anchored nanomotor. We expect that such motion-based bioassays would lead to remarkable sensitivity, reflecting the ability to detect single-binding events.</p><p>Motion of Au-Pt catalytic nanomotors in a 5% H2O2 solution containing 11 common cations. (A) Image displaying 3-sec track lines for the movement of 5 randomly selected nanomotors in 11 different 100 µM metal-nitrate salt solutions (of K+, Pd2+, Ni2+, Mn2+, In3+, Ag+, Cd2+, Ca2+, Cu2+, Pb2+ and Bi3+). (B) Corresponding bar graph comparing the average nanomotors speed (conditions, as in A). Error bars for n=20.</p><p>Track lines of nanomotors illustrating the distances traveled by five Au-Pt nanowires in the presence of different Ag(I) concentrations: 0 (A), 1 (B), 10 (C) and 100 (D) µM, along with 5 wt% H2O2 fuel solution. (E) A calibration curve for Ag(I) over the micromolar range (0.5–100 µM). Other conditions, as in Figure 1.</p>",
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"content": "A motion-based chemical sensing involving fuel-driven nanomotors is demonstrated. The new protocol relies on the use of an optical microscope for tracking changes in the speed of nanowire motors in the presence of the target analyte. Selective and sensitive measurements of trace silver ions are illustrated based on the dramatic and specific acceleration of bimetal nanowire motors in the presence of silver. Such nanomotor-based measurements would lead to a wide range of novel and powerful chemical and biological sensing protocols.",
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science.scicite_classification | science.scicite_classification.2378 | [
{
"content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nThe existing string matching approaches in [8], [10], and [4] were implemented.",
"role": "user"
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{
"content": "Method",
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.5436 | [
{
"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 Distributed File Systems \nChapter Title: Design Considerations \n1. Abstract of Cited Paper (BIB001): The Andrew File System is a location-transparent distributed tile system that will eventually span more than 5000 workstations at Carnegie Mellon University. Large scale affects performance and complicates system operation. In this paper we present observations of a prototype implementation, motivate changes in the areas of cache validation, server process structure, name translation, and low-level storage representation, and quantitatively demonstrate Andrews ability to scale gracefully. We establish the importance of whole-file transfer and caching in Andrew by comparing its performance with that of Sun Microsystems NFS tile system. We also show how the aggregation of files into volumes improves the operability of the system. \n2. Abstract of Cited Paper (BIB002): Scale should be recognized as a primary factor influencing the architecture and implementation of distributed systems. This paper uses Andrew, a distributed environment at Carnegie Mellon University, to validate this proposition. The design of Andrew is dominated by considerations of performance, operability and security. Caching of information and placing trust in as few machines as possible emerge as two general principles that enhance scalability. The separation of concerns made possible by specialized mechanisms is also valuable. Heterogeneity is a natural consequence of growth and anticipating it in the initial stages of system design is important. A location transparent shared file system considerably enhances the usability of a distributed environment.\n\nReview Chapter:",
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"content": "Since its introduction in 1985, the Sun Microsystems Network File System (NFS) has been widely used in industry and academia. In addition to its technical innovations it has played a significant educational role in exposing a large number of users to the benefits of a distributed file system. Other vendors now support NFS and a significant fraction of the user community perceives it to be a de facto standard. Portability and heterogeneity are two considerations that have played a dominant role in the design of NFS. Although the original file system model was based on Unix, NFS has been ported to to non-Unix operating systems such as PC-DOS. To facilitate portability, Sun makes a careful distinction between the NFS protocol, and a specific implementation of an NFS server or client. The NFS protocol defines an RPC interface that allows a server to export local files for remote access. The protocol does not specify how the server should implement this interface, nor does it mandate how the interface should be used by a client. Design details such as caching, replication, naming, and consistency guarantees may vary considerably in different NFS implementations. In order to focus our discussion, we restrict our attention to the implementation of NFS provided by Sun for its workstations that run the SunOS flavor of Unix. Unless otherwise specified, the term ''NFS'' will refer to this implementation in the rest of this paper. The term ''NFS protocol'' will continue to refer to the generic interface specification. SunOS defines a level of indirection in the kernel that allows file system operations to be intercepted and transparently routed to a variety of local and remote file systems. This interface, often referred to as the vnode interface after the primary data structure it exports, has been incorporated into many other versions of Unix. With a view to simplifying crash recovery on servers, the NFS protocol is designed to be stateless. Consequently, servers are not required to maintain contextual information about their clients. Each RPC request from a client contains all the information needed to satisfy the request. To some degree functionality and Unix compatibility have been sacrificed to meet this goal. Locking, for instance, is not supported by the NFS protocol, since locks would constitute state information on a server. SunOS does, however, provide a separate lock server to perform this function. Sun workstations are often configured without a local disk. The ability to operate such workstations without significant performance degradation is another goal of NFS. Early versions of Sun workstations used a separate remote-disk network protocol to support diskless operation. This protocol is no longer necessary since the kernel now transforms all its device operations into file operations. A high-level overview of NFS is presented by Walsh et al . Details of its design and implementation are given by Sandberg et al . Kleiman describes the vnode interface, while Rosen et al comment on the portability of NFS. The DOMAIN system, built by Apollo Computers Inc., is a distributed workstation environment whose development began in the early 1980s. The goal of this system was to provide a usable and efficient computing base for a close-knit team of collaborating individuals. Athough scale was not a dominant design consideration, large Apollo installations now exist. The largest of these is located at the Apollo corporate headquarters and encompasses over 3500 nodes. Apollo workstations range in hardware capability from small, diskless units to large configurations with disks and other peripherals. The underlying network technology is a proprietary 12 Mbit token ring BIB001 . Installations may choose to treat some of their nodes as dedicated servers that run only system software, and other nodes as clients performing user computations. Such a dichotomy is only a matter of convention. The DOMAIN software treats all nodes as peers. Andrew is a distributed workstation environment that has been under development at Carnegie Mellon University since 1983. It combines the rich user interface characteristic of personal computing with the data sharing simplicity of timesharing. The primary data-sharing mechanism is a distributed file system spanning all the workstations. Using a set of trusted servers, collectively called Vice, the Andrew file system presents a homogeneous, locationtransparent file name space to workstations. Clients and servers both run the 4.3 BSD version of Unix. It is a relatively heavyweight operation to configure a machine as an Andrew server. This is in contrast to systems such as Sun NFS, where it is trivial for any machine to export a subset of its local file system. Scalability is the dominant design consideration in Andrew. Many design decisions in Andrew are influenced by its anticipated final size of 5000 to 10000 nodes, Careful design is necessary to provide good performance at large scale and to facilitate system administration. Scale also renders security a serious concern, since it has to be enforced rather than left to the good will of the user community. The goals and directions of the Andrew project have been described by Morris et al . The file system has been discussed extensively in papers focusing on architecture , performance BIB002 , security , and the influence of scale BIB003 . The Andrew file system has undergone one complete revision, and a second revision is under way .",
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science.qasa_abstractive_qa | science.qasa_abstractive_qa.1506 | [
{
"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: The details of text-conditioning in text-to-image diffusion models are of high importance for visual quality and semantic fidelity. Ramesh et al. ramesh2022hierarchical use CLIP text embeddings that are translated into image embeddings using a learned prior, while Saharia et al. saharia2022photorealistic use a pre-trained T5-XXL language model raffel2020exploring . In our work, we use the latter.Language models like T5-XXL generate embeddings of a tokenized text prompt, and vocabulary encoding is an important pre-processing step for prompt embedding. In order to transform a text prompt \\mathbf{P} into a conditioning embedding \\mathbf{c}, the text is first tokenized using a tokenizer f using a learned vocabulary. Following saharia2022photorealistic , we use the SentencePiece tokenizer kudo2018sentencepiece . After tokenizing a prompt \\mathbf{P} using tokenizer f we obtain a fixed-length vector f(\\mathbf{P}). The language model \\Gamma is conditioned on this token identifier vector to produce an embedding \\mathbf{c}\\coloneqq\\Gamma(f(\\mathbf{P})). Finally, the text-to-image diffusion model is directly conditioned on \\mathbf{c}.\n\nInquiry: Which language model is used for vocabulary encoding and why?",
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"content": "CLIP and T5-XXL language models are used for translating noise into image embeddings. Authors’ used T5-XXL for their model. Vocabulary encoding is a pre-processing step for these language models which is used to convert the prompt into a condition embedding vector.",
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science.acl_arc_intent_classification | science.acl_arc_intent_classification.389 | [
{
"content": "Examine the given text from a research paper in the field of NLP. Your task is to identify the role of the citation within the context provided. Focus on understanding the intent behind the citation and classify it accordingly.\n\nSection Title:\nrelated work\n\nText Before Citation:\nThe feature of head word trigger which we apply to the log-linear model is motivated by the trigger-based approach (Hasan and Ney, 2009). Besides, our system complexity is not increased because no additional language model is introduced. The basic difference of our method from (Shen et al., 2008) is that we keep rules that both sides should be relaxed-wellformed dependency structure, not just the target side.\n\nCitation Text:\nThe feature of head word trigger which we apply to the log-linear model is motivated by the trigger-based approach ( Hasan and Ney , 2009 ) .\n\nText After Citation:\nHasan and Ney (2009) introduced a second word to trigger the target word without considering any linguistic information. Furthermore, since the second word can come from any part of the sentence, there may be a prohibitively large number of parameters involved. Besides, He et al. (2008) built a maximum entropy model which combines rich context information for selecting translation rules during decoding. However, as the size of the corpus increases, the maximum entropy model will become larger.",
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"content": "Motivation",
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science.bioasq_yesno_qa | science.bioasq_yesno_qa.956 | [
{
"content": "Examine the provided biomedical text and determine the answer to the question. Your response should be either \"yes\" or \"no\" based on the information given.\n\nQuestion: Does nintedanib hold promise for lung disease associated with systemic sclerosis?\n\nText: The patient developed progressive lung fibrosis under several immunosuppressants and was started on nintedanib, with clinical and functional stabilization. Nintedanib is a tyrosine-kinase inhibitor that blocks several profibrotic pathways, inhibiting proliferation and migration of fibroblasts and decreasing the synthesis of extracellular matrix proteins. It is approved for idiopathic lung fibrosis and has demonstrated good results in inhibiting migration and proliferation of systemic sclerosis dermal fibroblasts, constituting a promising agent for systemic sclerosis-associated lung fibrosis.\nBACKGROUND: Nintedanib is an inhibitor targeting platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases that has recently been approved for the treatment of idiopathic pulmonary fibrosis.\nCONCLUSION: Nintedanib targets core features of SSc in Fra2-transgenic mice and ameliorates histological features of pulmonary arterial hypertension, destructive microangiopathy and pulmonary and dermal fibrosis. These data might have direct implications for the ongoing phase III clinical trial with nintedanib in SSc-associated interstitial lung disease.\nIn light of the ongoing advances in our understanding of the pathogenic mechanisms underlying interstitial lung disease in systemic sclerosis, this review also summarizes novel treatment approaches, presenting clinical and preclinical evidence for rituximab, tocilizumab, pirfenidone, and nintedanib, as well as hematopoietic stem cell transplantation and lung transplantation.\nPirfenidone and nintedanib are emerging agents that exert pleiotropic effects, reflective of the multiple mechanistic pathways of IPF.\nDesign of a randomised, placebo-controlled clinical trial of nintedanib in patients with systemic sclerosis-associated interstitial lung disease (SENSCIS™).\nThe SENSCIS™ trial is a randomised, placebo-controlled Phase III trial that will evaluate the efficacy and safety of nintedanib in patients with SSc-ILD (NCT02597933).\nCONCLUSIONS: This trial will assess the efficacy and safety of nintedanib in patients with SSc-ILD.\nNintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease.\nNintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD.\nMETHODS We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis.\nCONCLUSIONS Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis.\nPotential of Nintedanib in Treatment of Progressive Fibrosing Interstitial Lung Diseases.\nAnti-fibrotic nintedanib-a new opportunity for systemic sclerosis patients?\nNewer agents with anti-fibrotic properties, such as pirfenidone or nintedanib, might hold promise also for the pulmonary fibrosis seen in sarcoidosis.\nThis suggests that nintedanib inhibits fundamental processes in the pathogenesis of fibrosis.\nThis suggests that nintedanib and pirfenidone , drugs known to slow disease progression in patients with idiopathic pulmonary fibrosis , may also slow the progression of ILD associated with systemic autoimmune diseases\nIn the SENSCIS® trial , nintedanib reduced the rate of ILD progression in patients with systemic sclerosis-associated ILD\nNintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD.\nThe goal of the present study was to determine the effects of nintedanib on a cellular model of SSc-associated interstitial lung disease (ILD).\nOBJECTIVES Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF) and was demonstrated to slow disease progression in patients with IPF by reducing decline in forced vital capacity by 50%.\nNintedanib: new indication for systemic sclerosis-associated interstitial lung disease.\nNintedanib (Ofev™), an oral triple kinase inhibitor targeting pro-fibrotic pathways, has been used for treatment of idiopathic pulmonary fibrosis (IPF).\nThese data might have direct implications for the ongoing phase III clinical trial with nintedanib in SSc-associated interstitial lung disease.\nBased on positive results from phase III, placebo-controlled, randomized comparative clinical trial conducted in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib received marketing approval in the United States and Japan for the treatment of SSc-ILD.\nNintedanib is an intracellular inhibitor of tyrosine kinases that has been approved for treatment of IPF and has recently been shown to reduce the rate of lung function decline in patients with ILD associated with systemic sclerosis (SSc-ILD).",
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"content": "yes",
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.38441 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nSynthesis of phosphoramidites of isoGNA, an isomer of glycerol nucleic acid\n\nContent Extracts:\nIntroduction\n<p>Acyclic nucleic acids have garnered a lot of attention and are becoming an important component in nucleic acid chemistry [1][2][3]. Lately, there has been an explosion in the number of investigated candidates [4][5][6][7]. We have recently reported on the base-pairing properties of isoGNA, an isomer of glycerol derived nucleic acid (Figure 1) [8]. Our motivation was driven by the question \"how structurally simple and minimal can an oligonucleotide be and still exhibit base-pairing?\" When we studied isoGNA we were surprised to find that the base-pairing properties were unpredictably different from other closely related acyclic nucleic acids [8]. This indicated that the nature of the backbone exerts a strong influence on the disposition of the nucleobases, and there seems to be no straightforward correlation between the nature of the backbone and base-pairing properties [9].</p><p>We are continuing our investigation of isoGNA oligonucleotides within the context of chimeric sequences and collaborative intercalation studies and thus have a continuing need for the synthesis of isoGNA building blocks. While iso-glycerol nucleosides are known [10][11][12][13][14][15], the published synthetic routes and efficiencies of these vary widely and primarily depend on the nature of the nucleobase. Herein, we detail our synthetic efforts and the current improvements for the synthesis of all four isoGNA nucleosides and their phosphoramidites.</p>\n\nInitial synthetic routes\n<p>We started with commercially available (S)-solketal (1), which was protected as the benzyl ether 2. Ketal deprotection followed by the silylation of the primary hydroxy group with tertbutyldiphenylsilyl chloride provided the substrate 4, which is suitable for the introduction of the canonical nucleobases by a S N 2 displacement reaction. At this point, we chose the Mitsunobu reaction (Scheme 1), which has been widely employed [16]. The reaction with the N 3 -benzoyl protected thymine delivered 5 in good yield. However, the reaction with N 6 -benzoyladenine proved problematic and no product was detected. Therefore, in the adenine case, we tried a direct S N 2 reaction of N 6 -benzoyladenine with tosyl derivative 6, which was only moderately successful (30% yield of 7). Unexpectedly, in both the thymine and adenine cases, the subsequent debenzylation reaction failed under a variety of conditions (H 2 , 10% Pd/C, MeOH or EtOAc; Pd/C, DMF, cyclohexadiene; 10% Pd/C, NH 4 HCOO, acetone, reflux; 10% Pd-black, DMF, cyclohexadiene; (CH 3 ) 3 SiI, CHCl 3 , 25 °C), for reasons that were not obvious to us. Consequently, we abandoned this approach and pursued a different protecting group approach.</p><p>We silylated 1 to afford 8 whose ketal was deprotected followed by tritylation to give the derivative 10, which is expected to be suited for the introduction of nucleobases by an S N 2 reaction (Scheme 2). Once again, the Mitsunobu reaction with thymine proceeded smoothly. However, the reaction with Scheme 2: Preparation of thymine and adenine containing phosphoramidites of isoGNA.</p><p>N 6 -benzoyladenine proved problematic and did not proceed even with the tosyl derivative 14. The solubility issues with benzoylated adenine and the bulk of the O-TBDPS group may be the underlying reasons behind this difficulty. Therefore, we proposed to use a doubly N 6 -protected adenine, the N 6 -benzoyl-Boc derivative 16, which was synthesized starting from N 6 -benzoyladenine in two steps. N 6 -Benzoyladenine was treated with 2.6 equiv (Boc) 2 O to afford N 6 -benzoyl-N 6 ,N 9 -di-Boc-adenine 15; sat. aq NaHCO 3 /MeOH (1:2) conditions cleaved the N 9 -Boc group of 15 specifically [17,18] to yield 16. The use of 16 in the subsequent Mitsunobu reaction afforded 68% of the desired product 17. With derivatives 11 and 17 in hand we proceeded to prepare the corresponding phosphoramidite derivatives 13 and 19, respectively, under standard conditions as outlined in Scheme 2.</p><p>We proceeded to prepare the cytosine-and guanine-containing phosphoramidite by using the tritylated intermediate 10 as the starting point (Scheme 3). In the cytosine series we found that the normal N 4 -benzoyl or N 4 -acetyl protected cytosine did not give satisfactory yields under the Mitsunobu conditions. The best yields were achieved with N 4 -isobutyrylcytosine as the nucleophile [19][20][21]. In the guanine series, the N 2 -isobutyryl, O 6 -diphenylcarbamoyl protected guanine worked well (Scheme 3) [22].</p><p>With all the four phosphoramidites in hand we proceeded to the automated synthesis of the oligomers, which proceeded smoothly with ≥95% coupling efficiency as determined by trityl assays. It was at the stage of the removal of the protecting groups to afford the free oligos that we encountered a severe problem with the adenine derivative. While the aqueous ammonia/methylamine base deprotection removed all base labile protecting groups (acetate, isobutyrate, diphenylcarbamoyl groups), the N 6 -Boc protecting group on adenine was impervious. We tried different acidic conditions (trifluoroacetic acid, acetic acid with heat, AlCl 3 [23][24][25]), but all of these conditions started to degrade the oligomer without completely removing the tert-Boc group (as seen by MALDI-TOF mass spectral data in combination with ion-exchange HPLC monitoring) [8].</p><p>Scheme 4: Preparation of adenine containing phosphoramidite of isoGNA.</p>\n\nImproved synthesis of adenine-isoGNA building block\n<p>We went back in our synthesis in order to address the adenine protecting group problem and to re-work the inefficient Mitsunobu reaction of N 6 -benzoyladenine. We explored various conditions (different solvents, temperature etc.) and found that the sonication [26] of the reaction mixture by using N 6 -benzoyladenine in anhydrous dioxane led to respectable yields (34-36%) of 26 accompanied by a (unidentified) byproduct (Scheme 4). Without sonication no product 26 was formed (by TLC).</p><p>However, the yield of the sonication reaction varied capriciously and the isolation of the compound was complicated by interference from the DEAD side-products during column chromatographic purification. We did manage to get enough amounts of 26 to prepare the phosphoramidite 28, and proceeded with the oligomer synthesis for our studies. However, this was far from satisfactory, and the continued demand for isoGNA oligomers within our group and our collaborative work prompted to look for an improvement of the preparation of the adenine building block. Considering the possible reasons for the inefficient reaction of the protected adenine derivatives in the Mitsunobu reaction, we focused on the modification of adenine in order to improve its solubility.</p><p>We considered three different derivatives of adenine based on increased solubility: 6-chloroadenine has been utilized to overcome the solubility and regioselectivity (N 7 versus N 9 nucleosidation) issues. Yet, the conversion of the chloro to the NH 2 group is not efficient enough to consider this option an attractive one [27]. The second option was the N 6 ,N 6 -dibenzoyladenine derivative, but this compound was found to be highly unstable for isolation and handling (one of the N 6 -benzoyl group falls off very easily). The third option was the use of the N 6 ,N 6 -di-Boc-adenine derivative, even though this entails the difficulty in removing these Boc groups, which are incompatible with the oligonucleotide backbone. Therefore, we consid-Scheme 5: Mitsunobu reaction with the di-Boc-adenine.</p><p>ered the option of removing these Boc groups after the Mitsunobu reaction is performed, and to introduce the N 6 -benzoyl group before the oligo stage.</p><p>The Schneller group has reported that N 6 -amino-di-Bocprotected adenine undergoes an efficient reaction under classic Mitsunobu conditions as a result of its increased solubility [28]. The regioselective attack at the N 9 -position is a consequence of the steric bulk of the di-Boc protection at the N 6 -position, which renders the N 7 -position inaccessible. As expected, a high yield was observed under mild conditions with substrates containing a secondary alcohol [28].</p><p>Di-Boc protected adenine was readily prepared via protection and followed by selective deprotection according to a literature procedure [17,18]. The Mitsunobu reaction between the di-Bocadenine and 10 was investigated, and it was found that dioxane as a solvent almost doubled the yield (74%) compared to THF (36%; Scheme 5). Interestingly, sonication afforded no tangible advantage. Doubling the amount of DIAD or di-Boc-adenine or PPh 3 did not give increased yields. The desired product 29 was easily purified on silica gel due to its lower polarity (when compared with the N 6 -benzoyladenine reaction).</p><p>Initially, we tried to simultaneously deprotect both Boc groups and the TBDPS group in the presence of TBAF in a one-pot Scheme 6: An attempt to remove both Boc and silyl groups simultaneously. a TFA (99%) was added under ice-bath (−2 to 2 °C) cooling. b The ratio is roughly calculated by the intensity of visualized spots on TLC by UV lamp. c This reaction was performed on a large scale.</p><p>reaction [29]. However, only the TBDPS group was removed and a quantitative amount of mono-protected compound 30 was produced (Scheme 6). The fluoride ion was not effective enough to remove at least one of the Boc groups in 29. We checked the deprotection conditions for the removal of the Boc moiety by fluoride ions on the model substrate N 6 ,N 6 -di-Bocadenine, and found that it was very challenging because free adenine was not afforded even under reflux with 1 M TBAF for 4 days.</p><p>Finally, we decided to remove the Boc groups on adenine with trifluoroacetic acid (TFA), even though we also expected the loss of the DMTr group on 29. When 29 was treated with 20% of TFA in CH 2 Cl 2 , a mixture of 32 and 33 formed after 4 h. The TBDPS moiety was found to be stable under these conditions (Table 1, entry 1). 50% of TFA in CH 2 Cl 2 completely removed both Boc groups on adenine at either 4 °C or rt to afford the desired 33 in 87% yield.</p><p>The trityl group was reintroduced on 33 under standard conditions to give 34, and subsequent benzoylation afforded 26 in overall good yields (Scheme 7). The NMR spectra of 26 were in good agreement with those data obtained previously [8] via Mitsunobu reaction with N 6 -benzoyladenine.</p><p>Overall, 26 was afforded in 43% yield from the Mitsunobu reaction of 10 with N 6 ,N 6 -di-Boc-adenine. In addition to the slight improvement compared to the direct Mitsunobu reaction of 10 with N 6 -benzoyladenine, this protocol allows for the synthesis of large amounts of 26 with an exact control of the regioselectivity at the N 9 -position of adenine.</p><p>Having solved the \"adenine problem\", we focused on each of the remaining steps and optimized the synthesis of other isoGNA phosphoramidites. For example, the deprotection of 8 to 9 was initially achieved by the treatment with conc. HCl. However, in scaling up the reaction, the loss of the silyl group was found to occur. Therefore, we sought an alternative route and found that the deprotection mediated by vanadium trichloride gave the desired product 9 cleanly in large-scale reactions [30]. The desilylation of intermediates 11, 20 and 26 was effected by the treatment of 1 M TBAF in THF at 0 °C to room temperature. In the case of guanine derivative 23, we observed that the use of the triethylamine•HF complex instead of TBAF was preferable at room temperature. The free alcohols 12, 18, 21 and 24 were phosphitylated under standard conditions to obtain the phosphoramidites suitable for the automated solid phase synthesis.</p>\n\nConclusion\n<p>We have described herein improvements to and the optimization of the synthesis of isoGNA phosphoramidite building blocks. We observed that the Boc protecting group on adenine while not being compatible with oligonucleotide chemistry, can nevertheless be used as a temporary protecting group, which is extremely useful for increasing the solubility and regioselectivity of adenine in the Mitsunobu reaction. The optimized procedures described here allowed us to access a stable supply of isoGNA phosphoramidites for further investigation in our laboratory.</p>",
"role": "user"
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{
"content": "IsoGNA, an isomer of glycerol nucleic acid GNA, is a flexible (acyclic) nucleic acid with bases directly attached to its linear backbone. IsoGNA exhibits (limited) base-pairing properties which are unique compared to other known flexible nucleic acids. Herein, we report on the details of the preparation of isoGNA phosphoramidites and an alternative route for the synthesis of the adenine derivative. The synthetic improvements described here enable an easy access to isoGNA and allows for the further exploration of this structural unit in oligonucleotide chemistry thereby spurring investigations of its usefulness and applicability.",
"role": "assistant"
}
]
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science.acl_arc_intent_classification | science.acl_arc_intent_classification.1079 | [
{
"content": "Examine the given text from a research paper in the field of NLP. Your task is to identify the role of the citation within the context provided. Focus on understanding the intent behind the citation and classify it accordingly.\n\nSection Title:\nNone\n\nText Before Citation:\nFor this research, we used a coreference resolution system ((Harabagiu and Maiorano, 1999)) that implements different sets of heuristics corresponding to various forms of coreference. For example, CogNIAC (Baldwin, 1997), a system based on seven ordered heuristics, generates high-precision resolution (over 90%) for some cases of pronominal reference. Nevertheless, recent results show that knowledge-poor methods perform with amazing accuracy (cfXXX (Mitkov, 1998), (Kennedy and Boguraev, 1996) (Kameyama, 1997)).\n\nCitation Text:\nFor this research , we used a coreference resolution system ( ( Harabagiu and Maiorano , 1999 ) ) that implements different sets of heuristics corresponding to various forms of coreference .\n\nText After Citation:\nThis system, called COCKTAIL, resolves coreference by exploiting several textual cohesion constraints (e.g. term repetition) combined with lexical and textual coherence cues (e.g. subjects of communication verbs are more likely to refer to the last person mentioned in the text). These constraints are implemented as a set of heuristics ordered by their priority. Moreover, the COCKTAIL framework uniformly addresses the problem of interaction between different forms of coreference, thus making the extension to multilingual coreference very natural.",
"role": "user"
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{
"content": "Uses",
"role": "assistant"
}
]
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science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.4990 | [
{
"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:\nFor the webportal \"Who is in the News!\" with statistics about the appearence of persons in written news we developed an extension, which measures the relationship of public persons depending on a time parameter, as the relationship may vary over time. On a training corpus of English and German news articles we built a measure by extracting the persons occurrence in the text via pretrained named entity extraction and then construct time series of counts for each person. Pearson correlation over a sliding window is then used to measure the relation of two persons.\n\nCited Works Summary:\n[1]: Recent methods for learning vector space representations of words have succeeded in capturing fine-grained semantic and syntactic regularities using vector arithmetic, but the origin of these regularities has remained opaque. We analyze and make explicit the model properties needed for such regularities to emerge in word vectors. The result is a new global logbilinear regression model that combines the advantages of the two major model families in the literature: global matrix factorization and local context window methods. Our model efficiently leverages statistical information by training only on the nonzero elements in a word-word cooccurrence matrix, rather than on the entire sparse matrix or on individual context windows in a large corpus. The model produces a vector space with meaningful substructure, as evidenced by its performance of 75 on a recent word analogy task. It also outperforms related models on similarity tasks and named entity recognition.",
"role": "user"
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{
"content": "[1] combine the global matrix factorization and local context window methods in the \"GloVe\" method for word representation https: nlp.stanford.edu projects glove .",
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science.craftchem_ner | science.craftchem_ner.498 | [
{
"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:\nWethereforealsotestedthisnovelredfluorescentprotein(RFP)inEScellsandmice.",
"role": "user"
},
{
"content": "[\"protein\"]",
"role": "assistant"
}
]
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science.craftchem_ner | science.craftchem_ner.2687 | [
{
"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:\nRunningTest90MinLater",
"role": "user"
},
{
"content": "[]",
"role": "assistant"
}
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science.multixscience_multidoc_summarization | science.multixscience_multidoc_summarization.1069 | [
{
"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:\nTemporal action proposal generation is an challenging and promising task which aims to locate temporal regions in real-world videos where action or event may occur. Current bottom-up proposal generation methods can generate proposals with precise boundary, but cannot efficiently generate adequately reliable confidence scores for retrieving proposals. To address these difficulties, we introduce the Boundary-Matching (BM) mechanism to evaluate confidence scores of densely distributed proposals, which denote a proposal as a matching pair of starting and ending boundaries and combine all densely distributed BM pairs into the BM confidence map. Based on BM mechanism, we propose an effective, efficient and end-to-end proposal generation method, named Boundary-Matching Network (BMN), which generates proposals with precise temporal boundaries as well as reliable confidence scores simultaneously. The two-branches of BMN are jointly trained in an unified framework. We conduct experiments on two challenging datasets: THUMOS-14 and ActivityNet-1.3, where BMN shows significant performance improvement with remarkable efficiency and generalizability. Further, combining with existing action classifier, BMN can achieve state-of-the-art temporal action detection performance.\n\nCited Works Summary:\n[1]: 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.\n\n[2]: Recently convolutional neural network (CNN) promotes the development of stereo matching greatly. Especially those end-to-end stereo methods achieve best performance. However less attention is paid on encoding context information, simplifying two-stage disparity learning pipeline and improving details in disparity maps. Differently we focus on these problems. Firstly, we propose an one-stage context pyramid based residual pyramid network (CP-RPN) for disparity estimation, in which a context pyramid is embedded to encode multi-scale context clues explicitly. Next, we design a CNN based multi-task learning network called EdgeStereo to recover missing details in disparity maps, utilizing mid-level features from edge detection task. In EdgeStereo, CP-RPN is integrated with a proposed edge detector HED @math based on two-fold multi-task interactions. The end-to-end EdgeStereo outputs the edge map and disparity map directly from a stereo pair without any post-processing or regularization. We discover that edge detection task and stereo matching task can help each other in our EdgeStereo framework. Comprehensive experiments on stereo benchmarks such as Scene Flow and KITTI 2015 show that our method achieves state-of-the-art performance.\n\n[3]: Stereo matching algorithms usually consist of four steps, including matching cost calculation, matching cost aggregation, disparity calculation, and disparity refinement. Existing CNN-based methods only adopt CNN to solve parts of the four steps, or use different networks to deal with different steps, making them difficult to obtain the overall optimal solution. In this paper, we propose a network architecture to incorporate all steps of stereo matching. The network consists of three parts. The first part calculates the multi-scale shared features. The second part performs matching cost calculation, matching cost aggregation and disparity calculation to estimate the initial disparity using shared features. The initial disparity and the shared features are used to calculate the prior and posterior feature constancy. The initial disparity, the prior and posterior feature constancy are then fed to a sub-network to refine the initial disparity through a Bayesian inference process. The proposed method has been evaluated on the Scene Flow and KITTI datasets. It achieves the state-of-the-art performance on the KITTI 2012 and KITTI 2015 benchmarks while maintaining a very fast running time.\n\n[4]: Recent work has shown that depth estimation from a stereo pair of images can be formulated as a supervised learning task to be resolved with convolutional neural networks (CNNs). However, current architectures rely on patch-based Siamese networks, lacking the means to exploit context information for finding correspondence in ill-posed regions. To tackle this problem, we propose PSMNet, a pyramid stereo matching network consisting of two main modules: spatial pyramid pooling and 3D CNN. The spatial pyramid pooling module takes advantage of the capacity of global context information by aggregating context in different scales and locations to form a cost volume. The 3D CNN learns to regularize cost volume using stacked multiple hourglass networks in conjunction with intermediate supervision. The proposed approach was evaluated on several benchmark datasets. Our method ranked first in the KITTI 2012 and 2015 leaderboards before March 18, 2018. The codes of PSMNet are available at: https: github.com JiaRenChang PSMNet.",
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{
"content": "Correlation matching algorithms are widely used in many computer vision tasks, such as image registration, action recognition and stereo matching. Specifically, stereo matching aims to find corresponding pixels from stereo images. For each pixel in left image of a rectified image pair, the stereo matching method need to find corresponding pixel in right image along horizontal direction, or we can say finding right pixel with minimum cost. Thus, the cost minimization of all left pixels can be denoted as a cost volume, which denotes each left-right pixel pair as a point in volume. Based on cost volume, many recent works [2] [1] [3] achieve end-to-end network via generating cost volume directly from combining two feature maps, using correlation layer [1] or feature concatenation [4] . Inspired by cost volume, our proposed BM confidence map contains pairs of temporal starting and ending boundaries as proposals, thus can directly generate confidence scores for all proposals using convolutional layers. We propose BM layer to efficiently generate BM feature map via sampling feature among starting and ending boundaries of each proposal simultaneously.",
"role": "assistant"
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science.data_reco_mcq_sc | science.data_reco_mcq_sc.627 | [
{
"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 mutual information maximizing model to learn a smooth dialogue response from both preceding dialogue history and following\n\nKeywords: dialogue generation text\n\nDataset Information:\nDailyDialog: DailyDialog is a high-quality multi-turn open-domain English dialog dataset. It contains 13,118 dialogues split into a training set with 11,118 dialogues and validation and test sets with 1000 dialogues each.\nMedDG: MedDG is a large-scale high-quality Medical Dialogue dataset related to 12 types of common Gastrointestinal diseases. It contains more than 17K conversations collected from the online health consultation community.\nMEDIA: The MEDIA French corpus is dedicated to semantic extraction from speech in a context of human/machine dialogues. The corpus has manual transcription and conceptual annotation of dialogues from 250 speakers.\nAVSD: The Audio Visual Scene-Aware Dialog (AVSD) dataset, or DSTC7 Track 3, is a audio-visual dataset for dialogue understanding. The goal with the dataset and track was to design systems to generate responses in a dialog about a video, given the dialog history and audio-visual content of the video.\n\nAvailable Datasets: A: DailyDialog B: MedDG C: MEDIA D: AVSD",
"role": "user"
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{
"content": "DailyDialog",
"role": "assistant"
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science.healthver_entailment | science.healthver_entailment.2707 | [
{
"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: Social Distancing Key to Lowering COVID-19 Disease Risk\n\nResearch Abstract:\nBackground: The Greek authorities implemented the strong social distancing measures within the first few weeks after the first confirmed case of the virus to curtail the COVID-19 growth rate.\nObjectives: To estimate the effect of the two-stage strong social distancing measures, the closure of all non-essential shopping centers and businesses on March 16 and the shelter in place orders (SIPOs) on March 23 on the COVID-19 growth rate in Greece Methods: We obtained data on COVID-19 cases in Greece from February 26th through May 4th from publicly available sources.\nAn interrupted time-series regression analysis was used to estimate the effect of the measures on the exponential growth of confirmed COVID-19 cases, controlling for the number of daily testing, and weekly fixed-effects.\nResults: The growth rate of the COVID-19 cases in the pre-policies implementation period was positive as expected (p=0.003).\nBased on the estimates of the interrupted time-series, our results indicate that the SIPO on March 23 significantly slowed the growth rate of COVID-19 in Greece (p=0.04).\nHowever, we did not find evidence on the effectiveness of standalone and partial measures such as the non-essential business closures implemented on March 16 on the COVID-19 spread reduction.\nDiscussion: The combined social distancing measures implemented by the Greek authorities within the first few weeks after the first confirmed case of the virus reduced the COVID-19 growth rate.\nThese findings provide evidence and highlight the effectiveness of these measures to flatten the curve and to slow the spread of the virus.",
"role": "user"
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{
"content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"Discussion: The combined social distancing measures implemented by the Greek authorities within the first few weeks after the first confirmed case of the virus reduced the COVID-19 growth rate.\"]}",
"role": "assistant"
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science.gnormplus_ner | science.gnormplus_ner.147 | [
{
"content": "Examine the text provided from a scientific article. Identify entities and classify them.\n\nPresent your findings in a JSON format: {\"Gene\": [\"SSX\", ...]}. If no entities are found, use an empty list.\n\nText:\n\np57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. Cyclin-dependent kinases (Cdks) are positive regulators of cell proliferation, whereas Cdk inhibitors (CKIs) inhibit proliferation. We describe a new CKI, p57KIP2, which is related to p21CIP1 and p27KIP1. p57KIP2 is a potent, tight-binding inhibitor of several G1 cyclin/Cdk complexes, and its binding is cyclin dependent. Unlike CIP1, KIP2 is not regulated by p53. Overexpression of p57KIP2 arrests cells in G1. p57KIP2 proteins have a complex structure. Mouse p57KIP2 consists of four structurally distinct domains: an amino-terminal Cdk inhibitory domain, a proline-rich domain, an acidic-repeat region, and a carboxy-terminal domain conserved with p27KIP1. Human p57KIP2 appears to have conserved the amino- and carboxy-terminal domains but has replaced the internal regions with sequences containing proline-alanine repeats. In situ hybridization during mouse embryogenesis revealed that KIP2 mRNA displays a striking pattern of expression during development, showing high level expression in skeletal muscle, brain, heart, lungs, and eye. Most of the KIP2-expressing cells are terminally differentiated, suggesting that p57KIP2 is involved in decisions to exit the cell cycle during development and differentiation. Human KIP2 is located at 11p15.5, a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome, a familial cancer syndrome, marking it as a candidate tumor suppressor. The discovery of a new member of the p21CIP1 inhibitor family with novel structural features and expression patterns suggests a complex role for these proteins in cell cycle control and development.",
"role": "user"
},
{
"content": "{\"Gene\": [\"candidate tumor suppressor\", \"p27KIP1\", \"Cdk inhibitor\", \"Cdk\", \"proline-alanine repeats\", \"p57KIP2\", \"Cdks\", \"KIP2\", \"tight-binding inhibitor\", \"CKI\", \"p21CIP1\", \"Cdk inhibitors\", \"amino-terminal Cdk inhibitory domain\", \"Cyclin-dependent kinases\", \"CKIs\", \"carboxy-terminal domain\", \"amino- and carboxy-terminal domains\", \"CIP1\", \"acidic-repeat region\", \"G1 cyclin\", \"p53\", \"proline-rich domain\"]}",
"role": "assistant"
}
]
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science.data_reco_mcq_sc | science.data_reco_mcq_sc.1361 | [
{
"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 interactive environment for spatial layout composition via conversational interactions. The proposed system supports multiple\n\nKeywords: conversational spatial reasoning text\n\nDataset Information:\nHoME: HoME (Household Multimodal Environment) is a multimodal environment for artificial agents to learn from vision, audio, semantics, physics, and interaction with objects and other agents, all within a realistic context. HoME integrates over 45,000 diverse 3D house layouts based on the SUNCG dataset, a scale which may facilitate learning, generalization, and transfer.\nCOCO: The MS COCO (Microsoft Common Objects in Context) dataset is a large-scale object detection, segmentation, key-point detection, and captioning dataset. The dataset consists of 328K images.\nUDIVA: UDIVA is a new non-acted dataset of face-to-face dyadic interactions, where interlocutors perform competitive and collaborative tasks with different behavior elicitation and cognitive workload. The dataset consists of 90.5 hours of dyadic interactions among 147 participants distributed in 188 sessions, recorded using multiple audiovisual and physiological sensors.\nInteriorNet: InteriorNet is a RGB-D for large scale interior scene understanding and mapping. The dataset contains 20M images created by pipeline: (A) the authors collected around 1 million CAD models provided by world-leading furniture manufacturers.\n\nAvailable Datasets: A: HoME B: COCO C: UDIVA D: InteriorNet",
"role": "user"
},
{
"content": "COCO",
"role": "assistant"
}
]
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science.healthver_entailment | science.healthver_entailment.1266 | [
{
"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: Dogs may be able to spread coronavirus to humans despite showing no symptoms\n\nResearch Abstract:\nLittle information on the SARS-CoV-2 virus in animals is available to date.\nWhereas no one husbandry animal case has been reported to date, which would have significant implications in food safety, companion animals play a role in COVID-19 epidemiology that opens up new questions.\nThere is evidence that SARS-CoV-2 can infect felines, dogs and minks, and there is evidence of human-to-animal infection.\nLikewise, the S protein nucleotide sequence of the SARS-CoV-2 virus isolated in domestic animals and humans is identical, and the replication of the SARS-CoV-2 in cats is efficient.\nBesides, the epidemiological evidence for this current pandemic indicates that the spillover to humans was associated with close contact between man and exotic animals, very probably in Chinese wet markets, thus there is a growing general consensus that the exotic animal markets, should be strictly regulated.\nThe examination of these findings and the particular role of animals in COVID-19 should be carefully analyzed in order to establish preparation and containment measures.\nAnimal management and epidemiological surveillance must be also considered for COVID-19 control, and it can open up new questions regarding COVID-19 epidemiology and the role that animals play in it.",
"role": "user"
},
{
"content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"There is evidence that SARS-CoV-2 can infect felines, dogs and minks, and there is evidence of human-to-animal infection.\", \"Likewise, the S protein nucleotide sequence of the SARS-CoV-2 virus isolated in domestic animals and humans is identical, and the replication of the SARS-CoV-2 in cats is efficient.\"]}",
"role": "assistant"
}
]
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.11930 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nIn silico improvement of \\xce\\xb23-peptide inhibitors of p53\\xe2\\x80\\xa2hDM2 and p53\\xe2\\x80\\xa2hDMX\n\nContent Extracts:\n\n<p>There is great interest in molecules that inhibit interactions between p53 and its negative regulators hDM2 and hDMX, as these molecules have validated potential against cancers that overexpress one or both of these oncoproteins.1,2 We reported that substituted β3-peptides can inhibit these interactions3,4 and, more recently, that minimally cationic β3-peptides are sufficiently cell permeable to upregulate p53-dependent genes in live cells.5,6 These observations, coupled with the established intracellular stability of β-peptides7–9 and the recently reported structures of hDM210 and hDMX,11 motivated us to exploit computational methods to identify β-peptides with improved potency and/or selectivity. This exercise successfully identified a new β3-peptide, β53-16, that possesses the desirable attribute of high affinity for hDM2 and hDMX and identifies the 3,4-dichlorophenyl moiety as a novel determinant of hDMX affinity.</p><p>Our computational modeling began with the application of Visual Molecular Dynamics (VMD)12 to generate a model of previously reported β53-8 bound to the p53 binding site on hDM2 (Figure 1A). In this model, β53-8 is bound as a 14-helix that is slightly unwound at the C-terminus, mimicking its conformation in solution.13 The three hDM2 hydrophobic pockets occupied in the native structure by the p53 side chains of Leu26, Trp23 and Phe19 10 are occupied in the modeled complex by the corresponding β3-amino acid side chains at positions 3, 6, and 9. An analogous model of β53-8 bound to hDMX was also prepared (Figure 1B).11</p><p>We then applied a hierarchical computational strategy to search for alternative side chains that would improve packing at one or both interfaces. With the de novo design program BOMB14 we screened over ten thousand β53-8 analogs containing substituted aromatic and non-aromatic heterocycles and short hydrocarbon side chains in place of Leu26, Trp23 and Phe19.10 About 50 candidates were identified by scoring and visualization for evaluation with MCPRO.15 Binding free energies were predicted via Monte Carlo Free Energy Perturbation (MC/FEP) calculations using the OPLS-AA force field16 for the protein-ligand complex and the TIP4P model for water.17 In these simulations, the protein backbones remained fixed; the affinities of the eight most interesting and synthetically accessible compounds (Figure 1C) were subsequently reevaluated in a second round of MC/FEP calculations that permitted backbone motions.18</p><p>The models were first validated by evaluating whether they would predict the large increase in hDM2 affinity realized when the tryptophan side chain at position 6 is replaced by 6-chlorotryptophan (6-ClW) (compare β53-8 and β53-13,Figure 1C).19 The calculations predict that substitution of 6-ClW at position 6 should significantly improve binding to hDM2 (ΔΔG = –2.1 kcal•mol−1) but not hDMX (ΔΔG = +1.0 kcal•mol−1,Figure 2C). These predictions are fully aligned with the experimental results: the stability of the hDM2•β53-13 complex is significantly higher (Kd = 30.1 nM, ΔG = –10.25 kcal•mol−1) than that of the hDM2•β53-8 complex (Kd = 204 nM, ΔG = –9.12 kcal•mol−1), whereas the stabilities of the analogous hDMX complexes are comparable (Kd = 1.6 and 2.1 µM for β53-13 and β53-8, respectively). The improvement in hDM2 but not hDMX affinity upon substitution of 6-ClW is consistent with results observed in the context of previously reported ligands.20–23</p><p>The models were further validated by their ability to predict the large increase in hDM2 and hDMX affinity observed for β-peptides containing a central meta-trifluoromethyl phenyl substituent (CF3F) when compared with an unsubstituted phenyl ring (compare β53-12 with β53-14,Figure 1C). The calculations predict that the CF3F side chain should favor binding to both hDM2 and hDMX (ΔΔG = –4.8 and –4.6 kcal•mol−1, respectively). This increase was also realized experimentally, albeit in an attenuated way: the stability of the hDM2•β53-12 complex is significantly higher (Kd = 28.2 nM, ΔG = –10.29 kcal•mol−1) than that of the hDM2•β53-14 complex (Kd = 816 nM, ΔG = –8.3 kcal•mol−1); analogous differences are seen for the hDMX complexes (Figure 2).24</p><p>Next we examined whether the affinity of β53-12 could be increased further by substituting the leucine side chain at position 6 with one of eight cyclic and acyclic hydrocarbon alternatives. Although few promising candidates emerged from the BOMB and MC/FEP analyses, we did investigate β53-17, in which the Leu side chain is replaced by Ile. This substitution was predicted to slightly favor the binding of both hDM2 and hMDX (ΔΔGbind = –0.9 and –0.3 kcal•mol−1, respectively). However, no increase in affinity was observed, and these molecules were not studied further. We note that 53-17 is significantly less 14-helical than 53-12 as judged by circular dichroism analysis (Figure SI-1). As the computational model does not account for changes in β-peptide secondary structure, it is possible that the observed change in secondary structure accounts for the poor agreement between prediction and experiment in this case. The predictions may be also be affected by uncertainty in the structures of unliganded hDM2 and hDMX as the 23 N-terminal residues of both proteins are only partially resolved due to their flexibility.25,26</p><p>Based on these observations, we returned attention to the central side chain of the hDM2/hDMX epitope and evaluated the relative hDM2 and hDMX affinities of hundreds of β53-12 analogs containing substituted phenylalanine analogs at position 6. This analysis suggested that β-peptides containing either meta-chlorophenylalanine or para-chlorophenylalanine at this position would show improved affinity for both hDM2 and hDMX when compared with β53-14 (−3.5 kcal•mol−1 > ΔΔGbind > −2.5 kcal•mol−1). Indeed, the stability of the hDM2•β53-15 complex (meta-chloro substituent,Figure 1C) is significantly higher (Kd = 150 nM, ΔG = −9.3 kcal•mol−1) than that of hDM2·β53-14; analogous differences are observed for the hDMX complexes (Figure 2). However, as predicted, the stabilities of the β53-15 complexes were not greater than those of the β53-12 complexes. Therefore, since the gains in affinity for the para-chlorophenylalanine were predicted to be similar to those of 53-15, this additional analog was not tested experimentally.</p><p>Finally we examined the effect of a meta,para-dichlorophenylalanine side chain at the central position of the recognition epitope (β53-16,Figure 1), whose inclusion was predicted to significantly improve affinity for both hDM2 and hDMX compared to β53-14 (ΔΔGbind = −4.4 and −5.4 kcal•mol−1, respectively. Indeed, the stabilities of both hDM2•β53-16 and hDMX•β53-16 are significantly higher than the corresponding β53-14 complexes (Kd = 27.6 nM and 155 nM, respectively for β53-16,Figure 2). They also equal or exceed the stabilities of the corresponding complexes with 53-12. Competition fluorescence polarization experiments confirm that β53-16 competes with p53AD for binding to hDM2 and hDMX and shows improved inhibitory potency towards hDMX (Figure SI-2).</p><p>Thus, β53-16 offers significantly improved affinity for hDMX without loss of affinity for hDM2. Analysis of the MC/FEP simulations suggests more favorable interaction of the dichlorophenyl group with residues 50–54 in hDMX than with equivalent residues 54–58 in hDM2. We subsequently examined whether the affinity of β53-16 could be improved further upon replacement of the adjacent phenylalanine side chain with one of twelve substituted analogs. This scan failed to identify promising substitutions as the phenylalanine side chain appears to bind tightly to the hydrophobic pocket of both proteins; however minor gains in affinity for both hDM2 and hDMX were predicted for a para-fluorophenylalanine substitution (ΔΔGbind = −0.4 and −0.9 kcal•mol−1, respectively). No increase in affinity was observed experimentally with this peptide, β53-18, so further modification at this position was not pursued (Figure 1, Table 1). β53-16 represents the highest affinity β3-peptide for hDMX reported to date, with significantly higher affinity than the prototypic hDM2 ligand, Nutlin-3. Thus, β53-16 embodies the pan-specificity of well known peptidic hDM2/hDMX inhibitors27,28 without the limitations of protease sensitivity or poor uptake.</p><p>Computationally generated models of β53-8 (blue) in complex with (a) hDM2 and (b) hDMX illustrating differences in binding site topologies. (c) Helical net representations of β3-peptides studied herein.</p><p>Direct fluorescence polarization analysis of the affinity of each β-peptide shown for (A) hDM2 and (B) hDMX. (C) Comparison of calculated and experimental binding free energies expressed in terms of ΔΔGbind relative to the standard shown (kcal•mol−1); Kd values in nM units.</p>",
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"content": "There is great interest in molecules capable of inhibiting the interactions between p53 and its negative regulators hDM2 and hDMX, as these molecules have validated potential against cancers in which one or both oncoproteins are overexpressed. We reported previously that appropriately substituted \\xce\\xb23-peptides inhibit these interactions and, more recently, that minimally cationic \\xce\\xb23-peptides are sufficiently cell permeable to upregulate p53-dependent genes in live cells. These observations, coupled with the known stability of \\xce\\xb2-peptides in a cellular environment, and the recently reported structures of hDM2 and hDMX, motivated us to exploit computational modeling to identify \\xce\\xb2-peptides with improved potency and/or selectivity. This exercise successfully identified a new \\xce\\xb23-peptide, \\xce\\xb253-16, that possesses the highly desirable attribute of high affinity for both hDM2 as well as hDMX and identifies the 3,4-dichlorophenyl moiety as a novel determinant of hDMX affinity.",
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science.craftchem_ner | science.craftchem_ner.2962 | [
{
"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:\nInotherstudies,CLN3/batteninproteinlocalizationhasbeenreportedtopartiallyoverlapwithlateendosomesandlysosomesinnon-neuronalcells[7],andtolysosomes,synaptosomes[8]andendosomes[9,25]inneurons.",
"role": "user"
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{
"content": "[\"protein\"]",
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science.cdr_ner | science.cdr_ner.289 | [
{
"content": "Examine the provided text to identify entities. Focus on extracting relevant information.\n\nPresent your findings in a structured JSON format. Each category should list the entities found.\n\nSource Material:\n\nRanitidine-induced acute interstitial nephritis in a cadaveric renal allograft. Ranitidine frequently is used for preventing peptic ulceration after renal transplantation. This drug occasionally has been associated with acute interstitial nephritis in native kidneys. There are no similar reports with renal transplantation. We report a case of ranitidine-induced acute interstitial nephritis in a recipient of a cadaveric renal allograft presenting with acute allograft dysfunction within 48 hours of exposure to the drug. The biopsy specimen showed pathognomonic features, including eosinophilic infiltration of the interstitial compartment. Allograft function improved rapidly and returned to baseline after stopping the drug.",
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"content": "{\"Chemical\": [\"Ranitidine\", \"ranitidine\"], \"Disease\": [\"interstitial nephritis\"]}",
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science.scientific_papers_summarization_single_doc_pubmed | science.scientific_papers_summarization_single_doc_pubmed.7239 | [
{
"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:\nheart rate , perhaps the most commonly measured vital sign in clinical practice , is a key determinant of myocardial metabolism and cardiac output .\ntachycardia , conventionally defined as an atrial and/or ventricular rate of > 100 beats per minute ( bpm ) has an arbitrary and debated definition .\nnevertheless , tachycardia can be of importance , since it can cause myocardial ischemia , hypotension , low cardiac output , peripheral hypoperfusion , severe symptoms ( chest pain , weakness , syncope , lightheadedness ) , cardiomyopathy , cardiac arrest and death .\ntachycardias can be broadly classified as : sinus tachycardia ( appropriate physiologically and inappropriate ) ; postural orthostatic tachycardia syndrome ( pots ) ; supraventricular tachycardia ( atrial tachycardia , av nodal reentrant tachycardia and av reentrant tachycardia ) ; atrial flutter with rapid ventricular response ; atrial fibrillation with rapid ventricular response ; junctional tachycardia ; or ventricular tachycardia .\nsinus tachycardia ( heart rate > 100 bpm ) is the form encountered most commonly in clinical practice .\nthe vast majority of sinus tachycardia is physiological and associated with catecholaminergic triggers ( e.g. emotions , physical activity , and other stresses ) .\nthe evaluation and management of persistent sinus tachycardia involves careful assessment of whether tachycardia is an appropriate response or not , the discussion of which is beyond the scope of this manuscript .\na small percentage of patients can have persistent sinus tachycardia without any underlying illness or structural heart disease , and are classified as having inappropriate sinus tachycardia .\ninappropriate sinus tachycardia is under - recognized , can be associated with debilitating symptoms and poses significant management challenges .\npostural orthostatic tachycardia syndrome ( pots ) , a neurally - mediated disorder ( defined as orthostatic tachycardia of > 30 beats from baseline or a heart rate > 120 bpm with no significant blood pressure changes ) , can be associated with significant symptoms .\nsupraventricular tachycardia ( i.e. tachycardia requiring tissue above the his bundle to perpetuate ) can be associated with severe symptoms , but is rarely life - threatening .\nventricular tachyarrhythmias can be idiopathic ( in the setting of a structurally normal heart ) to life - threatening ( in the setting of structural heart disease including cardiomyopathy ) .\npersistent tachycardia of any form can cause tachycardia - mediated cardiomyopathy ( tmc ) , can precipitate heart failure and can result in death . if tmc is the direct consequence of tachycardia , it is referred to as tachycardia - induced cardiomyopathy or \ntmc is partially or completely reversible , when measured by heart failure symptoms and left ventricular ejection fraction , once the culprit tachycardia is treated adequately .\natrial fibrillation with persistent rapid ventricular rates is the most common cause . sinus tachycardia and pots\nthyrotoxicosis resulting in persistent sinus tachycardia or atrial fibrillation and consequent high output heart failure does not usually cause tmc .\nthe primary management strategy in tmc is focused on aggressive attempts to control tachycardia with the aim of improving heart failure symptoms and reversing left ventricular dysfunction . depending on the clinical condition of the patient and type of tachycardia , rate control and/or rhythm control strategies are usually employed .\nunderlying disease conditions , if present , should be optimized as much as possible and as soon as possible . if successful rate control or tachycardia elimination can reverse heart failure symptoms and cardiomyopathy , tmc is confirmed . in patients with tmc , standard heart failure therapy ( beta - blockers , angiotensin - converting enzyme inhibitors , and spironolactone ) can attenuate neurohumoral response and affect favorable remodeling .\nbeta - blockers , calcium - channel antagonists and/or digoxin are commonly utilized for rate control .\nthe optimal rate control strategy in tmc is yet to be identified , although a combination of drugs is often needed for adequate rate control ; a beta - blocker combined with digoxin may have superior benefits .\nthe requirements for adequate rate control in tmc remain uncertain . in permanent atrial fibrillation , lenient rate control ( resting ventricular\nrate < 110 bpm ) has been shown to have similar short - term outcomes to a strict rate control approach ( resting heart rate < 80 bpm and exercise heart rate < 110 bpm ) . whether a lenient approach to rate control applies to patients at risk of developing tmc is unlikely but requires further evaluation . in patients with atrial fibrillation - mediated tmc , who are difficult to rate control and\nin whom a rhythm control strategy is not feasible or desired , av node ablation with pacemaker implantation provides an effective means of rate control .\nrecent data , however , arguably point to a cardiac resynchronization therapy ( crt ) pacing approach .\nalthough rate control is important in atrial fibrillation - mediated tmc , rhythm control may be important as well , as irregularity of the rhythm may also result in development of cardiomyopathy and heart failure . further \nrate control in atrial fibrillation may be a misnomer , as the rate is never exactly as it would be in sinus rhythm .\nrhythm control strategies involve chronic or intermittent use of antiarrhythmic drugs , pharmacological or electrical cardioversion , and catheter ablation . a hemodynamically unstable patient with atrial fibrillation and rapid ventricular rates often needs emergent cardioversion .\nintravenous ibutilide , a class iii antiarrhythmic drug , can be effective for pharmacological cardioversion .\nthe dose is 1 mg over 10 minutes , but carries a risk of qt prolongation and polymorphic ventricular tachycardia , and therefore requires several hours of telemetry monitoring following the dose .\nvernakalant , an atrium - specific k+ channel blocker , has been shown to be effective in restoring sinus rhythm , may not affect qt prolongation as much , and can be a safer option .\nit is critical in tmc patients to maintain sinus rhythm in the long - term .\namiodarone , which blocks multiple cardiac ion channels , is most commonly used for this purpose and is superior to sotalol , another class iii antiarrhythmic drug . however , long - term use of amiodarone has the potential for extracardiac toxicity ( hypo- and hyperthyroidism , abnormal liver enzymes , neuropathy , dermatitis , optic neuritis , and interstitial lung disease ) .\nclose follow - up of thyroid and liver function every 6 months should be performed .\nan underutilized , but highly effective , drug is dofetilide , a pure class iii antiarrhythmic drug with no beta - blocking properties ( unlike sotalol ) .\nno head - to - head comparison has been undertaken with amiodarone but , when used properly and with careful monitoring , this drug can be quite effective in maintaining sinus rhythm without substantial risk for qt prolongation and torsade de pointes .\ndofetilide requires initiation in the hospital with strict electrocardiographic supervision . dosing depends on the initial qtc , renal function and concomitant qt - prolonging drugs .\ncatheter ablation has emerged as a promising therapy to maintain sinus rhythm in patients with both paroxysmal and persistent atrial fibrillation . in patients with atrial fibrillation and heart failure , catheter ablation of atrial fibrillation can improve quality of life and left ventricular function . in a systematic review of the efficacy of catheter ablation in atrial fibrillation patients with\nconcomitant left ventricular dysfunction , sinus rhythm was maintained in 57% of patients following a single procedure .\nthe success rate increased to 82% with more than one procedure and/or use of antiarrhythmic drug therapy .\nthe mean increase in left ventricular ejection fraction was 13.3% , suggesting effectiveness of catheter ablation in this tmc population . whether or not rhythm control is superior to rate control in tmc patients with atrial fibrillation is not fully established .\nlarge randomized studies of atrial fibrillation patients ( af - chf , affirm ) have shown that rate control was equivalent to rhythm control for hard clinical endpoints for the patients who were selected to be enrolled .\nhowever , it is likely that the pathophysiology of atrial fibrillation - mediated tmc varies in the patient population studied in these trials , and these results may not apply to tmc patients\n. moreover , these studies compared rate control to antiarrhythmic drugs , mostly amiodarone , and the toxicity of antiarrhythmic drugs may offset benefits gained from maintaining sinus rhythm . in the real world , achieving and monitoring rate control is a challenge in the cardiomyopathy patient . in patients with drug - refractory atrial fibrillation and heart failure ,\npulmonary vein isolation has been shown to have better outcomes than av node ablation and crt pacing , suggesting the superiority of rhythm control .\na recent randomized trial ( aatac - af ) compared catheter ablation with amiodarone for rhythm control of persistent atrial fibrillation in patients with heart failure and cardiomyopathy .\na total of 203 patients were followed for 24 months and catheter ablation was shown to be far superior to amiodarone in freedom from atrial fibrillation ( 70% in the ablation arm vs. 34% in the amiodarone arm ) , quality of life , hospitalization rate , and mortality . left ventricular ejection fraction improved 9.67.4% in the ablation arm vs. 4.26.2% in the amiodarone arm ( p<0.01 ) ( nct00729911 ) . for atrial flutter and supraventricular tachycardias ( atrial tachycardia ,\nav nodal reentry tachycardia , av reentrant tachycardias , permanent junctional reciprocating tachycardia ) , a curative strategy by catheter ablation should be pursued whenever possible with a goal of complete elimination of the tachycardia .\nsimilarly , early use of catheter ablation should be employed for tmc due to idiopathic ventricular tachycardias and/or frequent ventricular premature beats , as it can achieve a complete cure . in summary ,\nour management approach for patients with suspected tmc is to pursue an aggressive rhythm control strategy whenever possible , with the goal of restoring and maintaining sinus rhythm .\naggressive rate control should be pursued in situations where rhythm control is not feasible or desired .\nconcomitant heart failure therapy with angiotensin - converting enzyme inhibitors and beta - blockers adds value .\nonce pathologic tachycardia is controlled or eliminated , gradual recovery in left ventricular function and heart failure symptoms is the rule in a patient with tmc .\na major factor affecting prognosis is tachycardia recurrence . in a study of 24 patients with tmc and heart failure ,\n5 patients had recurrent tachycardia after recovery in left ventricular function and all had rapid decline in ventricular function within 6 months of recurrence , suggesting that structural abnormalities at the ultrastructural level persist despite tachycardia resolution .\nthus , careful follow - up and monitoring for arrhythmia recurrence is necessary for these patients .\nsudden death has been reported in tmc patients even after recovery in ventricular function , highlighting the fact that tachycardia should be controlled before cardiomyopathy ensues .\ntachycardia , a common problem in clinical practice , can be secondary to physiological and/or pathological causes .\none major adverse consequence of pathological tachycardia is development of cardiomyopathy with subsequent heart failure .\nearly recognition is important , and an aggressive approach towards rate and rhythm control of the culprit tachycardia can result in resolution of symptoms and partial or complete recovery of left ventricular function\nclose surveillance for arrhythmia recurrence during follow - up is warranted to avoid further decline in ventricular function .\njude medical and abiomed , and a member of the speaker 's bureau at pfizer / bms .\nbrian olshansky is a consultant at boston scientific , medtronic , daichi sankyo , biotronik , cardionomics , biocontrol , amarin , boehringer ingelheim , and on - x .",
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"content": "tachycardia , conventionally , but arbitrarily , defined as an atrial and/or ventricular rate of > 100 beats per minute , is encountered commonly and can be physiological or pathological in origin \n . various adverse consequences from tachycardia have been recognized , and an important one is the association between persistent tachycardia and cardiomyopathy . in this article \n , we provide an up - to - date review on the etiology of tachycardia , management strategies , and the prognosis of patients presenting with tachycardia and cardiomyopathy .",
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science.bc7_litcovid_topic_classification | science.bc7_litcovid_topic_classification.3247 | [
{
"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 -1 ribosomal frameshifting is vital for the translation of the open reading frame (ORF)1b in SARS-CoV-2. The products of ORF1b participate in viral replication. Therefore, changing the frameshift frequency reduces the survival of the virus. This study aimed to successfully develop a toolkit for screening antiviral drugs. Finally, the FDA-approved drug library was screened, revealing that ivacaftor and (-)-Huperzine A worked well in changing the -1 ribosomal frameshifting of SARS-CoV-2 in vitro.",
"role": "user"
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{
"content": "[\"Treatment\", \"Mechanism\"]",
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.5191 | [
{
"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: Crosstalk in stereoscopic displays: a review \nChapter Title: Optical Sensors \n1. Abstract of Cited Paper (BIB001): In 1853, William Rollman 1 developed the inexpensive and easy to use anaglyph method for displaying stereoscopic images. Although it can be used with nearly any type of full-color display, the anaglyph method compromises the accuracy of color reproduction, and it often suffers from cros- stalk (or ghosting) between the left- and right-eye image channels. Crosstalk degrades the ability of the observer to fuse the stereoscopic image, and hence reduces the quality of the 3-D image. Crosstalk is present in various levels with most stereoscopic displays; however, it is often particularly evident with anaglyphic 3-D images. This paper summarizes the results of two projects that characterized the presence of anaglyphic crosstalk due to spectral issues on 13 LCD monitors, 14 plasma displays, and a CRT monitor when used with 25 different pairs of anaglyph 3-D glasses. A mathematical model was used to predict the amount of crosstalk in anaglyphic 3-D images when different combinations of displays and glasses are used, and therefore highlight displays, glasses, and combinations thereof which exhibit lower levels of crosstalk when displaying anaglyphic 3-D images. The anaglyph method of displaying stereoscopic images uses a complementary color-coding technique to send sepa- rate left and right views to an observer's two eyes. The two perspective images of a stereo-pair are stored in comple- mentary color channels of the display, and the observer wears a pair of glasses containing color filters which act to pass the correct image but block the incorrect image to each \n2. Abstract of Cited Paper (BIB002): Although a naked-eye 3D display is more convenient to watch for a viewer, so far and in the near future the image ::: quality of a stereo display watched with special glasses is still much better than the former. e.g. the viewing angle, the ::: crosstalk, the resolution, etc. While focusing on the glasses-type stereo display, the image performance of a time ::: multiplexed shutter-glasses-type 3D display should be better than that of a spatial multiplexed polarization-encoded 3D ::: display. Shutter-glasses-type 3D display was implemented many years ago by CRT. However, due to the generation ::: supersedure the CRT was replaced by LCD, the shutter-glasses solution couldn't work for several years as a result of the ::: long response time of LCD. Thanks to the development of over-drive technology, the response time of LCD is getting ::: faster, and a 100-120Hz panel refresh rate is possible. Therefore, 3D game fans have a very good opportunity to watch ::: full resolution, large viewing angle and low crosstalk stereo LCDs again. In this paper, a 120Hz LCD and an LED ::: dynamic backlight to overcome the hold-type characteristic of an LCD are used to implement a time-multiplexed 3D ::: display. A synchronization circuit is developed to connect the time scheme of the vertical sync. signal from the display ::: card, the scanning backlight and the shutter glasses. The crosstalk under different scanning conditions is measured. \n3. Abstract of Cited Paper (BIB003): — The cause of the angular dependence of 3-D technology that requires the use of eyeglasses with linear or circular polarization is analyzed. For 3-D technology that requires the use of eyeglasses, anisotropic media such as a polarizer or retardation film determines the polarization state. Therefore, the angular behavior of 3-D display performance is also affected by the characteristics of the anisotropic media that have intrinsic angular dependence. Various conditions of the optic axes of the imaging display and eyeglasses are investigated to understand their effect on 3-D display performance. The result shows that some conditions of the optic axes can cause non-negligible degradation of 3-D display performance. \n4. Abstract of Cited Paper (BIB004): In this paper we propose a method to characterize polarization based stereoscopic 3D displays using multispectral ::: Fourier optics viewing angle measurements. Full polarization analysis of the light emitted by the display in the full ::: viewing cone is made at 31 wavelengths in the visible range. Vertical modulation of the polarization state is observed ::: and explained by the position of the phase shift filter into the display structure. In addition, strong spectral dependence of ::: the ellipticity and polarization degree is observed. These features come from the strong spectral dependence of the phase ::: shift film and introduce some imperfections (color shifts and reduced contrast). Using the measured transmission ::: properties of the two glasses filters, the resulting luminance across each filter is computed for left and right eye views. ::: Monocular contrast for each eye and binocular contrasts are performed in the observer space, and Qualified Monocular ::: and Binocular Viewing Spaces (QMVS and QBVS) can be deduced in the same way as auto-stereoscopic 3D displays ::: allowing direct comparison of the performances. \n5. Abstract of Cited Paper (BIB005): In this paper, we investigated performance analysis methods of auto-stereoscopic 3D displays in an optical point of view. This paper provides optical measurement and analysis methods for auto-stereoscopic displays. Issues discussed include: (1) optimum viewing distance; (2) luminance & contrast ratio; (3) color performance; (4) 3D point crosstalk; (5) spatial crosstalk; (6) ortho-stereoscopy angle/pseudo-stereoscopy angle; (7) luminance difference ratio. \n6. Abstract of Cited Paper (BIB006): Crosstalk is probably one of the main perceptual factors contributing to perceived image quality and visual comfort. The Video Quality Experts Group (VQEG) within their 3D video quality project is ... \n7. Abstract of Cited Paper (BIB007): Crosstalk is a critical factor determining the image quality of stereoscopic displays. Also known as ghosting or leakage, high levels of crosstalk can make stereoscopic images hard to fuse and lack fidelity; hence it is important to achieve low levels of crosstalk in the development of high-quality stereoscopic displays. In the wider academic literature, the terms crosstalk, ghosting and leakage are often used interchangeably and unfortunately very few publications actually provide a descriptive or mathematical definition of these terms. Additionally the definitions that are available are sometimes contradictory. This paper reviews how the terms crosstalk, ghosting and associated terms (system crosstalk, viewer crosstalk, gray-to-gray crosstalk, leakage, extinction and extinction ratio, and 3D contrast) are defined and used in the stereoscopic literature. Both descriptive definitions and mathematical definitions are considered. \n8. Abstract of Cited Paper (BIB008): With the recent introduction of Blu-ray 3D players and 3D televisions in the consumer market, people can watch 3D movies at home. 3D displays, however, still have imperfections, but there are no clear criteria to quantify performance differences. Standardized physical measurements in combination with perceptually relevant interpretation can help consumers in their buying decision. \n9. Abstract of Cited Paper (BIB009): 3D crosstalk is a major contributor to 3D quality loss and visual fatigue on stereoscopic displays. This paper presents several 3D crosstalk measurement methods and discusses the coherence between methods, towards the derivation of meaningful quality indicators. It also identifies the need of synthetic indicators for complex crosstalk effects. \n10. Abstract of Cited Paper (BIB010): Crosstalk is one of the main display-related perceptual factors degrading image quality and causing visual discomfort on 3D-displays. It causes visual artifacts such as ghosting effects, blurring, and lack of color fidelity which are considerably annoying and can lead to difficulties to fuse stereoscopic images. On stereoscopic LCD with shutter-glasses, crosstalk is mainly due to dynamic temporal aspects: imprecise target luminance (highly dependent on the combination of left-view and right-view pixel color values in disparity regions) and synchronization issues between shutter-glasses and LCD. These different factors influence largely the reproducibility of crosstalk measurements across laboratories and need to be evaluated in several different locations involving similar and differing conditions. In this paper we propose a fast and reproducible measurement procedure for crosstalk based on high-frequency temporal measurements of both display and shutter responses. It permits to fully characterize crosstalk for any right/left color combination and at any spatial position on the screen. Such a reliable objective crosstalk measurement method at several spatial positions is considered a mandatory prerequisite for evaluating the perceptual influence of crosstalk in further subjective studies.\n\nReview Chapter:",
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"content": "An optical measurement device, such as a photometer or a radiometer, can be used to measure crosstalk. The spectral sensitivity of the sensor(s) used should match the spectral sensitivity of the human visual system (photopic vision) so that the measurements are representative of what a human observer would see. [95] Examples of sensors that have been used to measure crosstalk include: Integrated Photomatrix Inc. IPL10530 DAL photo-diode, BIB001 Ocean Optics USB2000 spectroradiometer, BIB002 Konica Minolta CS1000 spectroradiometer, BIB004 Konica Minolta CS-100 spot chroma meter, BIB003 Eldim EZContrastMS, BIB005 and Photo Research PR-705. BIB007 Many other devices can also be used for this purpose. In the first instance, the optical sensor will be placed at the left eye position (either behind the left eye of the 3D glasses, or in the left eye viewing zone for an autostereoscopic display) and a series of measurements taken with a crosscombination of the image channels set at various specified levels. This is then repeated for the other eye position(s). In the case of black-white crosstalk, the two gray-levels will be black and white (see Sec. 2.2.2) and for gray-togray crosstalk a much greater number of measurements will be taken for a selection of gray-level combinations (Sec. 2.2.4). Crosstalk may also be characterized spatially across the display, BIB011 BIB006 or for different horizontal and vertical viewing angles, in which case the number of measurements can increase significantly, resulting in a much more complex crosstalk dataset-in which case the automation of the taking of the measurements can be advantageous. Efforts to standardize crosstalk measurement methods are currently under way and being published by ICDM, IEC, ISO, and others. BIB008 BIB009 Ensuring the accuracy and reproducibility of crosstalk measurements between different measurement sensors, measurement methods and laboratories is an important problem and work is continuing in this area. BIB011 BIB010 BIB007",
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.12141 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nPharmacokinetics of a Long-Acting Nanoformulated Dolutegravir Prodrug in Rhesus Macaques\n\nContent Extracts:\nTEXT\n<p>Antiretroviral drug (ARV) therapy allows those infected with human immunodeficiency virus (HIV) to live normal productive lives (1, 2). Nonetheless, adherence to lifelong daily multidrug regimens and viral resistance continue (3–8). End-organ disease, drug-drug interactions, cost, short pharmacologic duration, and access are further limitations. We posit that long-acting ARVs can overcome these restrictions (7, 9–12). In a step to transform existing ARVs into long-acting medicines, we increased the hydrophobicity and lipophilicity of ARVs through carboxy-ester myristoylation, affecting tissue and cell penetrance (13, 14). In the current report, this approach was developed for dolutegravir (DTG), a second-generation integrase strand transfer inhibitor with high viral resistance barriers (15, 16). Native orally administered DTG demonstrates a plasma half-life of 13 to 14 h (17–19), with >99% plasma albumin and alpha 1-acid glycoprotein binding. A daily or twice-daily dosing is required to maintain therapeutic plasma concentrations above a protein-adjusted 90% inhibitory concentration (PA-IC90) of 64 ng/ml (15, 17–19). To extend the pharmacokinetic properties of DTG, a nanoformulated prodrug derivative (nanoformulated myristoylated dolutegravir [NMDTG]) was made. Intramuscular injections with 45 mg/kg of body weight led to drug levels in mice above the PA-IC90 for 56 days (our unpublished data) and were then affirmed in nonhuman primates.</p><p>Myristoylated DTG (MDTG) was prepared by a one-step synthesis and then encased into a nanoformulation (our unpublished data). Synthesis and quality control measures were maintained through the Nebraska Nanomedicine Production Plant using good laboratory practice (GLP) protocols following U.S. Food and Drug Administration (FDA) guidelines (20) (see the supplemental material). The prepared suspensions were homogenized at 20,000 lb/in2 using an Avestin EmulsiFlex-C3 high-pressure homogenizer (Avestin, Inc., Ottawa, Ontario, Canada). Particle sizes, polydispersity indices, and zeta potentials were determined by dynamic light scattering (Malvern Zetasizer Nano ZSP; Malvern Instruments, Westborough, MA). MDTG concentrations in the nanosuspensions were determined by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS; Waters Acquity XevoTQ-S micro system; Waters Corp., Milford, MA) (see supplemental material). Endotoxin content was determined by Lonza Limulus Amebocyte Lysate Pyrogent-500 tests (Lonza, Walkersville, MD). Animal studies were conducted in accordance with the University of Nebraska Medical Center Institutional Animal Care and Use Committee, according to federal guidelines. Three male rhesus macaques (9 to 10 kg; purchased from PrimeGen) were anesthetized with 10 mg/kg ketamine and injected intramuscularly (i.m.) with undiluted NMDTG suspension (38.5 mg/kg in 2.67 to 3.50 ml). Blood was collected into potassium-EDTA tubes before NMDTG administration, days 1, 4, and 7 after administration, and weekly thereafter to day 91. Plasma and peripheral blood mononuclear cells (PBMCs) were obtained for complete blood counts, metabolic panels, and DTG and MDTG drug quantitation. These were performed by the Nebraska Medical Center Pathology and Microbiology laboratory and by the Nebraska Nanomedicine Production Plant GLP laboratory using UPLC-MS/MS, respectively (see supplemental material). Animal health and injection site reactions were monitored daily. NMDTG was manufactured in three separate batches with reproducible characteristics, as summarized in Table 1. Nanoparticle sizes varied from 275.8 to 338.6 nm, with a narrow polydispersity index (0.20 to 0.25) and a negative zeta potential (−18.9 to −22.3 mV). MDTG concentrations in the nanosuspensions were from 111.9 to 126.6 mg/ml. The DTG concentration was below the limit of detection (0.2 ng/ml). To ensure aseptic preparation of the nanosuspensions, the endotoxin levels in the prepared nanoformulations were determined. Formulation endotoxin concentrations were below 5 endotoxin units (EU)/kg.</p>\n\n\n<p>Physicochemical characteristics of NMDTG batches</p><p>Animals are those for which each formulation batch was prepared.</p><p>PDI, polydispersity index.</p>\n\nTEXT\n<p>A single i.m. injection of NMDTG was administered to three rhesus macaques. Neutrophil, lymphocyte, and monocyte counts determined prior to NMDTG administration and weekly after administration (Fig. 1) were consistent. A solitary increase in neutrophil counts was recorded at day 70 and reflected the development of an abscess near the site of injection in a single animal and was deemed not to be drug associated. Full resolution was made by drainage and antibiotic treatment. An initial mild redness and swelling observed at the injection site were resolved in all animals by day 7. Liver and kidney metabolic profiles were unchanged in all animals following NMDTG treatment (see Tables S1 to S3 in the supplemental material). No weight changes or adverse physical signs were recorded in any of the animals after formulation injection (data not shown). Parent and prodrug concentrations in plasma and blood leukocytes were determined following NMDTG administration. Plasma DTG concentrations peaked at day 1 at 602 ± 269 ng/ml and remained above the protein-adjusted 90% inhibitory concentration (PA-IC90) of 64 ng/ml for 35 days (Fig. 2A) and above 10 ng/ml for 91 days. The extended pharmacokinetic profile of NMDTG was demonstrated by the assessment of DTG plasma half-life (t1/2; 467 ± 28 h) and mean residence time (MRT; 691.7 ± 98.4 h) (Table 2). Plasma prodrug concentrations, although varied, remained above the limit of detection (at or around 10 ng/ml) for 42 days. MDTG was observed in blood leukocytes (Fig. 2B) through day 42; however, DTG concentrations were at the limit of detection after 14 days. The pharmacokinetic (PK) parameters of both MDTG and DTG in PBMCs reflected those in plasma, especially the half-lives, which indicates that the intracellular and plasma concentrations were in equilibrium. Similar to plasma, an extended half-life was observed for both MDTG (t1/2 = 542 h) and DTG (t1/2= 460 h) in PBMCs (Table 3).</p>\n\n\n<p>White blood cell counts following NMDTG administration in rhesus macaques. Complete blood count (CBC) samples were collected into EDTA tubes and assessed by manual differentiation. Data are expressed as mean ± standard deviation (n = 3).</p><p>Plasma (A) and blood leukocyte (B) DTG and MDTG concentrations following NMDTG administration in rhesus macaques. Data are expressed as mean ± standard deviation (A, n = 3; B, n = 2 to 3). Dashed line indicates DTG PA-IC90 of 64 ng/ml.</p><p>PK parameters for DTG and MDTG</p><p>In the units of measure for the area under the concentration-time curve (AUC) data, 1 ml is equivalent to 100 × 106 cells. λZ, individual estimate of the terminal elimination rate constant; AUClast, AUC 0 h to last time point; AUC0–∞, AUC from 0 h to infinity; Vβ, volume of distribution at β phase; CL, clearance; MRT, mean residence time. PK parameters are calculated from the mean of the results from 3 monkeys.</p><p>SEM, standard error of the mean; ND, not determined.</p><p>PBMC PK parameters for DTG and MDTG</p><p>In the units of measure for the AUC data, 1 ml is equivalent to 100 × 106 cells. λZ, individual estimate of the terminal elimination rate constant; AUClast, AUC 0 h to last time point; AUC0–∞, AUC from 0 h to infinity; Vβ, volume of distribution at β phase; CL, clearance; MRT, mean residence time. PK parameters are calculated from the mean of the results from 3 monkeys.</p>\n\nTEXT\n<p>The idea of long-acting injectable drugs for the chronic treatment of disease has found therapeutic precedent in the areas of antipsychotics and contraception (21–24). The development of long-acting injectables for antiretroviral drugs has great promise. This includes, but is not limited to, the potential to improve regimen adherence, reduction of drug side effects, and reduce the development of drug resistance (10, 25), as well as the potential to serve as a preexposure prophylaxis regimen (10, 17, 21). To prove practical for human use, the medicines need to provide prophylactic prevention of human immunodeficiency virus type 1 (HIV-1) infection when given at intervals of once a month or longer (10, 11, 17). Our laboratories have been at the forefront of this effort by using chemical modifications of hydrophilic and hydrophobic drugs to improve drug hydrophobicity and lipophilicity (13, 14). Incorporation of the hydrophobic lipophilic derivatives into nanoformulations has produced injectable formulations of drugs that can be administered monthly to target viral cell and tissue reservoirs and suppress HIV infection in humanized mouse models (13, 14, 26). The present data demonstrate that a single i.m. injection of long-acting NMDTG provides plasma drug levels above the PA-IC90 in rhesus macaques for 1 month and can greatly extend drug half-life. The relatively higher MDTG levels compared to those of DTG in PBMCs indicate that the nanoformulation is taken into mononuclear phagocytes that can act as secondary drug depots, as we have observed in rodent studies (27, 28). The study illustrates that these formulations can be reproducibly and safely produced, and with additional modest modifications in volume and in hydrophobicity, they could be ready for human clinical trial scale-ups. This is a major step forward in the development and production of a long-acting DTG formulation. Additional drug and formulation modifications are in development to effectively realize a translatable formulation that can be delivered in a clinically relevant dose volume and provide, following a single injection, plasma drug levels at 1 month above the trough concentration (Ctrough) level of 840 ng/ml observed in adults given a 50-mg daily oral dose of DTG (19).</p>\n\n\n<p>Supplemental material for this article may be found at https://doi.org/10.1128/AAC.01316-17.</p>",
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"content": "ABSTRACTA nanoformulated myristoylated dolutegravir prodrug (NMDTG) was prepared using good laboratory practice protocols. Intramuscular injection of NMDTG (118 ± 8 mg/ml, 25.5 mg of DTG equivalents/kg of body weight) to three rhesus macaques led to plasma DTG levels of 86 ± 12 and 28 ± 1 ng/ml on days 35 and 91, respectively. The NMDTG platform showed no significant adverse events. Further modification may further extend the drug's apparent half-life for human use.",
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science.pico_ner | science.pico_ner.2807 | [
{
"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\nContribution of endogenous bradykinin to fibrinolysis , inflammation , and blood product transfusion following cardiac surgery : a randomized clinical trial . Bradykinin increases during cardiopulmonary bypass ( CPB ) and stimulates the release of nitric oxide , inflammatory cytokines , and tissue-type plasminogen activator ( t-PA ) , acting through its B2 receptor . This study tested the hypothesis that endogenous bradykinin contributes to the fibrinolytic and inflammatory response to CPB and that bradykinin B2 receptor antagonism reduces fibrinolysis , inflammation , and subsequent transfusion requirements . Patients ( N = 115 ) were prospectively randomized to placebo , ε-aminocaproic acid ( EACA ) , or HOE 140 , a bradykinin B2 receptor antagonist . Bradykinin B2 receptor antagonism decreased intraoperative fibrinolytic capacity as much as EACA , but only EACA decreased D-dimer formation and tended to decrease postoperative bleeding . Although EACA and HOE 140 decreased fibrinolysis and EACA attenuated blood loss , these treatments did not reduce the proportion of patients transfused . These data suggest that endogenous bradykinin contributes to t-PA generation in patients undergoing CPB , but that additional effects on plasmin generation contribute to decreased D-dimer concentrations during EACA treatment .",
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"content": "{\"Intervention\": [], \"Outcome\": [\"fibrinolytic and inflammatory response to CPB and that bradykinin B2 receptor antagonism reduces fibrinolysis , inflammation , and subsequent transfusion requirements .\", \"inflammation\", \"fibrinolysis\", \"blood product transfusion\", \"release of nitric oxide , inflammatory cytokines , and tissue-type plasminogen activator ( t-PA )\"], \"Participant\": [\"following cardiac surgery :\", \"Patients ( N = 115 )\", \"cardiopulmonary bypass ( CPB )\"]}",
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science.bioasq_yesno_qa | science.bioasq_yesno_qa.813 | [
{
"content": "Examine the provided biomedical text and determine the answer to the question. Your response should be either \"yes\" or \"no\" based on the information given.\n\nQuestion: Is pimavanserin effective for Parkinson's disease psychosis?\n\nText: Two cases of Parkinson's disease with an unusual delusional misidentification, intermetamorphosis, are presented, along with their improvement with pimavanserin, a novel atypical antipsychotic medication.\nRATIONALE: Pimavanserin, a selective serotonin 2A receptor inverse agonist, is a promising candidate for treating Parkinson's disease psychosis.\nOBJECTIVE: Our aim was to describe the efficacy and tolerability of pimavanserin, a highly selective serotonin 5-HT2A receptor inverse agonist/antagonist indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP), using the metrics of number needed to treat (NNT) and number needed to harm (NNH).\nPimavanserin: novel pharmacotherapy for Parkinson's disease psychosis.\nINTRODUCTION: Pimavanserin is the first FDA-approved atypical antipsychotic drug indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP)\nA pivotal phase III clinical trial demonstrated significant improvement in PDP symptoms in patients receiving pimavanserin compared to placebo-treated patients.\nPimavanserin's mechanism of action might contribute to its unique psychopharmacological properties in the improved treatment of PDP, and perhaps psychosis in other diseases including schizophrenia and dementia-related psychosis.\nPimavanserin (Nuplazid™) for the treatment of Parkinson disease psychosis: A review of the literature.Options for the treatment of Parkinson disease psychosis are limited.\nPimavanserin for the treatment of Parkinson's disease psychosis.Pimavanserin is an antipsychotic with a unique mechanism of action (5-HT2A receptor inverse agonist) and no measurable dopaminergic activity; it has been demonstrated to be efficacious, well tolerated and safe for the treatment of PDP.\nA Retrospective Study of Pimavanserin Use in a Movement Disorders Clinic.Pimavanserin, a 5-HT2A inverse agonist, was commercially released in the United States in April 2016 for the treatment of Parkinson disease psychosis.\nreceptor inverse agonist pimavanserin was recently approved by the US FDA for the treatment of PDP and may prove to be a more targeted therapy without the downsides of atypical antipsychotics.\nEvidence-Based Review of Pharmacotherapy Used for Parkinson's Disease Psychosis.Despite lack of rigor in study designs, published data to date suggest that clozapine and pimavanserin should be considered drugs of choice to treat PD psychosis.\nPimavanserin: A novel therapeutic option for Parkinson disease psychosis.While pimavanserin appears to be a safe, effective, and well-tolerated therapeutic option for PDP, additional clinical trials and open-label extension studies are needed to determine the long-term safety and efficacy of this promising therapy.\nObjective: Pimavanserin is the first United States Food and Drug Administration (FDA)-approved treatment for Parkinson's disease psychosis (PDP).\nPimavanserin: A Novel Drug Approved to Treat Parkinson's Disease Psychosis.\nCONCLUSIONS Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease.\nOBJECTIVE To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.\nRESULTS Pimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease.\nBACKGROUND Pimavanserin is a selective 5-HT2A receptor inverse agonist and antagonist approved in the USA for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.\nPimavanserin is the first FDA-approved atypical antipsychotic drug indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP).\nINTERPRETATION Pimavanserin may benefit patients with Parkinson's disease psychosis for whom few other treatment options exist.\nPimavanserin (ACP-103) is a selective inverse agonist of the 5-hydroxytryptamine 2A (5-HT2A) receptor intended to treat patients with Parkinson's disease psychosis (PDP).\nINTERPRETATION Pimavanserin showed efficacy in patients with Alzheimer's disease psychosis at the primary endpoint (week 6) with an acceptable tolerability profile and without negative effect on cognition.\n[Pimavanserin: a new treatment for the Parkinson's disease psychosis].\nPimavanserin, a serotonin(2A) receptor inverse agonist, for the treatment of parkinson's disease psychosis.\nPimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved in the U.S. for treating hallucinations and delusions associated with Parkinson's disease psychosis (PDP).\nPimavanserin: A Novel Antipsychotic for Parkinson's Disease Psychosis.\nCONCLUSIONS Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease.\nOBJECTIVE To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.\nRESULTS Pimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease.\nIf this is granted, we believe the evidence of Pimavanserin efficacy, safety and tolerability will position this medication as the first choice for treatment of Parkinson's disease psychosis.\nThe development of pimavanserin as an antipsychotic opened a new therapeutic avenue in the treatment of PDP as well as targeting psychosis in other disorders such as Alzheimer's disease.\nOBJECTIVE To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of pimavanserin for the treatment of hallucinations and delusions of Parkinson's disease psychosis (PDP).\nINTERPRETATION Pimavanserin may benefit patients with Parkinson's disease psychosis for whom few other treatment options exist.\n<b>OBJECTIVE</b>: To summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.\nData were available from 616 patients with Parkinson's disease with hallucinations and delusions who received at least 1 dose of pimavanserin, with a total exposure of 825 patient-years in the Parkinson's disease psychosis population.<br><b>RESULTS</b>: Pimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease.\nPimavanserin did not worsen motor function, an adverse effect commonly observed with other antipsychotics, probably because of a lack of consequential dopamine binding.<br><b>CONCLUSIONS</b>: Pimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease.\nPimavanserin (Nuplazid™) is a selective and potent serotonin 2A (5-HT2A) receptor inverse agonist and antagonist developed by ACADIA Pharmaceuticals that has been approved in the US as a treatment for patients with hallucinations and delusions associated with Parkinson's disease psychosis.\nThis article summarizes the milestones in the development of pimavanserin leading to this first approval for the treatment of hallucinations and delusions in patients with Parkinson's disease psychosis.\nIn a Phase 2 study with pimavanserin in Alzheimer's disease psychosis, pimavanserin significantly (p=0.045) improved psychosis at Week 6 vs. placebo on the NPI-NH Psychosis Score (PS).\nTo summarize the US Food and Drug Administration's (FDA's) review of the safety and effectiveness for pimavanserin, an atypical antipsychotic, for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.\nPimavanserin is the only FDA-approved treatment for the hallucinations and delusions seen in patients with psychosis of Parkinson's disease.\nPimavanserin 34 mg/d was effective in treating hallucinations and delusions associated with Parkinson's disease.",
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"content": "yes",
"role": "assistant"
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science.scientific_lay_summarisation_plos_single_doc_summ | science.scientific_lay_summarisation_plos_single_doc_summ.8473 | [
{
"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: Experimental Transmission of Leishmania infantum by Two Major Vectors: A Comparison between a Viscerotropic and a Dermotropic Strain\nContent:\nAbstract:\nWe quantified Leishmania infantum parasites transmitted by natural vectors for the first time. Both L. infantum strains studied, dermotropic CUK3 and viscerotropic IMT373, developed well in Phlebotomus perniciosus and Lutzomyia longipalpis. They produced heavy late-stage infection and colonized the stomodeal valve, which is a prerequisite for successful transmission. Infected sand fly females, and especially those that transmit parasites, feed significantly longer on the host( 1. 5–1. 8 times) than non-transmitting females. Quantitative PCR revealed that P. perniciosus harboured more CUK3 strain parasites, while in L. longipalpis the intensity of infection was higher for the IMT373 strain. However, in both sand fly species the parasite load transmitted was higher for the strain with dermal tropism( CUK3). All but one sand fly female infected by the IMT373 strain transmitted less than 600 promastigotes; in contrast, 29% of L. longipalpis and 14% of P. perniciosus infected with the CUK3 strain transmitted more than 1000 parasites. The parasite number transmitted by individual sand flies ranged from 4 up to 4. 19×104 promastigotes; thus, the maximal natural dose found was still about 250 times lower than the experimental challenge dose used in previous studies. This finding emphasizes the importance of determining the natural infective dose for the development of an accurate experimental model useful for the evaluation of new drugs and vaccines.\nIntroduction:\nLeishmania are intracellular protozoan parasites that establish infection in mammalian hosts following transmission through the bite of an infected phlebotomine sand fly. Visceral leishmaniasis, caused by Leishmania donovani in the Old World and L. infantum in both the Old and New World, invariably leads to death if left untreated[1]. Despite the fact that parasites from the L. donovani complex are mainly associated with disseminated infection of the spleen and liver, it has been shown that L. infantum can also cause cutaneous lesions[2]–[5]. A novel focus of cutaneous leishmaniasis caused by L. infantum was recently described in the Cukurova region in Turkey[6]. During the natural transmission of Leishmania into the dermis, sand flies deposit pharmacologically active saliva[7] and egest parasite-released glycoconjugates, the promastigote secretory gel[8]. Both substances modulate the immune response of the bitten host and enhance the severity of infection( reviewed by[9]). The ideal leishmaniasis model to test therapeutics and immunoprophylaxis candidates should reproduce the biological and immunological aspects of natural infection and disease. Different approaches regarding the parasite number and route of inoculation have been tested in order to develop an accurate experimental model for the L. donovani complex, most of them using subcutaneous, intraperitoneal or intravenous injections of millions of axenic promastigotes or amastigotes[10]–[11]. Although in some studies up to 107 parasites have been co-inoculated into the dermis with small amounts of sand fly saliva, is not clear how well these experiments mimic natural transmission[12]–[13]. The number of L. infantum parasites inoculated by infected vectors during natural transmission was not previously known, even though a determination of the natural infective dose is crucial for the development of an accurate experimental model to evaluate new drugs and vaccine candidates. In the L. major- P. duboscqi model, it was demonstrated that the number of promastigotes inoculated by individual sand flies ranged between 10 and 1×105 Leishmania[14]. The average number of L. infantum parasites egested was recently reported[15], but the technique used( feeding the pool of infected L. longipalpis through chick skin membrane on culture medium) did not allow an evaluation of the variation in numbers delivered by individual sand flies. Thus, the main aims of this work were to determine the transmission rate and the number of promastigotes inoculated into the skin of mice by individual sand fly females. Phlebotomus perniciosus and Lutzomyia longipalpis, two main vectors of L. infantum in the Mediterranean basin and in the New World, respectively[16], were experimentally infected by L. infantum dermotropic and viscerotropic parasites.\nDiscussion:\nFor the first time, we have quantified the number of parasites belonging to L. infantum dermotropic and viscerotropic strains transmitted to the dermis of experimental mice by individual sand fly females. The only previous attempt to calculate the number of transmitted L. infantum parasites was performed just recently[15], with the average number of promastigotes inoculated by 63 L. longipalpis into culture medium through a chicken membrane skin being 457 parasites, with 95%( 431 promastigotes) of these corresponding to metacyclic parasites. However, these results do not allow us to take into consideration the individual variability of parasite transmission by a single specimen. The wide range of parasites inoculated per individual sand fly in our study( from 4 up to 4. 19×104 promastigotes) is in accordance to data previously obtained with other Leishmania-vector combinations[14],[17], although the approach using microcapillaries as artificial feeding systems[17] could have interfered with the normal sand fly feeding behaviour. In our study, Phlebotomus perniciosus harboured more L. infantum dermotropic parasites of the CUK3 strain, while in L. longipalpis the intensity of infection was higher for the viscerotropic strain IMT373. However, in both sand fly species the parasite load transmitted was higher for the strain with dermal tropism. All but one sand fly female infected by IMT373 strain transmitted less than 600 promastigotes, the exception being a L. longipalpis female that inoculated 1240 parasites. On the other hand, 29% of L. longipalpis and 14% of P. perniciosus infected with the CUK3 strain transmitted more than 1000 parasites. The majority of transmitting females inoculated less than 600 parasites. As most of these females were fully engorged by blood we may expect that their feeding pumps( the cibarial and pharyngeal pumps) and stomodeal valve were functioning normally. On the other hand, in those transmitting more than 1000 parasites there was a significant correlation between the pre-feeding load and the number of parasites transmitted. We suggest that these females with high dose deliveries regurgitated parasites because of impaired stomodeal valve function[18]. This would be consistent with previous studies[19],[20] which have demonstrated an opened stomodeal valve due to the physical presence of a parasite plug and damage of the chitin layer of the valve by Leishmania chitinase. Infected sand fly females, and especially those that transmit parasites, feed longer on hosts than non-transmitting ones do. Lutzomyia longipalpis females transmitting dermotropic CUK3 strain parasites took an average of 1. 5 times longer to complete a bloodmeal compared to specimens infected but not transmitting, and 1. 8 times longer than uninfected females. Similarly, P. perniciosus infected by CUK3 and IMT373 take 1. 5 and 1. 2 times more time for a blood meal. Most of the infected sand flies exposed to anaesthetized mice did not demonstrate increased probing, but rather remained feeding for longer periods until either they were fully or partially engorged. This is in agreement with data previously published on the L. longipalpis-L. mexicana combination[21]. Although only one dermotropic and one viscerotropic L. infantum strains were evaluated, the significant variation in inoculum size between them allow us to hypothetise that the infectious dose delivered by vector sand flies may be an inherent character of each Leishmania strain. Moreover, the infectious dose might be a determining factor in the outcome of Leishmania infection. Local cutaneous lesions might result from a high-dose inoculum of dermotropic Leishmania resulting in a strong local immune response, whereas dissemination to internal organs might be the result of infected sand flies delivering a low number of parasites below the threshold required to produce/develop a localized and restraining immune response. This hypothesis corresponds with the data of Kimblin et al.[14] on the L. major-P. duboscqi combination. These authors evaluated the impact of inoculum size on infection outcome by comparing L. major infections with high( 5×103) and low( 1×102) dose intradermally inoculated by needle in the ears of C57BL/6 mice, and observed the rapid development of large lesions in the ears of mice receiving the high-dose inoculum. In contrast, the low dose resulted in only minor pathology but a higher parasite titre during the chronic phase[14]. Nevertheless, it will be necessary to evaluate more L. infantum strains with visceral and cutaneous tropism in order to determine if differences detected in our study were due to individual stock characteristics or if they are associated with parasite tropism in vertebrate hosts. In conclusion, we have demonstrated that individual sand flies transmit Leishmania parasites in a wide dose range. However, the maximal natural dose found was still about 250 times lower than the challenge dose used for the L. donovani complex in most previous experimental works. This finding emphasizes the importance of determining the natural infective dose for the development of an accurate experimental model, which is crucial for the evaluation of new drugs and vaccine candidates against leishmaniasis.",
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"content": "Leishmaniasis is a disease caused by protozoan parasites which are transmitted through the bites of infected insects called sand flies . The World Health Organization has estimated that leishmaniases cause 1 . 6 million new cases annually , of which an estimated 1 . 1 million are cutaneous or mucocutaneous , and 500 , 000 are visceral , the most severe form of the disease and fatal if left untreated . The development of a more natural model is crucial for the evaluation of new drugs or vaccine candidates against leishmaniases . The main aim of this study was to quantify the number of Leishmania infantum parasites transmitted by a single sand fly female into the skin of a vertebrate host ( mouse ) . Two L . infantum strains , viscerotropic IMT373 and dermotropic CUK3 , were compared in two natural sand fly vectors: Phlebotomus perniciosus and Lutzomyia longipalpis . We found that the parasite number transmitted by individual sand flies ranged from 4 up to 4 . 19×104 . The maximal natural infective dose found in our experiments was about 250 times lower than the experimental challenge dose used in most previous studies .",
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science.data_reco_mcq_mc | science.data_reco_mcq_mc.421 | [
{
"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 bidirectional LSTM model for learning general sentence representations. The proposed model is a general method\n\nKey Terms: sentence modeling\n\nDataset Summaries:\nSST: The Stanford Sentiment Treebank is a corpus with fully labeled parse trees that allows for a complete analysis of the compositional effects of sentiment in language. The corpus is based on the dataset introduced by Pang and Lee (2005) and consists of 11,855 single sentences extracted from movie reviews.\nPenn Treebank: The English Penn Treebank (PTB) corpus, and in particular the section of the corpus corresponding to the articles of Wall Street Journal (WSJ), is one of the most known and used corpus for the evaluation of models for sequence labelling. The task consists of annotating each word with its Part-of-Speech tag.\nSentEval: SentEval is a toolkit for evaluating the quality of universal sentence representations. SentEval encompasses a variety of tasks, including binary and multi-class classification, natural language inference and sentence similarity.\nIMPPRES: An IMPlicature and PRESupposition diagnostic dataset (IMPPRES), consisting of >25k semiautomatically generated sentence pairs illustrating well-studied pragmatic inference types.\nINTERACTION Dataset: The INTERACTION dataset contains naturalistic motions of various traffic participants in a variety of highly interactive driving scenarios from different countries. The dataset can serve for many behavior-related research areas, such as 1) intention/behavior/motion prediction, 2) behavior cloning and imitation learning, 3) behavior analysis and modeling, 4) motion pattern and representation learning, 5) interactive behavior extraction and categorization, 6) social and human-like behavior generation, 7) decision-making and planning algorithm development and verification, 8) driving scenario/case generation, etc.\nMultiNLI: The Multi-Genre Natural Language Inference (MultiNLI) dataset has 433K sentence pairs. Its size and mode of collection are modeled closely like SNLI.\n\nDataset Options: A: SST B: Penn Treebank C: SentEval D: IMPPRES E: INTERACTION Dataset F: MultiNLI",
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"content": "[\"SST\", \"SentEval\", \"MultiNLI\"]",
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science.pubmedqa_qa | science.pubmedqa_qa.344 | [
{
"content": "Analyze the given text and respond to the inquiry. Choose from: \"YES\", \"NO\", or \"MAYBE\".\n\nText:\n(UNLABELLED) Cyclical pamidronate therapy in a 2-year-old child with skeletal fragility resulted in remodelling of vertebral fractures and improvement in bone mineral density (BMD) at distal radial and spinal sites. The BMD at both sites decreased precipitously within 24 months of stopping treatment, raising the question as to whether bisphosphonates can be stopped in a growing child with skeletal fragility.\n(INTRODUCTION) At age 23 months, a male toddler sustained a low trauma fracture of his right femur. Skeletal radiographs revealed generalised osteopenia with multiple vertebral body fractures. He was diagnosed with type IV osteogenesis imperfecta; however, no mutations were found in COL1A1 or COL1A2 genes.\n(METHODS) This case report presents bone densitometry data before, during and after bisphosphonate treatment. Axial QCT was main outcome from 2 years of age; DXA and pQCT were taken after age 5.\n(RESULTS) QCT confirmed that he had low spinal trabecular volumetric BMD (Z-score -2.4). After 4 years of treatment his vertebral fractures had been remodelled and all bone densitometry values (QCT, DXA and pQCT) were within normal range and therefore treatment was discontinued. Shortly after this he suffered stress fractures of his left mid tibia and at the sclerotic metaphyseal line corresponding to his first APD treatment. He had marked reduction in spinal trabecular and distal radial vBMD; change in BMAD was less marked.\n\nInquiry:\nCan bisphosphonate treatment be stopped in a growing child with skeletal fragility?\n\nResponse:",
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{
"content": "MAYBE",
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science.scicite_classification | science.scicite_classification.3802 | [
{
"content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nThe third category of techniques uses local spatio-temporal features [16, 27, 14, 8, 22] which have recently become a very popular video representation method for action recognition.",
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"content": "Background",
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science.craftchem_ner | science.craftchem_ner.2620 | [
{
"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:\nThus,theremarkableincreaseinenduranceisthephysiologicmanifestationofmusclefibertransformation.",
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science.chemsum_single_document_summarization | science.chemsum_single_document_summarization.31326 | [
{
"content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nTertiary amine synthesis via reductive coupling of amides with Grignard reagents\n\nContent Extracts:\nIntroduction\n<p>Tertiary amines are chemical motifs commonly found in molecules of importance to chemistry, biology and medicine. Their Lewis basic properties arising from the lone pair of electrons make them ideal as ligands for transition metal catalysts and organometallic complexes. Moreover, the Brønsted basicity of the tertiary amine moiety has been exploited extensively for sequestering acidic side products in coupling reactions, and, in metal-free catalysts exploiting acid/base equilibria for substrate activation in enantioselective carbon-carbon bond formation. 1 In nature they are oen found contained within alkaloid secondary metabolites produced by organisms such as bacteria, fungi, and plants. Classical synthetic routes typically rely on C-N bond forming reactions such as amine-carbonyl reductive amination, amine alkylation and C-N cross-coupling. 1,2 However, amine synthesis through carbon-carbon bond formation alpha to nitrogen offers complementarity especially for accessing a-branched products, and, as such, the synthetic utility of the Petasis-Mannich reaction 3 as well as the directed amine lithiation/functionalisation approach of Beak,Hoppe,and others, Furthermore, a-functionalisation of amines via radical intermediates produced through photoredox activation have recently been achieved. 5 Reductive functionalisation of amide functionality to generate carbon-carbon bonds alpha to nitrogen has also been demonstrated as a viable approach for amine synthesis. [6][7][8] In this context, approaches using stoichiometric amounts of strongly electrophilic reagents, such as Tf 2 O and POCl 3 , for amide pre-activation prior to reductive functionalisation, have been described 9 (Scheme 1A). Weinreb amides have also been demonstrated as alternative substrates for reductive preactivation, using stoichiometric DIBAL-H or Schwartz's reagent (Cp 2 ZrHCl), affording alkoxy amine products aer, for example, allylation and cyanation reactions in the presence of Lewis acids for reactive iminium ion formation 10 (Scheme 1B). Although the above stoichiometric approaches are demonstrably successful, catalysed variants of these reductive functionalization processes offer a number of potential bene-ts, especially in terms of chemoselectivity and functional group tolerance. For example, in presence of Vaska's complex and (Me 2 HSi) 2 O (TMDS), Chida/Sato 11 demonstrated the formation of hemiaminal intermediates from Weinreb amide substrates, which with the assistance of stoichiometric BF 3 $Et 2 O, undergo substitution by preformed nucleophiles such as silyl ketene acetals and allyltin reagents. Our group, and others, have been exploring amine synthesis through exploitation of enamine and iminium ion intermediates formed by catalytic partial reduction of tertiary amides. 12 In this respect, we have reported the iridium catalysed reductive intramolecular nitro-Mannich reaction of lactams for the synthesis of bicyclic nitroamines, and the broad-scope iridium catalysed reductive Strecker reaction of tertiary amides for the efficient synthesis of a-amino nitrile products.</p><p>In a continuation of our program, and with the ultimate aim of expanding the range of amine products accessible using the two stage reductive activation approach, we considered a reductive coupling of tertiary amides and Grignard reagents (Scheme 1C). Grignard reagents are widely available commercial organometallic reagents and are simply and reliably prepared in the laboratory. Similarly, tertiary amides are commonly found in biologically active natural products and drug compounds, and are widespread throughout pharmaceutical and agrochemical companies. When combined with the ease at which they can be prepared through standard amide coupling reactions, 13 a mild reductive coupling protocol that could efficiently and chemoselectively target this functional group to generate tertiary amine products from Grignard reagents would likely nd numerous applications in preparative scale synthesis, library generation, late-stage functionalisation, and total synthesis alike. Herein we wish to report our ndings.</p>\n\nResults and discussion\n<p>We chose the reductive benzylation of dimethyl benzoylamide as a model reaction and selected Vaska's catalyst and tetramethyldisiloxane (TMDS) for the key reductive activation step (Table 1). Initial investigations employing THF or toluene as the reaction solvent were encouraging; in both cases a two-stage protocolwhere the reductive activation step (using 1 mol% Vaska's catalyst and 2 eq. of TMDS) was allowed to run to completion prior to addition of benzylmagnesium chloride (1 M in THF)afforded moderate yet encouraging yields of the desired tertiary amine 1 (entry 1 and 2). Further studies iden-tied dichloromethane as the solvent of choice and the ideal concentration of amide starting material to be 0.1 M. Following optimisation, our two-stage one-pot protocol enabled the synthesis of 1 in 89% isolated yield aer ash column chromatography (entry 6).</p><p>With optimised conditions in hand the scope of the reductive benzylation reaction with respect to the tertiary amide was assessed (Scheme 2). Benzoylamides derived from cyclic amines pyrrolidine, azepine, azocane, morpholine and 6,7-dimethoxytetrahydroisoquinoline respectively, all furnished the target tertiary amines (2-6) in good to excellent yields (70-90%).</p><p>Methylbenzylbenzoylamide was also a good substrate yielding benzylamine (7) in excellent yield and thus expanding the potential application of the protocol to secondary amine synthesis via subsequent hydrogenolysis. The Weinreb amide of benzoic acid was an excellent substrate and afforded a-benzylated methoxyamine product 8 in 87% yield. Methylaniline derived benzoyl amide was also amenable to reductive benzylation, and furnished a substituted aniline product 9. The acceptable yield of 57% in this case required the use of an increased loading of Vaska's complex (5 mol%) in the initial reductive activation step to overcome diminished substrate reactivity. Great tolerance with respect to the arene moiety of the dimethylamide was witnessed under the optimised reaction conditions. Thus electron decient, electron-rich and halogensubstituted benzoic acid derivatives gave the respective tertiary amine products (14-18) in yields ranging from 84 to 97%. Similarly a 2-furanyl substrate gave the desired amine product (19) in 94% yield. Aliphatic dimethyl amides, derived from n-decanoic acid, cyclohexane carboxylic acid and pivalic acid were all good substrates for the reductive alkylation protocol and yielded tertiary amine products 10-12 in respectable yields. N-Formyl piperidine was also an excellent substrate and gave product 13 in 82% yield. The ability to dialkylaminomethylate organomagnesium reagents using tertiary formamides should nd many synthetic applications within target synthesis, methodology development and drug discovery programs. Unfortunately, under the current reaction conditions, reductive coupling of lactams with Grignard reagents were not successful. 14 Despite the use of a relatively reactive organometallic coupling partner (BnMgCl) the functional group tolerance of the reductive functionalisation reaction was found to be high. Nitrile, aryl ketone, pinacol boronate ester, tert-butyl carbamate and ester functionality all survived when the amount of Grignard reagent in the second stage was lowered to 1.2 equivalents and the reaction temperature kept below 0 C. The ability to tolerate halide functionality and pinacol boronate esters establishes this transformation as fully compatible with other cross-coupling reactions, indicating its potential for the synthesis of amine derived building blocks.</p><p>To demonstrate the synthetic utility of this newly developed reductive carbon-carbon bond forming methodology, we selected several amine-containing drug molecules as targets. NMDA receptor antagonists, diphenidine (25), methoxphenidine (26) and uorolintane (27), which are generally used as dissociative anesthetics, 15 were obtained directly and efficiently by submitting the corresponding and readily prepared parent amides to the standard protocol. Likewise ephenidine (28), a secondary amine drug molecule, 16 was synthesised by partial hydrogenolysis of the initially generated tertiary amine from its benzylethyl benzoylamide precursor, in 67% yield over the two steps. Furthermore, piperazine-derived</p><p>Scheme 2 Scope with respect to the tertiary amide. Standard condition: amide 0.3 mmol, IrCl(CO)(PPh 3 ) 2 1 mol%, TMDS 0.6 mmol, CH 2 Cl 2 3 mL, BnMgCl 0.6 mmol; isolated yields are given; Bpin ¼ pinacol boronate; Boc ¼ t-butyloxy carbonyl. a 5 mol% of IrCl(CO)(PPh 3 ) 2 was used; b performed at 0 C for 6 h after the addition of BnMgCl (1.2 eq.); c Pd/C catalysed hydrogenolysis of the N-benzyl group was performed on the tertiary amine product and overall yield is given.</p><p>opioid analgesic drug MT-45(29) 17 was prepared in near quantitative yield.</p><p>The scope with respect to the Grignard reagent was also found to be broad. As depicted in Scheme 3, methyl, linear-alkyl and branched-alkyl magnesium reagents were compatible with this protocol and yielded amine products (30-32) in good to excellent yields. (Trimethylsilyl)methylmagnesium chloride was also an excellent reagent for new carbon-carbon bond formation under the standard conditions. Importantly, a reductive methylation of N,N-dimethyl-p-toluamide was carried out on gram scale following the standard protocol and afforded methylated product 34 in 85% yield. Reductive vinylation using vinylmagnesium bromide and reductive alkynylation using hexynyl magnesium bromide yielded allylamine 35 and propargylamine 36 in 74% and 86% yield, respectively. Phenyl magnesium bromide was also found to be a competent nucleophilic coupling partner and afforded benzylic tertiary amine product 37 in 66% respectively. Reductive phenylation [or (hetero)arylation] of amides will likely nd many applications within the pharmaceutical sector and here we have exemplied it through the synthesis of the antiemetic piperazine-containing drug cinnarizine (38). 18 Using the twostep protocol 38 was successfully synthesised in 67% yield using phenylmagnesium bromide in the carbon-carbon bondforming step.</p><p>Encouraged by the high reactivity of the silylated hemiaminal intermediates towards organomagnesium reagents, we then chose to apply Knochel-type Grignard reagents to the new reductive carbon-carbon bond forming methodology. The diversity of organomagnesium reagents accessible by the Knochel procedure is impressive and would therefore boost the nature and type of amine products accessible using this approach. 19 To this end, para-triuoromethylphenyl organomagnesium reagent, prepared by magnesium/iodide exchange with isopropylmagnesium bromide, was investigated in the reductive arylation of the pyrrolidine amide of benzoic acid and indeed was found to be compatible with our protocol, yielding 39 in 65% yield. Similarly a range of aryl and pyrimidine-based heteroaryl Knochel-type Grignard reagents were successfully generated, then reacted with N-formyl piperidine following our standard protocol, furnishing homologated amine products (40-42) in satisfactory yields. Furthermore, organomagnesium reagents derived from a-D-glucofuranose and cholesterol derivatives using the Knochel procedure were also compatible.</p><p>The synthetic utility of this chemistry was further demonstrated through the late stage reductive functionalisation of drug molecules. Thus, piperine 20 (an extract of black pepper used as traditional medicine and insecticide) was successfully modied by benzylation (45, 93%) and butenylation (46, 83%). Also, the psychoactive drug pexide 21 underwent a reductive coupling reaction with benzylmagnesium chloride affording 47 in 73% yield. While by magnesium/proton exchange of the acetylenic proton of pargyline 22 (an irreversible selective monoamine oxidase MAO-B inhibitor) and then homologation with N-formyl piperidine, amine derivative 48 was obtained in 54% yield.</p>\n\nConclusions\n<p>A new two-stage, iridium catalysed reductive coupling of tertiary amides and Grignard reagents has been developed. Due to its good functional group tolerance, high chemoselectivity and broad scope with respect to both the amide and Grignard coupling partners, this new and practical methodology should nd many synthetic applications in research laboratories within both industry and academia.</p>",
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"content": "A new iridium catalyzed reductive coupling reaction of Grignard reagents and tertiary amides affording functionalised tertiary amine products via an efficient and technically-simple one-pot, two-stage experimental protocol, is reported. The reactionwhich can be carried out on gram-scale using as little as 1 mol% Vaska's complex [IrCl(CO)(PPh 3 ) 2 ] and TMDS as the terminal reductant for the initial reductive activation steptolerates a broad range of tertiary amides from (hetero)aromatic to aliphatic (branched, unbranched and formyl) and a wide variety of alkyl (linear, branched), vinyl, alkynyl and (hetero)aryl Grignard reagents. The new methodology has been applied directly to bioactive molecule synthesis and the high chemoselectivity of the reductive coupling of amide has been exploited in late stage functionalization of drug molecules. This reductive functionalisation of tertiary amides provides a new and practical solution to tertiary amine synthesis.Scheme 1 Reductive functionalisation of amides with carboncentered nucleophiles.",
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science.acl_arc_intent_classification | science.acl_arc_intent_classification.1274 | [
{
"content": "Examine the given text from a research paper in the field of NLP. Your task is to identify the role of the citation within the context provided. Focus on understanding the intent behind the citation and classify it accordingly.\n\nSection Title:\nintroduction\n\nText Before Citation:\nThe BEETLE II system architecture is designed to overcome these limitations (Callaway et al., 2007). It also becomes more difficult to experiment with different tutorial policies within the system due to the inherent completixites in applying tutoring strategies consistently across a large number of individual hand-authored remediations. author a different remediation dialogue for every possible dialogue state.\n\nCitation Text:\nThe BEETLE II system architecture is designed to overcome these limitations ( Callaway et al. , 2007 ) .\n\nText After Citation:\nIt uses a deep parser and generator, together with a domain reasoner and a diagnoser, to produce detailed analyses of student utterances and generate feedback automatically. This allows the system to consistently apply the same tutorial policy across a range of questions. To some extent, this comes at the expense of being able to address individual student misconceptions. However, the systemâs modular setup and extensibility make it a suitable testbed for both computational linguistics algorithms and more general questions about theories of learning.",
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"content": "Background",
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science.mslr2022_ms2_multidoc_summarization | science.mslr2022_ms2_multidoc_summarization.13539 | [
{
"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: Plasma Calcitonin Gene-Related Peptide in Diagnosing and Predicting Paediatric Migraine\nSummary: To investigate the role of plasma calcitonin gene-related peptide ( CGRP ) in paediatric migraine , we prospect ively collected 134 blood sample s during or between attacks from 66 migraine , 33 non-migraine headache ( non-migraine ) and 22 non-headache patients , aged 4–18 years . Plasma CGRP concentrations were measured by enzyme-linked immunosorbent assay and disability by Pediatric MIgraine Disability ASsessment ( PedMIDAS ) question naire . Migraineurs had higher plasma CGRP levels than non-migraine patients ( P = 0.007 ) . The attack level was higher than the non-attack level in migraine ( P = 0.036 ) , but not in non-migraine , patients . This was also revealed in paired comparison ( n = 9 , P = 0.015 vs. n = 4 , P = 0.47 ) . Using a threshold of 55.1 pg/ml , the sensitivity of the attack level in predicting migraine was 0.81 , and specificity 0.75 . The PedMIDAS score tended to be higher in the high CGRP ( > 200 pg/ml , n = 7 ) group than in the low ( < 200 pg/ml , n = 33 ) group ( 26.07 vs. 19.32 , P = 0.16 ) using Mann – Whitney test . Plasma CGRP is useful for diagnosis in paediatric migraine\n\n\nReport 2:\nTitle: β‐Endorphin in Plasma and Monocytes in Juvenile Headache\nSummary: Interictal serum levels of serotonin and plasma and mononuclear cell concentrations of β‐endorphin were measured in 20 juvenile patients ( 13 suffering from migraine without aura and 7 from episodic tension‐type headache ) before and after 3 months of L‐5‐hydroxytryptophan treatment ( 5 mg/ kg/day ) and compared with a control group of 17 headache‐free healthy subjects\n\n\nReport 3:\nTitle: What do plasma beta‐endorphin levels reveal about endogenous opioid analgesic function?\nSummary: Plasma levels of beta‐endorphin ( BE ) , an endogenous opioid analgesic , are often reported as they relate to acute and chronic pain outcomes . However , little is known about what resting plasma BE levels might reveal about functioning of the endogenous opioid antinociceptive system . This study directly examined associations between resting plasma BE and subsequent endogenous opioid analgesic responses to acute pain in 39 healthy controls and 37 individuals with chronic low back pain ( LBP ) . Resting baseline levels of plasma BE were assessed . Next , participants received opioid blockade ( 8 mg naloxone i.v . ) or placebo in a double‐blind , r and omized , crossover design . Participants then underwent two acute pain stimuli : finger pressure ( FP ) pain and ischaemic ( ISC ) forearm pain . Blockade effects ( naloxone minus placebo pain ratings ) were derived to index endogenous opioid analgesic function . In placebo condition analyses for both pain stimuli , higher resting BE levels were associated with subsequently greater reported pain intensity ( p 's < 0.05 ) , with this effect occurring primarily in healthy controls ( BE × Participant Type interactions , p 's < 0.05 ) . In blockade effect analyses across both pain tasks , higher resting plasma BE predicted less subsequent endogenous opioid analgesia ( smaller blockade effects ; p 's < 0.05 ) . For the ISC task , these links were significantly more prominent in LBP participants ( BE × Participant Type Interactions , p 's < 0.05 ) . Results suggest that elevated resting plasma BE may be a potential biomarker for reduced endogenous opioid analgesic capacity , particularly among individuals with chronic pain . Potential clinical implication s are discussed\n\n\nReport 4:\nTitle: Evidence for increased plasma levels of calcitonin gene-related peptide in migraine outside of attacks\nSummary: & NA ; Although calcitonin gene‐related peptide ( CGRP ) has been shown to be elevated in jugular venous blood of adult migraineurs during acute migraine attacks , it remains unknown whether CGRP is increased outside of attacks in jugular or cubital venous blood . The aim of the present study was to compare interictal plasma levels of CGRP in adult migraine patients and in healthy controls . Twenty patients with a diagnosis of migraine with or without aura and 20 healthy controls were included . In blood from the cubital vein , CGRP levels were significantly higher in patients ( 75±8 pmol/l ( mean±SEM ) ) than in controls ( 49±3 pmol/l ) ( P=0.005 ) . The subgroup of patients suffering exclusively from migraine without aura ( n=14 ) also had significantly higher levels of CGRP ( 82±10 pmol/l ) than controls ( n=20 ; 49±3 pmol/l ) ( P=0.001 ) . The findings could not be explained by confounding factors such as age , sex or use of contraceptive pills . We therefore conclude that CGRP is increased in cubital venous blood of migraineurs outside of attack . It is hypothesized that this finding may reflect a long‐lasting or permanent abnormal neurogenic vascular control in patients with migraine\n\n\nReport 5:\nTitle: Glial Cell Line-Derived Neurotrophic Factor and Somatostatin Levels in Cerebrospinal Fluid of Patients Affected by Chronic Migraine and Fibromyalgia\nSummary: The aim of the present study was to verify cerebrospinal fluid ( CSF ) levels of glial cell line-derived neurotrophic factor ( GDNF ) and somatostatin , both measured by sensitive immunoassay , in : 16 chronic migraine ( CM ) patients , 15 patients with an antecedent history of migraine without aura diagnosed as having probable chronic migraine ( PCM ) and probable analgesic-abuse headache ( PAAH ) , 20 patients affected by primary fibromyalgia syndrome ( PFMS ) , and 20 control subjects . Significantly lower levels of GDNF and somatostatin were found in the CSF of both CM and PCM + PAAH patients compared with controls ( GDNF = P < 0.001 , P < 0.002 ; somatostatin = P < 0.002 , P < 0.0003 ) , without significant difference between the two groups . PFMS patients , with and without analgesic abuse , also had significantly lower levels of both somatostatin and GDNF ( P < 0.0002 , P < 0.001 ) , which did not differ from those of CM and PCM + PAAH patients . A significant positive correlation emerged between CSF values of GDNF and those of somatostatin in CM ( r = 0.70 , P < 0.02 ) , PCM + PAAH ( r = 0.78 , P < 0.004 ) , and PFMS patients ( r = 0.68 , P < 0.008 ) . Based on experimental findings , it can be postulated that reduced CSF levels of GDNF and somatostatin in both CM and PCM + PAAH patients can contribute to sustained central sensitization underlying chronic head pain . The abuse of simple or combination analgesics does not seem to influence the biochemical changes investigated , which appear to be more strictly related to the chronic pain state , as demonstrated also for fibromyalgia\n\n\nReport 6:\nTitle: Premenstrual failure of alpha‐adrenergic stimulation on hypothalamus‐pituitary responses in menstrual migraine.\nSummary: & NA ; In nine women suffering from menstrual migraine ( MM ) , and in six healthy asymptomatic volunteers , plasma beta‐endorphin ( beta‐EP ) , growth hormone ( GH ) , norepinephrine ( NE ) , and 3‐methoxy‐4‐hydroxyphenylethyleneglycol ( MHPG ) concentrations were measured in response to clonidine ( 0.075 mg , i.v . ) stimulation . In MM patients clonidine testing was performed in both the early and the late luteal phases of the menstrual cycle . Premenstrual symptoms were prospect ively evaluated in the actual cycle using the Moos Menstrual Distress Question naire . beta‐EP ( after gel chromatography ) and GH were measured using radioimmunoassay . NE and MHPG were evaluated by HPLC using electrochemical detection . In both phases of the menstrual cycle clonidine significantly reduced NE and MHPG levels in MM patients and controls in a similar way . In MM patients beta‐EP and GH plasma levels were stimulated by clonidine only in the early luteal phase , whereas they remained unchanged when they were stimulated in the premenstrual period . In controls the response of both hormones was not affected by the menstrual cycle . The lack of hormonal response to clonidine in MM may suggest a postsynaptic alpha 2‐adrenoreceptor hyposensitivity during the premenstrual period . This demonstrates a transient vulnerability of the neuroendocrine/neurovegetative systems , and could thus be a factor facilitating the precipitation of both behavioral changes and migraine attacks\n\n\nReport 7:\nTitle: Cerebrospinal fluid sodium increases in migraine.\nSummary: BACKGROUND Pharmaceuticals with calcium- or sodium-channel-blocking activity have proven useful for migraine prophylaxis , and calcium channel , sodium transporter , and sodium channel gene mutations have been found in familial hemiplegic migraine . However , it is not known whether calcium or sodium homeostasis is altered in migraine . OBJECTIVE To compare levels of sodium , calcium , potassium , and magnesium in cerebrospinal fluid ( CSF ) and blood plasma between migraineurs and controls . METHODS We recruited 20 migraineurs without aura and 11 controls prospect ively , and studied migraineurs in sick ( MH(+ ) ) and well ( MH(- ) ) states . We collected lumbar CSF and venous blood plasma , quantified elements with ion-selective electrodes or colorimetry , and determined osmolality by depression of freezing point . We compared levels of Na(+ ) , Ca(2 + ) , K(+ ) , and Mg among and also within subjects who were studied in both MH(+ ) and MH(- ) states . RESULTS Mean CSF Na(+ ) levels were increased by 3 mmol/L in MH(+ ) compared with MH(- ) and by 4 mmol/L compared to controls ( P < 0.005 ) . In 4 subjects who were sample d in both MH(+ ) and MH(- ) states , mean CSF Na(+ ) concentration increased by 2 mmol/L in the MH(+ ) state compared with the MH(- ) state ( P < 0.05 ) . Simultaneous plasma Na(+ ) levels did not differ among the 3 clinical groups , nor did osmolality , total Ca and Ca(2 + ) , K(+ ) , and total Mg levels in CSF . CONCLUSIONS Compared to both controls and the MH(- ) state , CSF Na(+ ) concentration increased in MH(+ ) independently from other clinical or pharmacological fluctuations , CSF concentrations of Ca(2 + ) , Mg , and K(+ ) , and blood plasma Na(+ ) levels . These results implicate a deviation of Na(+ ) homeostasis in migraine . The modestly elevated extracellular Na(+ ) in MH(+ ) may cause the neural changes that underlie clinical features of migraine\n\n\nReport 8:\nTitle: Peripheral Levels of BDNF and NGF in Primary Headaches\nSummary: Neurotrophins , such as brain-derived neurotrophic factor ( BDNF ) and nerve growth factor ( NGF ) , have been implicated in the generation and modulation of pain . To investigate whether alterations in neurotrophin levels can be detected in subjects suffering from nociceptive disorders , such as primary headaches , we determined the peripheral ( platelet and plasma ) levels of BDNF and NGF in patients suffering from migraine , with or without aura , or cluster headache ( CH ) , in the interictal phase , and in healthy volunteers . All primary headaches patients studied showed significantly decreased platelet levels of BDNF ( migraine vs. controls P < 0.001 ; CH vs. controls P < 0.01 ) , while a selective reduction of platelet NGF was observed in migraine sufferers and not in CH patients compared with control subjects ( migraine vs. controls P < 0.001 ) . These changes were not accompanied by significant modifications of neurotrophin plasma levels . Our findings show for the first time that changes in peripheral levels of neurotrophines ( BDNF and NGF ) occur in patients suffering from different types of primary headaches , suggesting a potential involvement of BDNF and NGF in the pathophysiology of these disorders , and raising the possibility that differences in peripheral neurotrophins may help to distinguish migraine biologically from CH",
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"content": "Conclusions Glutamate , β-EP , CGRP and NGF concentrations are altered in CSF and , except for NGF , also in blood of migraineurs .",
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.5014 | [
{
"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 Noise Cancellation Techniques for Cognitive Radio \nChapter Title: Singular Value Decomposition Based Denoising \n1. Abstract of Cited Paper (BIB001): Spectrum sensing is key to many applications like dynamicspectrum access (DSA) systems or telecom regulators who need to measure utilization of frequency bands. The International Telecommunication Union (ITU) recommends a 10 dB threshold above the noise to decide whether a channel is occupied or not. However, radio frequency (RF) receiver front-ends are non-ideal. This means that the obtained data is distorted with noise and imperfections from the analog front-end. As part of the front-end the automatic gain control (AGC) circuitry mainly affects the sensing performance as strong adjacent signals lift the noise level. To enhance the performance of spectrum sensing significantly we focus in this article on techniques to remove the noise caused by the AGC from the sensing data. In order to do this we have applied matrix factorization techniques, i.e., SVD (singular value decomposition) and NMF (non-negative matrix factorization), which enables signal space analysis. In addition, we use live measurement results to verify the performance and to remove the effects of the AGC from the sensing data using above mentioned techniques, i.e., applied on block-wise available spectrum data. In this article it is shown that the occupancy in the industrial, scientific and medical (ISM) band, obtained by using energy detection (ITU recommended threshold), can be an overestimation of spectrum usage by 60%.\n\nReview Chapter:",
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"content": "Singular Value Decomposition (SVD) is one of the useful matrix decomposition methods that enables the factorization of a matrix. For a matrix A, SVD factorizes An into the product of a unitary matrix , a diagonal matrix , and another unitary matrix BIB001 .If matrix A is m x n matrix, will be the unitary matrix m x m, with non-negative real numbers m x n diagonal matrix is and is the n x n unitary matrix. The , of are the singular values of A and the left-singular vectors of A are the m columns of while right-singular vectors are the n columns of . SVD being numerically stable produces non-negative eigenvalues which makes it a preferable choice over Eigen decomposition BIB001 . As discussed in the previous sections, signal processing to sense theavailability of spectrumis one of the primary tasks of cognitive radio. Secondorder statistical dataand covariance matrix are commonly used methods to analyze a set of data, in this case, which would be sensed spectrum.The above-mentioned matrix factorization technique opts to reduce the dimension of the sample covariance matrix retaining animportant set of information which can be used to distinguish different components of a signal such as noise. In BIB002 , the factorization technique -SVD is employed to detect noise anomalies in the 2.4 GHz band. It is notable to point out that SVD was employed instead of Eigen decomposition to differentiate the noise components in the signal. SVD's numerical stability and non-negative eigenvalue output make it a desirable choice for data analysis. Work in BIB002 first defines an unbiased data matrix, M in order to decompose the sample covariance matrix of the sensed 2.4GHz band and is expressed as - Then SVD of matrix M results in the factorization, as defined in (6) -= Σ The , of are the singular values of M and from the knowledge of principal component analysis (PCA), the columns of W thatare known to be the left singular vectors are the eigenvectors of whereas the columns of U which are the right singular vectors are known to be the eigenvectors of . From the decomposed covariance matrix we can get the eigenvectors and eigenvalues, as described by [40 -42] . With these obtained eigenvectors BIB002 creates � of the measured data X, a projection of the measured data that only contains the strongest signal space component and is expressed as - The L components refer to the L principal components of X. Because of the necessity to perform, PCA requires mean subtraction which results in adding E[X] to X. This addition results in generating undesired outputs from SVD and disrupts the non-negative constraints.",
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science.bc7_litcovid_topic_classification | science.bc7_litcovid_topic_classification.2 | [
{
"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: In December 2019, the novel coronavirus (SARS-CoV-2) infection was first reported in Wuhan city, central China, which has spread rapidly. The common clinical features of patients with SARS-CoV-2 infection included fever, fatigue, and damage to the respiratory or digestive system. However, it is still unclear whether SARS-CoV-2 infection could cause damage to the central nervous system (CNS) inducing psychiatric symptoms. CASE REPORT: Herein, we present the first case of SARS-CoV-2 infection with manic-like symptoms and describe the diagnosis, clinical course, and treatment of the case, focusing on the identifications of SARS-CoV-2 in the specimen of cerebrospinal fluid (CSF). The patient developed manic-like symptoms when his vital signs recovered on illness day 17. After manic-like attack, the detection of SARS-CoV-2 specific IgG antibody in CSF was positive, while the reverse transcriptase-polymerase chain reaction (RT-PCR) on CSF for the SARS-CoV-2 was negative. The patient received Olanzapine for treatment and his mood problems concurrently improved as indicated by scores of Young Manic Rating Scale (YMRS). LIMITATION: This is a single case report only, and the RT-PCR test for SARS-CoV-2 in CSF was not performed simultaneously when SARS-CoV-2 was positive in samples of sputum and stool. CONCLUSION: This first case of COVID-19 patient with manic-like symptoms highlights the importance of evaluation of mental health status and may contribute to our understanding of potential risk of CNS impairments by SARS-CoV-2 infection.",
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"content": "[\"Case Report\"]",
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science.bioasq_factoid_qa | science.bioasq_factoid_qa.1090 | [
{
"content": "Given the following biomedical passages, answer the question succinctly. Ensure your response is precise and limited to the answer only.\n\nQuestion: What is the target of a drug pidilizumab?\n\nPassages: We present results from the first study to evaluate the immune modulating antibody MDV9300 (pidilizumab) in pediatric patients with DIPG.\nThis has prompted multiple large ongoing phase III trials with the expectation for fast-track FDA approvals to satisfy unmet medical needs. Compounds targeting the programmed death-1 pathway that are in clinical trials fall into two major categories, namely antiprogrammed death-1 antibodies: Nivolumab, MK-3475, and pidilizumab; and antiprogrammed death-ligand 1 antibodies: MPDL3280A, BMS-936559, MEDI4736, and MSB0010718C.\nNivolumab, pembrolizumab (formerly known as MK-3475 and lambrolizumab), and pidilizumab are anti-PD-1 antibodies in clinical development for melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers, lymphoma, and several other cancers.\nRecent successes in early Phase I/II trials using anti-checkpoint inhibitor antibodies such as nivolumab or pidilizumab directed against PD-1 in the setting of Hodgkin's and non-Hodgkin's lymphomas validate the therapeutic utility of reversing B cell-mediated immune suppression.\nRECENT FINDINGS: Recent studies have evaluated the prevalence and prognostic implications of PD-1, PD-L1/2 expression in various lymphoma subtypes. We present an overview of the clinical trials evaluating pidilizumab, nivolumab, and pembrolizumab in patients with lymphoid malignancies, and highlight some of the more promising agents in this class, currently in development.\nBACKGROUND: This meta-analysis has been conducted to determine the risk of elevated transaminases associated with immune checkpoint inhibitors use in patients with cancer.METHODS: Studies eligible for our analysis included randomized Phase II and III trials of patients with cancer on ipilimumab, nivolumab, pembrolizumab, tremelimumab and pidilizumab, which describe events of elevated transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)].\nAIM: We performed a meta-analysis of the risk of selected gastrointestinal toxicities associated with immune checkpoint inhibitors.PATIENTS & METHODS: Eligible studies included randomized trials of patients with solid tumors on ipilimumab, nivolumab, pembrolizumab, tremelimumab, pidilizumab and atezolizumab, describing events of diarrhea, vomiting or colitis.\nThere are other perspective immune modulating agents, such as anti-PD 1 antibodies (nivolumab, pembrolizumab, pidilizumab) and anti-PD L1 antibodies.\nHigh levels of peripheral blood Tregs prior to therapy were associated with decreased progression-free survival in FL patients treated with either chemotherapy or combination immunotherapy that targeted CD20 and PD-1 with monoclonal antibodies rituximab and pidilizumab, respectively.\nMonoclonal antibodies to PD-1 (eg, nivolumab, lambrolizumab, and pidilizumab) and PD-L1 (MPDL3280A and BMS-936559) are in various stages of clinical development.\nWe did this phase 2 trial to investigate the activity of pidilizumab, a humanised anti-PD1 monoclonal antibody, with rituximab in patients with relapsed follicular lymphoma.\nPidilizumab is an mAb that binds to PD-1 and is a safe and well-tolerated therapy.\nThere are other perspective immune modulating agents, such as anti-PD 1 antibodies (nivolumab, pembrolizumab, pidilizumab) and anti-PD L1 antibodies.\nCompounds targeting the programmed death-1 pathway that are in clinical trials fall into two major categories, namely antiprogrammed death-1 antibodies: Nivolumab, MK-3475, and pidilizumab; and antiprogrammed death-ligand 1 antibodies: MPDL3280A, BMS-936559, MEDI4736, and MSB0010718C.\nignancies. Pidilizumab is an mAb that binds to PD-1 and is a safe and well-tolera\n, pembrolizumab (formerly known as MK-3475 and lambrolizumab), and pidilizumab are anti-PD-1 antibodies in clinical development for melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers, lymphoma, and several other cancers. Long-term survi\nMonoclonal antibodies to PD-1 (eg, nivolumab, lambrolizumab, and pidilizumab) and PD-L1 (MPDL3280A and BMS-936559) are in various stages of clinical development.",
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"content": "programmed death-1 pathway.",
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science.chemdner_ner | science.chemdner_ner.1142 | [
{
"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\nMolecular mechanism by which a potent hepatitis C virus NS3-NS4A protease inhibitor overcomes emergence of resistance. Although optimizing the resistance profile of an inhibitor can be challenging, it is potentially important for improving the long term effectiveness of antiviral therapy. This work describes our rational approach toward the identification of a macrocyclic acylsulfonamide that is a potent inhibitor of the NS3-NS4A proteases of all hepatitis C virus genotypes and of a panel of genotype 1-resistant variants. The enhanced potency of this compound versus variants D168V and R155K facilitated x-ray determination of the inhibitor-variant complexes. In turn, these structural studies revealed a complex molecular basis of resistance and rationalized how such compounds are able to circumvent these mechanisms.",
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"content": "{\"Chemical\": [\"acylsulfonamide\"]}",
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science.scireviewgen_multidoc_summarization | science.scireviewgen_multidoc_summarization.1462 | [
{
"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: Software Defined Optical Networks (SDONs): A Comprehensive Survey \nChapter Title: E. Application Layer: Summary and Discussion \n1. Abstract of Cited Paper (BIB001): The process of planning a virtual topology for a Wavelength Devision Multiplexing (WDM) network is called Virtual Topology Design (VTD). The goal of VTD is to find a virtual topology that supports forwarding the expected traffic without congestion. In networks with fluctuating, high traffic demands, it can happen that no single topology fits all changing traffic demands occurring over a longer time. Thus, during operation, the virtual topology has to be reconfigured. Since modern networks tend to be large, VTD algorithms have to scale well with increasing network size, requiring distributed algorithms. Existing distributed VTD algorithms, however, react too slowly on congestion for the real-time reconfiguration of large networks. We propose Selfish Virtual Topology Reconfiguration (SVTR) as a new algorithm for distributed VTD. It combines reconfiguring the virtual topology and routing through a Software Defined Network (SDN). SVTR is used for online, on-the-fly network reconfiguration. Its integrated routing and WDM reconfiguration keeps connection disruption due to network reconfiguration to a minimum and is able to react very quickly to traffic pattern changes. SVTR works by iteratively adapting the virtual topology to the observed traffic patterns without global traffic information and without future traffic estimations. We evaluated SVTR by simulation and found that it significantly lowers congestion in realistic networks and high load scenarios. \n2. Abstract of Cited Paper (BIB002): Software defined networking (SDN), originally designed to operate on access Ethernet-based networks, has been recently proposed for different specific networking scenarios, including core or metro/aggregation networks. In this study, we extend this concept to enable a comprehensive control of a converged access, metro and edges of a core network. In particular, a generalized SDN controller is proposed for upstream global QoS traffic engineering of passive optical networks (PONs), Ethernet metro/aggregation segment and IP/MPLS networks through the adoption of an unique interface, in the framework of the Interface to the Routing System (I2RS). Extended OpenFlow functionalities and Path Computation Element Protocol (PCEP) interfaces are encompassed to achieve effective dynamic flow control. \n3. Abstract of Cited Paper (BIB003): In the High Speed Internet (HSI) service of the Fiber-To-The-Home (FTTH) networks, there are increasingly various applications, such as browsing, video streaming, large downloads and online games. They are competing for the fixed bandwidth on a best-effort basis, and finally resulting in the network congestion and poor quality of experience (QoE). Users want to improve the quality of certain applications. However, today's network service controller (e.g. Broadband Remote Access Server, BRAS) lacks mechanisms to meet the users' desire to enhance the QoE of specific applications. Moreover, BRAS still lacks mechanisms to allocate the bandwidth resources properly for users' different applications according to their “sweet points”. “Sweet points” is a specific bandwidth value. The QoE gets worse quickly when the bandwidth is smaller than the “sweet point”, and keeps the same approximately when the bandwidth is larger than the “sweet point”. In this paper, we proposed a novel BRAS architecture using Software-Defined Networking (SDN) technology, which can improve the user's QoE by adjusting the bandwidth of a specific application to its “sweet point” according to their requirements. To demonstrate the feasibility of our proposed novel BRAS, we built a prototype using SDN to help the user to adjust the bandwidth for the specific application and improve the users' QoE. The experimental results show that users could enhance the QoE of specific applications according to users' preference. \n4. Abstract of Cited Paper (BIB004): We propose joint bandwidth provisioning and base station caching for video delivery in software-defined PONs. Performance evaluation via custom simulation models reveals 30% increase in served video requests and 50% reduction in service response delays. \n5. Abstract of Cited Paper (BIB005): A hierarchically controlled IP+Optical multilayer Transport SDN architecture is proposed, which highlights flexible resource provisioning and dynamic cross-layer restorations. The proposals are also demonstrated via an implemented testbed prototype. \n6. Abstract of Cited Paper (BIB006): We test an end-to-end 1:1 protection scheme for a combined LR-PON access and core networks using separate but loosely coupled SDN controllers, over a Pan-European network. Fast recovery is achieved in 7ms in the access and 52ms in the core. \n7. Abstract of Cited Paper (BIB007): Increased network traffic has put great pressure on edge router. It tends to be more expensive and consumes more resources. Buffer is especially the most valuable resource in the router. Given the potential benefits of reducing buffer sizes, a lot of debate on buffer sizing has emerged in the past few years. The small buffer rule, for example, was challenged at edge router. Instead of buffer sizing, the goal of our work is to find out a way to relieve the pressure of edge router and logically enlarge its buffer size without incurring additional costs. In this paper, taking advantage of the global view of SDN, we proposed Software Defined Backpressure Mechanism (SD-BM) to alleviate the pressure of edge router. Particularly, we gave Refill and Software Defined Networking based RED (RS-RED) algorithm, which makes it possible to enlarge the network buffer logically and offloads traffic from busy egress router to free ingress devices. Simulation results show that it has comparable performance, both in time delay and loss rate, with edge router which has large buffer in traditional way. The results can have consequences for the design of edge router and the related network. \n8. Abstract of Cited Paper (BIB008): As networks grow in size, large-scale failures caused by disasters may lead to huge data loss, especially in an optical network employing wavelength-division multiplexing (WDM). Providing 100 % protection against disasters would require massive and economically unsustainable bandwidth overprovisioning, as disasters are difficult to predict, statistically rare, and may create large-scale failures. Backup reprovisioning schemes are proposed to remedy this problem, but in case of a large-scale disaster, even the flexibility provided by backup reprovisioning may not be enough, given the sudden reduction in available network resource, i.e., resource crunch. To mitigate the adverse effects of resource crunch, an effective resource reallocation is possible by exploiting service heterogeneity, specifically degraded-service tolerance, which makes it possible to provide some level of service, e.g., reduced capacity, to connections that can tolerate degraded service, versus no service at all. Software-Defined Networking (SDN) is a promising approach to perform such dynamic changes (redistribution of network resources) as it simplifies network management via centralized control logic. By exploiting these new opportunities, we propose a Backup Reprovisioning with Partial Protection (BRPP) scheme supporting dedicated-path protection, where backup resources are reserved but not provisioned (as in shared-path protection), such that the amount of bandwidth reserved for backups as well as their routings are subject to dynamic changes, given the network state, to increase utilization. The performance of the proposed scheme is evaluated by means of SDN emulation using Mininet environment and OpenDaylight as the controller. \n9. Abstract of Cited Paper (BIB009): Optical transport networks typically deploy dynamic restoration mechanisms in order to automatically recover optical connections disrupted by network failures. Elastic optical networks (EONs), currently emerging as the next-generation technology to be adopted in optical transport, introduce new challenges for traditional generic multiprotocol label-switching (GMPLS)-based restoration that may seriously impact the achievable recovery time. At the same time, the software-defined networking (SDN) framework is emerging as an alternative control plane. It is therefore important to investigate possible benefits provided by SDN in the implementation of restoration mechanisms for EONs. This paper proposes a dynamic restoration scheme for EONs based on the SDN framework. The proposed scheme contemporarily exploits centralized path computation and node configuration to avoid contentions during the recovery procedure with the final aim of minimizing the recovery time. The performance of the proposed scheme is evaluated by means of simulations in terms of recovery time and restoration blocking probability and compared against three reference schemes based on GMPLS and SDN. \n10. Abstract of Cited Paper (BIB010): Elastic optical networking (EON), with its flexible use of the optical spectrum, is a promising solution for future metro/core optical networking. For the deployment of EON in a real-operational scenario, the dynamic lightpath restoration, driven by an intelligent control plane, is a necessary network function. Dynamic restoration can restore network services automatically and, thus, greatly reduce the operational cost, compared with traditional manual or semistatic lightpath restoration strategies enabled by network operators via a network management system. To this end, in this paper, we present an OpenFlow-enabled dynamic lightpath restoration in elastic optical networks, detailing the restoration framework and algorithm, the failure isolation mechanism, and the proposed OpenFlow protocol extensions. We quantitatively present the restoration performance via control plane experimental tests on the Global Environment for Network Innovations testbed. \n11. Abstract of Cited Paper (BIB011): We demonstrate a cross-layer orchestration for packet service over IP-optical networks, in terms of availability and elasticity. Our orchestration built over the SDN concept self-adjusts and cost-efficiently responds to dynamics on network paths, impairments/failures, and topology. \n12. Abstract of Cited Paper (BIB012): Network virtualization is an emerging technique that enables multiple tenants to share an underlying physical infrastructure, isolating the traffic running over different virtual infrastructures/tenants. This technique aims to improve network utilization, while reducing the complexities in terms of network management for operators. Applied to this context, software-defined networking (SDN) paradigm can ease network configurations by enabling network programability and automation, which reduces the amount of operations required from both service and infrastructure providers. SDN techniques are decreasing vendor lock-in issues due to specific configuration methods or protocols. Application-based network operations (ABNO) are a toolbox of key network functional components with the goal of offering application-driven network management. Service provisioning using ABNO may involve direct configuration of data plane elements or delegate it to several control plane modules. We validate the applicability of ABNO to multitenant virtual networks in multitechnology optical domains based on two scenarios, in which multiple control plane instances are orchestrated by the architecture. Congestion detection and failure recovery are chosen to demonstrate fast recalculation and reconfiguration, while hiding the configurations in the physical layer from the upper layer.\n\nReview Chapter:",
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"content": "The SDON QoS application studies have mainly examined traffic and network management mechanisms that are supported through the OpenFlow protocol and the central SDN controller. The studied SDON QoS applications are structurally very similar in that the traffic conditions or network states (e.g., congestion levels) are probed or monitored by the central SDN controller. The centralized knowledge of the traffic and network is then utilized to allocate or configure resources, such as DC resources in BIB001 , application bandwidths in BIB004 , and topology configurations or routes in BIB002 - BIB003 , BIB008 . Future research on SDON QoS needs to further optimize the interactions of the controller with the network applications and data plane to quickly and correctly react to changing user demands and network conditions, so as to assure consistent QoS. The specific characteristics and requirements of video streaming applications have been considered in the few studies on video QoS - BIB005 . Future SDON QoS research should consider a wider range of specific prominent application traffic types with specific characteristics and requirements, e.g., Voice over IP (VoIP) traffic has relatively low bit rate requirements, but requires low end-to-end latency. Very few studies have considered security and access control for SDONs. The thorough study of the broad topic area of security and privacy is an important future research direction in SDONs, as outlined in Section VIII-C Energy efficiency is similarly a highly important topic within the SDON research area that has received relatively little attention so far and presents overarching research challenges, see Section VIII-I. One common theme of the SDON application layer studies focused on failure recovery and restoration has been to exploit the global perspective of the SDN control. The global perspective has been exploited for for improved planning of the recovery and restoration BIB009 , BIB013 , BIB006 as well as for improved coordination of the execution of the restoration processes BIB010 , BIB011 . Generally, the existing failure recovery and restoration studies have focused on network (routing) domain that is owned by a particular organizational entity. Future research should seek to examine the tradeoffs when exploiting the global perspective of orchestration of multiple routing domains, i.e., the failure recovery and restoration techniques surveyed in this section could be combined with the multidomain orchestration techniques surveyed in Section VII. One concrete example of multidomain orchestration could be to coordinate the specific LR-PON access network protection and failure recovery BIB007 with protection and recovery techniques for metropolitan and core network domains, e.g., BIB009 , BIB013 , BIB012 , BIB006 , for improved end-to-end protection and recovery.",
"role": "assistant"
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science.acl_arc_intent_classification | science.acl_arc_intent_classification.1207 | [
{
"content": "Examine the given text from a research paper in the field of NLP. Your task is to identify the role of the citation within the context provided. Focus on understanding the intent behind the citation and classify it accordingly.\n\nSection Title:\nNone\n\nText Before Citation:\nIf each word's translation is treated as a sense tag (Resnik and Yarowsky 1997), then "translational" collocations have the unique property that the collocate and the word sense are one and the same! in bitext space is another kind of collocation. The ratio links(u, v) I cooc (u, v), for several values of cooc(u, v).\n\nCitation Text:\nIf each word 's translation is treated as a sense tag ( Resnik and Yarowsky 1997 ) , then `` translational '' collocations have the unique property that the collocate and the word sense are one and the same !\n\nText After Citation:\nMethod B exploits this property under the hypothesis that "one sense per collocation" holds for translational collocations. This hypothesis implies that if u and v are possible mutual translations, and a token u co-occurs with a token v in the bitext, then with very high probability the pair (u, v) was generated from the same concept and should be linked. To test this hypothesis, I ran one iteration of Method A on 300,000 aligned sentence pairs from the Canadian Hansards bitext. I then plotted the",
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"content": "Uses",
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science.healthver_entailment | science.healthver_entailment.1617 | [
{
"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: Hydroxychloroquine Is Ineffective In Treatment Of Patients Hospitalized With Covid-19\n\nResearch Abstract:\nBackgrounds.\nSince COVID-19 outbreak, various agents have been tested but no proven effective therapies have been identified.\nThis has led to a lot of controversies among associated researches.\nHence, in order to address the issue of using hydroxychloroquine in treating COVID-19 patients, we conducted a systematic review and meta-analysis.\nMethods.\nA thorough search was carried out to find relevant studies in MEDLINE, medRxiv, PubMed, Cochrane Database, China Academic Journals Full-text Database and Web of Science.\nTwo investigators independently reviewed 274 abstracts and 23 articles.\nThe trials which evaluated hydroxychloroquine for treatment of COVID-19 were included for this systematic review.\nTwo investigators assessed quality of the studies and data extraction was done by one reviewer and cross checked by the other.\nResults.\nFive trials involving 677 patients were included while conducting the meta-analysis.\nCompared with the control group, hydroxychloroquine with or without azithromycin showed benefits in positive-to-negative conversion of SARS-CoV-2 (odds ratio [OR], 1.95 [95% CI,0.19 to 19.73] and a reduction in progression rate (OR, 0.89 [95% CI, 0.58 to 1.37]), but without demonstrating any statistical significance.\nThis systematic review has also suggested a possible synergistic effect of the combination therapy which included hydroxychloroquine and azithromycin.\nHowever, the use of hydroxychloroquine alone was associated with increased mortality in COVID-19 patients.\nConclusion.\nThe use of hydroxychloroquine with or without azithromycin for treatment of COVID-19 patients, seems to be effective.\nThe combination of hydroxychloroquine and azithromycin has shown synergic effects.\nHowever, mortality rate was increased when the treatment was conducted with hydroxychloroquine.",
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"content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"Since COVID-19 outbreak, various agents have been tested but no proven effective therapies have been identified.\", \"However, the use of hydroxychloroquine alone was associated with increased mortality in COVID-19 patients.\", \"However, mortality rate was increased when the treatment was conducted with hydroxychloroquine.\"]}",
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science.mslr2022_cochrane_multidoc_summarization | science.mslr2022_cochrane_multidoc_summarization.2051 | [
{
"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:\nEffects of an exercise and manual therapy program on physical impairments, function and quality-of-life in people with osteoporotic vertebral fracture: a randomised, single-blind controlled pilot trial.\nReport Abstract 1:\nThis randomised, single-blind controlled pilot trial aimed to determine the effectiveness of a physiotherapy program, including exercise and manual therapy, in reducing impairments and improving physical function and health-related quality of life in people with a history of painful osteoporotic vertebral fracture.\n 20 participants were randomly allocated to an intervention (n = 11) or control (n = 9) group. The intervention group attended individual sessions with an experienced clinician once a week for 10 weeks and performed daily home exercises with adherence monitored by a self-report diary. The control group received no treatment. Blinded assessment was conducted at baseline and 11 weeks. Questionnaires assessed self-reported changes in back pain, physical function, and health-related quality of life. Objective measures of thoracic kyphosis, back and shoulder muscle endurance (Timed Loaded Standing Test), and function (Timed Up and Go test) were also taken.\n Compared with the control group, the intervention group showed significant reductions in pain during movement (mean difference (95% CI) -1.8 (-3.5 to -0.1)) and at rest (-2.0 (-3.8 to -0.2)) and significantly greater improvements in Qualeffo physical function (-4.8 (-9.2 to -0.5)) and the Timed Loaded Standing test (46.7 (16.1 to 77.3) secs). For the perceived change in back pain over the 10 weeks, 9/11 (82%) participants in the intervention group rated their pain as 'much better' compared with only 1/9 (11%) participants in the control group.\n Despite the modest sample size, these results support the benefits of exercise and manual therapy in the clinical management of patients with osteoporotic vertebral fractures, but need to be confirmed in a larger sample.\n NCT00638768.\n\n\nReport Title 2:\nEffect of exercise on mobility, balance, and health-related quality of life in osteoporotic women with a history of vertebral fracture: a randomized, controlled trial.\nReport Abstract 2:\nThe aim of this randomized controlled trial was to evaluate the effect of a 3-month course of exercises on mobility, balance, disease-specific, and generic health-related quality of life (HRQOL) for women with osteoporosis and a history of vertebral fractures. Our results showed that exercises improved their mobility, balance, and HRQOL.\n The aim was to evaluate the effect of a 3-month course of circuit exercises plus a 3-h lesson on how to cope with osteoporosis on mobility, balance, and the HRQOL for postmenopausal women (60-84 years) with osteoporosis and a history of vertebral fracture. Our hypothesis was that a 3-month course would have a significantly positive effect on the women's mobility and balance as well as on their HRQOL.\n The participants (89) were randomized to an intervention group (IT) or a control group (CT) and assessed at baseline at 3 months and at 12 months with measurement of maximum walking speed (MWS), Timed Up and GO (TUG), Functional Reach (FR), the Quality of Life Questionnaire issued by the European Foundation for Osteoporosis ('QUALEFFO-41') and the General Health Questionnaire (GHQ-20). The sample size was calculated with reference to walking speed (primary outcome), and the statistical approaches used were Student's t test or the chi-square test.\n At 3 months, better results were registered on the primary outcome, MWS as well as TUG, FR, sum score of GHQ-20, and \"QUALEFFO-41: mental function\" in the IT compared with the CT. At 12 months, those in the IT had a better result on the primary outcome, MWS as well as TUG, \"QUALEFFO-41: total score\" \"QUALEFFO-41: mental function\", \"QUALEFFO-41: physical function\", and \"QULEFFO-41: pain\" compared with CT.\n Circuit exercises will improve mobility and health-related quality of life of elderly women with osteoporosis and a history of vertebral fractures.\n\n\nReport Title 3:\nPositive effects of physiotherapy on chronic pain and performance in osteoporosis.\nReport Abstract 3:\nThe aim of this placebo-controlled, randomized, single-masked study was to establish the effects of a 10-week ambulatory exercise programme for osteoporotic patients on pain, use of analgesics, functional status, quality of life, balance and muscle strength. Fifty-three ambulatory postmenopausal women with at least one spinal crush fracture and pains within the last 3 years were randomized for physiotherapeutic training twice a week for 10 weeks or no training. The training included general training of balance and muscle strength, with stabilization of the lumbar spine. The participants were tested at baseline, week 5 and week 10 with a balance test, muscle strength test and questionnaires on pain, use of analgesics, functional status and quality of life. Twelve weeks after the supervised training had finished (week 22) they answered the same questionnaires. The study groups were comparable at baseline. The training group had a significant reduction in use of analgesics (p = 0.02) and pain level (p = 0.01) during the training period. Distribution of functional score improved; the improvement was reduced at week 22. Quality of life score improved significantly throughout the study (p = 0.0008), even after week 22. Balance improved non-significantly (p = 0.08). Quadriceps muscle strength improved significantly after 5 weeks (p = 0.04). Back extensor muscle strength improved almost significantly (p = 0.09). In conclusion, this training programme for osteoporotic patients improved balance and level of daily function and decreased experience of pain and use of analgesics. Quality of life was improved even beyond the active training period.\n\n\nReport Title 4:\nEfficacy of home-based exercise for improving quality of life among elderly women with symptomatic osteoporosis-related vertebral fractures.\nReport Abstract 4:\nThis randomized controlled trial was designed to investigate the effect of a 6-month home-based exercise program versus control (usual activities) on quality of life for postmenopausal women with osteoporosis who had at least one vertebral fracture. Twelve-month assessments of outcomes were completed to determine if women would continue exercising with minimal supervision and if benefit could be sustained. The home exercise program followed a \"lifestyle exercise\" approach where participants completed exercises 60 min per day, 3 days a week and could complete exercises in small periods of time throughout the day. Exercise activities included stretching, strength training and aerobics (i.e. walking). Participants were assessed at baseline, 6 months, and 12 months using the Osteoporosis Quality of Life Questionnaire (OQLQ), the Sickness Impact Profile (SIP), a balance test, and the Timed Up And Go test. Bone mineral density was assessed at baseline and 12 months for both the lumbar spine and femoral neck. Quality of life (OQLQ) improved over 6 months in the exercise group compared to the control group in the domains of symptoms (P=0.003), emotion (P=0.01) and leisure (P=0.03). Results from the balance test indicated a greater effect in the exercise group over 12 months (P<0.05). There were no significant differences between groups in measures of Timed Up and Go, SIP at 6 and 12 months, and femoral neck and lumbar spine bone mineral density at 12 months. Home-based exercise with minimal supervision improves quality of life in elderly women with vertebral fractures. Future research is needed to determine if home exercise programs reduce falls and fall-related injuries in the elderly.\n\n\nReport Title 5:\nGroup treatment improves trunk strength and psychological status in older women with vertebral fractures: results of a randomized, clinical trial.\nReport Abstract 5:\nTo assess whether group exercise and coping classes reduce physical and psychological impairments and functional disability in older women with prevalent vertebral fractures (VFs).\n Randomized, controlled trial (modified cross-over) with site as unit of assignment; testing at baseline and 3, 6, 9, and 12 months.\n Nine North Carolina retirement communities.\n One hundred eighty-five postmenopausal Caucasian women (mean age 81), each with at least one VFs.\n The intervention group had 6 months of exercise (3 meetings weekly, 45 minutes each) and coping classes (2 meetings weekly, 45 minutes each) in Phase 1, followed by 6 months of self-maintenance. The control group had 6 months of health education control intervention (1 meeting weekly, 45 minutes) in Phase 1, followed by the intervention described above.\n Change in trunk extension strength, change in pain with activities, and change in psychological symptoms.\n Between-group differences in the change in trunk extension strength (10.68 foot pounds, P<.001) and psychological symptoms (-0.08, P=.011) were significant for Phase 1. Changes in pain with activities did not differ between groups (-0.03, P=.64); there was no change in the pain endpoint. In Phase 2, controls showed significant changes in trunk strength (15.02 foot pounds, P<.001) and psychological symptoms (-0.11, P=.006) from baseline. Change in pain with activities was not significant (-0.03, P=.70). During self-maintenance, the intervention group did not worsen in psychological symptoms, but improved trunk extension strength was not maintained.\n Weak trunk extension strength and psychological symptoms associated with VFs can be improved in older women using group treatment, and psychological improvements are retained for at least 6 months.\n Copyright 2004 American Geriatrics Society",
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"content": "No definitive conclusions can be made regarding the benefits of exercise for individuals with vertebral fracture. Although individual trials did report benefits for some pain, physical function and quality of life outcomes, the findings should be interpreted with caution given that findings were inconsistent and the quality of evidence was very low. The small number of trials and variability across trials limited our ability to pool outcomes or make conclusions. Evidence regarding the effects of exercise after vertebral fracture, particularly for men, is scarce. A high-quality randomized trial is needed to inform exercise prescription for individuals with vertebral fractures.",
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science.healthver_entailment | science.healthver_entailment.286 | [
{
"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: Anti-inflammatory drugs, which includes steroids such as prednisone and non-steroidal drugs like ibuprofen, work by decreasing inflammation\n\nResearch Abstract:\n: The COVID-19 pandemic is challenging our cardiovascular care of patients with heart diseases.\nIn the setting of pericardial diseases, there are two possible different scenarios to consider: the patient being treated for pericarditis who subsequently becomes infected with SARS-CoV-2, and the patient with COVID-19 who develops pericarditis or pericardial effusion.\nIn both conditions, clinicians may be doubtful regarding the safety of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, colchicine, and biological agents, such as anti-IL1 agents (e.g. anakinra), that are the mainstay of therapy for pericarditis.\nFor NSAIDs, there is no clear scientific evidence linking ibuprofen and other NSAIDs to worsening of COVID-19; however, it seems prudent to continue them, if necessary to control pericarditis, and on the other hand, to prefer paracetamol for fever and systemic symptoms related to COVID-19.\nTreatments with corticosteroids, colchicine, and anakinra appear well tolerated in the context of COVID-19 infection and are currently actively evaluated as potential therapeutic options for COVID infection at different stages of the disease.\nOn this basis, currently most treatments for pericarditis do not appear contraindicated also in the presence of possible COVID-19 infection and should not be discontinued, and some (corticosteroids, colchicine, and anakinra) can be considered to treat both conditions.",
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{
"content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"For NSAIDs, there is no clear scientific evidence linking ibuprofen and other NSAIDs to worsening of COVID-19; however, it seems prudent to continue them, if necessary to control pericarditis, and on the other hand, to prefer paracetamol for fever and systemic symptoms related to COVID-19.\"]}",
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]
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