gebhart/patrepeval huggingface dataset:
A convenient new procedure for converting primary amides into nitriles (2006)

An operationally simple and high-yielding procedure has been developed for the conversion of primary amides to the corresponding nitriles, using ethyl dichlorophosphate/DBU as the mild dehydrating agent.
Anti-inflammatory activity of neutrophil elastase inhibitors. (2003)

Neutrophil elastase is a protease that is involved in the tissue destruction and inflammation that characterize numerous diseases, including hereditary emphysema, chronic obstructive pulmonary disease, cystic fibrosis, adult respiratory distress syndrome, ischemic-reperfusion injury and rheumatoid arthritis. Thus, elastase has been the object of extensive research to develop potent inhibitors that target its destructive and pro-inflammatory action. This review focuses on the anti-inflammatory activity of inhibitors that are currently, or were until recently in development, including purified or recombinantly produced endogenous inhibitors, genetically modified recombinant protein inhibitors and synthetic small-molecule inhibitors.
The DNA Sensor, Cyclic GMP–AMP Synthase, Is Essential for Induction of IFN-β during Chlamydia trachomatis Infection (2014)

IFN-β has been implicated as an effector of oviduct pathology resulting from genital chlamydial infection in the mouse model. In this study, we investigated the role of cytosolic DNA and engagement of DNA sensors in IFN-β expression during chlamydial infection. We determined that three-prime repair exonuclease-1, a host 3' to 5' exonuclease, reduced IFN-β expression significantly during chlamydial infection using small interfering RNA and gene knockout fibroblasts, implicating cytosolic DNA as a ligand for this response. The DNA sensor cyclic GMP-AMP synthase (cGAS) has been shown to bind cytosolic DNA to generate cyclic GMP-AMP, which binds to the signaling adaptor stimulator of IFN genes (STING) to induce IFN-β expression. We determined that cGAS is required for IFN-β expression during chlamydial infection in multiple cell types. Interestingly, although infected cells deficient for STING or cGAS alone failed to induce IFN-β, coculture of cells depleted for either STING or cGAS rescued IFN-β expression. These data demonstrate that cyclic GMP-AMP produced in infected cGAS(+)STING(-) cells can migrate into adjacent cells via gap junctions to function in trans in cGAS(-)STING(+) cells. Furthermore, we observed cGAS localized in punctate regions on the cytosolic side of the chlamydial inclusion membrane in association with STING, indicating that chlamydial DNA is most likely recognized outside the inclusion as infection progresses. These novel findings provide evidence that cGAS-mediated DNA sensing directs IFN-β expression during Chlamydia trachomatis infection and suggest that effectors from infected cells can directly upregulate IFN-β expression in adjacent uninfected cells during in vivo infection, contributing to pathogenesis.
The Political Dynamics of Human Mobility: Migration out of, as and into Violence (2016)

Abstract Simplistic correlations between human mobility and political violence are on the rise in the European discourse on immigration, especially – but not only – in populist rhetoric. This not only lacks an empirical foundation, but also leads to simplistic solutions for a major political and humanitarian challenge of our time. However, we still lack comprehensive knowledge on the migration‐violence nexus. By bringing insights from migration studies and peace and conflict studies into fruitful dialogue, this contribution aims to fill this gap. It first maps some of the central questions regarding the migration‐violence nexus. Second, and on this basis, it proposes an analytical framework for future research which encompasses the interdependence of violence‐migration dynamics on and between the macro, meso and micro levels by examining human mobility as: (1) a movement out of (physical and structural) violence; (2) a violent process in and of itself; (3) a path into (physical and structural) violence; and (4) it formulates some recommendations that can provide a more holistic basis for policy programmes regarding human mobility.
Thrombolysis for acute ischaemic stroke (2009)

Overall, thrombolytic therapy appears to result in a significant net reduction in the proportion of patients dead or dependent in activities of daily living. This overall benefit was apparent despite an increase both in deaths (evident at seven to 10 days and at final follow up) and in symptomatic intracranial haemorrhages. Further trials are needed to identify which patients are most likely to benefit from treatment and the environment in which thrombolysis may best be given in routine practice.
Coalescence, torus formation and breakup of sedimenting drops: experiments and computer simulations (2001)

The motion and shape evolution of viscous drops made from a dilute suspension of tiny, spherical glass beads sedimenting in an otherwise quiescent liquid is investigated both experimentally and theoretically for conditions of low Reynolds number. In the (presumed) absence of any significant interfacial tension, the Bond number [Bscr ] = (Δρ) gR 2 /σ is effectively infinite. The key stages of deformation of single drops and pairs of interacting drops are identified. Of particular interest are (i) the coalescence of two trailing drops, (ii) the subsequent formation of a torus, and (iii) the breakup of the torus into two or more droplets in a repeating cascade. To overcome limitations of the boundary-integral method in tracking highly deformed interfaces and coalescing and dividing drops, we develop a formal analogy between drops of homogeneous liquid and a dilute, uniformly distributed swarm of sedimenting particles, for which only the 1/ r far-field hydrodynamic interactions are important. Simple, robust numerical simulations using only swarms of Stokeslets reproduce the main phenomena observed in the classical experiments and in our flow-visualization studies. Detailed particle image velocimetry (PIV) for axisymmetric configurations enable a mechanistic analysis and confirm the theoretical results. We expose the crucial importance of the initial condition – why a single spherical drop does not deform substantially, but a pair of spherical drops, or a bell-shaped drop similar to what is actually formed in the laboratory, does undergo the torus/breakup transformation. The extreme sensitivity of the streamlines to the shape of the ring-like swarm explains why the ring that initially forms in the experiments does not behave like the slender open torus analysed asymptotically by Kojima, Hinch &amp; Acrivos (1984). Essentially all of the phenomena described above can be explained within the realm of Stokes flow, without resort to interfacial tension or inertial effects.
Concerted Signaling by Retinal Ganglion Cells (1995)

To analyze the rules that govern communication between eye and brain, visual responses were recorded from an intact salamander retina. Parallel observation of many retinal ganglion cells with a microelectrode array showed that nearby neurons often fired synchronously, with spike delays of less than 10 milliseconds. The frequency of such synchronous spikes exceeded the correlation expected from a shared visual stimulus up to 20-fold. Synchronous firing persisted under a variety of visual stimuli and accounted for the majority of action potentials recorded. Analysis of receptive fields showed that concerted spikes encoded information not carried by individual cells; they may represent symbols in a multineuronal code for vision.
The Epigenetic Regulator G9a Mediates Tolerance to RNA Virus Infection in Drosophila (2015)

Little is known about the tolerance mechanisms that reduce the negative effects of microbial infection on host fitness. Here, we demonstrate that the histone H3 lysine 9 methyltransferase G9a regulates tolerance to virus infection by shaping the response of the evolutionary conserved Jak-Stat pathway in Drosophila. G9a-deficient mutants are more sensitive to RNA virus infection and succumb faster to infection than wild-type controls, which was associated with strongly increased Jak-Stat dependent responses, but not with major differences in viral load. Genetic experiments indicate that hyperactivated Jak-Stat responses are associated with early lethality in virus-infected flies. Our results identify an essential epigenetic mechanism underlying tolerance to virus infection.
The Efficacy of Alefacept in the Treatment of Chronic Plaque Psoriasis (2004)

With the completion of several phase 2 and phase 3 clinical studies, the efficacy and tolerability of alefacept in patients with chronic plaque psoriasis is now well studied. The majority of patients treated with a single course of intravenous or intramuscular alefacept experienced a clinically meaningful response. The efficacy of alefacept correlated with its ability to selectively target and reduce the number of pathogenic memory T cells. A second course of alefacept resulted in further clinical improvement, with increasing response rates and prolonged response duration following treatment cessation. Sub-population analyses demonstrated that alefacept is effective in a broad spectrum of patients with psoriasis, regardless of disease severity, history of and response to prior antipsoriatic treatment, or whether patients are refractory to or have contraindications to other systemic psoriasis therapies or phototherapy.
Cytokines in Cartilage Injury and Repair (2001)

Joint injury results in cartilage lesions that are characterized by a poor repair response, and such lesions often progress to osteoarthritis. Acute joint injury or chronic exposure of cartilage to an abnormal biochemical or biomechanical environment results in the activation of chondrocytes. This chondrocyte response is manifested by enhanced cell proliferation and death, matrix degradation, and new matrix synthesis. Cytokines are important stimuli of this chondrocyte activation response and trigger joint inflammation that can accompany cartilage injury. The presence of cytokines in cartilage is associated with abnormal extracellular matrix remodeling and loss, therefore defining them as a class of targets for therapeutic interventions. Insight into intracellular signaling mechanisms that are activated by cytokines may provide the basis for pharmacologic interventions that promote cartilage repair.
Deep Learning at Chest Radiography: Automated Classification of Pulmonary Tuberculosis by Using Convolutional Neural Networks (2017)

Purpose To evaluate the efficacy of deep convolutional neural networks (DCNNs) for detecting tuberculosis (TB) on chest radiographs. Materials and Methods Four deidentified HIPAA-compliant datasets were used in this study that were exempted from review by the institutional review board, which consisted of 1007 posteroanterior chest radiographs. The datasets were split into training (68.0%), validation (17.1%), and test (14.9%). Two different DCNNs, AlexNet and GoogLeNet, were used to classify the images as having manifestations of pulmonary TB or as healthy. Both untrained and pretrained networks on ImageNet were used, and augmentation with multiple preprocessing techniques. Ensembles were performed on the best-performing algorithms. For cases where the classifiers were in disagreement, an independent board-certified cardiothoracic radiologist blindly interpreted the images to evaluate a potential radiologist-augmented workflow. Receiver operating characteristic curves and areas under the curve (AUCs) were used to assess model performance by using the DeLong method for statistical comparison of receiver operating characteristic curves. Results The best-performing classifier had an AUC of 0.99, which was an ensemble of the AlexNet and GoogLeNet DCNNs. The AUCs of the pretrained models were greater than that of the untrained models (P < .001). Augmenting the dataset further increased accuracy (P values for AlexNet and GoogLeNet were .03 and .02, respectively). The DCNNs had disagreement in 13 of the 150 test cases, which were blindly reviewed by a cardiothoracic radiologist, who correctly interpreted all 13 cases (100%). This radiologist-augmented approach resulted in a sensitivity of 97.3% and specificity 100%. Conclusion Deep learning with DCNNs can accurately classify TB at chest radiography with an AUC of 0.99. A radiologist-augmented approach for cases where there was disagreement among the classifiers further improved accuracy. <sup>©</sup> RSNA, 2017.
A comparative study of functional properties of calf chymosin and its recombinant forms (2006)

The action of calf chymosin obtained from transgenic sheep milk and the recombinant protein expressed in yeast Kluyveromyces lactis (Maxiren) on fluorogenic peptide substrates, namely Abz-A-A-F-F-A-A-Ded, Abz-A-A-F-F-A-A-pNA, Abz-A-F-F-A-A-Ded, Abz-A-A-F-F-A-Ded, Abz-A-A-F-F-Ded, Abz-A-A-F-F-pNA, and heptapeptide L-S-F-M-A-I-P-NH2, a fragment of κ-casein (the native chymosin substrate), was investigated. It has been established that transgenic chymosin and recombinant chymosin (Maxiren) differ from the native enzyme in their action on low molecular weight substrates, whereas there was no difference in enzymatic action on protein substrates. Pepstatin, a specific inhibitor of aspartic proteinases, inhibits the recombinant chymosin forms less efficiently than the native enzyme. Perhaps this is associated with local conformational changes in the substrate binding site of recombinant chymosin occurring during the formation of the protein globule.
The 6-Deoxytetracyclines. VII. Alkylated Aminotetracyclines Possessing Unique Antibacterial Activity (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe 6-Deoxytetracyclines. VII. Alkylated Aminotetracyclines Possessing Unique Antibacterial ActivityMichael J. Martell and James H. BootheCite this: J. Med. Chem. 1967, 10, 1, 44–46Publication Date (Print):January 1, 1967Publication History Published online1 May 2002Published inissue 1 January 1967https://pubs.acs.org/doi/10.1021/jm00313a009https://doi.org/10.1021/jm00313a009research-articleACS PublicationsRequest reuse permissionsArticle Views502Altmetric-Citations66LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Current Advances in the Use of Lasers in Periodontal Therapy: A Laser‐Assisted New Attachment Procedure Case Series (2013)

Introduction : The focus of periodontal surgical procedures has shifted over the past three decades from a philosophy based on resection (subtractive) to one of regeneration of lost tissues (additive). This shift has had particular significance in cases of advanced periodontitis. When a patient presents with severe attachment loss, regeneration cannot take place until the etiologic factors have been effectively managed or reversed and the disease progression arrested. Traditional surgical techniques have been successful in facilitating access and addressing the goal of “pocket elimination.” However, such surgical methods often result in unpleasant side effects, which can be painful and disfiguring. Clinicians have come to accept previous tissue breakdown as often irreversible. Additionally, the theory behind conventional pocket elimination was to produce an environment that promoted ongoing disease control by facilitating personal oral hygiene. At its best, traditional pocket surgery often falls short of achieving these goals and objectives. Additionally, conventional resective surgical techniques do not adequately address esthetic concerns, whereas surgical techniques, which are directed toward regeneration, have as their ideal outcome the preservation and/or restoration of lost periodontal tissues. Case Series: This case series presents six clinical cases illustrating favorable results using laser‐assisted new attachment procedure. In all cases, mobility and other manifestations of occlusal pathology were assessed. Occlusion was carefully addressed and managed using a combination of procedures. Conclusions: The results of recent research on a specific free‐running, pulsed neodymium‐doped:yttrium–aluminum–garnet (Nd:YAG) laser suggest that this laser provides a viable alternative to traditional periodontal surgery. Properly applying the laser has been shown to produce less bleeding, swelling, and discomfort. The Nd:YAG laser appears to address the cause of periodontal disease rather than the effects by specifically targeting identifiable periodontal pathogens. Regeneration of periodontal tissues is the gold standard by which dentists measure treatment effectiveness. Evidence has emerged that the Nd:YAG laser provides an enhanced method for achieving this elusive goal while eliminating many of the negative sequelae, which have been historically associated with conventional pocket elimination surgery. It should be noted that the information in the paper does not refer to all Nd:YAG lasers, but to one specific type of Nd:YAG laser. There are specific differences between individual YAG lasers, and this one is unique.
Effect of Deuterium Oxide on Wound Healing, Collagen and Metabolism of Rats (1964)

IT has been found that molecular forms of proteins are significantly different in deuterium oxide from those in water. For example, ovalbumin undergoes urea denaturation more slowly in deuterium oxide than in water,1 ribonuclease dissolved in deuterium oxide is more stably held in the alpha-helix form than then in water,2 and collagen is more stable in deuterium oxide solutions of acetic acid than it is in water solutions of this acid. The last is evidenced by the markedly greater viscosity of these solutions of deuterium and acetic acid at a given temperature than solutions of water and acetic acid, the . . .
Bidirectional fiber amplifiers (1992)

The authors propose new bidirectional erbium-doped fiber amplifier repeaters for bidirectional fiber networks and OTDR fault detection. At each repeater the counterpropagating signals are separated, amplified separately, and then recombined. Signal separation is done by directional couplers with intrinsic 6-dB coupling loss, or by optical circulators with no intrinsic loss. Although the 3-dB input directional coupler loss can be compensated with a few milliwatts extra pump power, it increases the amplifier noise figure by 3 dB. The pump power required to compensate for the output directional coupler loss increases with the output signal power to 3 dB when the amplifier is saturated. The saturation output power of the directional coupler module is approximately 3 dB lower than the optical circulator. Multiple reflection induced relative intensity noise is reduced by assigning nonoverlapping optical bands to the signals in the two directions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Polymorphism in Molecular Crystals (2007)

Polymorphism — the multiplicity of structures or forms — is a term used in many disciplines. In chemistry, it refers to the existence of more than one crystal structure for a particular chemical substance. The properties of a substance are determined by its composition and by its structure. In the last three decades there has been a sharp rise in the interest in polymorphic systems, as an intrinsically interesting phenomenon and as an increasingly important component in the development and marketing of a variety of materials based on organic molecules (e.g., pharmaceuticals, dyes, pigments, explosives, etc.). This book summarizes and brings up to date (as of 2002) the current knowledge and understanding of polymorphism of molecular crystals, and concentrates it in one comprehensive source. The opening chapter deals with nomenclature, a historical perspective of the phenomenon, and the industrial and commercial importance of polymorphism. This is followed by chapters covering fundamental concepts used in the description and study of polymorphism, thermodynamic and kinetic aspects of polymorph formation, the control of the polymorph obtained, analytical techniques for studying and characterizing polymorphs, conformational polymorphism, and the use of polymorphism to study structure-property relations in molecular crystals. Three individual chapters cover aspects of polymorphism in pharmaceuticals, dyes and pigments, and high energy materials. A final chapter covers some aspects of polymorphism and patents, another aspect of the subject of particular importance to the pharmaceutical industry.
Comment: Analyses of models of ion actions under the combined action of AC and DC magnetic fields (2006)

I show that the interaction of weak DC and ELF magnetic fields with contained ions cannot generate significant biological effects through changing the character of the ion orbits.
Ultra-Deep Sequencing of Intra-host Rabies Virus Populations during Cross-species Transmission (2013)

One of the hurdles to understanding the role of viral quasispecies in RNA virus cross-species transmission (CST) events is the need to analyze a densely sampled outbreak using deep sequencing in order to measure the amount of mutation occurring on a small time scale. In 2009, the California Department of Public Health reported a dramatic increase (350) in the number of gray foxes infected with a rabies virus variant for which striped skunks serve as a reservoir host in Humboldt County. To better understand the evolution of rabies, deep-sequencing was applied to 40 unpassaged rabies virus samples from the Humboldt outbreak. For each sample, approximately 11 kb of the 12 kb genome was amplified and sequenced using the Illumina platform. Average coverage was 17,448 and this allowed characterization of the rabies virus population present in each sample at unprecedented depths. Phylogenetic analysis of the consensus sequence data demonstrated that samples clustered according to date (1995 vs. 2009) and geographic location (northern vs. southern). A single amino acid change in the G protein distinguished a subset of northern foxes from a haplotype present in both foxes and skunks, suggesting this mutation may have played a role in the observed increased transmission among foxes in this region. Deep-sequencing data indicated that many genetic changes associated with the CST event occurred prior to 2009 since several nonsynonymous mutations that were present in the consensus sequences of skunk and fox rabies samples obtained from 20032010 were present at the sub-consensus level (as rare variants in the viral population) in skunk and fox samples from 1995. These results suggest that analysis of rare variants within a viral population may yield clues to ancestral genomes and identify rare variants that have the potential to be selected for if environment conditions change.