gebhart/patrepeval huggingface dataset:
Amyloid-beta immunotherapy: the hope for Alzheimer disease? (2016)

Alzheimer disease (AD) is the most prevalent form of dementia of adult-onset, characterized by progressive impairment in cognition and memory. There is no cure for the disease and the current treatments are only symptomatic. Drug discovery is an expensive and time-consuming process; in the last decade no new drugs have been found for AD despite the efforts of the scientific community and pharmaceutical companies. The Aβ immunotherapy is one of the most promising approaches to modify the course of AD. This therapeutic strategy uses synthetic peptides or monoclonal antibodies (mAb) to decrease the Aβ load in the brain and slow the progression of the disease. Therefore, this article will discuss the main aspects of AD neuropathogenesis, the classical pharmacologic treatment, as well as the active and passive immunization describing drug prototypes evaluated in different clinical trials.
Multiplexed Nucleic Acid Programmable Protein Arrays (2017)

<b>Rationale:</b> Cell-free protein microarrays display naturally-folded proteins based on just-in-time <i>in situ</i> synthesis, and have made important contributions to basic and translational research. However, the risk of spot-to-spot cross-talk from protein diffusion during expression has limited the feature density of these arrays. <b>Methods:</b> In this work, we developed the Multiplexed Nucleic Acid Programmable Protein Array (M-NAPPA), which significantly increases the number of displayed proteins by multiplexing as many as five different gene plasmids within a printed spot. <b>Results:</b> Even when proteins of different sizes were displayed within the same feature, they were readily detected using protein-specific antibodies. Protein-protein interactions and serological antibody assays using human viral proteome microarrays demonstrated that comparable hits were detected by M-NAPPA and non-multiplexed NAPPA arrays. An ultra-high density proteome microarray displaying > 16k proteins on a single microscope slide was produced by combining M-NAPPA with a photolithography-based silicon nano-well platform. Finally, four new tuberculosis-related antigens in guinea pigs vaccinated with Bacillus Calmette-Guerin (BCG) were identified with M-NAPPA and validated with ELISA. <b>Conclusion:</b> All data demonstrate that multiplexing features on a protein microarray offer a cost-effective fabrication approach and have the potential to facilitate high throughput translational research.
Behavioral resource-aware model inference (2014)

Software bugs often arise because of differences between what developers think their system does and what the system actually does. These differences frustrate debugging and comprehension efforts. We describe Perfume, an automated approach for inferring behavioral, resource-aware models of software systems from logs of their executions. These finite state machine models ease understanding of system behavior and resource use.
Transformation of Cl bonding structures on Si(100)-(2×1) (1992)

The digital electron-stimulated-desorption ion angular distribution (ESDIAD) method has been used to observe the existence and the irreversible thermal transformation between different bonding structures for Cl on the Si(100)-(2\ifmmode\times\else\texttimes\fi{}1) surface. The ESDIAD pattern produced from dissociative chemisorption of ${\mathrm{Cl}}_{2}$ at 120 K shows intense normal emission of ${\mathrm{Cl}}^{+}$, plus lower intensity of ${\mathrm{Cl}}^{+}$ emission focused along the [011] and [011\ifmmode\bar\else\textasciimacron\fi{}] axes (the axes of ${\mathrm{Si}}_{2}$ dimer orientations in two domains). Upon annealing (T\ensuremath{\le}673 K), the ${\mathrm{Cl}}^{+}$ ESDIAD pattern is irreversibly transformed into a four-beam pattern with a twofold azi- muthal symmetry in the plane of each dimer axis, indicative of the formation of energetically stable Si-Cl bonds inclined 25\ifmmode^\circ\else\textdegree\fi{}\ifmmode\pm\else\textpm\fi{}4\ifmmode^\circ\else\textdegree\fi{} from the surface normal.
Interleukin-6 Affects Insulin Secretion and Glucose Metabolism of Rat Pancreatic Isletsin Vitro* (1990)

Recently it has been postulated that interleukin-1 (IL-1) locally released by infiltrating mononuclear cells may destroy the pancreatic B cells during the development of insulin-dependent diabetes mellitus. Since IL-1 is a potent inducer of interleukin-6 (IL-6) in various cells, it is conceivable that IL-6 is a second mediator of the IL-1 action. In the present study the effects of IL-6 alone or in combination with IL-1 were studied on pancreatic islet function in vitro after tissue culture and compared with the effects observed after exposure to IL-1 only. Rat pancreatic islets were cultured in medium RPMI 1640 + 10% calf serum with or without the addition of human recombinant IL-6 (500-5000 pg/ml) for 48 h. The medium insulin accumulation was increased by 40-50% after culture with 500-2000 pg/ml IL-6, but was similar to the controls at 5000 pg/ml. When islets were cultured for 18 h only, also 5000 pg/ml IL-6 stimulated the medium insulin accumulation. IL-6 did not affect the islet insulin content and the rates of islet (pro)insulin and total protein biosynthesis. It inconsistently decreased the islet DNA content. In short-term experiments after 48-h culture with IL-6, there was a dose-dependent inhibition of the glucose-stimulated insulin release. On the other hand, islets cultured with IL-6 (5000 pg/ml) exhibited an elevated glucose oxidation and oxygen uptake, but a lower ATP content at 16.7 mM glucose and an unaffected glucose utilization and glutamine oxidation compared to the controls. This raises the possibility that IL-6 had induced a condition with an increased energy expenditure, resulting in an enhanced mitochondrial metabolism of glucose. Islets cultured with human recombinant IL-1 beta (25 units/ml) showed a strong inhibition of the insulin accumulation in the culture medium and of glucose-stimulated insulin release and a marked decrease in the islet DNA and insulin content. A combination of IL-1 (25 U/ml) + IL-6 (1000 pg/ml) did not alter the inhibitory action of IL-1 alone. The present findings thus show that IL-6 induces a dissociation between insulin secretion and glucose oxidation in islets in vitro. This has not been observed in islets exposed to IL-1, which suggests that IL-6 does not solely mediate the inhibitory effects of IL-1 on islet function.(ABSTRACT TRUNCATED AT 250 WORDS)
Double Generative Adversarial Networks for Conditional Independence\n Testing (2020)

In this article, we study the problem of high-dimensional conditional\nindependence testing, a key building block in statistics and machine learning.\nWe propose an inferential procedure based on double generative adversarial\nnetworks (GANs). Specifically, we first introduce a double GANs framework to\nlearn two generators of the conditional distributions. We then integrate the\ntwo generators to construct a test statistic, which takes the form of the\nmaximum of generalized covariance measures of multiple transformation\nfunctions. We also employ data-splitting and cross-fitting to minimize the\nconditions on the generators to achieve the desired asymptotic properties, and\nemploy multiplier bootstrap to obtain the corresponding $p$-value. We show that\nthe constructed test statistic is doubly robust, and the resulting test both\ncontrols type-I error and has the power approaching one asymptotically. Also\nnotably, we establish those theoretical guarantees under much weaker and\npractically more feasible conditions compared to the existing tests, and our\nproposal gives a concrete example of how to utilize some state-of-the-art deep\nlearning tools, such as GANs, to help address a classical but challenging\nstatistical problem. We demonstrate the efficacy of our test through both\nsimulations and an application to an anti-cancer drug dataset. A Python\nimplementation of the proposed procedure is available at\nhttps://github.com/tianlinxu312/dgcit.\n
A geological fingerprint of low‐viscosity fault fluids mobilized during an earthquake (2009)

The absolute value of stress on a fault during slip is a critical unknown quantity in earthquake physics. One of the reasons for the uncertainty is a lack of geological constraints in real faults. Here we calculate the slip rate and stress on an ancient fault in a new way based on rocks preserved in an unusual exposure. The study area consists of a fault core on Kodiak Island that has a series of asymmetrical intrusions of ultrafine‐grained fault rock into the surrounding cataclasite. The intrusive structures have ductile textures and emanate upward from a low‐density layer. We interpret the intrusions as products of a gravitational (Rayleigh‐Taylor) instability where the spacing between intrusions reflects the preferred wavelength of the flow. The spacing between intrusions is 1.4 ± 0.5 times the thickness of the layer. This low spacing‐to‐thickness ratio cannot be explained by a low Reynolds number flow but can be generated by one with moderate Reynolds numbers. Using a range of density contrasts and the geometry of the outcrop as constraints, we find that the distance between intrusions is best explained by moderately inertial flow with fluid velocities on the order of 10 cm/s. The angle that the intrusions are bent over implies that the horizontal slip velocity was comparable to the vertical rise velocity, and therefore, the fault was slipping at a speed of order 10 cm/s during emplacement. These slip velocities are typical of an earthquake or its immediate afterslip and thus require a coseismic origin. The Reynolds number of the buoyant flow requires a low viscous stress of at most 20 Pa during an earthquake.
The design and implementation of an intrusion tolerant system (2003)

We describe the implementation of an intrusion tolerant system for providing Internet services to known users through secure connections. Network attacks are treated as maliciously devised conditions to exploit design, implementation, or configuration faults, intrusions (successful attacks) are treated as failures, and their effects are mitigated by using the three pillars of fault tolerance: detection, isolation, and recovery. Fundamental to our approach is the use of diverse process pairs, which provides partial solutions to detection and isolation problems. The architecture uses the comparison of outputs from diverse applications to provide a significant and novel intrusion detection capability. The diverse applications also strengthen isolation by forcing attacks to exploit independent vulnerabilities. The isolation of intrusions is mainly achieved with an out-of-band control system. The control system not only provides separation between the primary and backup system, it also initiates attack diagnosis, attack blocking, and recovery, which is accelerated by on-line repair.
A new method of synthesis of alkyl‐glycidyl esters of dicarboxylic acids in high yields (1990)

A series of new alkyl‐glycidyl esters of dicarboxylic acids which could be used as PVC plasticizers were synthesized. The method adopted is a new synthetic process which can be carried out in two stages. During the first stage, the carboxylic acid anhydride reacts with the salt of the alcohol, and the sodium salt produced reacts with epichlorhydrin in the presence of a catalyst to yield an alkyl‐glycidyl ester. The specific reactions give pure products in high yields. The reaction of phthalic acid bisodium salt with epichlorhydrin, as well as the reaction of phthaloyl chloride with glycidol, gave diglycidyl phthalate in 36% and 22% yields, respectively.
Abstract 9599: Impact of Sex on Outcomes After WATCHMAN FLX Implantation (2022)

Introduction: Female sex is an established, non-modifiable risk factor for adverse outcomes in atrial fibrillation (AF) patients. Left atrial appendage occlusion (LAAO) has been shown to be generally safe and effective for stroke prevention in patients with AF. Data on sex-based outcomes with WATCHMAN FLX is lacking. Methods: WATCHMAN FLX patients from the National Cardiovascular Data Registry LAAO Registry between August 5th 2020 and March 31st 2021 were analyzed. Results: Women at baseline had a higher average CHA 2 DS 2 -VASc score, were more likely to have a history of transient ischemic attack, thromboembolic event, peripheral or carotid artery disease, fall risk, and chronic lung disease than men. Conversely, history of congestive heart failure, left ventricular dysfunction, hypertension, diabetes, vascular disease, abnormal renal function, cardiomyopathy, non-paroxysmal atrial fibrillation, myocardial infarction, prior cardiac interventions, alcohol use, antiplatelet medication use and non-steroidal anti-inflammatory drug use were all reduced in women compared to men. The early safety endpoint was similar between women and men ( Table ). At 45 days, unadjusted rates of major adverse events were higher in women than men mainly due to differences in major bleeding and pericardial effusion ( Table ). The risk of death was lower in women than men at 45 days. Rates of stroke, major vascular complications, systemic thromboembolism, myocardial infarction, and device-related thrombus were not significantly different between sexes. Adjusted outcomes will be available at the time of the presentation. Conclusions: In this national unselected cohort, there are significant sex-based differences in baseline characteristics and comorbidity burden. Women experienced more major adverse events after LAAO than men. Additional research to determine the underlying mechanisms of the increased risk in women and strategies for closing the gap between sexes are needed.
Factors affecting auditory streaming of random tone sequences (2014)

As the frequency separation of A and B tones in an ABAABA tone sequence increases the tones are heard to split into separate auditory streams (fission threshold). The phenomenon is identified with our ability to ‘hear out’ individual sound sources in natural, multisource acoustic environments. One important difference, however, between natural sounds and the tone sequences used in most streaming studies is that natural sounds often vary unpredictably from one moment to the next. In the present study, fission thresholds were measured for ABAABA tone sequences made more or less predictable by sampling the frequencies, levels or durations of the tones at random from normal distributions having different values of sigma (0–800 cents, 0–8 dB, and 0–40 ms, respectively, for frequency, level, and duration). Frequency variation on average had the greatest effect on threshold, but the function relating threshold to sigma was non-monotonic; first increasing then decreasing for the largest value of sigma. Differences in the sigmas for A and B tones tended to reduce thresholds, but covariance in the A and B tones had little effect. The results suggest that the principles of perceptual organization underlying streaming may differ for predictable and unpredictable tone sequences.
Inhibition of Zinc Metallopeptidases in Cardiovascular Disease - From Unity to Trinity, or Duality? (2009)

The fusion of therapeutics and diagnostic medicine in an effort to provide individualized pharmacotherapy frequently requires the manipulation of drugs that target different enzymes and receptors. To this end, and as a strategy to increase the efficiency of drug development pipelines, new chemical entities are often developed that interact with more than one target. Angiotensin-converting enzyme (ACE), its homologue ACE2, neutral endopeptidase (NEP) and endothelin-converting enzyme (ECE-1) are metallopeptidases that are involved in the metabolism of biologically active peptides that impact on the regulation of the cardiovascular system. The benefit of the ACE/NEP; NEP/ECE and ACE/NEP/ECE dual and triple inhibitors is not only their possible increased efficacy with respect to blood pressure control, but also their other activities, such as antiproliferative, anti-fibrotic and anti-inflammatory, mediated by angiotensin II and atrial natriuretic peptide. Over the last few years a number of three-dimensional structures of these metallopeptidases have advanced our understanding of the mode of interaction between various ligands and their target binding sites. This information is invaluable in the rational design of new and improved drugs. Here we review the structural basis for the design of single and multiple metallopeptidase inhibitors for the treatment of cardiovascular disease. Moreover, we present recent advances in the development of ACE/ECE-1 inhibitors that are likely to have high potency and improved side effect profiles.
Notice of Retraction: A dynamic algorithm for gate assignments under varied flight delay information (2010)

This article has been retracted by the publisher.
On-Off Kinetics of Engagement of FNI Modules of Soluble Fibronectin by β-Strand Addition (2015)

Intrinsically disordered sequences within bacterial adhesins bind to E-strands in the β-sheets of multiple FNI modules of fibronectin (FN) by anti-parallel β-strand addition, also called tandem β-zipper formation. The FUD segment of SfbI of Streptococcus pyogenes and Bbk32 segment of BBK32 of Borrelia burgdorferi, despite being imbedded in different adhesins from different bacteria, target the same 2-5,8-9 FNI modules, 2-5,8-9 FNI, in the N-terminal 70-kDa region (FN70K) of FN. To facilitate further comparisons, FUD, Bbk32, two other polypeptides based on SfbI that target 1-5 FNI (HADD) and 2-5 FNI (FRD), and mutant Bbk32 (ΔBbk32) were produced with fluorochromes placed just outside of the binding sequences. Unlabeled FUD competed ~ 1000-fold better for binding of labeled Bbk32 to FN than unlabeled Bbk32 competed for binding of labeled FUD to FN. Binding kinetics were determined by fluorescence polarization in a stopped-flow apparatus. On-rates for FUD, Bbk32, HADD, and FRD were similar, and all bound more rapidly to FN70K fragment than to full length FN. In stopped-flow displacement and size exclusion chromatographic assays, however, k off for FUD or HADD to FN70K or FN was considerably lower compared to k off of FRD or Bbk32. FUD and Bbk32 differ in the spacing between sequences that interact with 3FNI and 4FNI or with 5FNI and 8FNI. ΔBbk32, in which 2 residues were removed from Bbk32 to make the spacing more like FUD, had a k off intermediate between that of Bbk32 and FUD. These results indicate a "folding-after-binding" process after initial association of certain polypeptide sequences to FN that results in formation of a stable complex and is a function of number of FNI modules engaged by the polypeptide, spacing of engagement sites, and perhaps flexibility within the polypeptide-FN complex. We suggest that contributions of SfbI and BBK32 adhesins to bacterial pathogenicity may be determined in part by stability of adhesin-FN complexes.
Unexpected neuroprotection observed with the adenosine A2A receptor agonist CGS 21680 (1996)

The selective adenosine A2A receptor agonists 2-[p-(2-carboxethyl)phenylethylaminol-5′-N-ethylcarboxyamidoadenosine (CGS 21680), N-[2-(3,5-dimethoxyphenyl)ethyl]adenosine (DPMA) and metrifudil were investigated for their ability to prevent the loss of pyramidal CA1 neurons in the hippocampus following 5 min of severe temporary forebrain ischemia in mongolian gerbils. CGS 21680, when administered at 18.7 μmol/kg 30 and 120 min following reperfusion, exhibited highly significant protection against neuronal loss, but was inactive at 5.6 μmol/kg. DPMA, a more potent agonist at A1 and A2A receptors, was inactive up to a dose of 19 μmol/kg. Metrifudil (equipotent with CGS 21680 at A2A >25 times more potent at A1) gave a modest degree of protection at 26 μmol/kg and was inactive at 7.8 μmol/kg. CGS 21680 showed an equal degree of hypothermia at 5.6 and 18.7 μmol/kg, suggesting that this was not the prime mode of action. While the effect of metrifudil may be the result of its higher A1 receptor affinity, the mode of action of CGS 21680 has not been established; the data, however, suggest that a non-A1 non-A2A receptor mechanism may possibly be involved. Drug Dev. Res. 39:108–114 © 1997 Wiley-Liss, Inc.
Automated Comparison of Pathology Reports for On-the-job Assessment of Residents. (2019)

The clinical competency of residents at teaching hospitals is always under scrutiny. Ideally, assessment should reflect competency on-the-job, under realistic circumstances, and include evaluating their medical reports. Currently, the assessment is done manually by the attending physicians, which adds to the cognitive load. In this study, we developed an automated system for assessing medical resident's pathology reports. Our system used natural language processing (NLP) techniques to identify different lexical and semantic similarity scores at sentence level as well as chunk level. We then used supervised learning to classify the reports into three categories- No Change (NC), Minor Changes (MiC), and major changes (MaC), reflecting how much the attending physician's report differs from that of the resident. Our system was able to classify the reports with an accuracy of 73.6%. Although moderately successful, our work shows the potential and future of automated assessment systems in the biomedical domain.
Phosphatidylinositol 3'-kinase, mTOR, and Glycogen synthase kinase-3β mediated regulation of p21 in human urothelial carcinoma cells (2011)

PI3-kinase and AKT cause an upregulation of p21 by suppressing GSK-3β activity and activating mTOR in both cultured human urothelial carcinoma cells and mouse urothelial cells in vivo.
Synthèse et caractérisation de copolymères cellulose–poly(méthacrylate de méthyle): Greffage par le système acide de Caro–ion Fe3+ (1967)

Abstract Le méthacrylate de méthyle a été greffé a la cellulose en utilisant l'acide de Caro en présence de sel ferrique comme initiateur. L'effet de la durée du greffage, de la concentration en ions ferriques et du rapport cellulose‐monomere sur le pourcentage du greffage a été étudié. Au départ d'études du mécanisme de réaction, a des composés modèles, on a admis que les greffages ne se passent pas via les unités glycols 1,2 ou à l'unité hémiacétalique ' la fin de la molécule cellulosique. Des dégradations concommittantes de la cellulose en cours de la copolymérisation greffée a été examinée. Une relation linéaire entre le pourcentage de greffage et le nombre de chaînes cellulosiques briées par hydrolyse a été trouvée, d'où il semble que la structure du copolymère greffé était plutôt du type séquencé. La structure du copolymere greffé a aussi été étudiée par détermination des poids moléculaires des branches de polyméthacrylate de méthyle greffées apres hydrolyse de la chaîne cellulosique. Dans tous les cas, indépendamment des conditions de réaction, les poids moléculaires des ramifications greffées étaient tres élevés et leur nombre faible. Le nombre de branches greffées par chaîne cellulosique a été calculé au départ du pourcentage de greffage, des poids moléculaires des branches de polyméthacrylate et des poids moléculaires de la chaîne cellulosique. Ce nombre a été comparé au nombre de liens cellulosiques brisés en cours de greffage.
Transition metal-doped TiO2and ZnO—present status of the field (2005)

There has been considerable recent interest in the design of diluted magnetic semiconductors, with a particular focus on the exploration of different semiconductor hosts. Among these, the oxide-based diluted magnetic semiconductors are attracting increasing attention, following reports of room temperature ferromagnetism in anatase TiO2 and wurtzite ZnO doped with a range of transition metal ions. In this review we summarize the current status of oxide-based diluted magnetic semiconductors, and discuss the influence of growth method, substrate choice, and temperature on the microstructure and subsequent magnetic properties of thin films. We outline the experimental conditions that promote large magnetization and high ferromagnetic Curie temperature. Finally, we review the proposed mechanisms for the experimentally observed ferromagnetism and compare the predictions to the range of available data.