gebhart/patrepeval huggingface dataset:
The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis. (2000)

Epidemiological and animal studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce colon cancer risk. NSAIDs nonselectively inhibit both the constitutive cyclooxygenase (COX) 1 associated with side effects and the desired therapeutic target COX-2, which is induced in inflammation and neoplasia. We used the adenomatous polyposis coli (Apc) mutant Min mouse model to determine whether the selective COX-2 inhibitor celecoxib is effective for adenoma prevention and/or regression, and whether it might be safer than the nonselective NSAID previously shown to be most effective in this model, piroxicam. Min mice (n = 120) were randomized to treatment with celecoxib (0, 150, 500, or 1500 ppm celecoxib mixed in the diet) or piroxicam. To distinguish prevention from regression effects, groups were treated either "early" (before adenomas develop) or "late" (after most adenomas are established). Celecoxib caused dramatic reductions in both the multiplicity and size of tumors in a dose-dependent manner (P < 0.01). Early treatment with 1500 ppm of celecoxib was effective for prevention, decreasing tumor multiplicity to 29% and tumor size to only 17% of controls (P < 0.01). Late treatment demonstrated regression effects, reducing tumor multiplicity and size by about half. In contrast to the significant toxicity of piroxicam, which caused ulcers complicated by perforation and bleeding, celecoxib caused no gastrointestinal side effects and did not inhibit platelet thromboxane B2 at plasma drug levels similar to those obtained in early clinical trials in humans. These results provide the first evidence that selective inhibitors of COX-2 are safe and effective for the prevention and regression of adenomas in a mouse model of adenomatous polyposis and strongly support ongoing clinical trials in humans with the same syndrome. The broader population of patients with common sporadic adenomas that have somatic mutations of the same gene (APC) may also benefit from this treatment approach.
Catalytic Plasticity of Fatty Acid Modification Enzymes Underlying Chemical Diversity of Plant Lipids (1998)

Higher plants exhibit extensive diversity in the composition of seed storage fatty acids. This is largely due to the presence of various combinations of double or triple bonds and hydroxyl or epoxy groups, which are synthesized by a family of structurally similar enzymes. As few as four amino acid substitutions can convert an oleate 12-desaturase to a hydroxylase and as few as six result in conversion of a hydroxylase to a desaturase. These results illustrate how catalytic plasticity of these diiron enzymes has contributed to the evolution of the chemical diversity found in higher plants.
Glycosylation of human pancreatic ribonuclease: differences between normal and tumor states (2002)

Characterization of the N-glycans from human pancreatic ribonuclease (RNase 1) isolated from healthy pancreas and from pancreatic adenocarcinoma tumor cells (Capan-1 and MDAPanc-3) revealed completely different glycosylation patterns. RNase 1 from healthy cells contained neutral complex biantennary structures, with smaller amounts of tri- and tetraantennary compounds, and glycans with poly-N-acetyllactosamine extensions, all extensively fucosylated. In contrast, RNase 1 glycans from tumor cells (Capan-1) were fucosylated hybrid and complex biantennary glycans with GalNAc-GlcNAc antennae. RNase 1 glycans from Capan-1 and MDAPanc-3 cells also contained sialylated structures completely absent in the healthy pancreas. Some of these features provide distinct epitopes that were clearly detected using monoclonal antibodies against carbohydrate antigens. Thus monoclonal antibodies to Lewis(y) reacted only with normal pancreatic RNase 1, whereas, in contrast, monoclonal antibodies to sialyl-Lewis(x) and sialyl-Lewis(a) reacted only with RNase 1 secreted from the tumor cells. These glycosylation changes in a tumor-secreted protein, which reflect fundamental changes in the enzymes involved in the glycosylation pathway, open up the possibility of using serum RNase 1 as a tumor marker of pancreatic adenocarcinoma.
High Voltage GaN Switch Reliability FIT rates and PPM reliability based on standards from: Joint Electron Device Engineering Council (JEDEC), Automotive Electronics Council (AEC) and German Electrical and Electronic Manufacturers' Association (ZVEI) (2018)

Adoption of any semiconductor technology by the power conversion market requires the understanding of fundamental failure modes, acceleration factors and reliability statistics. This study shows how GaN products from Transphorm can meet this challenge, especially in the critical High Voltage Off State (HVOS) reliability stress test. The anticipated failure rate during a product's first 10 to 20 years of use is of particular interest as it has direct impact on warranty costs. This market requirement can be addressed by testing to failure statistically significant samples of devices, and analyzing the data with appropriate models. The methods developed for measuring GaN reliability on large samples will be discussed, which are wholly based on existing industrial and automotive standards. The resulting data can be used to supplement qualification testing results when the failure modes and acceleration factors are well understood.
Epstein‐Barr Virus: The First Human Tumor Virus and its Role in Cancer (1999)

The Epstein-Barr virus (EBV) is classically associated with three malignancies, Burkitt's lymphoma. B-cell lymphoproliferative syndromes, and nasopharyngeal carcinoma, and, more recently, with Hodgkin's disease, T-cell lymphomas, and gastric carcinoma, as well as being the causal agent for infectious mononucleosis. The relation of the virus to the malignancies varies from primary etiologic agent to necessary or contributory cofactor. Clonal EBV episomes are found in all the malignant conditions. EBV infects both epithelial and lymphoid cells, providing a pathobiological basis for these diverse associations. Most of the malignancies occur after years of viral dormancy and are accompanied or triggered by viral reactivation, in contrast to infectious mononucleosis, which results from primary infection with EBV. The EBV-associated malignancies offer insights into the causation and early detection of cancer. The molecular virology and pathobiology of EBV infection states provide the basis for the specific diagnosis of these diseases and a framework for new therapies.
Generation and characterization of chimeric recombinant AAV vectors (2003)

Although most animal experiments with recombinant adeno-associated virus (AAV) vectors have been based on AAV serotype 2, recent studies showed that AAV vectors based on AAV serotype 1 performed more efficiently in muscle and other tissues. On the other hand, AAV2-based vectors can be readily purified by heparin column. To combine the advantages of both types of vectors, we developed a strategy to generate chimeric vectors by using a mixture of AAV helper plasmids encoding both serotypes in the transfection process. Because the AAV packaging machinery cannot distinguish between closely related AAV1 and AAV2 capsid proteins, each packaged virion contains capsid proteins from both serotypes. As expected, the resulting chimeric vectors could be purified by heparin column. Neutralizing antibody assays showed that the chimeric vectors can be inhibited by either AAV1 or AAV2 antiserum. In vivo, the chimeric vectors direct levels of expression similar to those of AAV1 in muscle or AAV2 in liver; that is, they combine the best transduction characteristics of both parent vectors. In summary, this study provides a straightforward method for combining various properties of different AAV serotypes into one vector. Potential limitations of the chimeric vectors are also discussed.
Human 5-HT1 Receptor Subtypes Exhibit Distinct G Protein Coupling Behaviors in Membranes from Sf9 Cells (1997)

The G protein coupling behavior of four human 5-hydroxytryptamine receptor subtypes (5-HT1A, 5-HT1B, 5-HT1D, and 5-HT1E) has been studied in membranes from Sf9 cells expressing the individual receptors. The 5-HT1A and 5-HT1B receptors exhibited both high- and low-affinity states for agonist, with the majority of the receptors in a low-affinity state. Addition of purified G protein subunits to membranes expressing either 5-HT1A or 5-HT1B receptors shifted the majority of the receptors to a high-affinity state in the absence, but not in the presence, of guanine nucleotides. The alphai1, alphai2, alphai3, and alphao subunits were able to shift the receptors to a high-affinity state with either betagammabrain or betagammaretina while alphat subunits were inactive regardless of which betagamma preparation was used. A significantly higher affinity for agonist was observed with both receptors in the presence of alphai3 subunits compared with either alphai2 or alphao subunits, while a significantly lower concentration of alpha subunits was required for a maximal affinity shift of 5-HT1A receptors compared with 5-HT1B receptors (EC50 values of 6.4 and 12. 0 nM, respectively). The 5-HT1D and 5-HT1E receptors exhibited only a single affinity state for agonist. Addition of purified G protein subunits to membranes containing 5-HT1D receptors caused a small increase in affinity for agonist that was only partially reversed by guanine nucleotides while the addition of purified G protein subunits to membranes containing 5-HT1E receptors had no affect on agonist binding. Thus when expressed in an identical membrane environment these four closely related 5-HT1 receptor subtypes exhibit different G protein coupling behaviors.
The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic β cell growth (2002)

Diabetes is caused by an absolute (type 1) or relative (type 2) deficiency of insulin-producing β cells. The mechanisms governing replication of terminally differentiated β cells and neogenesis from progenitor cells are unclear. Mice lacking insulin receptor substrate-2 (Irs2) develop β cell failure, suggesting that insulin signaling is required to maintain an adequate β cell mass. We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses β cell failure in Irs2–/– mice through partial restoration of β cell proliferation and increased expression of the pancreatic transcription factor pancreas/duodenum homeobox gene-1 (Pdx1). Foxo1 and Pdx1 exhibit mutually exclusive patterns of nuclear localization in β cells, and constitutive nuclear expression of a mutant Foxo1 is associated with lack of Pdx1 expression. We show that Foxo1 acts as a repressor of Foxa2-dependent (Hnf-3β–dependent) expression from the Pdx1 promoter. We propose that insulin/IGFs regulate β cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts.
Lonely in the crowd: Recollections of bullying (2004)

This study examined the long‐term correlates of victimization in school with aspects of functioning in adult life, using a specially designed Retrospective Bullying Questionnaire, which also included questions about short‐term effects (e. g. suicidal ideation and intrusive memories) and victimization experiences in adulthood. Current relationship quality was assessed in terms of self‐perception, attachment style and friendship quality. In total, 884 adults (35% male) from two occupations (teacher, student) and three countries (Spain, Germany, UK) participated. Victims and especially stable victims (in both primary and secondary school) scored lower on general self‐esteem and higher on emotional loneliness, and reported more difficulties in maintaining friendships, than non‐victims. Victims in secondary school had a lower self‐esteem in relation to the opposite sex and were more often fearfully attached. The data revealed additional differences by gender, occupation and country level, but no further interactions with victim status. This indicates a general association between victimization in school and quality of later life predominately robust to variations in gender, occupation and country. Possible limitations caused by the retrospective nature of victimization reports are acknowledged.
Techniques for environment parameter estimation during telemanipulation (2008)

Teleoperation allows surgeons to perform an operation that is remote in distance and/or scale. Extracting information about a patient, particularly the dynamic model of tissues, during a surgical procedure may be useful for improving telemanipulator control, developing simulations, and performing automated diagnosis. This study examines automated environment parameter identification methods for bilateral telemanipulation, with a focus on surgical applications. We first present a multi-estimator technique and demonstrate that, in practice, it finds the best estimator for a Kelvin-Voigt material. Using a one-degree-of-freedom teleoperation system, cubes with various material properties were palpated to acquire data under three control conditions: teleoperation without persistent excitation, teleoperation in which the operator mimics persistent excitation, and autonomous control with persistent excitation. The estimation performance of three online estimation techniques (recursive least-squares, adaptive identification, and multi-estimator) are compared. Neither the cube type nor the control condition affected the estimation performance. By considering practical aspects, recursive least-squares or multi-estimator would be suitable for online estimation of the tissue property.
Unexpected substrate specificity of T4 DNA ligase revealed byin vitroselection (1993)

We have used in vitro selection techniques to characterize DNA sequences that are ligated efficiently by T4 DNA ligase. We find that the ensemble of selected sequences ligates about 50 times as efficiently as the random mixture of sequences used as the input for selection. Surprisingly many of the selected sequences failed to produce a match at or close to the ligation junction. None of the 20 selected oligomers that we sequenced produced a match two bases upstream from the ligation junction.
Optimistic distributed simulation based on transitive dependency tracking (1997)

In traditional optimistic distributed simulation protocols, a logical process (LP) receiving a straggler rolls back and sends out anti-messages. The receiver of an anti-message may also roll back and send out more anti-messages. So a single straggler may result in a large number of anti-messages and multiple rollbacks of some LPs. In the authors' protocol, an LP receiving a straggler broadcasts its rollback. On receiving this announcement, other LPs may roll back but they do not announce their rollbacks. So each LP rolls back at most once in response to each straggler. Anti-messages are not used. This eliminates the need for output queues and results in simple memory management. It also eliminates the problem of cascading rollbacks and echoing, and results in faster simulation. All this is achieved by a scheme for maintaining transitive dependency information. The cost incurred includes the tagging of each message with extra dependency information and the increased processing time upon receiving a message. They also present the similarities between the two areas of distributed simulation and distributed recovery. They show how the solutions for one area can be applied to the other area.
Kinetics of emulsifier-free emulsion polymerization of methyl methacrylate (1996)

The influences of polymerization temperature, initiator and monomer concentrations, ionic strength of the aqueous phase, as well as ethylene glycol dimethacrylate (EGDM) co-monomer, on the kinetics of the emulsifier-free emulsion polymerization of methyl methacrylate (MMA) and on the properties of the resulting poly(methyl methacrylate) (PMMA) lattices were studied. The polymerizations were carried out using potassium persulfate (KPS) as the initiator. Monodisperse PMMA lattices with particle diameters varying between 0.14–0.37 μm and polymer molecular weights of the order 0.4 × 106 to 1.2 × 106 g/mol were prepared. The initial rate of polymerization increases with increasing temperature, KPS-MMA mole ratio, EGDM content, or with decreasing ionic strength of the aqueous phase. It was shown that the bead size can be limited by reducing the monomer concentration or by using the cross-linking agent EGDM. The ionic strength of the aqueous phase has a dominant effect on final particle diameter and polymer molecular weight. The uniformity of the latex particles increases as the temperature increases or as the initiator concentration decreases. The experimental results can be reasonably interpreted by the homogeneous nucleation mechanism of the emulsifier-free emulsion polymerization of MMA. © 1996 John Wiley & Sons, Inc.
Fluorescent Nano-Optodes for Glucose Detection (2010)

We have designed fluorescent nanosensors based on ion-selective optodes capable of detecting small molecules. By localizing the sensor components in a hydrophobic core, these nanosensors are able to monitor dynamic changes in concentration of the model analyte, glucose. The nanosensors demonstrated this response in vitro and also when injected subcutaneously into mice. The response of the nanosensors tracked changes in blood glucose levels in vivo that were comparable to measurements taken using a glucometer. The development of these nanosensors offers an alternative, minimally invasive tool for monitoring glucose levels in such fields as diabetes research. Furthermore, the extension of the ion-selective optode sensor platform to small molecule detection will allow for enhanced monitoring of physiological processes.
Machine Learning Approaches to Early Fault Detection and Identification in NFV Architectures (2020)

Virtualization technologies become pervasive in networking, as a way to better exploit hardware capabilities and to quickly deploy tailored networking solutions for customers. But these new programmability abilities of networks also come with new management challenges: it is critical to quickly detect performance degradation, before they impact Quality of Service (QoS) or produce outages and alarms, as this takes part in the closed loop that adapts resources to services. This paper addresses the early detection, localization and identification of faults, before alarms are produced. We rely on the abundance of metrics available on virtualized networks, and explore various data preprocessing and classification techniques. As all Machine Learning approaches must be fed with large datasets, we turn to our advantage the softwarization of networks: one can easily deploy in a cloud the very same software that is used in production, and analyze its behaviour under stress, by fault injection.
Activation of Mac-1 (CD11b/CD18)-bound factor X by released cathepsin G defines an alternative pathway of leucocyte initiation of coagulation (1996)

Leucocyte initiation of coagulation preserves the haemostatic balance and may aberrantly contribute to vascular injury. In addition to the extrinsic activation mediated by tissue factor: factor VIIa, monocytes express an alternative procoagulant response after binding of the zymogen factor X to the integrin Mac-1 (CD11b/CD18). Here, factor X-activating activity was found in purified monocyte granules, and coincided with size-chromatographed fractions containing cathepsin G. In contrast, elastase-containing granule fractions did not activate factor X. In the presence of Ca2+ ions, purified cathepsin G, but not elastase, cleaved factor X to a approximately 54 kDa catalytically active derivative, structurally indistinguishable from the procoagulant product generated on monocytes after binding to Mac-1. Factor X activation by purified cathepsin G involved limited proteolysis of a novel Leu177-Leu178 peptide bond in the zymogen's activation peptide. Cathepsin G activation of factor X was completely inhibited by alpha 1 antichymotrypsin, or soybean trypsin inhibitor, or by a neutralizing antiserum to cathepsin G, while eglin, or an anti-elastase antibody, were ineffective. Affinity chromatography on active-site-dependent inhibitors Glu-Gly-Arg-chloromethyl ketone or benzamidine completely abolished factor Xa activity generated by cathepsin G. Cathepsin G was not constitutively detected on the monocyte surface by flow cytometry. However, inflammatory stimuli, including formyl peptide or phorbol ester, or Mac-1 engagement with its ligands fibrinogen, factor X or serum-opsonized zymosan, triggered monocyte degranulation and cathepsin G activation of factor X. These findings demonstrate that monocytes can alternatively initiate coagulation in a sequential three-step cascade, including (i) binding of factor X to Mac-1, (ii) discharge of azurophil granules, and (iii) limited proteolytic activation of membranebound factor X by cathepsin G. By rapidly forming thrombin and factor Xa in a protected membrane microenvironment, this pathway may contribute a "priming' signal for clotting, anticoagulation and vascular cell signal transduction, in vivo.
Effect of Dichloroacetate on Recovery of Brain Lactate, Phosphorus Energy Metabolites, and Glutamate during Reperfusion after Complete Cerebral Ischemia in Rats (1992)

The effects of dichloroacetate (DCA) on brain lactate, intracellular pH (pHi), phosphocreatine (PCr), and ATP during 60 min of complete cerebral ischemia and 2 h of reperfusion were investigated in rats by in vivo 1H and 31P magnetic resonance spectroscopy; brain lactate, water content, cations, and amino acids were measured in vitro after reperfusion. DCA, 100 mg/kg, or saline was infused before or immediately after the ischemic period. Preischemic treatment with DCA did not affect brain lactate or pHi during ischemia, but reduced lactate and increased pHi after 30 min of reperfusion (p < 0.05 vs. controls) and facilitated the recovery of PCr and ATP during reperfusion. Postischemic DCA treatment also reduced brain lactate and increased pHi during reperfusion compared with controls (p < 0.05), but had little effect on PCr, ATP, or Pi during reperfusion. After 30 min of reperfusion, serum lactate was 67% lower in the postischemic DCA group than in controls (p < 0.05). The brain lactate level in vitro was 46% lower in the postischemic DCA group than in controls (p < 0.05). DCA did not affect water content or cation concentrations in either group, but it increased brain glutamate by 40% in the preischemic treatment group (p < 0.05). The potential therapeutic effects of DCA on brain injury after complete ischemia may be mediated by reduced excitotoxin release related to decreased lactic acidosis during reperfusion.