gebhart/patrepeval huggingface dataset:
Cross-species Vascular Endothelial Growth Factor (VEGF)-blocking Antibodies Completely Inhibit the Growth of Human Tumor Xenografts and Measure the Contribution of Stromal VEGF (2005)

To fully assess the role of VEGF-A in tumor angiogenesis, antibodies that can block all sources of vascular endothelial growth factor (VEGF) are desired. Selectively targeting tumor-derived VEGF overlooks the contribution of host stromal VEGF. Other strategies, such as targeting VEGF receptors directly or using receptor decoys, result in inhibiting not only VEGF-A but also VEGF homologues (e.g. placental growth factor, VEGF-B, and VEGF-C), which may play a role in angiogenesis. Here we report the identification of novel anti-VEGF antibodies, B20 and G6, from synthetic antibody phage libraries, which block both human and murine VEGF action in vitro. Their affinity-improved variants completely inhibit three human tumor xenografts in mice of skeletal muscle, colorectal, and pancreatic origins (A673, HM-7, and HPAC). Avastin, which only inhibits the tumor-derived human VEGF, is approximately 90% effective at inhibiting HM-7 and A673 growth but is <50% effective at inhibiting HPAC growth. Indeed, HPAC tumors contain more host stroma invasion and stroma-derived VEGF than other tumors. Thus, the functional contribution of stromal VEGF varies greatly among tumors, and systemic blockade of both tumor and stroma-derived VEGF is sufficient for inhibiting the growth of tumor xenografts.
New anticoagulants (2004)

Anticoagulants are pivotal agents for prevention and treatment of thromboembolic disorders. Limitations of existing anticoagulants, vitamin K antagonist and heparins, have led to the development of newer anticoagulant therapies. These anticoagulants have been designed to target specific coagulation enzymes or steps in the coagulation pathway. New anticoagulants that are under evaluation in clinical trials include: (1) inhibitors of the factor VIIa/tissue factor pathway; (2) factor Xa inhibitors, both indirect and direct; (3) activated protein C and soluble thrombomodulin; and (4) direct thrombin inhibitors. Although most of these are parenteral agents, several of the direct inhibitors of factor Xa and thrombin are orally active. Clinical development of these therapies often starts with studies in the prevention of venous thrombosis before evaluation for other indications, such as prevention of cardioembolism in patients with atrial fibrillation or prosthetic heart valves. At present, the greatest clinical need is for an oral anticoagulant to replace warfarin for long-term prevention and treatment of patients with venous and arterial thrombosis. Ximelagatran, an oral direct thrombin inhibitor, is the first of a series of promising new agents that might fulfill this need. Large phase 3 trials evaluating ximelagatran for the secondary prevention of venous thromboembolism and prevention of cardioembolic events in patients with atrial fibrillation have been completed.
Motor Power/Current Measurement for Improving Rod Pump Efficiencies (1997)

ABSTRACT The development of accurate digital measurement of instantaneous power during a pump stroke has made possible a very quick and detailed analysis of the efficiency of the pumping system. The efficiency is then used as the benchmark for determining whether a complete well performance analysis is warranted from the standpoint of making best use of personnel and economic resources to increase oil production. In addition, power measurement provides direct information about lifting cost per barrel of fluid and barrel pf oil produced, electrical and mechanical loading of the prime mover, peak power demand, power factor and minimum required ratings. These results give operating personnel information regarding potential problems and give to management a complete picture of the distribution of pumping costs. The power measurements are also converted, by the software, to instantaneous torque and presented as continuous torque curves for the upstroke and downstroke. This allows determination of the existing level of counterbalance and provides the most rapid and accurate method for counterbalance adjustment to achieve lower torque loading on the gear box and reduced energy utilization. One of the principal advantages of this balancing method is that counterbalance adjustment can be made without need for an accurate description of the pumping unit's geometry which is often unknown or inaccurate. The effect of counterweight displacement on torque and power is observed immediately by repeating the power measurement after relocating the counterweights. This paper presents a series of case studies showing the application of power measurement to a variety of pumping systems and components, including conventional, Mark II, Rotaflex units and high efficiency motors.
Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor? (2012)

Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population worldwide and may confer increased cardiometabolic risk with consequent adverse cardiovascular outcomes independent of traditional cardiovascular risk factors and the metabolic syndrome. It is characterized almost universally by insulin resistance and is strongly associated with type 2 diabetes and obesity. Non-alcoholic fatty liver disease is a marker of pathological ectopic fat accumulation combined with a low-grade chronic inflammatory state. This results in several deleterious pathophysiological processes including abnormal glucose, fatty acid and lipoprotein metabolism, increased oxidative stress, deranged adipokine profile, hypercoaguability, endothelial dysfunction, and accelerated progression of atherosclerosis. This ultimately leads to a dysfunctional cardiometabolic phenotype with cardiovascular mortality representing the main mode of premature death in NAFLD. This review is aimed at introducing NAFLD to the clinical cardiologist by discussing in-depth the evidence to date linking NAFLD with cardiovascular disease, reviewing the likely mechanisms underlying this association, as well as summarizing from a cardiologist's perspective, current and potential future treatment options for this increasingly prevalent disease.
Automated pavement distress data collection and analysis: a 3-D approach (2002)

This paper describes a 3-D automated pavement distress data collection and analysis system based on NRC's Biris sensor technology. The paper introduces the problem to be solved, the selected design criteria, and the adopted solution to monitor the quality of road surfaces. The system geometry for the acquisition of the three-dimensional coordinates of pavement surface distresses is presented. Multiple feature extraction and system integration concepts are given with emphasis placed on the real-time processing of the raw data by a parallel array of processors. Advantages and disadvantages of this technology are discussed. System performances and experimental results are provided.
Human Embryonic Stem Cells Develop Into Multiple Types of Cardiac Myocytes (2003)

Human embryonic stem (hES) cells can differentiate in vitro, forming embryoid bodies (EBs) composed of derivatives of all three embryonic germ layers. Spontaneously contracting outgrowths from these EBs contain cardiomyocytes (CMs); however, the types of human CMs and their functional properties are unknown. This study characterizes the contractions and action potentials (APs) from beating EB outgrowths cultured for 40 to 95 days. Spontaneous and electrical field-stimulated contractions were measured with video edge-detection microscopy. beta-Adrenergic stimulation with 1.0 micromol/L isoproterenol resulted in a significant increase in contraction magnitude. Intracellular electrical recordings using sharp KCl microelectrodes in beating EB outgrowths revealed three distinct classes of APs: nodal-like, embryonic atrial-like, and embryonic ventricular-like. The APs were described as embryonic based on the relatively depolarized resting membrane potential and slow AP upstroke. Repeated impalements of an individual beating outgrowth revealed a reproducible AP morphology recorded from different cells, suggesting that each outgrowth is composed of a predominant cell type. Complex functional properties typical of cardiac muscle were observed in the hES cell-derived CMs including rate adaptation of AP duration and provoked early and delayed afterdepolarizations. Repolarization of the AP showed a significant role for IKr based on E-4031 induced prolongation of AP duration as anticipated for human CMs. In conclusion, hES cells can differentiate into multiple types of CMs displaying functional properties characteristic of embryonic human cardiac muscle. Thus, hES provide a renewable source of distinct types of human cardiac myocytes for basic research, pharmacological testing, and potentially therapeutic applications.
Inhibition of Escherichia coli Acetyl Coenzyme A Carboxylase by Acyl-Acyl Carrier Protein (2001)

Escherichia coli acetyl coenzyme A carboxylase (ACC), the first enzyme of the fatty acid biosynthetic pathway, is inhibited by acylated derivatives of acyl carrier protein (ACP). ACP lacking an acyl moiety does not inhibit ACC. Acylated derivatives of ACP having chain lengths of 6 to 20 carbon atoms were similarly inhibitory at physiologically relevant concentrations. The observed feedback inhibition was specific to the protein moiety, as shown by the inability of the palmitoyl thioester of spinach ACP I to inhibit ACC.
Antiganglioside antibodies and their pathophysiological effects on Guillain-Barre syndrome and related disorders--A review (2009)

Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy which can cause acute quadriplegia. Infection with micro-organisms, including Campylobacter jejuni (C. jejuni), Haemophilus influenzae, and Cytomegalovirus (CMV), is recognized as a main triggering event for the disease. Lipooligosaccharide (LOS) genes are responsible for the formation of human ganglioside-like LOS structures in infectious micro-organisms that can induce GBS. Molecular mimicry of LOSs on the surface of infectious agents and of ganglioside antigens on neural cells is thought to induce cross-reactive humoral and cellular immune responses. Patients with GBS develop antibodies against those gangliosides, resulting in autoimmune targeting of peripheral nerve sites, leading to neural damage. Heterogeneity of ganglioside expression in the peripheral nervous system (PNS) may underlie the differential clinical manifestation of the GBS variants. Recent studies demonstrate that some GBS sera react with ganglioside complexes consisting of two different gangliosides, such as GD1a and GD1b, or GM1 and GD1a, but not with each constituent ganglioside alone. The discovery of antiganglioside complex antibodies not only improves the detection rate of autoantibodies in GBS, but also provides a new concept in the antibody-antigen interaction through clustered carbohydrate epitopes. Although ganglioside mimicry is one of the possible etiological causes of GBS, unidentified factors may also contribute to the pathogenesis of GBS. While GBS is not considered a genetic disease, host factors, particularly human lymphocyte antigen type, appear to have a role in the pathogenesis of GBS following C. jejuni infection.
Multiwavelength line-rate-independent optical digital cross-connects based on low-gain fiber amplifiers (1994)

We experimentally demonstrated a multiwavelength, line-rate independent optical digital cross-connect system (DCS) by using cascaded low-gain erbium-doped fiber amplifiers as the switching elements in a dilated Benes architecture.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Inhibitor Binding Studies on Enoyl Reductase Reveal Conformational Changes Related to Substrate Recognition (1999)

Enoyl acyl carrier protein reductase (ENR) is involved in fatty acid biosynthesis. In Escherichia coli this enzyme is the target for the experimental family of antibacterial agents, the diazaborines, and for triclosan, a broad spectrum antimicrobial agent. Biochemical studies have suggested that the mechanism of diazaborine inhibition is dependent on NAD(+) and not NADH, and resistance of Brassica napus ENR to diazaborines is thought to be due to the replacement of a glycine in the active site of the E. coli enzyme by an alanine at position 138 in the plant homologue. We present here an x-ray analysis of crystals of B. napus ENR A138G grown in the presence of either NAD(+) or NADH and the structures of the corresponding ternary complexes with thienodiazaborine obtained either by soaking the drug into the crystals or by co-crystallization of the mutant with NAD(+) and diazaborine. Analysis of the ENR A138G complex with diazaborine and NAD(+) shows that the site of diazaborine binding is remarkably close to that reported for E. coli ENR. However, the structure of the ternary ENR A138G-NAD(+)-diazaborine complex obtained using co-crystallization reveals a previously unobserved conformational change affecting 11 residues that flank the active site and move closer to the nicotinamide moiety making extensive van der Waals contacts with diazaborine. Considerations of the mode of substrate binding suggest that this conformational change may reflect a structure of ENR that is important in catalysis.
A simple graph-based intermediate representation (1995)

We present a graph-based intermediate representation (IR) with simple semantics and a low-memory-cost C++ implementation. The IR uses a directed graph with labeled vertices and ordered inputs but unordered outputs. Vertices are labeled with opcodes, edges are unlabeled. We represent the CFG and basic blocks with the same vertex and edge structures. Each opcode is defined by a C++ class that encapsulates opcode-specific data and behavior. We use inheritance to abstract common opcode behavior, allowing new opcodes to be easily defined from old ones. The resulting IR is simple, fast and easy to use.
Biglycan recruits utrophin to the sarcolemma and counters dystrophic pathology in mdx mice (2010)

Duchenne muscular dystrophy (DMD) is caused by mutations in dystrophin and the subsequent disruption of the dystrophin-associated protein complex (DAPC). Utrophin is a dystrophin homolog expressed at high levels in developing muscle that is an attractive target for DMD therapy. Here we show that the extracellular matrix protein biglycan regulates utrophin expression in immature muscle and that recombinant human biglycan (rhBGN) increases utrophin expression in cultured myotubes. Systemically delivered rhBGN up-regulates utrophin at the sarcolemma and reduces muscle pathology in the mdx mouse model of DMD. RhBGN treatment also improves muscle function as judged by reduced susceptibility to eccentric contraction-induced injury. Utrophin is required for the rhBGN therapeutic effect. Several lines of evidence indicate that biglycan acts by recruiting utrophin protein to the muscle membrane. RhBGN is well tolerated in animals dosed for as long as 3 months. We propose that rhBGN could be a therapy for DMD.
Budgeted online collective inference (2015)

Updating inference in response to new evidence is a fundamental challenge in artificial intelligence. Many real problems require large probabilistic graphical models, containing millions of interdependent variables. For such large models, jointly updating the most likely (i.e., MAP) configuration of the variables each time new evidence is encountered can be infeasible, even if inference is tractable. In this paper, we introduce budgeted online collective inference, in which the MAP configuration of a graphical model is updated efficiently by revising the assignments to a subset of the variables while holding others fixed. The goal is to selectively update certain variables without sacrificing quality with respect to full inference. To formalize the consequences of partially updating inference, we introduce the concept of inference regret. We derive inference regret bounds for a class of graphical models with strongly-convex free energies. These theoretical insights, combined with a thorough analysis of the optimization solver, motivate new approximate methods for efficiently updating the variable assignments under a budget constraint. In experiments, we demonstrate that our algorithms can reduce inference time by 65% with accuracy comparable to full inference.
Growth and Phosphorus Metabolism in Premature Infants Fed Human Milk, Fortified Human Milk, or Special Premature Formula (1987)

Human milk promotes less than optimal growth and is associated with phosphorus deficiency and decreased bone mineralization in very-low-birth-weight (VLBW) infants. In this study, the effects of feeding premature infants either human milk (HM), fortified human milk (FHM), or special premature formula (Similac Special Care [SSC]) on growth, phosphorus metabolism, and serum type I procollagen (pColl-I-C) were evaluated. Infants fed FHM exhibited a rate of weight gain and an increase in head circumference comparable with infants fed SSC and significantly greater than infants fed HM, despite the fact that both the FHM group and the HM group demonstrated biochemical evidence of phosphorus deficiency. The pColl-I-C concentrations in VLBW infants were tenfold to 20-fold greater than concentrations in normal children older than 2 years of age. The pColl-I-C levels correlated positively with weight gain and were significantly greater in the FHM and SSC groups than in the HM group. By contrast, serum alkaline phosphatase levels did not correlate with weight gain and were significantly lower in the rapidly growing SSC group than in either of the two groups with phosphorus deficiency and presumed poor bone mineralization. We conclude that the serum pColl-I-C concentration is a biochemical marker of growth in VLBW infants and may prove useful as a predictor of growth responses to various nutritional and therapeutic interventions.
Neuromorphic pitch attitude regulation of an underwater telerobot (1990)

The experimental results of using trained neural networks to regulate the pitch attitude of an underwater telerobot are presented. The neuromorphic control algorithm developed for teaching the networks is a direct application of the back-propagation entrainment method, with those modifications required to pose the problem in a control systems framework. The networks perform in the field as predicted by simulation results; however, it is observed that the complexity of the calculations required can create unacceptable delays when using a single serial microprocessor to compute the control. This problem becomes especially acute when scaling the architecture to more complex neural topologies. Special-purpose hardware, which directly implements the neural equations and, hence, realizes the benefits of the natural parallelism of these models, is seen as a necessary development for the effective use of neural controllers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Interchangeability and specificity of components from the quorum-sensing regulatory systems of Vibrio fischeri and Pseudomonas aeruginosa (1994)

Autoinduction is a conserved mechanism of cell density-dependent gene regulation that occurs in a variety of gram-negative bacteria. Autoinducible luminescence in Vibrio fischeri requires a transcriptional activator, LuxR, while a LuxR homolog, LasR, activates elastase expression in Pseudomonas aeruginosa. Both LuxR and LasR require specific signal molecules, called autoinducers, for activity. We show here the activation in Escherichia coli of the V. fischeri luminescence (lux) operon by LasR and of the P. aeruginosa elastase gene (lasB) by LuxR when each is in the presence of its cognate autoinducer. Neither LuxR nor LasR showed appreciable activity with the heterologous V. fischeri or P. aeruginosa autoinducer. This supports the view that there is a direct interaction of each transcriptional activator with its proper autoinducer and suggests that there are conserved, autoinduction-related elements within the promoter regions of these genes.
The rat casein multigene family. Fine structure and evolution of the beta-casein gene. (1985)

Eight overlapping phage clones, spanning 34.4 kilobase pairs of genomic DNA, containing the 7.2-kilobase pair rat beta-casein gene have been isolated and characterized. The first 510 base pairs (bp) of 5' flanking, 110 bp of 3' flanking, and all the exon/intron junctions have been sequenced. The beta-casein gene contains 9 exons ranging in size from 21 to 525 bp. We have attempted to identify potential regulatory elements by searching for regions of sequence homology shared between milk protein genes which respond similarly to lactogenic hormones and by searching for previously reported hormone receptor-binding sites. Within the conserved first 200 bp of 5' flanking sequences 3 regions of greater than 70% homology were observed between the rat beta- and gamma-casein genes. One of these contains a region 90% homologous to the chicken progesterone receptor-binding site. The conserved 5' noncoding region, the highly conserved signal peptide, and the hydrophobic carboxyl-terminal region of the protein are each encoded by a separate exon. In contrast the evolutionarily conserved phosphorylation site of beta-casein is formed by an RNA-splicing event. The exons which encode the phosphorylation sites of beta-casein appear to have resulted from an intragenic duplication. Based upon the exon structure of the casein genes, an evolutionary model of intragenic and intergenic exon duplications for this gene family is proposed.
A Cyclic Dimer of Metalloporphyrin Forms a Highly Stable Inclusion Complex with C60 (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTA Cyclic Dimer of Metalloporphyrin Forms a Highly Stable Inclusion Complex with C60Kentaro Tashiro, Takuzo Aida, Jiang-Yu Zheng, Kazushi Kinbara, Kazuhiko Saigo, Shigeru Sakamoto, and Kentaro YamaguchiView Author Information Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan, Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan, Chemical Analysis Center, Chiba University, Yayoi-cho, Inage-ku, Chiba 2638522, Japan Cite this: J. Am. Chem. Soc. 1999, 121, 40, 9477–9478Publication Date (Web):September 28, 1999Publication History Received12 July 1999Published online28 September 1999Published inissue 1 October 1999https://doi.org/10.1021/ja992416mCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views3129Altmetric-Citations288LEARN 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 InReddit Read OnlinePDF (125 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Aromatic compounds,Hydrocarbons,Mixtures,Pyrroles,Zinc Get e-Alerts