gebhart/patrepeval huggingface dataset:
Expression of the neutral amino acids transporter ASCT1 in esophageal carcinomas. (2001)

Cancers cells utilize more glucose and amino acids than their benign counterparts. Overexpression of the facilitative glucose transporter Glut1 in human cancers was found to correlate with aggressive biologic behavior. The aim of this work was to determine whether the neutral amino acid transporter ASCT1 is expressed in human esophageal carcinomas, and to correlate the findings with Glut1 expression. Sections of formalin-fixed and paraffin-embedded tissue from 42 cases of esophageal carcinomas were entered in the study. Immunohistochemical staining was performed using a rabbit anti-ASCT1 IgG developed in our laboratory, and anti-Glut1 antibody, using standard avidin-streptavidine immunoperoxidase method. Sections of formalin-fixed and paraffin-embedded HepG2 cells were used as positive controls. The percent of ASCT1-positive cells was scored. Statistical analysis was performed using Fisher's exact test. ASCT1 immunoreactivity was cytoplasmic, whereas Glut1 was membranous. Significantly more adenocarcinomas expressed ASCT1 than squamous cell carcinomas (p < 0.0001), whereas Glut1 expression was similar in both tumor types. There was no association between the expression of either transporter and lymph node metastasis. Glut1 was expressed more often in the better differentiated than the poorly differentiated squamous carcinomas (p = 0.003). These results suggest that unlike in squamous cell carcinoma, ASCT1 plays a significant role in the recruitment of amino acids in adenocarcinoma of the esophagus, and suggest that the metabolic needs, and uptake of nutrients, are regulated differently in these two tumor types. Additional studies with larger number of patients are needed to determine the biological significance of ASCT1 expression in esophageal carcinomas.
Psychiatry & the psychedelic drugs. Past, present & future (2017)

The classical psychedelic drugs, including psilocybin, lysergic acid diethylamide and mescaline, were used extensively in psychiatry before they were placed in Schedule I of the UN Convention on Drugs in 1967. Experimentation and clinical trials undertaken prior to legal sanction suggest that they are not helpful for those with established psychotic disorders and should be avoided in those liable to develop them. However, those with so-called 'psychoneurotic' disorders sometimes benefited considerably from their tendency to 'loosen' otherwise fixed, maladaptive patterns of cognition and behaviour, particularly when given in a supportive, therapeutic setting. Pre-prohibition studies in this area were sub-optimal, although a recent systematic review in unipolar mood disorder and a meta-analysis in alcoholism have both suggested efficacy. The incidence of serious adverse events appears to be low. Since 2006, there have been several pilot trials and randomised controlled trials using psychedelics (mostly psilocybin) in various non-psychotic psychiatric disorders. These have provided encouraging results that provide initial evidence of safety and efficacy, however the regulatory and legal hurdles to licensing psychedelics as medicines are formidable. This paper summarises clinical trials using psychedelics pre and post prohibition, discusses the methodological challenges of performing good quality trials in this area and considers a strategic approach to the legal and regulatory barriers to licensing psychedelics as a treatment in mainstream psychiatry. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.
99m Tc Annexin V Imaging of Neonatal Hypoxic Brain Injury (2000)

Apoptosis may develop after HII even in brains that appear normal on diffusion-weighted and perfusion MR. These data suggest a role of radiolabeled annexin V screening of neonates at risk for the development of cerebral palsy.
[Clinical utility of receptor imaging in the assessment of liver function]. (1992)

Technetium-99m diethylene triamine pentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed receptor-binding radiopharmaceutical, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of hepatocytes. Clinical utility of TcGSA was evaluated in 3 control subjects with normal livers and in 54 patients with various liver diseases. The parameter, Receptor Index, was derived from liver and heart time-activity data and is the ratio of radioactivity of the liver over the radioactivity of the liver plus heart at 15 min after the intravenous injection of 3 mg of TcGSA. Receptor concentration ([R]o) was obtained by kinetic analysis of liver and heart time-activity data using pharmacokinetic nonlinear modeling. Values for the Receptor Index and [R]o was statistically different in the control subjects and in patients with mild, moderate, and severe liver diseases. Good correlations were obtained between the Receptor Index, [R]o and conventional liver function tests, such as Child-Turcotte criteria score, prothrombin time, and indocyanine green test. Receptor Index and [R]o were properly estimated even in patients with obstructive jaundice or remarkable portocaval shunt. These data suggest that the receptor imaging as well as its parameters, Receptor Index and [R]o, is a potentially practical and reliable diagnostic method for estimating the functioning hepatocyte mass and for assessing liver function.
Performance study of dispatching algorithms in multi-tier web architectures (2002)

The number and heterogeneity of requests to Web sites are increasing also because the Web technology is becoming the preferred interface for information systems. Many systems hosting current Web sites are complex architectures composed by multiple server layers with strong scalability and reliability issues. In this paper we compare the performance of several combinations of centralized and distributed dispatching algorithms working at the first and second layer, and using different levels of state information. We confirm some known results about load sharing in distributed systems and give new insights to the problem of dispatching requests in multi-tier cluster-based Web systems.
Combined effect of anti‐high‐mobility group box‐1 monoclonal antibody and peramivir against influenza A virus‐induced pneumonia in mice (2018)

Human pandemic H1N1 2009 influenza virus causes significant morbidity and mortality with severe acute lung injury due to the excessive inflammatory reaction, even with neuraminidase inhibitor use. The anti-inflammatory effect of anti-high-mobility group box-1 (HMGB1) monoclonal antibody (mAb) against influenza pneumonia has been reported. In this study, we evaluated the combined effect of anti-HMGB1 mAb and peramivir against pneumonia induced by influenza A (H1N1) virus in mice. Nine-week-old male C57BL/6 mice were inoculated with H1N1 and treated with intramuscularly administered peramivir at 2 and 3 days post-infection (dpi). The anti-HMGB1 mAb or a control mAb was administered at 2, 3, and 4 dpi. Survival rates were assessed, and lung lavage and pathological analyses were conducted at 5 and 7 dpi. The combination of peramivir with the anti-HMGB1 mAb significantly improved survival rate whereas the anti-HMGB1 mAb alone did not affect virus proliferation in the lungs. This combination therapy also significantly ameliorated histopathological changes, neutrophil infiltration, and macrophage aggregation by inhibiting HMGB1, inflammatory cytokines, and oxidative stress. Fluorescence immunostaining showed that the anti-HMGB1 mAb inhibited HMGB1 translocation from type I alveolar epithelial cells. In summary, combining anti-HMGB1 with conventional anti-influenza therapy might be useful against severe influenza virus infection.
pH Dependencies of the Tetrahymena Ribozyme Reveal an Unconventional Origin of an Apparent pKa (1996)

The L-21 ScaI ribozyme derived from the Tetrahymena thermophila pre-rRNA group I intron catalyzes a site-specific endonucleolytic cleavage of RNA, DNA, and chimeric RNA/DNA oligonucleotides: CCCUCUA5 + G-->CCCUCU + GA5. The pH-rate dependence was determined for the reaction of the E.G complex with the oligonucleotide substrate d(CCCUC)r(U)d(A5) [(kcat/Km)S conditions]. Although it was shown that the pH dependence is not affected by specific buffers, there is inhibition by specific monovalent cations. The intrinsic pH-rate dependence is log-linear with slope 1 below pH 7, displays an apparent pKa of 7.6, remains nearly level until pH 8.5, and then begins to fall. Two models to explain the apparent pKa were ruled out: (1) the pKa represents loss of a proton from the nucleophilic 3' OH of G, and (2) the pKa arises from a change in rate-limiting step from a pH-dependent to a pH-independent step. In addition, these models, or others involving a single titration, cannot account for the decrease in activity at high pH. A third, unconventional, model is consistent with all of the data. It involves inactivation of the ribozyme by any of several independent titrations of groups with pKa values considerably higher than the apparent pKa of 7.6. The data are consistent with loss of catalytic function upon release of a proton from any one of 19 independent sites with pKa = 9.4 (the unperturbed pKa of N1 of G and N3 of U in solution). Independent experiments investigating the effect of pH on different reaction steps supported this model and suggested the identity of some of the required protons. This mechanism of inactivation is expected to generally affect the behavior of RNAs at pH values removed from the pKa of the titrating bases.
Computer Vision for Autonomous Vehicles: Problems, Datasets and State of the Art (2020)

Recent years have witnessed enormous progress in AI-related fields such as computer vision, machine learning, and autonomous vehicles. As with any rapidly growing field, it becomes increasingly difficult to stay up-to-date or enter the field as a beginner. While several survey papers on particular sub-problems have appeared, no comprehensive survey on problems, datasets, and methods in computer vision for autonomous vehicles has been published. This monograph attempts to narrow this gap by providing a survey on the state-of-the-art datasets and techniques. Our survey includes both the historically most relevant literature as well as the current state of the art on several specific topics, including recognition, reconstruction, motion estimation, tracking, scene understanding, and end-to-end learning for autonomous driving. Towards this goal, we analyze the performance of the state of the art on several challenging benchmarking datasets, including KITTI, MOT, and Cityscapes. Besides, we discuss open problems and current research challenges. To ease accessibility and accommodate missing references, we also provide a website that allows navigating topics as well as methods and provides additional information.
Preventing Type II Diabetes Mellitus (2004)

Burgeoning obesity is increasing the prevalence of type II diabetes mellitus. As a consequence, there will be an even greater burden of cardiovascular disease, end-stage renal disease, blindness, and lower extremity amputations. If diagnosed, impaired glucose tolerance presents an opportunity for intervention that potentially could delay or prevent the development of diabetes. Recent prospective studies document the effectiveness of exercise and weight reduction in preventing diabetes. Metformin is less effective than intense lifestyle interventions. Acarbose, losartan, orlistat, pravastatin, ramipril, and hormone replacement therapy are associated with lower rates of the development of diabetes. The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial and the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial were designed to assess not only the prevention of diabetes but also the impact on cardiovascular morbidity and mortality.
Macrophages in Drosophila embryos and L2 cells exhibit scavenger receptor-mediated endocytosis. (1992)

Mammalian macrophage scavenger receptors exhibit unusually broad binding specificity and are implicated in atherosclerosis and host defense. Scavenger receptor-like endocytosis was observed in Drosophila melanogaster embryos and in primary embryonic cell cultures. This receptor activity was expressed primarily by macrophages. The Drosophila Schneider L2, but not the Kc, cell line also exhibited a scavenger receptor-mediated endocytic pathway similar to its mammalian counterpart. L2 receptors mediated high-affinity internalization and subsequent temperature- and chloroquine-sensitive degradation of 125I-labeled acetylated low density lipoprotein and displayed characteristic ligand specificity. These findings suggest that scavenger receptors mediate important, well-conserved functions and raise the possibility that they may be pattern recognition receptors that arose early in the evolution of host defense mechanisms. They also establish additional systems for the investigation of endocytosis in Drosophila and scavenger receptor function in disease, host defense, and development.
Released Form of CNTF Receptor α Component as a Soluble Mediator of CNTF Responses (1993)

The alpha component of the receptor for ciliary neurotrophic factor (CNTF) differs from other known growth factor receptors in that it is anchored to cell membranes by a glycosylphosphatidylinositol linkage. One possible function of this type of linkage is to allow for the regulated release of this receptor component. Cell lines not normally responsive to CNTF responded to treatment with a combination of CNTF and a soluble form of the CNTF alpha receptor component. These findings not only demonstrate that the CNTF receptor alpha chain is a required component of the functional CNTF receptor complex but also reveal that it can function in soluble form as part of a heterodimeric ligand. Potential physiological roles for the soluble CNTF receptor are suggested by its presence in cerebrospinal fluid and by its release from skeletal muscle in response to peripheral nerve injury.
A novel three-dimensional object detection with the modified You Only Look Once method (2018)

Three-dimensional object detection aims to produce a three-dimensional bounding box of an object at its full extent. Nowadays, three-dimensional object detection is mainly based on red green blue-depth (RGB-D) images. However, it remains an open problem because of the difficulty in labeling for three-dimensional training data. In this article, we present a novel three-dimensional object detection method based on two-dimensional object detection, which only takes a set of RGB images as input. First, aiming at the requirement of three-dimensional object detection and the low location accuracy of You Only Look Once, a modified two-dimensional object detection method based on You Only Look Once is proposed. Then, using a set of images from different visual angles, three-dimensional geometric data are reconstructed. In addition, making use of the modified You Only Look Once method, the two-dimensional object bounding boxes of the forward and side views are obtained. Finally, according to the transformation between the two-dimensional pixel coordinate and the three-dimensional space coordinate, the two-dimensional object bounding box is mapped onto the reconstructed three-dimensional scene to form the three-dimensional object box. Because this method only needs the collection of two-dimensional images to train the modified You Only Look Once model, it has a wide range of applications. The experimental results show that the modified You Only Look Once model can improve the location accuracy, and our algorithm can effectively realize the three-dimensional object detection without depth images.
Fungal yapsins and cell wall: a unique family of aspartic peptidases for a distinctive cellular function (2006)

A novel class of aspartic peptidases known as fungal yapsins, whose first member ScYps1p was identified more than a decade ago in Saccharomyces cerevisiae, is characteristically modified by the addition of a glycophosphatidylinositol moiety and has a preference for cleaving substrates C-terminally to mono- and paired-basic residues. Over the years, several other members, first in S. cerevisiae and then in other fungi, have been identified. The implication of fungal yapsins in cell-wall assembly and/or remodelling had been suspected for many years. However, it is only very recently that studies performed on S. cerevisae and Candida albicans have confirmed their importance for cell-wall integrity. Here, we review 16 years of research, covering all fundamental aspects of these unique enzymes, in an effort to track their functional significance. We also propose a nomenclature for fungal yapsins based on their sequence identity with the founding members of this family, the S. cerevisiae yapsins.
Surprise! Bayesian Weighting for De-Biasing Thematic Maps (2016)

Thematic maps are commonly used for visualizing the density of events in spatial data. However, these maps can mislead by giving visual prominence to known base rates (such as population densities) or to artifacts of sample size and normalization (such as outliers arising from smaller, and thus more variable, samples). In this work, we adapt Bayesian surprise to generate maps that counter these biases. Bayesian surprise, which has shown promise for modeling human visual attention, weights information with respect to how it updates beliefs over a space of models. We introduce Surprise Maps, a visualization technique that weights event data relative to a set of spatia-temporal models. Unexpected events (those that induce large changes in belief over the model space) are visualized more prominently than those that follow expected patterns. Using both synthetic and real-world datasets, we demonstrate how Surprise Maps overcome some limitations of traditional event maps.
Source injection induced off-state breakdown and its improvement by enhanced back barrier with fluorine ion implantation in AlGaN/GaN HEMTs (2008)

The mechanisms of AlGaN/GaN HEMT's off-state breakdown are investigated. Both the source- and gate-injection induced impact ionizations are identified with the former leading to premature three-terminal breakdown. A 35% improvement of the breakdown voltage could be achieved in an enhanced back barrier HEMT by implanting fluorine ions under the channel region and effectively block the source injection through the buffer layer.
The activity of daptomycin on Enterococcus faecium protoplasts: indirect evidence supporting a novel mode of action on lipoteichoic acid synthesis (1993)

The effect of daptomycin, an acidic lipopeptide antibiotic active against Gram-positives, was studied in Enterococcus faecium protoplasts. This antibiotic killed 99% of the protoplasts within 60 minutes of treatment, while vancomycin was ineffective, thus excluding peptidoglycan synthesis as the only target of the action of daptomycin. As previously seen with whole cells, in protoplasts lipoteichoic acid synthesis was the earliest and most strongly inhibited among types of macro-molecular synthesis. Radioactive daptomycin tightly bound only to the cytoplasmic membrane, in which the enzymes involved in lipoteichoic acid synthesis are located. These conclusions strongly support our previous proposal that daptomycin, though active against peptidoglycan synthesis, primarily inhibits lipoteichoic acid synthesis.
Human FcRn Transgenic Mice for Pharmacokinetic Evaluation of Therapeutic Antibodies (2006)

Therapeutic monoclonal antibodies are widely recognized to be a most promising means to treat an increasing number of human diseases, including cancers and autoimmunity. To a large extent, the efficacy of monoclonal antibody treatment is because IgG antibodies have greatly extended persistence in vivo. However, conventional rodent models do not mirror human antibody pharmacokinetics. The key molecule responsible for the extended persistence antibodies is the major histocompatibility complex class I family Fc receptor, FcRn. We describe human FcRn transgenic mouse models and how they can be exploited productively for the preclinical pharmacokinetic evaluation of therapeutic antibodies.
Taxol-based combination chemotherapy and other in vivo preclinical antitumor studies. (1993)

Taxol, dissolved in cremophor/ethanol (50/50), followed by further dilution with saline, was successfully administered intravenously (IV) to mice bearing subcutaneously (SC) implanted murine Madison 109 lung carcinoma (M109), M5076 sarcoma, or seven different human tumor xenografts, including A431 vulva; A2780 ovarian; LX-1, H2981, and L2987 lung; and RCA and HCT-116 colon carcinomas. Taxol was active in all these distal site tumor models except the M5076 sarcoma. Schedule dependency and dose-response evaluations involving Taxol were studied in the SC M109 model. Taxol was given IV, and all treatments were of 7 days' duration. Each schedule was evaluated using several dose levels designed to incorporate the likely optimal (and maximum tolerated) dose(s). On the best schedule, daily injections for 7 days, Taxol exhibited a flat dose response; that is, good activity was obtained at Taxol dose levels that were only a fraction of its maximum tolerated dose. This profile provided an advantageous opportunity to evaluate Taxol-based combination chemotherapy. In a format in which Taxol was given every day on days 1 through 5, IV, and other drugs were given on days 1 and 5 (IV or intraperitoneally, IP) versus SC M109, dose titrations of each agent were evaluated singularly and in various Taxol-based combinations. The combination of Taxol plus cisplatin yielded a delay in tumor growth (17.8 days) that was minimally superior (P < .05) to the best delays caused by either drug alone (e.g., 13.5 days for Taxol); there was no enhancement of lifespan beyond that obtained using Taxol alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Orexin receptor agonist Yan 7874 is a weak agonist of orexin/hypocretin receptors and shows orexin receptor-independent cytotoxicity (2017)

Two promising lead structures of small molecular orexin receptor agonist have been reported, but without detailed analyses of the pharmacological properties. One of them, 1-(3,4-dichlorophenyl)-2-[2-imino-3-(4-methylbenzyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl]ethan-1-ol (Yan 7874), is commercially available, and we set out to analyze its properties. As test system we utilized human OX1 and OX2 orexin receptor-expressing Chinese hamster ovary (CHO) K1 cells as well as control CHO-K1 and neuro-2a neuroblastoma cells. Gq-coupling was assessed by measurement of intracellular Ca2+ and phospholipase C activity, and the coupling to Gi and Gs by adenylyl cyclase inhibition and stimulation, respectively. At concentrations above 1 μM, strong Ca2+ and low phospholipase C responses to Yan 7874 were observed in both OX1- and OX2-expressing cells. However, a major fraction of the response was not mediated by orexin receptors, as determined utilizing the non-selective orexin receptor antagonist N-biphenyl-2-yl-1-{[(1-methyl-1H-benzimidazol-2-yl)sulfanyl]acetyl}-L-prolinamide (TCS 1102) as well as control CHO-K1 cells. Yan 7874 did not produce any specific adenylyl cyclase response. Some experiments suggested an effect on cell viability by Yan 7874, and we thus analyzed this. Within a few hours of exposure, Yan 7874 markedly changed cell morphology (shrunken, rich in vacuoles), reduced growth, promoted cell detachment, and induced necrotic cell death. The effect was equal in cells expressing orexin receptors or not. Thus, Yan 7874 is a weak partial agonist of orexin receptors. It also displays strong off-target effects in the same concentration range, culminating in necrotic cell demise. This makes Yan 7874 unsuitable as orexin receptor agonist.