gebhart/patrepeval huggingface dataset:
Metabolic Fate of Glucose in Purified Islet Cells (1997)

Previous studies in rat islets have suggested that anaplerosis plays an important role in the regulation of pancreatic beta cell function and growth. However, the relative contribution of islet beta cells versus non-beta cells to glucose-regulated anaplerosis is not known. Furthermore, the fate of glucose carbon entering the Krebs cycle of islet cells remains to be determined. The present study has examined the anaplerosis of glucose carbon in purified rat beta cells using specific 14C-labeled glucose tracers. Between 5 and 20 mM glucose, the oxidative production of CO2 from [3,4-14C]glucose represented close to 100% of the total glucose utilization by the cells. Anaplerosis, quantified as the difference between 14CO2 production from [3,4-14C]glucose and [6-14C]glucose, was strongly influenced by glucose, particularly between 5 and 10 mM. The dose dependence of glucose-induced insulin secretion correlated with the accumulation of citrate and malate in beta(INS-1) cells. All glucose carbon that was not oxidized to CO2 was recovered from the cells after extraction in trichloroacetic acid. This indirectly indicates that lactate output is minimal in beta cells. From the effect of cycloheximide upon the incorporation of 14C-glucose into the acid-precipitable fraction, it could be calculated that 25% of glucose carbon entering the Krebs cycle via anaplerosis is channeled into protein synthesis. In contrast, non-beta cells (approximately 80% glucagon-producing alpha cells) exhibited rates of glucose oxidation that were (1)/(3) to (1)/(6) those of the total glucose utilization and no detectable anaplerosis from glucose carbon. This difference between the two cell types was associated with a 7-fold higher expression of the anaplerotic enzyme pyruvate carboxylase in beta cells, as well as a 4-fold lower ratio of lactate dehydrogenase to FAD-linked glycerol phosphate dehydrogenase in beta cells versus alpha cells. Finally, glucose caused a dose-dependent suppression of the activity of the pentose phosphate pathway in beta cells. In conclusion, rat beta cells metabolize glucose essentially via aerobic glycolysis, whereas glycolysis in alpha cells is largely anaerobic. The results support the view that anaplerosis is an essential pathway implicated in beta cell activation by glucose.
FACETS: allele-specific copy number and clonal heterogeneity analysis tool for high-throughput DNA sequencing (2016)

Allele-specific copy number analysis (ASCN) from next generation sequencing (NGS) data can greatly extend the utility of NGS beyond the identification of mutations to precisely annotate the genome for the detection of homozygous/heterozygous deletions, copy-neutral loss-of-heterozygosity (LOH), allele-specific gains/amplifications. In addition, as targeted gene panels are increasingly used in clinical sequencing studies for the detection of 'actionable' mutations and copy number alterations to guide treatment decisions, accurate, tumor purity-, ploidy- and clonal heterogeneity-adjusted integer copy number calls are greatly needed to more reliably interpret NGS-based cancer gene copy number data in the context of clinical sequencing. We developed FACETS, an ASCN tool and open-source software with a broad application to whole genome, whole-exome, as well as targeted panel sequencing platforms. It is a fully integrated stand-alone pipeline that includes sequencing BAM file post-processing, joint segmentation of total- and allele-specific read counts, and integer copy number calls corrected for tumor purity, ploidy and clonal heterogeneity, with comprehensive output and integrated visualization. We demonstrate the application of FACETS using The Cancer Genome Atlas (TCGA) whole-exome sequencing of lung adenocarcinoma samples. We also demonstrate its application to a clinical sequencing platform based on a targeted gene panel.
Synthetic peptides containing T and B cell epitopes from human immunodeficiency virus envelope gp120 induce anti-HIV proliferative responses and high titers of neutralizing antibodies in rhesus monkeys. (1990)

We have previously described a synthetic peptide (T1-SP10) derived from two noncontiguous regions of HTLVIIIB envelope gp120 (T1, amino acids 428-443; SP10, amino acids 303-321) that induced type-specific anti-HIV neutralizing antibodies and T cell proliferative responses against native HIV gp120 when used as a carrier-free immunogen in goats. In this study, HTLVIIIB T1-SP10 synthetic peptides were used to immunize rhesus monkeys to determine if the peptides were capable of eliciting HIV-specific neutralizing antibody and proliferative responses in primates. Four compounds (alum, polyA:polyU, threonyl-muramyldipeptide (MDP) and IFA) were also compared for efficacy as adjuvants in this system. Rhesus monkeys immunized with T1-SP10 peptides generated high titers of antibodies against the immunogens and also against HTLVIIIB gp120. Sera from all four animals given T1-SP10 in IFA or threonyl-MDP neutralized infection by HTLVIIIB and blocked virus-dependent cell fusion events. A peak neutralization titer of 1:940 was seen in one animal given IFA (19600) and a titer of 1:900 was seen in one of the monkeys (17371) given threonyl-MDP. Proliferative responses of immune rhesus PBMC to T1-SP10 appeared after the first injection. After eight immunizations, two of eight monkeys (one injected with peptides in threonyl-MDP and one given peptides in IFA) had PBMC proliferative responses to native HTLVIIIB gp120. These data demonstrate that the carrier-free T1-SP10 synthetic peptide construct can induce high titers of neutralizing anti-HIV antibody responses and PBMC proliferative responses to HIV in primates.
Pharmacokinetic Interaction of Zonisamide in Rats. Effect of Other Antiepileptics on Zonisamide. (1992)

The pharmacokinetics of zonisamide (ZNS) and the effects of phenobarbital (PB), valproic acid (VPA), carbamazepine (CBZ) and phenytoin (PHT) on ZNS kinetics were investigated in rats. The effects of other antiepileptics on the serum protein binding, erythrocyte distribution and metabolism of ZNS were also studied in vitro to elucidate the mechanism of pharmacokinetic interaction of ZNS. ZNS showed a linear disposition kinetics after oral administration of ZNS within the dose examined. Moreover, the pharmacokinetic behaviors of ZNS were not altered after multiple dosing. The decreased t1/2 value of ZNS by PB or CBZ pretreatment and the increased Vd/F value of ZNS by VPA pretreatment were observed, although it showed no marked effect of PHT on ZNS kinetics. The enhanced metabolism of ZNS was observed by PB or CBZ pretreatment from an in vitro metabolism study. The serum protein binding and erythrocyte distribution of ZNS showed no significant change in the presence of other antiepileptics in vitro. These results indicate that the decreased t1/2 value of ZNS is attributable to the enzyme inducing effect of PB or CBZ, and that neither protein binding nor erythrocyte distribution of ZNS could be the reason for the increased Vd/F value of ZNS by VPA coadministration.
Intelligent Guidance for Headway and Lane Control (1989)

The principal objective of this study is to define techniques for using graphical imagery alone as guidance information for automotive headway and lane control. The goal is to accelerate, steer, and brake an automobile at normal speeds on both limited-access and conventional highways, including entry/exit ramps, multiple-lane roads, and undivided highways, and accounting for mixed traffic, road signs, traffic signals, and unexpected emergencies. It is expected that a system capable of performing these tasks would consist of one or more television cameras, pattern-recognition logic implemented in digital signal processing chips, a rule-based expert system for guidance and control, conventional motion sensors, and actuators for steering, braking, and throttle control.
Service Discovery and Service Access in Wireless Vehicular Networks (2008)

Robust and reliable service architectures must be designed to guarantee the success of future vehicular networks. This paper addresses service provisioning elements such as communication service models, service discovery and service access intended for vehicular environments. We propose a secure service access architecture based on the concept of district domains which are entities responsible for dispatching session parameters to on-demand users. The service architecture comprises the presence of public and private certificate authorities, session managers, policy entities, accounting and banking modules. The purpose of this architecture is to facilitate the delivery of secured information services offered at the roadside infrastructure.
HLA‐G and immune tolerance in pregnancy (2005)

Multiple mechanisms underlie the surprising willingness of mothers to tolerate genetically different fetal tissues during pregnancy. Chief among these is the choice of HLA-G, a gene with few alleles, rather than the highly polymorphic HLA-A and -B genes, for expression by the placental cells that interface directly with maternal blood and tissues. Novel aspects of this major histocompatibility complex class Ib gene include alternative splicing to permit production of membrane and soluble isoforms, deletions that dampen responses to interferons, and a shortened cytoplasmic tail that affects expression at the cell surface. Placental cells migrating into the maternal uterus synthesize both membrane and soluble isoforms, which interact with inhibitory receptors on leukocytes such as ILT2 and ILT4. Cytotoxic T lymphocytes either die or reduce production of one of their major coreceptor/activator cell surface molecules, CD8; natural killer cells are immobilized and mononuclear phagocytes are programmed into suppressive modes characterized by high production of anti-inflammatory cytokines. The idea that placental HLA-G proteins facilitate semiallogeneic pregnancy by inhibiting maternal immune responses to foreign (paternal) antigens via these actions on immune cells is now well established, and the postulate that the recombinant counterparts of these proteins may be used as powerful tools for preventing immune rejection of transplanted organs is gaining in popularity.
Preservation of Peripheral Nerve Grafts: A Comparison of Normal Saline, Htk Organ Preservation Solution, and Dmem Schwann Cell Culture Medium (1995)

The regeneration of peripheral nerve grafts was evaluated in a rat model, after pretreating the grafts with Schwann cell culture medium, HTK organ preservation solution, and normal saline, under cold ischemic conditions for different time periods. Following orthotopic replantation of the grafts into donor animals, the quality of regeneration was assessed after 6 weeks, compared to positive controls (autologous transplantation) and negative controls (acellular grafts). The regenerative quality in the Schwann cell culture groups with ischemic periods of 32 and 72 hr was comparable to normal controls. Significantly minor regeneration was detected in specimens undergoing 14 and 120 hr of ischemia in the Schwann cell culture medium and in the HTK and normal saline groups, regardless of ischemic time. Among the conclusions was that controlled proliferation of Schwann cells seems to be a basic principle for preservation of peripheral nerve grafts.
[Neurohistological findings in the parietal cortex of children with chromosome aberrations]. (1992)

In Golgi-Cox impregnated parietal cortex (regio postcentralis) of two children (20 months of age or 6 years of age) with Down's syndrome the pyramidal neurons of lamina III and V were investigated qualitatively and quantitatively. Fives types of pyramidal neurons were classified and compared statistically. As parameters for characterizing pyramidal neurons served dendritic lengths for all dendritic orders, within single dendritic fields, in apical and basal parts of the dendritic tree, and of the whole neuron. Normal values obtained in brains of the same age were not available, therefore, we compared our results with those published by other authors. To study the developmental stage of the pyramidal neurons in both our cases, we compared analogue pyramid types in both brains. The pyramidal neurons showed different qualitative abnormalities in their dendritic tree configuration. The comparison of quantitative parameters suggests the pyramidal cells of the older child show more degenerative changes, concerning especially lamina III pyramids but in lamina V pyramids as well. These changes might be structural correlates of the mental retardation: the 6 year old child was strongly retarded in clinical symptoms, too. The results are discussed and critically evaluated in view of the clinical signs of Morbus Down. Finally we should await the investigations of more cases for demonstrating the normal as well as the abnormal development of the human cerebral cortex.
Mixotrophs combine resource use to outcompete specialists: Implications for aquatic food webs (2003)

The majority of organisms can be grouped into those relying solely on photosynthesis (phototrophy) or those relying solely on the assimilation of organic substances (heterotrophy) to meet their requirements for energy and carbon. However, a special life history trait exists in which organisms combine both phototrophy and heterotrophy. Such "mixotrophy" is a widespread phenomenon in aquatic habitats and is observed in many protozoan and metazoan organisms. The strategy requires investment in both photosynthetic and heterotrophic cellular apparatus, and the benefits must outweigh these costs. In accordance with mechanistic resource competition theory, laboratory experiments revealed that pigmented mixotrophs combined light, mineral nutrients, and prey as substitutable resources. Thereby, they reduced prey abundance below the critical food concentration of competing specialist grazers [Rothhaupt, K. O. (1996) Ecology 77, 716-724]. Here, we demonstrate the important consequences of this strategy for an aquatic community. In the illuminated surface strata of a lake, mixotrophs reduced prey abundance steeply. The data suggest that, as a consequence, grazers from higher trophic levels, consuming both the mixotrophs and their prey, could not persist. Thus, the mixotrophs escaped from competition with and losses to higher grazers. Furthermore, the mixotrophs structured prey abundance along the vertical light gradient, creating low densities near the surface and a pronounced maximum of their algal prey at depth. Such deep algal accumulations are typical features of nutrient-poor aquatic habitats, previously explained by resource availability. We hypothesize instead that the mixotrophic grazing strategy is responsible for deep algal accumulations in many aquatic environments.
Minimum generation error training with direct log spectral distortion on LSPs for HMM-based speech synthesis (2008)

A minimum generation error (MGE) criterion had been proposed to solve the issues related to maximum likelihood (ML) based HMM training in HMM-based speech synthesis. In this paper, we improve the MGE criterion by imposing a log spectral distortion (LSD) instead of the Euclidean distance to define the generation error between the original and generated line spectral pair (LSP) coefficients. Moreover, we investigate the effect of different sampling strategies to calculate the integration of the LSD function. From the experimental results, using the LSDs calculated by sampling at LSPs achieved the best performance, and the quality of synthesized speech after the MGE-LSD training was improved over the original MGE training.
Comparison of Strategies for Sustaining Weight Loss<subtitle>The Weight Loss Maintenance Randomized Controlled Trial</subtitle> (2008)

clinicaltrials.gov Identifier: NCT00054925.
Biodistribution and radiation dosimetry of 18F-fluoro-A-85380 in healthy volunteers. (2003)

The amount of (18)F-fluoro-A-85380 required for adequate nAChR imaging results in an acceptable effective dose equivalent to the patient.
Ethanol Production by Thermophilic Bacteria: Fermentation of Cellulosic Substrates by Cocultures of Clostridium thermocellum and Clostridium thermohydrosulfuricum (1981)

The fermentation of various saccharides derived from cellulosic biomass to ethanol was examined in mono- and cocultures of Clostridium thermocellum strain LQRI and C. thermohydrosulfuricum strain 39E. C. thermohydrosulfuricum fermented glucose, cellobiose, and xylose, but not cellulose or xylan, and yielded ethanol/acetate ratios of >7.0. C. thermocellum fermented a variety of cellulosic substrates, glucose, and cellobiose, but not xylan or xylose, and yielded ethanol/acetate ratios of approximately 1.0. At nonlimiting cellulosic substrate concentrations ( approximately 1%), C. thermocellum cellulase hydrolysis products accumulated during monoculture fermentation of Solka Floc cellulose and included glucose, cellobiose, xylose, and xylobiose. A stable coculture that contained nearly equal numbers of C. thermocellum and C. thermohydrosulfuricum was established that fermented a variety of cellulosic substrates, and the ethanol yield observed was twofold higher than in C. thermocellum monoculture fermentations. The metabolic basis for the enhanced fermentation effectiveness of the coculture on Solka Floc cellulose included: the ability of C. thermocellum cellulase to hydrolyze alpha-cellulose and hemicellulose; the enhanced utilization of mono- and disaccharides by C. thermohydrosulfuricum; increased cellulose consumption; threefold increase in the ethanol production rate; and twofold decrease in the acetate production rate. The coculture actively fermented MN300 cellulose, Avicel, Solka Floc, SO(2)-treated wood, and steam-exploded wood. The highest ethanol yield obtained was 1.8 mol of ethanol per mol of anhydroglucose unit in MN300 cellulose.
Anti-CD20 Monoclonal Antibody (mAb) with Enhanced Affinity for CD16 Activates NK Cells at Lower Concentrations and More Effectively Than Rituximab ®. (2005)

Abstract Growing evidence indicates the affinity of mAb for CD16 (FcgRIII) plays a central role in the ability of the mAb to mediate anti-tumor activity. Both polymorphisms in CD16 and structure of mAb Fc can impact on the affinity between CD16 and mAb. Little is known about how affinity between mAb and CD16 impacts on the ability of mAb to activate NK cells. We evaluated how CD16 polymorphisms, and mAb with modified affinity for CD16, impact on NK cell phenotype and cytokine production. MAb consisted of R, anti-CD20 with enhanced affinity for CD20 (AME-133), and AME-133 with Fc engineered to have enhanced affinity for both CD20 and CD16 (Fc-eng-133). Peripheral blood mononuclear cells were obtained from normal subjects that were homozygous for high affinity CD16 (VV at position 158), homozygous low affinity (FF at 158), and heterozygotes and were mixed with mAb and Raji lymphoma cells at an effector:target ratio of 1:1. Higher concentrations of mAb were needed to induce CD16 modulation, CD54 upregulation, and IFNg production on NK cells from subjects with the lower affinity CD16 polymorphism. The dose of mAb needed to induce NK activation was lower with Fc-eng-133 irrespective of CD16 polymorphism. Measure of activation - % of NK cells CD54 bright: EC50 ng/ml (mean moAb concentration +/− SEM): N=4 per polymorphism R AME-133 Fc-eng-133 p&amp;lt;0.01 - R vs AME-133; R vs Fc-eng-133; AME-133 vs Fc-eng-133 for each polymorphism VV 6.2 +/− 1.0 3.9 +/− 0.5 1.0 +/− 0.3 VF 11.6 +/− 1.7 5.7 +/− 0.6 1.4 +/− 0.4 FF 29.9 +/− 10.6 11.5 +/− 2.5 2.8 +/− 0.3 p value VV vs FF &amp;lt;0.05 &amp;lt;0.05 &amp;lt;0.05 At saturating mAb concentrations, peak NK activation was greater for Fc engineered AME-133 when compared to R mAb for all samples studied Ratio of Fc-eng-133 to R % NK cells CD54 bright 1.35 +/− 0.07 IFNg production 2.64 +/− 0.43 These data indicate tumor cells coated with mAb with enhanced affinity for CD16 are more effective at activating NK cells at both low and saturating mAb concentrations irrespective of CD16 polymorphism, and provide further evidence for the clinical development of such mAb with the goal of improving clinical response to mAb.
Functional antagonists of sonic hedgehog reveal the importance of the N terminus for activity (1999)

During development, sonic hedgehog functions as a morphogen in both a short-range contact-dependent and in a long-range diffusable mode. Here, we show using a panel of sonic hedgehog variants that regions near the N terminus of the protein play a critical role in modulating these functions. In the hedgehog responsive cell line C3H10T1/2, we discovered that not only were some N-terminally truncated variants inactive at eliciting a hedgehog-dependent response, but they competed with the wild-type protein for function and therefore served as functional antagonists. These variants were indistinguishable from wild-type sonic hedgehog in their ability to bind the receptor patched-1, but failed to induce the hedgehog-responsive markers, Gli-1 and Ptc-1, and failed to promote hedgehog-dependent differentiation of the cell line. They also failed to support the adhesion of C3H10T1/2 cells to hedgehog-coated plates under conditions where wild-type sonic hedgehog supported binding. Structure-activity data indicated that the N-terminal cysteine plays a key regulatory role in modulating hedgehog activity. The ability to dissect patched-1 binding from signaling events in C3H10T1/2 cells suggests the presence of unidentified factors that contribute to hedgehog responses.
Formation of Uniform Aminosilane Thin Layers:  An Imine Formation To Measure Relative Surface Density of the Amine Group (1996)

The surface of a fused silica and oxidized silicon wafer (SiO2/Si(100)) was treated with (4-aminophenyl)trimethoxysilane (1), (3-aminopropyl)triethoxysilane (2), (3-aminopropyl)diethoxymethylsilane (3), and (3-aminopropyl)ethoxydimethylsilane (4) in solution. The thickness of thus formed aminosilane layers was determined with ellipsometry. In most cases silane coupling agents produce monolayers of 6−10 Å thickness, but reagent 2 gives multilayers with variable thickness (6−100 Å) depending upon the dipping time. The aminosilane layers were allowed to react with 4-nitrobenzaldehyde, and formation of the corresponding imines was confirmed by UV−vis spectroscopy. Relative surface density of the amines was calculated from the observed absorbance. In aqueous medium the imines were easily hydrolyzed to regenerate the amine group. The process, the formation, and the subsequent hydrolysis of the imines, can be repeated several times without any noticeable degradation of the absorption characteristics. The ellipsometric data and the measured absorbance show that 3 gives the most uniform molecular layer with the highest surface density of the amine functionality. Meanwhile, 2 provides multilayers lacking uniformity, and the other reagents produce uniform thin layers but with lower surface density of the amine.