gebhart/patrepeval huggingface dataset:
Globally Adaptive Load-Balanced Routing on Tori (2004)

We introduce a new method of adaptive routing on k-ary n-cubes, Globally Adaptive Load-Balance (GAL). GAL makes global routing decisions using global information. In contrast, most previous adaptive routing algorithms make local routing decisions using local information (typically channel queue depth). GAL senses global congestion using segmented injection queues to decide the directions to route in each dimension. It further load balances the network by routing in the selected directions adaptively. Using global information, GAL achieves the performance (latency and throughput) of minimal adaptive routing on benign traffic patterns and performs as well as the best obliviously load-balanced routing algorithm (GOAL) on adversarial traffic.
Expression status of BCL-6 and syndecan-1 identifies distinct histogenetic subtypes of Hodgkin's disease. (1998)

The tumor cells in most cases of Hodgkin's disease (HD) have been recently recognized to originate from the B-cell lineage, but their precise differentiation stage is not fully clarified. Recently, we have reported that the histogenesis of B-cell lymphomas may be assessed by monitoring the expression pattern of BCL-6, a transcription factor expressed in germinal center (GC) B cells, and CD138/syndecan-1 (syn-1), a proteoglycan associated with post-GC, terminal B-cell differentiation. In this study, we have applied these two markers to the study of HD histogenesis. We have found that in nodular lymphocyte predominance HD (NLPHD) tumor cells consistently display the BCL-6(+)/syn-1(-) phenotype, indicating their derivation from GC B cells. Conversely, classic HD (CHD) is heterogeneous because the tumor cells of a fraction of CHD display the BCL-6(-)/syn-1(+) phenotype of post-GC B-cells, whereas another fraction of CHD is constituted by a mixture of tumor cells reflecting the GC (BCL-6(+)/syn-1(-)) or post-GC (BCL-6(-)/syn-1(+)) phenotypes. BCL-6(-)/syn-1(+) tumor cells of CHD are mostly found surrounded by T cells expressing CD40L, consistent with the observation that CD40 signaling downregulates BCL-6 expression. These data indicate that tumor cells of NLPHD uniformly display a GC B-cell phenotype, whereas the phenotype of tumor cells of CHD appears to be modulated by the surrounding cellular background, particularly CD40L+ reactive T cells.
Tau Clearance Mechanisms and Their Possible Role in the Pathogenesis of Alzheimer Disease (2013)

One of the defining pathological features of Alzheimer disease (AD) is the intraneuronal accumulation of tau. The tau that forms these accumulations is altered both posttranslationally and conformationally, and there is now significant evidence that soluble forms of these modified tau species are the toxic entities rather than the insoluble neurofibrillary tangles. However there is still noteworthy debate concerning which specific pathological forms of tau are the contributors to neuronal dysfunction and death in AD. Given that increases in aberrant forms of tau play a role in the neurodegeneration process in AD, there is growing interest in understanding the degradative pathways that remove tau from the cell, and the selectivity of these different pathways for various forms of tau. Indeed, one can speculate that deficits in a pathway that selectively removes certain pathological forms of tau could play a pivotal role in AD. In this review we will discuss the different proteolytic and degradative machineries that may be involved in removing tau from the cell. How deficits in these different degradative pathways may contribute to abnormal accumulation of tau in AD will also be considered. In addition, the issue of the selective targeting of specific tau species to a given degradative pathway for clearance from the cell will be addressed.
Statistical threshold-voltage variation and its impact on supply-voltage scaling (1995)

A fundamental limit to the scaling of CMOS supply voltages (V<SUB>CC</SUB>) exists due to the statistical variation of MOSFET threshold voltage (V<SUB>T</SUB>). At the microscopic (device-to-device) level, an inherent variability in V<SUB>T</SUB> exists due to the randomness of the number of dopants in the depletion region of the MOSFET. As the number of dopants in the depletion region decreases with scaling, the V<SUB>T</SUB> variations will increase and become more significant. In addition to this fundamental variation in V<SUB>T</SUB>, systematic V<SUB>T</SUB> variations exist due to manufacturing fluctuations with the gate length, gate oxide thickness, implant uniformity, and anneal temperatures. For SRAM circuits, the V<SUB>T</SUB> mismatch caused by channel dopant fluctuations degrades the cell stability and limits the minimum operating voltage of the SRAM. For logic circuits, the systematic V<SUB>T</SUB> variations across a waver significantly increase the variation of the measured propagation delay on a wafer as V<SUB>CC</SUB> is scaled down towards the MOSFET V<SUB>T</SUB>. These limitations on V<SUB>CC</SUB> scaling pose additional challenges in the design and manufacturing of devices and circuits for low-power systems.
Decision Forests: A Unified Framework for Classification, Regression, Density Estimation, Manifold Learning and Semi-Supervised Learning (2012)

This review presents a unified, efficient model of random decision forests which can be applied to a number of machine learning, computer vision, and medical image analysis tasks. Our model extends existing forest-based techniques as it unifies classification, regression, density estimation, manifold learning, semisupervised learning, and active learning under the same decision forest framework. This gives us the opportunity to write and optimize the core implementation only once, with application to many diverse tasks. The proposed model may be used both in a discriminative or generative way and may be applied to discrete or continuous, labeled or unlabeled data. The main contributions of this review are: (1) Proposing a unified, probabilistic and efficient model for a variety of learning tasks; (2) Demonstrating margin-maximizing properties of classification forests; (3) Discussing probabilistic regression forests in comparison with other nonlinear regression algorithms; (4) Introducing density forests for estimating probability density functions; (5) Proposing an efficient algorithm for sampling from a density forest; (6) Introducing manifold forests for nonlinear dimensionality reduction; (7) Proposing new algorithms for transductive learning and active learning. Finally, we discuss how alternatives such as random ferns and extremely randomized trees stem from our more general forest model. This document is directed at both students who wish to learn the basics of decision forests, as well as researchers interested in the new contributions. It presents both fundamental and novel concepts in a structured way, with many illustrative examples and real-world applications. Thorough comparisons with state-of-the-art algorithms such as support vector machines, boosting and Gaussian processes are presented and relative advantages and disadvantages discussed. The many synthetic examples and existing commercial applications demonstrate the validity of the proposed model and its flexibility.
Cornexistin: A new fungal metabolite with herbicidal activity. (1991)

Cornexistin, a new compound demonstrating promising herbicidal activity, was purified from the culture filtrate of a newly-isolated fungus identified as Paecilomyces variotii SANK 21086. The compound was extracted with organic solvents from the culture filtrate, purified using column chromatography on Sephadex LH-20 and finally crystallized from methylene chloride. Following analysis of its physico-chemical properties it was identified to be a new compound belonging to the nonadride group. Chemical structure elucidation was conducted by analyses of various spectral data and the structure was finally confirmed by means of X-ray crystallographic analysis. Based on its herbicidal characteristics cornexistin may be classified as a postemergence herbicide active against certain young annual and perennial monocotyledonous and dicotyledonous plants with selective protection for corn.
Covalent and noncovalent DNA binding by mutants of vaccinia DNA topoisomerase I. (1992)

Analysis of vaccinia topoisomerase mutants that are impaired in DNA relaxation has allowed the identification of amino acid residues required for the transesterification step of catalysis. Missense mutations of wild-type residues Gly-132----Asp and Arg-223----Gln rendered the protein inert in formation of the covalent enzyme-DNA complex and hence completely inactive in DNA relaxation. Mutations of Thr-147----Ile and Gly-132----Ser caused severe defects in covalent adduct formation that correlated with the extent of inhibition of relaxation. None of these point mutations had an effect on noncovalent DNA binding sufficient to account for the defect in relaxation. Deletion of amino- or carboxyl-terminal portions of the polypeptide abrogated noncovalent DNA binding. Two distinct topoisomerase-DNA complexes were resolved by native gel electrophoresis. One complex, which was unique to those proteins competent in covalent adduct formation, contained topoisomerase bound to the 5'-portion of the incised DNA strand. The 3'-segment of the cleaved strand had dissociated spontaneously. This complex was isolated and shown to catalyze transfer of the covalently bound DNA to a heterologous acceptor oligonucleotide, thereby proving that the covalent adduct between protein and duplex DNA is a true intermediate in strand breakage and reunion. The role of the active site region of eukaryotic topoisomerase in determining sensitivity or resistance to camptothecin was examined by converting the active site region of the resistant vaccinia enzyme (SKRAY274) to that of the drug-sensitive yeast enzyme (SKINY). The SKINY mutation did not alter the resistance of the vaccinia enzyme to the cleavage-enhancing effects of camptothecin.
Monoclonal antibodies to estrophilin: probes for the study of estrogen receptors. (1980)

Splenic lymphocytes from a Lewis rat, immunized with purified estradiol-receptor complex of calf uterine nuclei, were fused with cells of three different mouse myeloma lines (P3-X63-Ag8, P3-NSI/I-Ag4-1, and Sp2/0-Ag14) to yield hybridoma cultures, 9% of which produced antibodies to the receptor protein (estrophilin). When cloned by limiting dilution, approximately 70% of the viable cultures secreted antiestrophilin antibody. When expanded in suspension culture, three clones derived from Sp2/0-Ag14 were found to secrete rat IgG (gamma 2a class), whereas seven other clones (from all three myeloma lines) secreted IgM. Monoclonal IgG shows comparable affinity for nuclear and extranuclear receptors, whereas IgM reacts preferentially with the nuclear form. Both classes of antibody react with unoccupied as well as with occupied receptor and do not interfere with its ability to bind to estradiol. By growing IgG-secreting clones in the presence of [35S]methionine, radiolabeled monoclonal antiestrophilin has been prepared. Unlike antiestrophilin antibody previously generated in the rabbit or the goat, which crossreacts with estrogen receptors from every animal species tested, antibodies produced by the Lewis rat and by hybridomas derived from its spleen cells react specifically with estrophilin from calf tissues. These monoclonal antibodies provide reagents for the application of immunochemical techniques to study estrogen receptors in calf target tissues.
Adult Hippocampal Neurogenesis, Synaptic Plasticity and Memory: Facts and Hypotheses (2007)

The demonstration that progenitor cells in regions of the adult mammalian brain such as the dentate gyrus of the hippocampus can undergo mitosis and generate new cells that differentiate into functionally integrated neurons throughout life has marked a new era in neuroscience. In recent years, a wide range of investigations has been directed at understanding the physiological mechanisms and functional relevance of this form of brain plasticity. Our current knowledge of adult hippocampal neurogenesis indicates that the production of new cells in the brain follows a multi-step process during which newborn cells are submitted to various regulatory factors that influence cell proliferation, maturation, fate determination and survival. As details of the dynamics of morphological maturation and functional integration of newborn neurons in corticohippocampal circuits have become clearer, an increasing number of studies have examined how environmental and/or behavioural factors can modulate neurogenesis and affect hippocampal-dependent learning and memory. In this article we present an overview of recent literature that relates neurogenesis to hippocampal function on the basis of correlative studies investigating the modulation of neurogenesis by learning and behavioural experience, and the consequences of the loss of hippocampal neurogenesis for memory function. We also highlight experimental evidence that immature neurons exhibit unique electrophysiological characteristics and therefore may constitute a specific cell population particularly inclined to undergo activity-dependent plasticity. Moreover, we review recent work that reveals an unsuspected mechanistic link between synaptic plasticity and the proliferation and survival of new hippocampal neurons. From the present background of research, we argue that the incorporation of functional adult-generated neurons into existing neural networks provides a higher capacity for plasticity, which may favour the encoding and storage of certain types of memories. Depending on their birth date and maturation stage, new neurons might be implicated in the encoding/storage process of the task at hand or may help future learning experience. Finally, we highlight critical issues to be addressed in order to decipher the exact contribution of newly generated neurons to cognitive functions.
Protein‐protein interactions as a target for drugs in proteomics (2003)

Protein-protein interactions play a central role in numerous processes in the cell and are one of the main fields of functional proteomics. This review highlights the methods of bioinformatics and functional proteomics of protein-protein interaction investigation. The structures and properties of contact surfaces, forces involved in protein-protein interactions, kinetic and thermodynamic parameters of these reactions were considered. The properties of protein contact surfaces depend on their functions. The contact surfaces of permanent complexes resemble domain contacts or the protein core and it is reasonable to consider such complex formation as a continuation of protein folding. Characteristics of contact surfaces of temporary protein complexes share some similarities with active sites of enzymes. The contact surfaces of the temporary protein complexes have unique structure and properties and they are more conservative in comparison with active site of enzymes. So they represent prospective targets for a new generation of drugs. During the last decade, numerous investigations were undertaken to find or design small molecules that block protein dimerization or protein(peptide)-receptor interaction, or, on the contrary, to induce protein dimerization.
Development of ammonia adsorption filter and its application to lsi manufacturing environment. (1995)

Activated carbon treated with a hydrogen salt is found to be effective in lowering ammonia concentration in LSI cleanrooms. Carbon block with a honeycomb structure and low pressure loss is utilized. The hydrogen salt contains neither phosphor nor metals. Its ammonia adsorption capacity is about 1000mol/m3 -carbon, This provides a lifetime of around two years in ordinary cleanrooms. A chemically amplified resist, known to be easily degraded by trace alkaline gases, is proved to maintain 0, 25-μm line and space patterns under hydrogen salt treated carbon filtered air, even when the patterns are developed 60 minutes after excimer laser exposure.
Comparison of two next-generation sequencing technologies for resolving highly complex microbiota composition using tandem variable 16S rRNA gene regions (2010)

High-throughput molecular technologies can profile microbial communities at high resolution even in complex environments like the intestinal microbiota. Recent improvements in next-generation sequencing technologies allow for even finer resolution. We compared phylogenetic profiling of both longer (454 Titanium) sequence reads with shorter, but more numerous, paired-end reads (Illumina). For both approaches, we targeted six tandem combinations of 16S rRNA gene variable regions, in microbial DNA extracted from a human faecal sample, in order to investigate their limitations and potentials. In silico evaluations predicted that the V3/V4 and V4/V5 regions would provide the highest classification accuracies for both technologies. However, experimental sequencing of the V3/V4 region revealed significant amplification bias compared to the other regions, emphasising the necessity for experimental validation of primer pairs. The latest developments of 454 and Illumina technologies offered higher resolution compared to their previous versions, and showed relative consistency with each other. However, the majority of the Illumina reads could not be classified down to genus level due to their shorter length and higher error rates beyond 60 nt. Nonetheless, with improved quality and longer reads, the far greater coverage of Illumina promises unparalleled insights into highly diverse and complex environments such as the human gut.
Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome (2018)

This study provides Class I evidence that for children with Dravet syndrome, CBD resulted in more AEs than placebo but was generally well-tolerated.
Fusion-active glycoprotein G mediates the cytotoxicity of vesicular stomatitis virus M mutants lacking host shut-off activity (2010)

The cytopathogenicity of vesicular stomatitis virus (VSV) has been attributed mainly to the host shut-off activity of the viral matrix (M) protein, which inhibits both nuclear transcription and nucleocytoplasmic RNA transport, thereby effectively suppressing the synthesis of type I interferon (IFN). The M protein from persistently VSV-infected cells was shown to harbour characteristic amino acid substitutions (M51R, V221F and S226R) implicated in IFN induction. This study demonstrates that infection of human fibroblasts with recombinant VSV containing the M51R substitution resulted in IFN induction, whereas neither the V221F nor the S226R substitution effected an IFN-inducing phenotype. Only when V221F was combined with S226R were the host shut-off activity of the M protein abolished and IFN induced, independently of M51R. The M33A substitution, previously implicated in VSV cytotoxicity, did not affect host shut-off activity. M-mutant VSV containing all four amino acid substitutions retained cytotoxic properties in both Vero cells and IFN-competent primary fibroblasts. Infected-cell death was associated with the formation of giant polynucleated cells, suggesting that the fusion activity of the VSV G protein was involved. Accordingly, M-mutant VSV expressing a fusion-defective G protein or with a deletion of the G gene showed significantly reduced cytotoxic properties and caused long-lasting infections in Vero cells and mouse hippocampal slice cultures. In contrast, a G-deleted VSV expressing wild-type M protein remained cytotoxic. These findings indicate that the host shut-off activity of the M protein dominates VSV cytotoxicty, whilst the fusion-active G protein is mainly responsible for the cytotoxicity remaining with M-mutant VSV.
Assessment of oral toxicity and safety of 9-cis-UAB30, a potential chemopreventive agent, in rat and dog studies (2011)

9-cis-UAB30 is a potential chemopreventative agent that has been shown to be effective on many different types of tumors. The safety and toxicity of 9-cis-UAB30 had not been previously established. These studies were conducted to evaluate the potential toxicity and pharmacokinetics in a rodent and a nonrodent species for the purpose of investigational new drug submission. Oral gavage administration of 9-cis-UAB30 at the doses 0, 3, 15, and 100 mg/kg/day to CD® rats for 28 days showed a dose-dependent (although not dose-proportional) increase in plasma drug levels in week 4. The liver was the target organ for toxicity of 9-cis-UAB30. Hepatomegaly along with increases in serum aspartate-aminotransferase and alkaline-phosphatase levels were seen in rats. Moderate hypoalbuminemia and hyperglobulinemia resulted in a decreased albumin/globulin ratio. Histopathology revealed hepatocellular change consistent with hepatic glycogen deposition. Toxicity studies in dogs did not show treatment-related toxicity at doses as high as 100 mg/kg/day (highest dose tested) administered by capsules for 28 days. No effects on the central nervous system (functional observational battery in rats) or cardiovascular function (safety pharmacology study in telemeterized dogs) were seen. The no observed adverse effect level (NOAEL) in the rat studies was 3 mg/kg/day; however, the adverse effects seen in rats receiving 15 mg/kg/day (the least observed adverse effect level) was a slight, but statistically significant, elevation in fibrinogen and decrease in prothrombin time, which may be a sign of some tendency for increased blood coagulation. The NOAEL in the dog study was at least 100 mg/kg/day.
GaInAsSb-AlGaAsSb tapered lasers emitting at 2 mu m (1993)

Tapered oscillators fabricated from GaInAsSb-AlGaAsSb quantum-well structure are reported for the first time. The quantum-well laser structure, grown by molecular beam epitaxy, has broad-stripe pulsed threshold current densities as low as 330 A/cm/sup 2/ at room temperature. One tapered laser emitting at 2.02 mu m has exhibited continuous wave (CW) output power up to 750 mW, with power in the near-diffraction-limited central lobe as high as 200 mW.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis (2000)

The ubiquitously expressed family of ID helix-loop-helix (HLH) proteins function as dominant negative regulators of basic HLH (bHLH) transcriptional regulators that drive cell lineage commitment and differentiation in metazoa. Recent data from cell line and in vivo studies have implicated the functions of ID proteins in other cellular processes besides negative regulation of cell differentiation. ID proteins play key roles in the regulation of lineage commitment, cell fate decisions and in the timing of differentiation during neurogenesis, lymphopoiesis and neovascularisation (angiogenesis). They are essential for embryogenesis and for cell cycle progression, and they function as positive regulators of cell proliferation. ID proteins also possess pro-apoptotic properties in a variety of cell types and function as cooperating or dominant oncoproteins in immortalisation of rodent and human cells and in tumour induction in Id-transgenic mice. In several human tumour types, the expression of ID proteins is deregulated, and loss- and gain-of-function studies implicate ID functions in the regulation of tumour growth, vascularisation, invasiveness and metastasis. More recent biochemical studies have also revealed an emerging 'molecular promiscuity' of mammalian ID proteins: they directly interact with and modulate the activities of several other families of transcriptional regulator, besides bHLH proteins.