gebhart/patrepeval huggingface dataset:
Ion Channel Stochasticity May Be Critical in Determining the Reliability and Precision of Spike Timing (1998)

The firing reliability and precision of an isopotential membrane patch consisting of a realistically large number of ion channels is investigated using a stochastic Hodgkin-Huxley (HH) model. In sharp contrast to the deterministic HH model, the biophysically inspired stochastic model reproduces qualitatively the different reliability and precision characteristics of spike firing in response to DC and fluctuating current input in neocortical neurons, as reported by Mainen & Sejnowski (1995). For DC inputs, spike timing is highly unreliable; the reliability and precision are significantly increased for fluctuating current input. This behavior is critically determined by the relatively small number of excitable channels that are opened near threshold for spike firing rather than by the total number of channels that exist in the membrane patch. Channel fluctuations, together with the inherent bistability in the HH equations, give rise to three additional experimentally observed phenomena: subthreshold oscillations in the membrane voltage for DC input, "spontaneous" spikes for subthreshold inputs, and "missing" spikes for suprathreshold inputs. We suggest that the noise inherent in the operation of ion channels enables neurons to act as "smart" encoders. Slowly varying, uncorrelated inputs are coded with low reliability and accuracy and, hence, the information about such inputs is encoded almost exclusively by the spike rate. On the other hand, correlated presynaptic activity produces sharp fluctuations in the input to the postsynaptic cell, which are then encoded with high reliability and accuracy. In this case, information about the input exists in the exact timing of the spikes. We conclude that channel stochasticity should be considered in realistic models of neurons.
Predictors of responses to immune checkpoint blockade in advanced melanoma (2017)

Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8<sup>+</sup> T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.
Correlation between the exposure of aromatic chromophores at the surface of the Fc domains of immunoglobulin G and their ability to bind complement (1977)

The recognition that certain biological effector functions associated with the Fc region of human IgG are mediated exclusively by either the Cgamma2 or Cgamma3 domains prompted a study of some of the physical properties of the isolated domains in an attempt to correlate these with functional differentiation. The degree of aromatic chromophore exposure of intact Fc and fragments corresponding to the Cgamma2 and Cgamma3 domains were determined by solvent perturbation difference spectroscopy using 20% ethylene glycol. For the monomeric Cgamma2 fragment one of the two tryptophans and all four of the tyrosines were exposed to solvent. In the pFc' fragment, which represented a dimer of two intact Cgamma3 domains, an average of 0.4 of the two tryptophans of 3.3 of the five tyrosines per chain were exposed. These data were consistent with the suggested involvement of tryptophan in complement fixation since Cgamma2 binds C1q but pFc' does not. Several fragments derived from the Cgamma3 region had previously been shown to have differing environments for their aromatic side chains from circular dichroism studies. These fragments have now been shown to exhibit different degrees of chromophore exposure to solvent. Removal of the carboxy-termimal heptapeptide from the intact, Cgamma3 domain resulted in a fragment not only showing a greater exposure of aromatic residues but also having the ability to bind Clq. Our data suggest that the structural requirements for C1Q binding may be quite commonplace within Fc, but tertiary folding limits their expression except in Cgamma2 in the native molecule. The solvent perturbation observed with Fc was somewhat lower than would have been expected from the results with the isolated domains, suggesting that interdomain interactions may result in burial of aromatic residues.
Canine susceptibility to human influenza viruses (A/pdm 09H1N1, A/H3N2 and B) (2014)

We investigated the infectivity and transmissibility of the human seasonal H3N2, pandemic (pdm) H1N1 (2009) and B influenza viruses in dogs. Dogs inoculated with human seasonal H3N2 and pdm H1N1 influenza viruses exhibited nasal shedding and were seroconverted against the viruses; this did not occur in the influenza B virus-inoculated dogs. Transmission of human H3N2 virus between dogs was demonstrated by observing nasal shedding and seroconversion in naïve dogs after contact with inoculated dogs. The seroprevalence study offered evidence of human H3N2 infection occurring in dogs since 2008. Furthermore, serological evidence of pdm H1N1 influenza virus infection alone and in combination with canine H3N2 virus was found in the serum samples collected from field dogs during 2010 and 2011. Our results suggest that dogs may be hosts for human seasonal H3N2 and pdm H1N1 influenza viruses.
The Sanger FASTQ file format for sequences with quality scores, and the Solexa/Illumina FASTQ variants (2009)

FASTQ has emerged as a common file format for sharing sequencing read data combining both the sequence and an associated per base quality score, despite lacking any formal definition to date, and existing in at least three incompatible variants. This article defines the FASTQ format, covering the original Sanger standard, the Solexa/Illumina variants and conversion between them, based on publicly available information such as the MAQ documentation and conventions recently agreed by the Open Bioinformatics Foundation projects Biopython, BioPerl, BioRuby, BioJava and EMBOSS. Being an open access publication, it is hoped that this description, with the example files provided as Supplementary Data, will serve in future as a reference for this important file format.
Relationship between P-glycoprotein expression and cyclosporin A in kidney. An immunohistological and cell culture study. (1995)

P-glycoprotein (P-gp), encoded in humans by the mdr-1 gene, acts physiologically as an efflux pump to expel hydrophobic substances from cells. This glycoprotein is closely related to multidrug resistance in tumor cells and can be modulated by cyclosporin A (CsA). We investigated the relationship between CsA and P-gp in 52 renal allograft biopsies and in cultures of Madin-Darby canine kidney (MDCK) renal tubule cells to determine whether the intrarenal accumulation of CsA or chronic stimulation with the drug modified the expression of P-gp. Expression of P-gp and CsA was analyzed by immunohistochemistry. Immunostaining was evaluated semiquantitatively. Modulation of P-gp in MDCK cells after chronic stimulation with CsA for 7, 30, and 60 days was analyzed by flow cytometry. P-gp and CsA immunostaining in renal post-transplant biopsies showed considerable overlap in all cases (Spearman's test, r = 0.577, P < 0.001). After 7 days in vitro, the number of cells expressing P-gp increased progressively; a further increase in mean fluorescence was found after 60 days (P < 0.001, Student's t-test). Our findings suggest that in non-neoplastic cells, CsA may stimulate P-gp as a mechanism of detoxification. Individual differences in the adaptive responses to glycoprotein may be responsible for the appearance of nephrotoxicity or a CsA-resistant rejection reaction in cases of overexpression on lymphocytes and macrophages.
Stepwise arteriovenous fate acquisition during mammalian vasculogenesis (2011)

Arteriovenous (AV) differentiation is a critical step during blood vessel formation and stabilization. Defects in arterial or venous fate lead to inappropriate fusion of vessels, resulting in damaging arteriovenous shunts. While many studies have unraveled the molecular underpinnings that drive AV fate, surprisingly, the spatiotemporal emergence of arteries and veins in mammalian embryos remains unknown. Here, we examine artery and vein specification and differentiation during vasculogenesis. We show that the first intraembryonic vessels formed are arteries, which differentiate in a stepwise manner. By contrast, veins emerge later, progressively forming after embryonic turning. In addition, we demonstrate that hemodynamic flow is not required for arterial specification, but is required for maintenance of select arterial markers. Together, our results provide a first spatiotemporal analysis of mammalian AV cell fate establishment and anatomy, as well as a delineation of a molecular toolkit for analysis of arteries and veins during early vessel development.
論《作死不離三兄弟》的烏托邦想像與意識形態 (2012)

二零零九年上映的印度電影《作死不離三兄弟》（下簡稱《作死》），自二零一一年九月在港上映以來，坊間一致好評，此電影上映至第十三周，票房已達一千九百萬；與此同時，《作死》在台灣也打破了上映時間最長紀錄；在中國內地方面，在此電影還未上映之前已在網絡上熱烈流傳，亦得到廣泛的正面評價。《作死》於二零一一年十二月在內地正式公映，贏盡票房和口碑，上映一月累積計票房已達一千三百萬元人民幣。雖然印度及中、港、台三地在文化傳統和經濟發展上有一定差別，但均面對相似的教育體制問題。該片如此廣受歡迎，在一定程度上說明該片在主題處理方面，成功接合了普遍的社會心理。\n法蘭克福學派批評文化工業蒙蔽大眾，電影被稱為「夢工廠」，尤其常被指責為意識形態的生產機器。不過，幻想永遠是妥協而生的產物，論者簡·蓋恩斯（Jane Gaines）引述弗雷德里克·詹姆遜（Fredric Jameson）的說法指出，大眾文化必須先提供些東西才能蒙蔽我們，假如缺乏了烏托邦功能，意識形態只能製造短暫的欺騙。本文將嘗試討論《作死》的烏托邦想像，分析該片所接合的社會現實及其超越社會現實的幻想，然後借鑒呂克·博爾坦斯基（Luc Boltanski） 對「新資本主義精神」的說法，檢視這種幻想與資本主義精神轉換的關係，從而說明該片的意識形態功能。
Genome sequence of Clostridium sporogenes DSM 795T, an amino acid-degrading, nontoxic surrogate of neurotoxin-producing Clostridium botulinum (2015)

Clostridium sporogenes DSM 795 is the type strain of the species Clostridium sporogenes, first described by Metchnikoff in 1908. It is a Gram-positive, rod-shaped, anaerobic bacterium isolated from human faeces and belongs to the proteolytic branch of clostridia. C. sporogenes attracts special interest because of its potential use in a bacterial therapy for certain cancer types. Genome sequencing and annotation revealed several gene clusters coding for proteins involved in anaerobic degradation of amino acids, such as glycine and betaine via Stickland reaction. Genome comparison showed that C. sporogenes is closely related to C. botulinum. The genome of C. sporogenes DSM 795 consists of a circular chromosome of 4.1 Mb with an overall GC content of 27.81 mol% harboring 3,744 protein-coding genes, and 80 RNAs.
Natriuretic Peptides Inhibit G Protein Activation (2000)

Atrial natriuretic peptide (ANP) inhibits the proliferation of many cells, in part through interfering with signal transduction enacted by G protein-coupled growth factor receptors. Signaling interactions between ANP and the G protein-coupled growth factor receptor ligand, endothelin-3 (ET-3), regulate astrocyte proliferation at a very proximal but undefined point. Here, we find that ANP inhibits the ability of ET-3 to activate Galpha(q) and Galpha(i) in these cells. ANP stimulated the translocation of endogenous regulators of G protein-signaling (RGS) proteins 3 and 4 from the cytosol to the cell membrane, and enhanced their association with Galpha(q) and Galpha(i). ANP effects were significantly blocked by HS-142-1, an inhibitor of guanylate cyclase activation, or by ET-3. KT5823, an inhibitor of cyclic GMP-dependent protein kinase (PKG) reversed the RGS translocation induced by ANP; conversely, expression of an active catalytic subunit of PKG-I, or 8-bromo-cyclic GMP stimulated RGS translocation. ANP caused the phosphorylation of both RGS proteins in a PKG-dependent fashion, and the expressed PKG (in the absence of ANP) also stimulated RGS phosphorylation. A novel cross-talk between PKG and RGS proteins is stimulated by ANP and leads to the increased translocation and association of RGS proteins with Galpha. The rapid inactivation of G proteins provides a mechanism by which ANP inhibits downstream signaling to the cell proliferation program.
Analysis of a denial of service attack on TCP (1997)

The paper analyzes a network based denial of service attack for IP (Internet Protocol) based networks. It is popularly called SYN flooding. It works by an attacker sending many TCP (Transmission Control Protocol) connection requests with spoofed source addresses to a victim's machine. Each request causes the targeted host to instantiate data structures out of a limited pool of resources. Once the target host's resources are exhausted, no more incoming TCP connections can be established, thus denying further legitimate access. The paper contributes a detailed analysis of the SYN flooding attack and a discussion of existing and proposed countermeasures. Furthermore, we introduce a new solution approach, explain its design, and evaluate its performance. Our approach offers protection against SYN flooding for all hosts connected to the same local area network, independent of their operating system or networking stack implementation. It is highly portable, configurable, extensible, and requires neither special hardware, nor modifications in routers or protected end systems.
Increased tolerance to two oomycete pathogens in transgenic tobacco expressing pathogenesis-related protein 1a. (1993)

Expression of pathogenesis-related protein 1a (PR-1a), a protein of unknown biochemical function, is induced to high levels in tobacco in response to pathogen infection. The induction of PR-1a expression is tightly correlated with the onset of systemic acquired resistance (SAR), a defense response effective against a variety of fungal, viral, and bacterial pathogens. While PR-1a has been postulated to be involved in SAR, and is the most highly expressed of the PR proteins, evidence for its role is lacking. In this report, we demonstrate that constitutive high-level expression of PR-1a in transgenic tobacco results in tolerance to infection by two oomycete pathogens, Peronospora tabacina and Phytophthora parasitica var. nicotianae.
Effect of Feeding Propionibacteria on Milk Production by Early Lactation Dairy Cows (2008)

This experiment was conducted to determine the effect of a direct-fed microbial agent, Propionibacterium strain P169 (P169), on rumen fermentation, milk production, and health of periparturient and early-lactation dairy cows. Starting 2 wk before anticipated calving, cows were divided into 2 groups and fed a control diet or the control diet plus 6 x 10(11) cfu/d of P169. Cows were changed to a lactation diet at calving, and treatments continued until 119 d in milk. Rumen fluid samples were taken about 1 wk before calving, and at 1 and 14 wk after calving. Cows fed P169 had lower concentrations of acetate (mol/100 mol of total volatile fatty acids) at all time points, greater concentrations of propionate on the first and last sampling points, and greater concentrations of butyrate on the first 2 time points. Concentrations of glucose in plasma and milk and plasma concentrations of beta-hydroxybutyrate were not affected by treatment. Cows fed P169 had greater concentrations of plasma nonesterified fatty acids on d 7 of lactation. The high nonesterified fatty acids at that time point was probably related to the high production of milk during that period by cows fed the additive. Cows fed P169 during the first 17 wk of lactation produced similar amounts of milk (44.9 vs. 45.3 kg/d, treatment vs. control) with similar composition as cows fed the control diet. Calculated net energy use for milk production, maintenance, and body weight change was similar between treatments, but cows fed the P169 consumed less dry matter (22.5 vs. 23.5 kg/d), which resulted in a 4.4% increase in energetic efficiency.
Villification in the mouse: Bmp signals control intestinal villus patterning (2015)

In the intestine, finger-like villi provide abundant surface area for nutrient absorption. During murine villus development, epithelial Hedgehog (Hh) signals promote aggregation of subepithelial mesenchymal clusters that drive villus emergence. Clusters arise first dorsally and proximally and spread over the entire intestine within 24 h, but the mechanism driving this pattern in the murine intestine is unknown. In chick, the driver of cluster pattern is tensile force from developing smooth muscle, which generates deep longitudinal epithelial folds that locally concentrate the Hh signal, promoting localized expression of cluster genes. By contrast, we show that in mouse, muscle-induced epithelial folding does not occur and artificial deformation of the epithelium does not determine the pattern of clusters or villi. In intestinal explants, modulation of Bmp signaling alters the spatial distribution of clusters and changes the pattern of emerging villi. Increasing Bmp signaling abolishes cluster formation, whereas inhibiting Bmp signaling leads to merged clusters. These dynamic changes in cluster pattern are faithfully simulated by a mathematical model of a Turing field in which an inhibitor of Bmp signaling acts as the Turing activator. In vivo, genetic interruption of Bmp signal reception in either epithelium or mesenchyme reveals that Bmp signaling in Hh-responsive mesenchymal cells controls cluster pattern. Thus, unlike in chick, the murine villus patterning system is independent of muscle-induced epithelial deformation. Rather, a complex cocktail of Bmps and Bmp signal modulators secreted from mesenchymal clusters determines the pattern of villi in a manner that mimics the spread of a self-organizing Turing field.
Fast checkpointing by Write Aggregation with Dynamic Buffer and Interleaving on multicore architecture (2009)

Large scale compute clusters continue to grow to ever-increasing proportions. However, as clusters and applications continue to grow, the Mean Time Between Failures (MTBF) has reduced from days to hours. As a result, fault tolerance within the cluster has become imperative. MPI, the de-facto standard for parallel programming, is widely used on such large clusters. Many MPI implementations use Checkpoint/Restart schemes using the Berkeley Lab Checkpoint Restart (BLCR) Library to achieve some level of fault tolerance. However, the performance of the Checkpoint/Restart mechanism does not scale well with increasing job size. As a result, the deployment of Checkpoint/Restart mechanisms for large scale parallel applications is compromised. In our previous work, we proposed a technique to aggregate certain categories of checkpoint writes to reduce the checkpointing overhead. However, an application still experiences slow checkpoint writing because it is blocked waiting for its checkpoint file writes to complete. In this paper, we propose the Write Aggregation with Dynamic Buffer and Interleaving scheme to reduce the overhead related to checkpoint creation. By aggregating all checkpoint writes into a dynamic buffer pool and overlapping the application progress with the file writes, our algorithm is able to significantly reduce checkpoint creation overhead. In the experiments using 64 processor cores, our design demonstrates a speedup of 2.62 times in terms of checkpoint creation time when compared to the original BLCR design. Our scheme also reduces the impact of checkpointing on the application execution time from 20% to 6% when 3 checkpoints are taken during an application run.
Comparison of the xylose reductase-xylitol dehydrogenase and the xylose isomerase pathways for xylose fermentation by recombinant Saccharomyces cerevisiae (2007)

Despite by-product formation, the XR-XDH xylose utilization pathway resulted in faster ethanol production than using the best presently reported XI pathway in the strain background investigated. The need for robust industrial yeast strains for fermentation of undetoxified spruce hydrolysates was also confirmed.
The role of sertraline in the management of depression. (1995)

Sertraline is a highly specific, potent inhibitor of serotonin reuptake. It exerts no clinically significant effects on norepinephrine and dopamine uptake and possess negligible binding affinity for histaminergic, muscarinic, dopaminergic, and adrenergic receptors. Its pharmacologic profile permits once-daily dosing while allowing plasma drug levels to equilibrate within 1 week. In multicenter, double-blind trials, sertraline proved superior to placebo and comparable to amitriptyline in ameliorating acute depression. Moreover, the drug has been shown to be effective in preventing relapses of the index episode and recurrence of further episodes over the long term. Sertraline has not been associated with sedating or anticholinergic effects, psychomotor impairment, or cardiovascular toxicity. Its principal side effects are generally transient and include mild-to-moderate nausea or diarrhea and sexual dysfunction (ejaculatory delay) in males. The safety margin of sertraline is wider than that of the tricyclic antidepressants. This serotonin reuptake inhibitor shows promise as an important therapeutic and prophylactic alternative in the pharmacologic management of depression.
Efficient recovery of infectious vesicular stomatitis virus entirely from cDNA clones. (1995)

Infectious vesicular stomatitis virus (VSV), the prototypic nonsegmented negative-strand RNA virus, was recovered from a full-length cDNA clone of the viral genome. Bacteriophage T7 RNA polymerase expressed from a recombinant vaccinia virus was used to drive the synthesis of a genome-length positive-sense transcript of VSV from a cDNA clone in baby hamster kidney cells that were simultaneously expressing the VSV nucleocapsid protein, phosphoprotein, and polymerase from separate plasmids. Up to 10(5) infectious virus particles were obtained from transfection of 10(6) cells, as determined by plaque assays. This virus was amplified on passage, neutralized by VSV-specific antiserum, and shown to possess specific nucleotide sequence markers characteristic of the cDNA. This achievement renders the biology of VSV fully accessible to genetic manipulation of the viral genome. In contrast to the success with positive-sense RNA, attempts to recover infectious virus from negative-sense T7 transcripts were uniformly unsuccessful, because T7 RNA polymerase terminated transcription at or near the VSV intergenic junctions.