gebhart/patrepeval huggingface dataset:
Bcl-6 and NF-κB cistromes mediate opposing regulation of the innate immune response (2010)

In the macrophage, toll-like receptors (TLRs) are key sensors that trigger signaling cascades to activate inflammatory programs via the NF-κB gene network. However, the genomic network targeted by TLR/NF-κB activation and the molecular basis by which it is restrained to terminate activation and re-establish quiescence is poorly understood. Here, using chromatin immunoprecipitation sequencing (ChIP-seq), we define the NF-κB cistrome, which is comprised of 31,070 cis-acting binding sites responsive to lipopolysaccharide (LPS)-induced signaling. In addition, we demonstrate that the transcriptional repressor B-cell lymphoma 6 (Bcl-6) regulates nearly a third of the Tlr4-regulated transcriptome, and that 90% of the Bcl-6 cistrome is collapsed following Tlr4 activation. Bcl-6-deficient macrophages are acutely hypersensitive to LPS and, using comparative ChIP-seq analyses, we found that the Bcl-6 and NF-κB cistromes intersect, within nucleosomal distance, at nearly half of Bcl-6-binding sites in stimulated macrophages to promote opposing epigenetic modifications of the local chromatin. These results reveal a genomic strategy for controlling the innate immune response in which repressive and inductive cistromes establish a dynamic balance between macrophage quiescence and activation via epigenetically marked cis-regulatory elements.
An in Vitro Assay Using Overexpressed Yeast SRP Demonstrates that Cotranslational Translocation Is Dependent upon the J-Domain of Sec63p (2003)

The signal recognition particle (SRP) is required for co-translational targeting of polypeptides to the endoplasmic reticulum (ER). Once at the membrane, the precursor interacts with a complex proteinaceous machinery that mediates its translocation across the bilayer. Genetic studies in yeast have identified a number of genes whose products are involved in this complex process. These mutants offer a potentially valuable resource with which to analyze the biochemical role played by each component in the pathway. However, such analyses have been hampered by the failure to reconstitute an efficient in vitro assay for SRP-dependent translocation. We report the construction of two multicopy vectors that allow overexpression of all seven gene products required to make SRP in the yeast Saccharomyces cerevisiae. The overexpressed subunits assemble into intact and functional SRP particles, and we further demonstrate that in vitro reconstitution of co-translational translocation is greatly enhanced using cytosol from the overexpression strain. We use this assay to demonstrate that Sec63p is required for co-translational translocation in vitro and specifically identify the "J-domain" of Sec63p as crucial for this pathway.
Atrasentan, an Endothelin-Receptor Antagonist for Refractory Adenocarcinomas: Safety and Pharmacokinetics (2002)

Adverse events were consistent with atrasentan's pharmacologic vasodilatory effect. Linear, dose-proportional pharmacokinetics suggest that atrasentan can be easily and consistently dosed.
Quality Control and Pre-Qualification of NGS Libraries Made from Clinical Samples. (2013)

We have compared sequencing metrics from different types of clinical samples and different methods of making NGS libraries, for purposes of quality control of the samples and sample preps. We have performed the metrics using the HiSeq and MiSeq, however the same QC metrics could be measured on other platforms. By choosing metrics that can be measured from small amounts of data (e.g., 300,000 reads), we can measure the quality of the clinical samples and NGS libraries in a highly multiplexed format, before spending considerable time and money for downstream processes such as sequence enrichment and NGS. More predictive than measurement of insert size and concentration, these metrics predict whether the amount and quality of genomic DNA, as well as the sample preparation method is sufficiently efficient to generate high coverage from deep sequencing. Sequencing results from sonicated human and bacterial DNA, as well as human maternal plasma show that different sample prep methods yield libraries of very different diversity, uniformity of coverage and background. Library quality can also vary considerably in different lots of reagents and also different number of amplification cycles.
Evaluation ofSalmonella typhimuriumMutants in a Model of Experimental Gastroenteritis (1999)

Salmonella typhimurium strains harboring independent, defined mutations in aroA, invA, ssrA, or msbB were assessed for their ability to induce fluid accumulation, tissue damage, and local inflammation in rabbit ileal loops. Three wild-type strains of S. typhimurium, TML, HWSH, and SL1344, and two mutant strains, S. typhimurium SL1344 ssrA and S. typhimurium SL1344 msbB, consistently induced fluid accumulation in the lumen of loops and inflammation of loop-associated tissues. In contrast, three different S. typhimurium aroA strains and an invA mutant of SL1344 did not induce significant fluid accumulation in the rabbit ileal loops. However, the S. typhimurium aroA strains did induce an inflammatory infiltrate and some local villus-associated damage, but the invA mutant did not. Histologically, wild-type S. typhimurium, S. typhimurium SL1344 ssrA, and S. typhimurium SL1344 msbB demonstrated more severe effects on villus architecture than S. typhimurium aroA strains, whereas S. typhimurium invA-infected loops showed no detectable damage. This suggests that villus damage most likely contributes to fluid accumulation within the loop.
Platelet inhibition with prasugrel (CS-747) compared with clopidogrel in patients undergoing coronary stenting: the subset from the JUMBO study (2006)

At the dosing regimens chosen in the JUMBO trial, it seems that prasugrel is a more potent antiplatelet agent than clopidogrel. Two episodes of profound platelet inhibition, which are not seen with clopidogrel, raise the possibility of higher bleeding risks especially during long term prasugrel use. Whether stronger platelet inhibition will yield better clinical outcomes and/or increased bleeding remains to be determined in an ongoing comparative phase 3 superiority trial (TRITON).
Fast and Highly Chemoselective Alkynylation of Thiols with Hypervalent Iodine Reagents Enabled through a Low Energy Barrier Concerted Mechanism (2014)

Among all functional groups, alkynes occupy a privileged position in synthetic and medicinal chemistry, chemical biology, and materials science. Thioalkynes, in particular, are highly useful, as they combine the enhanced reactivity of the triple bond with a sulfur atom frequently encountered in bioactive compounds and materials. Nevertheless, general methods to access these compounds are lacking. In this article, we describe the mechanism and full scope of the alkynylation of thiols using ethynyl benziodoxolone (EBX) hypervalent iodine reagents. Computations led to the discovery of a new, three-atom concerted transition state with a very low energy barrier, which rationalizes the high reaction rate. On the basis of this result, the scope of the reaction was extended to the synthesis of aryl- and alkyl-substituted alkynes containing a broad range of functional groups. New sulfur nucleophiles such as thioglycosides, thioacids, and sodium hydrogen sulfide were also alkynylated successfully to lead to the most general and practical method yet reported for the synthesis of thioalkynes.
Fibrin as an alternative biopolymer to type‐I collagen for the fabrication of a media equivalent (2002)

We report here on studies examining the use of fibrin as an alternative to collagen for the entrapment of neonatal aortic rat smooth muscle cells (SMCs) in the fabrication of media equivalents. The studies show increased collagen production by fibroblasts entrapped in fibrin, which suggests that fibrin may be used in the fabrication of tissue equivalents to promote increased protein synthesis and remodeling. However, one of the challenges of working with fibrin is the rapid degradation by SMCs. This degradation was effectively inhibited with the addition of epsilon-aminocaproic acid (EACA) to the culture medium in concentrations ranging from 0.25 to 1 mg/mL. We also present results showing that fibrin stimulates collagen production by SMCs. SMCs in fibrin produced 3.2 and 4.9 times the amount of collagen produced by SMCs in collagen when supplemented with 1 and 0.25 mg/mL EACA, respectively. More than half of the collagen produced appeared in the medium rather than the matrix. The collagen in the medium appeared to be processed beyond the proform and may be in an aggregate form. In addition, the presence of type-III collagen or a type-I trimer was indicated by the results of an analysis of the medium by autoradiography.
Calculation of linear and nonlinear intersubband optical absorptions in a quantum well model with an applied electric field (1987)

Analytic forms of the linear and the third-order nonlinear optical intersubband absorption coefficients are obtained for general asymmetric quantum well systems using the density matrix formalism, taking into account the intrasubband relaxation. Based on this model, we calculate the electric field dependence of the linear and the third-order nonlinear intersubband optical absorption coefficients of a semiconductor quantum well. The energy of the peak optical intersubband absorption is around 100 meV (wavelength is 12.4 μm). Thus, electrooptical modulators and photodetectors in the infrared regime can be built based on the physical mechanisms discussed here. The contributors to the nonlinear absorption coefficient due to the electric field include 1) the matrix element variation and 2) the energy shifts. Numerical results are illustrated.
PM2: High Performance Communication Middleware for Heterogeneous Network Environments (2000)

This paper introduces a high performance communication middle layer, called PM2, for hetero-geneous network environments. PM2 currently supports Myrinet, Ethernet, and SMP. Binary code written in PM2 or written in a communication library, such as MPICH-SCore on top of PM2, may run on any combination of those networks without re-compilation. According to a set of NAS parallel benchmark results, MPICH-SCore performance is better than dedicated communication libraries such as MPICH-BIP/SMP and MPICH-GM when running some benchmark programs.
Learning Features for Tracking (2007)

We treat tracking as a matching problem of detected key-points between successive frames. The novelty of this paper is to learn classifier-based keypoint descriptions allowing to incorporate background information. Contrary to existing approaches, we are able to start tracking of the object from scratch requiring no off-line training phase before tracking. The tracker is initialized by a region of interest in the first frame. Afterwards an on-line boosting technique is used for learning descriptions of detected keypoints lying within the region of interest. New frames provide new samples for updating the classifiers which increases their stability. A simple mechanism incorporates temporal information for selecting stable features. In order to ensure correct updates a verification step based on estimating homographies using RANSAC is performed. The approach can be used for real-time applications since on-line updating and evaluating classifiers can be done efficiently.
In Vitro Activities of Nontraditional Antimicrobials against Multiresistant Acinetobacter baumannii Strains Isolated in an Intensive Care Unit Outbreak (2000)

Fifteen multiresistant Acinetobacter baumannii isolates from patients in intensive care units and 14 nonoutbreak strains were tested to determine in vitro activities of nontraditional antimicrobials, including cefepime, meropenem, netilmicin, azithromycin, doxycycline, rifampin, sulbactam, and trovafloxacin. The latter five drugs were further tested against four of the strains for bactericidal or bacteriostatic activity by performing kill-curve studies at 0.5, 1, 2, and 4 times their MICs. In addition, novel combinations of drugs with sulbactam were examined for synergistic interactions by using a checkerboard configuration. MICs at which 90% of the isolates tested were inhibited for antimicrobials showing activity against the multiresistant A. baumannii strains were as follows (in parentheses): doxycycline (1 microg/ml), azithromycin (4 microg/ml), netilmicin (1 microg/ml), rifampin (8 microg/ml), polymyxin (0.8 U/ml), meropenem (4 microg/ml), trovafloxacin (4 microg/ml), and sulbactam (8 microg/ml). In the kill-curve studies, azithromycin and rifampin were rapidly bactericidal while sulbactam was more slowly bactericidal. Trovafloxacin and doxycycline were bacteriostatic. None of the antimicrobials tested were bactericidal against all strains tested. The synergy studies demonstrated that the combinations of sulbactam with azithromycin, rifampin, doxycycline, or trovafloxacin were generally additive or indifferent.
The Use of the Angular Transformation in Biological Assays (1947)

Abstract A comparison is made of the use of the angular transformation and the use of the probit transformation in evaluating results from biological assays having percentage responses. It is found that the angular transformation results in making the weights dependent on the number of animals used on each dose and if these are equal the weights are eliminated. The logit transformation is also cited. A two-dose assay design used in conjunction with the angular transformation results in a simplified calculation which can be put in the form of a graph and nomograph for use in the laboratory to estimate both potency and error of the assay as a per cent of the standard. A comparison of the calculation time involved shows that the probit method requires about twelve times as long as the angular transformation method involving graph and nomograph. A comparison of results obtained shows very little difference.
Basic algorithms for the programming of deep brain stimulation in Parkinson's disease (2006)

The clinical success of deep brain stimulation (DBS) for treating Parkinson's disease (PD) critically depends on the quality of postoperative neurological management. Movement disorder specialists becoming involved with this therapy need to acquire new skills to adapt optimally stimulation parameters and medication after implantation of a DBS system. At first glance, the infinite number of theoretically possible parameter combinations seems to make programming a complex and time-consuming art. This article outlines a stepwise and standardized approach, reducing the possible parameter settings in DBS to a few relevant combinations. The basic programming algorithms for thalamic, subthalamic, and pallidal stimulation in PD are explained and summarized in flowcharts.
The Role of Extracellular Matrix Proteins in the Control of Phagocytosis (1986)

The phagocytic function of human-peripheral-blood-derived mononuclear and polymorphonuclear leukocytes can be regulated by external stimuli. In particular, the extracellular matrix (ECM) proteins fibronectin and laminin and serum amyloid P component can increase the phagocytic activity of these cells. Phagocytosis enhancement by the ECM requires two distinct signals to the ingesting cell. First, a ligand for interaction of the target particle with phagocytic cells is required. Generally this occurs because of opsonins such as antibody or complement on the phagocytic target and is independent of the ECM proteins. The phagocytosis-enhancing effect of the connective tissue proteins also requires direct interaction of these proteins with phagocytic cells and occurs through cell surface receptors for these molecules. In the case of neutrophils, sensitivity to the phagocytosis-enhancing effects of connective tissue proteins requires prior stimulation with the chemotactic peptides C5a or f-met-leu-phe. The present state or knowledge of the mechanism of phagocytosis enhancement by ECM proteins and the implications of the phenomenon for host defense are discussed.
A Management Plan for Home Food Storage (1995)

Home food storage has been suggested for use during emergencies or disasters.Some families may store food as part of a prudent lifestyle.Whatever the reason, management is a vital part of any successful food storage program.Food is a perishable item even when it is preserved and requires appropriate care and use.Management of food storage will maximize nutritional quality and eliminate waste.This workbook is intended to provide an easy way to analyze meal planning, food preparation and storage in the home.The exercise is based on the idea that one should store the foods which are regularly eaten and are part of individualized or family eating patterns.Working through the steps will also give an overall view of eating habits including information on nutritional values of meals, shopping techniques and food preparation skills.This plan assumes there is adequate space to store moderate amounts of food in various forms and is based on a years planning time. Store What You Use !This list is not a perfect planner, but rather a tool to use in planning foods to "Store What You Use." !
Chronic Progression of Tubulointerstitial Damage in Proteinuric Renal Disease Is Mediated by Complement Activation (2003)

The mechanisms by which increased urinary protein concentrations lead to nephrotoxic injury are certain to be multifactorial and involve complex interactions between numerous pathways of cellular damage mediated by both cellular and humoral pathways. These may include a major role for the podocyte in glomerular diseases leading to chronic renal failure, the loss of microvascular endothelium, the albumin-induced upregulation of renal cytokines and growth factors that promote tubulointerstitial injury by inflammation and fibrogenesis, and the role of complement-mediated tubulointerstitial injury due to proteinuria. This review will focus on the last mechanism, and emphasize recent studies implicating a primary role for activation of complement in proteinuric urine as the principal mediator of tubulointerstitial damage and progressive renal disease in various experimental animal models of nephrosis. It will be our contention that intraluminal activation of the terminal complement cascade leading to the formation of the C5b-9 membrane attack complex is the principal mediator of chronic progressive interstitial damage and progressive renal failure irrespective of the type of primary glomerular injury. This paradigm has important implications for the potential therapeutic role of complement inhibitors that are currently being developed.
The motion of rigid particles in a shear flow at low Reynolds number (1962)

According to Jeffery (1923) the axis of an isolated rigid neutrally buoyant ellipsoid of revolution in a uniform simple shear at low Reynolds number moves in one of a family of closed periodic orbits, the centre of the particle moving with the velocity of the undisturbed fluid at that point. The present work is a theoretical investigation of how far the orbit of a particle of more general shape in a non-uniform shear in the presence of rigid boundaries may be expected to be qualitatively similar. Inertial and non-Newtonian effects are entirely neglected. The orientation of the axis of almost any body of revolution is a periodic function of time in any unidirectional flow, and also in a Couette viscometer. This is also true if there is a gravitational force on the particle in the direction of the streamlines. There is no lateral drift. On the other hand, certain extreme shapes, including some bodies of revolution, will assume one of two orientations and migrate to the bounding surfaces or to the centre of the flow. In any constant slightly three-dimensional uniform shear any body of revolution will ultimately assume a preferred orientation.
FramePlot: a new implementation of the Frame analysis for predicting protein-coding regions in bacterial DNA with a high G+C content (1999)

FramePlot is a web-based tool for predicting protein-coding regions in bacterial DNA with a high G + C content, such as Streptomyces. The graphical output provides for easy distinction of protein-coding regions from non-coding regions. The plot is a clickable map. Clicking on an ORF provides not only the nucleotide sequence but also its deduced amino acid sequence. These sequences can then be compared to the NCBI sequence database over the Internet. The program is freely available for academic purposes at http://www.nih.go.jp/jun/cgi-bin/frameplot.pl.
A Naturally Occurring, Soluble Antagonist of Human IL-23 Inhibits the Development and In Vitro Function of Human Th17 Cells (2010)

Th17 CD4 cells are critical to inflammation. Their secretion of IL-17 drives inflammation in human diseases, including inflammatory bowel disease. Differentiation of mature Th17 cells depends on stimulation with IL-6, TGF-β, and IL-21 and the induction of RORγt, but IL-23 is essential to Th17 phenotype, stability, and function. Induction of Th17 cells can be antagonized by IL-4 or IFN-γ, but mechanisms through which terminal differentiation can be inhibited have not been identified. Human IL-23Rα (HuIL23Rα)-chain mRNA transcripts exist that lack exon 9 ("Δ9"); these are translated to a truncated receptor containing the entire external domain. This soluble variant of the HuIL23Rα-chain antagonizes Th17 maturation. It is secreted and present at low levels in the blood. It represents 10% of HuIL23Rα-chain mRNA, binds IL-23 in solution, and inhibits the phosphorylation of STAT3 caused by IL-23. In in vitro Th17 cell differentiation experiments, Δ9 inhibits the production of the Th17-associated cytokines IL-17A and IL-17F. Δ9 does not bind IL-12; thus, it is a specific inhibitor of IL-23 and a modulator of Th17 cells. Our results indicate that this soluble form of HuIL23Rα likely functions to regulate Th17 activity.
Multicolor Super‐Resolution Fluorescence Imaging via Multi‐Parameter Fluorophore Detection (2011)

Understanding the complexity of the cellular environment will benefit from the ability to unambiguously resolve multiple cellular components, simultaneously and with nanometer-scale spatial resolution. Multicolor super-resolution fluorescence microscopy techniques have been developed to achieve this goal, yet challenges remain in terms of the number of targets that can be simultaneously imaged and the crosstalk between color channels. Herein, we demonstrate multicolor stochastic optical reconstruction microscopy (STORM) based on a multi-parameter detection strategy, which uses both the fluorescence activation wavelength and the emission color to discriminate between photo-activatable fluorescent probes. First, we obtained two-color super-resolution images using the near-infrared cyanine dye Alexa 750 in conjunction with a red cyanine dye Alexa 647, and quantified color crosstalk levels and image registration accuracy. Combinatorial pairing of these two switchable dyes with fluorophores which enhance photo-activation enabled multi-parameter detection of six different probes. Using this approach, we obtained six-color super-resolution fluorescence images of a model sample. The combination of multiple fluorescence detection parameters for improved fluorophore discrimination promises to substantially enhance our ability to visualize multiple cellular targets with sub-diffraction-limit resolution.