gebhart/patrepeval huggingface dataset:
Repeated TLR9 stimulation results in macrophage activation syndrome–like disease in mice (2011)

Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are 2 similar diseases characterized by a cytokine storm, overwhelming inflammation, multiorgan dysfunction, and death. Animal models of HLH suggest that disease is driven by IFN-γ produced by CD8⁺ lymphocytes stimulated by persistent antigen exposure. In these models and patients with "primary" HLH, the antigen persists due to genetic defects, resulting in ineffective cytotoxic responses by CD8⁺ T cells and poor pathogen clearance. However, infectious triggers are often not identified in patients with MAS, and some patients with HLH or MAS lack defects in cytotoxic T cell killing. Herein, we show that repeated stimulation of TLR9 produced an HLH/MAS-like syndrome on a normal genetic background, without exogenous antigen. Like previous HLH models, TLR9-induced MAS was IFN-γ dependent; however, unlike other models, disease did not require lymphocytes. We further showed that IL-10 played a protective role in this model and that blocking IL-10 signaling led to the development of hemophagocytosis. IL-10 may therefore be an important target for the development of effective therapeutics for MAS. Our data provide insight into MAS-like syndromes in patients with inflammatory diseases in which there is chronic innate immune activation but no genetic defects in cytotoxic cell function.
Mechanical Analysis and Optimal Design for Carbon Fiber Resin Composite Wound Hydrogen Storage Vessel With Aluminum Alloy Liner (2008)

The carbon fiber resin composite (CFRC) wound high-pressure vessel is the key equipment of high-pressure hydrogen storage technology. High pressure includes high energy in operation, so it is important to analyze the mechanics of this type of vessel. The constitutive performance of CFRC wound layer is anisotropic, and the layer arrangement is complexity, so it is difficult for mechanics analysis on a cylinder. Considering that the internal pressure in a cylinder is loaded by the aluminum alloy liner and the CFRC wound layers together, two models are built: The first model is the cylinder loaded by internal pressure in the hoop direction only. In this model, total hoop direction load is distributed into every layer under internal pressure. The second model is the cylinder loaded with the internal pressure on axial direction only. In this model, total axial load is distributed into all cylinders under internal pressure. Taking the boundary condition of continuous displacement between layers into account, a group of equations is built. From the equations, we can obtain the solutions of the internal pressures in hoop direction and axial direction loaded by every layer. After stresses are obtained, the optimal design can be done through this method. An example is given.
Sulindac Derivatives That Activate the Peroxisome Proliferator-activated Receptor γ but Lack Cyclooxygenase Inhibition (2008)

A series of novel derivatives of the nonsteroidal anti-inflammatory drug (NSAID) sulindac sulfide were synthesized as potential agonists of the peroxisome proliferator-activated receptor gamma (PPARgamma). Nonpolar and aromatic substitutions on the benzylidene ring as well as retention of the carboxylic acid side chain were required for optimal activity. Compound 24 was as potent a compound as any other in the series with an EC50 of 0.1 microM for the induction of peroxisome proliferator response element (PPRE)-luciferase activity. Direct binding of compound 24 to PPARgamma was demonstrated by the displacement of [(3)H]troglitazone, a PPARgamma agonist, in a scintillation proximity assay. Compound 24 also stimulated the binding of PPARgamma to a PPRE-containing oligonucleotide and induced expression of liver fatty-acid binding protein (L-FABP) and adipocyte fatty acid-binding protein (aP2), two established PPARgamma target genes. Taken together, these compounds represent potential leads in the development of novel PPARgamma agonists.
A random access photodiode array for intelligent image capture (1991)

A chip implementing random scan was designed, fabricated, and tested. The chip covers the basic requirements for random access and separation between the sampling and reading processes. In this way, a repeated reading of any pixel at any time can take place. The chip includes an 80*80 matrix of basic cells. Each cell consists of two stages: The first is based on a switch, whereas the second includes a buffer. The chip was fabricated in a 3- mu m CMOS process. It was found to operate functionally. However, the use of a standard process gave rise to the crosstalk phenomenon, which has yet to be overcome.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synergistic Roles for Receptor Occupancy and Aggregation in Integrin Transmembrane Function (1995)

Integrin receptors mediate cell adhesion, signal transduction, and cytoskeletal organization. How a single transmembrane receptor can fulfill multiple functions was clarified by comparing roles of receptor occupancy and aggregation. Integrin occupancy by monovalent ligand induced receptor redistribution, but minimal tyrosine phosphorylation signaling or cytoskeletal protein redistribution. Aggregation of integrins by noninhibitory monoclonal antibodies on beads induced intracellular accumulations of pp125FAK and tensin, as well as phosphorylation, but no accumulation of other cytoskeletal proteins such as talin. Combining antibody-mediated clustering with monovalent ligand occupancy induced accumulation of seven cytoskeletal proteins, including alpha-actinin, talin, and F-actin, thereby mimicking multivalent interactions with fibronectin or polyvalent peptides. Integrins therefore mediate a complex repertoire of functions through the distinct effects of receptor aggregation, receptor occupancy, or both together.
THE GENETIC STRUCTURE OF RNA TUMOR VIRUSES (1977)

INTRODUCTION . . . . . . . . . . . .. . . . . ....... . .... .... . . .. . . . . . . . . . . . . . . . . . . . .. . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 PHYSICAL PROPERTIES OF THE GENOME ... .. ... ... ... .. . .. ......... 204 Virion RNA . . . . . . . ... ... . . . . . . . . . . . . ..... . . ... . . .... . . . ... . . . .. . . . . . ... . ....... ... ... . ... .. . ... .. . . . . .. . . . . .. .. . .... . . . . . .. 204 Provirus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205 The 5' and 3' Termini . . . .. . . . ..... ... . . . . .. . .. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . 206 GENES OF RNA TUMOR VIRUSES ...... .. . .. ... . . . ... ... ... . 207 gag . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . ... . . . . ... . . . ... ... . . ...... ... . . . . . . . ... ... . ... ... . . . ... ... ... . . . . . . . . . .. . . . ... . ... ... . 207 pol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209 env . . .. ... . .. . . . ... ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... ..... . . . . . . . ... . . . . . . ... . . 211 src. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 RECOMBINATION .. ...... . . . ........ . .. ... . . .. ... . .. ..... . ..... .. ... ..... .... .... 2 1 6 GENE MAPPING ..... ..... ...... . .. . .. . ... . .. ...... .. .. . .. . ... . .. . .... .. . .. . . . . ... ... .. ... .. . .. . .. .. . ... .. .... . 21 R
Cache-conscious structure definition (1999)

A program's cache performance can be improved by changing the organization and layout of its data---even complex, pointer-based data structures. Previous techniques improved the cache performance of these structures by arranging distinct instances to increase reference locality. These techniques produced significant performance improvements, but worked best for small structures that could be packed into a cache block.This paper extends that work by concentrating on the internal organization of fields in a data structure. It describes two techniques--- structure splitting and field reordering ---that improve the cache behavior of structures larger than a cache block. For structures comparable in size to a cache block, structure splitting can increase the number of hot fields that can be placed in a cache block. In five Java programs, structure splitting reduced cache miss rates 10--27% and improved performance 6--18% beyond the benefits of previously described cache-conscious reorganization techniques.For large structures, which span many cache blocks, reordering fields, to place those with high temporal affinity in the same cache block can also improve cache utilization. This paper describes bbcache, a tool that recommends C structure field reorderings. Preliminary measurements indicate that reordering fields in 5 active structures improves the performance of Microsoft SQL Server 7.0 2--3%.
Nasal Route for Direct Delivery of Solutes to the Central Nervous System: Fact or Fiction? (1998)

During this century, several investigators reported that certain viruses, metals, drugs, and other solutes could bypass systemic circulation and enter the brain and/or cerebrospinal fluid directly following nasal administration. Although evidence clearly suggests that the olfactory epithelium and its olfactory cells play a major role, little is known about the mechanisms of direct transport of solutes into the brain. An overview of what is known about these mechanisms may aid in further research in this field, including studies of direct drug delivery to the central nervous system. This review, in addition to summarizing the literature to date, clearly describes the intricate association of the anatomical features involved in direct entry of solutes into the brain following nasal administration. To aid in the understanding of the possible routes a solute can take after nasal administration, the anatomy of the olfactory epithelium and surrounding tissues is described, and a detailed scheme delineating the emerging pathways is presented. Techniques used in delineating these pathways and studies supporting a particular pathway are discussed in greater detail. Finally, some factors influencing the direct transport of solutes to the cerebrospinal fluid and brain are summarized.
The Burden of Adult Hypertension in the United States 1999 to 2000 (2004)

This study aims to estimate the absolute number of persons with hypertension (the hypertension burden) and time trends using data from the National Health and Nutrition Examination Survey of United States resident adults who had hypertension in 1999 to 2000. This information is vitally important for health policy, medical care, and public health strategy and resource allocation. At least 65 million adults had hypertension in 1999 to 2000. The total hypertension prevalence rate was 31.3%. This value represents adults with elevated systolic or diastolic blood pressure, or using antihypertensive medications (rate of 28.4%; standard error [SE], 1.1), and adults who otherwise by medical history were told at least twice by a physician or other health professional that they had high blood pressure (rate of 2.9%; SE, 0.4). The number of adults with hypertension increased by approximately 30% for 1999 to 2000 compared with at least 50 million for 1988 to 1994. The 50 million value was based on a rate of 23.4% for adults with elevated blood pressure or using antihypertensive medications and 5.5% for adults classified as hypertensive by medical history alone (28.9% total; P<0.001). The approximately 30% increase in the total number of adults with hypertension was almost 4-times greater than the 8.3% increase in total prevalence rate. These trends were associated with increased obesity and an aging and growing population. Approximately 35 million women and 30 million men had hypertension. At least 48 million non-Hispanic white adults, approximately 9 million non-Hispanic black adults, 3 million Mexican American, and 5 million other adults had hypertension in 1999 to 2000.
Photochromic Activators of the Acetylcholine Receptor (1971)

Two photochromic activators of the electrogenic membrane of the electroplax of Electrophorus electricus are described. Trans-3,3'-bis[alpha-(trimethylammonium)methyl]azobenzene dibromide (Bis-Q), one of the most potent ever reported, is active at concentrations of less than 10(-7) M. Its cis isomer, which is obtained from the trans by exposure to light of 330 nm, is practically devoid of activity. Photoregulation of the potential of the membrane takes place in the presence of Bis-Q, presumably because of the conversion of the active trans isomer to the inactive cis isomer in the single-cell electroplax system. The second activator, 3-(alpha-bromomethyl)-3'-[alpha-(trimethylammonium)methyl]azobenzene bromide (QBr) can be covalently attached to the electroplax membrane after reduction of the membrane with dithiothreitol. Activation of the membrane is induced by the covalently linked reagent. Its cis isomer, obtained from the trans by exposure to light of 330 nm, is, like cis-Bis-Q, of very low activity. Both isomers of Bis-Q are equally active as inhibitors of acetylcholinesterase, 50% inhibition occurring at a concentration of 10(-5) M. The possibility of using trans-Bis-Q and trans-QBr to characterize and isolate the receptor protein is discussed.
Rational Design and Synthesis of Small Molecule, Non-oligosaccharide Selectin Inhibitors: (.alpha.-D-Mannopyranosyloxy)biphenyl-Substituted Carboxylic Acids (1995)

The calcium dependent E-selectin/sialyl Lewisx (sLex) interaction plays a key role in inflammation where it mediates the rolling of leukocytes prior to firm adhesion and extravasation from the vasculature. A model of E-selectin/sLex binding, along with previously reported structure-activity relationships of sLex-related oligosaccharide, was used in the rational design of non-oligosaccharide inhibitors of this pivotal interaction. A palladium-mediated biaryl-coupling (Suzuki) reaction was used as the key step to prepare a number of substituted biphenyls which were assayed for their ability to inhibit the binding of E-, P-, and L-selectin-IgG fusion proteins to sLex expressed on the surface of HL60 cells. Some of the compounds developed had greater in vitro potency than the parent sLex tetrasaccharide and are currently being evaluated in in vivo models of inflammation to select a candidate for clinical development.
Temperature-responsive compounds as in situ gelling biomedical materials (2012)

Aqueous solutions that undergo sol-to-gel transition as the temperature increases have been extensively studied during the last decade. The material can be designed by controlling the hydrophilic and hydrophobic balance of the material. Basically, the molecular weight of the hydrophilic block and hydrophobic block of a compound should be fine-tuned from the synthetic point of view. In addition, stereochemistry, microsequence, topology, and nanostructures of the compound also affect the transition temperature, gel window, phase diagram, and modulus of the gel. From a practical point of view, biodegradability, biocompatibility, and interactions between the material and drug or cell should be considered in designing a thermogelling material. The interactions are particularly important in that they control drug release profile and initial burst release of the drug in the drug delivery system, and affect cell proliferation, differentiation, and biomarker expression in three-dimensional cell culture and tissue engineering application. This review provides an in-depth summary of the recent progress of thermogelling systems including polymers, low molecular compounds, and nanoemulsions. Their biomedical applications were also comparatively discussed. In addition, perspectives on future material design of a new thermogelling material and its application are suggested.
Novel Routes for Improving Biocontrol Activity of Bacillus Based Bioinoculants (2015)

Biocontrol (BC) formulations prepared from plant-growth-promoting bacteria are increasingly applied in sustainable agriculture. Especially inoculants prepared from endospore-forming Bacillus strains have been proven as efficient and environmental-friendly alternative to chemical pesticides due to their long shelf life, which is comparable with that of agrochemicals. However, these formulations of the first generation are sometimes hampered in their action and do not fulfill in each case the expectations of the appliers. In this review we use the well-known plant-associated Bacillus amyloliquefaciens type strain FZB42 as example for the successful application of different techniques offered today by comparative, evolutionary and functional genomics, site-directed mutagenesis and strain construction including marker removal, for paving the way for preparing a novel generation of BC agents.
Regulation of Gonadotropins by Inhibin and Activin (2004)

Inhibin, activin, and follistatin were first identified as gonadal hormones that could exert selective effects on follicle-stimulating hormone (FSH) secretion without affecting luteinizing hormone (LH). Although the primary source of inhibin remains the gonad, both activin and follistatin are produced in extragonadal tissues and can exert effects on FSH through an autocrine-paracrine mechanism. These proteins can effect the regulation of the gonadotropins at many levels. First, activin can directly stimulate FSH biosynthesis and release from the gonadotrope cells of the pituitary gland. Second, activin up-regulates gonadotropin-releasing hormone receptor (GnRHR) gene expression, leading to alterations in the synthesis and release of both gonadotropins in response to GnRH. Third, activin can stimulate GnRH release from GnRH neurons in the hypothalamus and thereby affect FSH and LH secretion. Both inhibin and follistatin can negatively regulate these effects by preventing activin binding to the activin receptor at the cell membrane and blocking activation of downstream signal transduction pathways. This review concentrates on the mechanisms through which inhibin, activin, and follistatin regulate the gonadotropins. We discuss the expression of inhibin/activin subunits and receptors throughout the hypothalamus and pituitary and their role in the regulation of FSH and LH. The mechanisms of inhibin and activin signaling are also reported, with particular attention to developments in our understanding of inhibin receptor action and activin-induced transcriptional regulation of the FSHbeta gene promoter. Finally, we present recent findings that other members of the transforming growth factor beta superfamily may also play an important role in transcriptional regulation of the pituitary gonadotropins.
Membrane Transport, Sensing and Signaling in Plant Adaptation to Environmental Stress (2011)

Plants are generally well adapted to a wide range of environmental conditions. Even though they have notably prospered in our planet, stressful conditions such as salinity, drought and cold or heat, which are increasingly being observed worldwide in the context of the ongoing climate changes, limit their growth and productivity. Behind the remarkable ability of plants to cope with these stresses and still thrive, sophisticated and efficient mechanisms to re-establish and maintain ion and cellular homeostasis are involved. Among the plant arsenal to maintain homeostasis are efficient stress sensing and signaling mechanisms, plant cell detoxification systems, compatible solute and osmoprotectant accumulation and a vital rearrangement of solute transport and compartmentation. The key role of solute transport systems and signaling proteins in cellular homeostasis is addressed in the present work. The full understanding of the plant cell complex defense mechanisms under stress may allow for the engineering of more tolerant plants or the optimization of cultivation practices to improve yield and productivity, which is crucial at the present time as food resources are progressively scarce.
Growth of human normal erythroid progenitors in liquid culture: A comparison with colony growth in semisolid culture (1991)

Most studies of erythropoiesis in vitro have employed cloning methods in semisolid medium. We have recently described a two-step liquid culture procedure that supports the proliferation and differentiation of human erythroid progenitors. In the present study, we have modified the procedure to allow large-scale cultures of erythroid cells derived from normal donors. The culture is divided into two phases. In the first phase, which is erythropoietin (Epo) independent, the early erythroid progenitors multiply and differentiate. In the second, Epo-dependent phase, they mature into orthochromatic normoblasts and enucleated erythrocytes. Using this procedure, erythroid cell yield reached 7.5 x 10(6)/ml and a total of 7 x 10(8) cells could be harvested per blood unit. A comparison of the growth of erythroid cells in liquid culture to their colony growth in semisolid culture indicated that cell growth was superior: 1) in liquid culture in terms of cell yield per originally cultured mononuclear cell, 2) per ml culture and per culture surface area and in the purity of the resultant erythroid cell population. In addition, it permits easier manipulation of the culture condition and components and sampling of greater than 1 x 10(7) cells at each maturation stage subsequent to the proerythroblast stage. This liquid culture procedure might provide an important experimental tool for studying erythroid cell development.
Primary structure and function of a second essential member of the heterooligomeric TCP1 chaperonin complex of yeast, TCP1 beta. (1994)

A role for heterooligomeric TCP1 complex as a chaperonin in the eukaryotic cytosol has recently been suggested both by structural similarities with other chaperonins and by in vitro experiments showing it to mediate ATP-dependent folding of actin, tubulin, and luciferase. Here we present the primary structure of a second subunit of the complex and present genetic and functional analyses. The TCP1 beta amino acid sequence, predicted from the cloned gene, bears 35% identity to TCP1, termed here TCP1 alpha, containing the same highly conserved residues found in the collective sequence of chaperonins. The predicted product was identified as the fastest-migrating species of the TCP1 complex purified from soluble extracts of yeast. The TCP1 beta gene, like TCP1 alpha, is essential. Strains containing lethal disruptions of either gene could not be rescued by additional copies of the other. Spores bearing disruption of either gene germinated as single, large-budded cells. Similarly, large-budded cells were observed following shift to 37 degrees C of strains carrying temperature-sensitive mutations in either TCP1 alpha or TCP1 beta. The arrested cells contained replicated DNA present in single nuclear masses, associated with abnormal tubulin staining patterns, supporting the assertion that mitotic spindle formation and function are impaired. We conclude that TCP1 beta supplies an essential function that partially overlaps with that of TCP1 alpha in acting as a molecular chaperone in tubulin and spindle biogenesis.