gebhart/patrepeval huggingface dataset:
Hepatic Hepcidin Protects against Polymicrobial Sepsis in Mice by Regulating Host Iron Status (2014)

AbstractAbstract Disruption of mouse hepatic hepcidin expression led to significant increases in organ damage and mortality when sepsis was produced. Decreasing the iron levels in these mice improved survival. Background: Hepcidin is a master regulator of iron metabolism primarily produced by the liver. Markedly increased hepcidin levels have been observed in septic individuals, while decreased hepatic hepcidin expression has been demonstrated in liver diseases that tend to develop into sepsis. However, the role of liver hepcidin in sepsis remains unknown. Methods: Mouse hepatic hepcidin expression was silenced using adenovirus-mediated hepcidin-specific short hairpin RNA injected via the tail vein. Sepsis was induced by cecal ligation and puncture, and the outcome (n = 23 for hepcidin knockdown mice, n = 15 for controls) and pathogenic changes (n = 5) related to sepsis were evaluated. The impact of alteration of iron status on the survival rate of hepatic hepcidin knockdown mice (n = 18 to 19) was also investigated. Results: Disruption of liver hepcidin expression increased serum iron level (537.8 ± 28.1 μg/dl [mean ± SD] vs. 235.9 ± 62.2 μg/dl; P &lt; 0.05) and reduced iron content in the spleen macrophages at the steady state. Hepatic hepcidin knockdown mice not only showed increased 7-day mortality (73.9% vs. 46.7%; P &lt; 0.05), but also had exacerbated organ damage and oxidative stress, as well as compromised host inflammatory responses and bacterial clearance at 24 h after polymicrobial sepsis. Treating the hepatic hepcidin knockdown mice with low-iron diet plus iron chelation decreased systemic iron content (serum level: 324.0 ± 67.4 μg/dl vs. 517.4 ± 13.4 μg/dl; P &lt; 0.05) and rescued the mice from lethal sepsis (7-day survival: 36.8% vs. 83.3%; P &lt; 0.01). Conclusions: Hepatic hepcidin plays an important role in sepsis through regulation of iron metabolism. The findings may have potential therapeutic implications for liver diseases in which hepcidin expression is decreased.
Criteria for the evaluation of text storage and retrieval software (1988)

Criteria to evaluate and select software for online text information storage and retrieval software are presented in the form of a checklist. The list has a hierarchical structure; the headings are Input of information, Indexing, Interactive searching for information, and Output features, with, additionally, a few remarks about Current awareness, Security/Privacy/Authorisation, Read‐only version, and Integration with other programs.
Novel Retinoid X Receptor Antagonists:  Specific Inhibition of Retinoid Synergism in RXR−RAR Heterodimer Actions (2002)

Several 2-(arylamino)pyrimidine-5-carboxylic acids were designed as novel retinoid X receptor (RXR) antagonists. Compound 6a or 6b alone did not exhibit differentiation-inducing activity toward HL-60 cells and did not affect the activity of a retinoic acid receptor (RAR) agonist, Am80, but did inhibit the synergistic activity of an RXR agonist, PA024 (3), in the presence of Am80. The activity of 6 was ascribed to selective antagonism at the RXR site of RXR-RAR heterodimers.
Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study (2012)

Treatment with subcutaneous secukinumab 3 × 75 mg and 3 × 150 mg met the primary outcome of PASI 75 response achievement after 12 weeks, demonstrating efficacy in moderate-to-severe psoriasis.
Project Gel a Randomized Rectal Microbicide Safety and Acceptability Study in Young Men and Transgender Women (2016)

ClinicalTrials.gov NCT01283360.
Different adhesion properties of highly and poorly metastatic HT-29 colon carcinoma cells with extracellular matrix components: role of integrin expression and cytoskeletal components (1999)

Integrin-mediated tumour cell adhesion to extracellular matrix (ECM) components is an important step in the development of metastatic lesions. Thus, integrin expression and integrin-mediated adhesion of colon carcinoma cells to various ECM components was examined. Poorly (HT-29P) and highly (HT-29LMM) liver-metastatic colon carcinoma cells were used to study the rates of adhesion to collagen I (C I), collagen IV (C IV), laminin (LN), fibronectin (FN), or vitronectin (VN) in a static adhesion assay (10-120 min). Cells were untreated or treated with oligopeptides (RGD, GRGDS, YIGSR, RGES), anti-integrin antibodies, or colchicine, nocodazole, cycloheximide, acrylamide or cytochalasin D (to disrupt cytoskeletal structures). Both cell lines expressed similar patterns of integrin expression (alpha2, alpha3, ,alpha6, alphav, beta1, beta4, and beta5) by immunocytochemistry and immunoprecipitation. HT-29LMM cells showed significantly higher rates of adhesion to LN (P < 0.001) and FN (P < 0.001), but significantly poorer rates of adhesion to C I (P < 0.05) and C IV (P < 0.001) than HT-29P cells, respectively, adhesion to VN was insignificant. RGD and GRGDS inhibited HT-29LMM cell adhesion to FN only. Pretreatment with anti-beta, or anti-alpha2 integrin subunits suppressed adhesion to C I and C IV, and adhesion to LN was inhibited with anti-beta1 or anti-alpha6 integrin. Anti-beta1 or anti-alphav blocked adhesion to FN. Pretreatment of cells with cytochalasin D, cycloheximide or acrylamide inhibited adhesive interactions of both cell lines to the ECM components. In contrast, colchicine and nocodazole had no effect. The results demonstrate that adhesion of HT-29 cells to ECM is mediated, in part, by different integrins, depending on the substrate. Poorly and highly metastatic HT-29 cells possessed different patterns of adhesion to the various ECM substrates, but these differences were not due to different expression of integrin subunits. The results also suggested that the initial adhesion of poorly or highly metastatic HT-29 cells to ECM components requires, in part, the presence of native action and intermediate filaments, but not of microtubules. Thus the adhesion of tumour cells to ECM components may be dependent on signal transduction and assembly of microfilaments.
Observation of Photovoltaic Action from Photoacid-Modified Nafion Due to Light-Driven Ion Transport (2017)

Replacing passive ion-exchange membranes, like Nafion, with membranes that use light to drive ion transport would allow membranes in photoelectrochemical technologies to serve in an active role. Toward this, we modified perfluorosulfonic acid ionomer membranes with organic pyrenol-based photoacid dyes to sensitize the membranes to visible light and initiate proton transport. Covalent modification of the membranes was achieved by reacting Nafion sulfonyl fluoride poly(perfluorosulfonyl fluoride) membranes with the photoacid 8-hydroxypyrene-1,3,6-tris(2-aminoethylsulfonamide). The modified membranes were strongly colored and maintained a high selectivity for cations over anions. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and ion-exchange measurements together provided strong evidence of covalent bond formation between the photoacids and the polymer membranes. Visible-light illumination of the photoacid-modified membranes resulted in a maximum power-producing ionic photoresponse of ∼100 μA/cm<sup>2</sup> and ∼1 mV under 40 Suns equivalent excitation with 405 nm light. In comparison, membranes that did not contain photoacids and instead contained ionically associated Ru<sup>II</sup>-polypyridyl coordination compound dyes, which are not photoacids, exhibited little-to-no photoeffects (∼1 μA/cm<sup>2</sup>). These disparate photocurrents, yet similar yields for nonradiative excited-state decay from the photoacids and the Ru<sup>II</sup> dyes, suggest temperature gradients were not likely the cause of the observed photovoltaic action from photoacid-modified membranes. Moreover, spectral response measurements supported that light absorption by the covalently bound photoacids was required in order to observe photoeffects. These results represent the first demonstration of photovoltaic action from an ion-exchange membrane and offer promise for supplementing the power demands of electrochemical processes with renewable sunlight-driven ion transport.
High-efficiency FET/microstrip-patch oscillators (1994)

The author discusses class-C FET/patch oscillators; in these, the microstrip-patch antenna serves multiple purposes: the patch radiates energy, acts as a resonant load, and as a feedback network. These integrated antenna/oscillators are capable of efficiencies which approach conventional non-radiating oscillator designs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
General solutions for stress-induced polarization in optical fibers (1991)

General solutions of thermal stresses and material birefringence in polarization-maintaining optical fibers are presented. The solutions give the stresses and birefringence at every point in the cross section of various fibers. The fundamental solution of the stress field is constructed by using the complex variable method in elasticity. When the cores, inner claddings, or stress-inducing regions are ellipses, circles, or bow-tie shapes, exact closed-form solutions can be found. The average core birefringence and center core birefringence of elliptical core, elliptical cladding, twin core, Panda, and bow-tie fibers are calculated and compared. Among these fibers, the bow-tie fiber shows the highest birefringence.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Reverse time migration with random boundaries (2009)

Reading wavefield checkpoints from disk is quickly becoming the bottleneck in Reverse Time Migration. We eliminate the need to write the wavefields to disk by creating an increasingly random boundary around the computational domain when propagating source function. The wave‐field that encounters the boundary region is pseudo‐randomized. Reflections off the random layer have minimal coherent correlation with the receiver wave‐field but can be reformed by running the wave equation in the reverse direction. This allows the source to first be propagated to the maximum recording time and then to be backward propagated simultaneously with receiver wave‐field significantly reducing memory and IO requirements. We demonstrate the methodology on the Sigsbee synthetic and show that it it significantly reduces coherent correlations.
Cloning and Sequencing of the Coenzyme B12-binding Domain of Isobutyryl-CoA Mutase from Streptomyces cinnamonensis, Reconstitution of Mutase Activity, and Characterization of the Recombinant Enzyme Produced inEscherichia coli (1999)

Isobutyryl-CoA mutase (ICM) catalyzes the reversible, coenzyme B(12)-dependent rearrangement of isobutyryl-CoA to n-butyryl-CoA, which is similar to, but distinct from, that catalyzed by methylmalonyl-CoA mutase. ICM has been detected so far in a variety of aerobic and anaerobic bacteria, where it appears to play a key role in valine and fatty acid catabolism. ICM from Streptomyces cinnamonensis is composed of a large subunit (IcmA) of 62.5 kDa and a small subunit (IcmB) of 14.3 kDa. icmB encodes a protein of 136 residues with high sequence similarity to the cobalamin-binding domains of methylmalonyl-CoA mutase, glutamate mutase, methyleneglutarate mutase, and cobalamin-dependent methionine synthase, including a conserved DXHXXG cobalamin-binding motif. Using IcmA and IcmB produced separately in Escherichia coli, we show that IcmB is necessary and sufficient with IcmA and coenzyme B(12) to afford the active ICM holoenzyme. The large subunit (IcmA) forms a tightly associated homodimer, whereas IcmB alone exists as a monomer. In the absence of coenzyme B(12), the association between IcmA and IcmB is weak. The ICM holoenzyme appears to comprise an alpha(2)beta(2)-heterotetramer with up to two molecules of bound coenzyme B(12). The equilibrium constant for the ICM reaction at 30 degrees C is 1.7 in favor of isobutyryl-CoA, and the pH optimum is near 7.4. The K(m) values for isobutyryl-CoA, n-butyryl-CoA, and coenzyme B(12) determined with an equimolar ratio of IcmA and IcmB are 57 +/- 13, 54 +/- 12, and 12 +/- 2 microM, respectively. A V(max) of 38 +/- 3 units/mg IcmA and a k(cat) of 39 +/- 3 s(-1) were determined under saturating molar ratios of IcmB to IcmA.
Dewarping of document image by global optimization (2005)

This paper proposes a novel dewarping technique for document images of bound volumes. This technique is a kind of model fitting techniques for estimating the warp of each text line by fitting some elastic curve model to the text line. Differing from conventional techniques, the proposed technique is applicable to document images including local irregularities such as formulae, short text lines, and figures, since the proposed technique dewarps whole document images by fitting splines while considering the global optimality that specifies the desirable relationship among the splines. The experimental results on several document images including the local irregularities indicated the effectiveness of the proposed technique. The experimental result also indicated the effectiveness of the vertical division of a document image into some partial document images for more accurate dewarping.
Relationship between in vivo degradative rates and isoelectric points of proteins. (1975)

Previous studies have shown that in mammalian cells proteins of large molecular weight are degraded more rapidly than small ones. Evidence is presented here that half-lives of proteins are also related to their isoelectric points. A double-isotope method was used to compare degradative rates of soluble proteins separated by isoelectric focusing. In rat liver, skeletal muscle, kidney, and brain, more rapid rates of catabolism were found for acidic protein fractions than for neutral or basic ones. Acidic proteins also tended to be degraded faster in several mouse tissues. A literature survey confirmed this trend. For 22 proteins from rat liver, a highly significant correlation was found between rates of degradation and isoelectric points (r = 0.824; P less than 0.01). This relationship between isoelectric point and half-life appears to be distinct from that between protein size and half-life.
Reflection Electron Microscopy and Spectroscopy for Surface Analysis (1996)

This book give an overview of reflection electron microscopy using both image and diffraction to study surface crystallography. Electron energy loss spectroscopy is also discussed as a tool to analyse the chemical and structural aspects of surfaces. The author gives an extensive and complete presentation of the techniques with many practical examples and the theoretical background necessary to explain the experimental observations. Theoretical approaches are discussed in detail: kinematical and dynamical theory and multislice theories for image and diffraction studies. FORTRAN source codes are included for calculating crystal structure data and electron energy loss spectra in different scattering geometries.
Two Independent Prostate Cancer Risk–Associated Loci at 11q13 (2009)

Single nucleotide polymorphisms (SNP) at 11q13 were recently implicated in prostate cancer risk by two genome-wide association studies and were consistently replicated in multiple study populations. To explore prostate cancer association in the regions flanking these SNPs, we genotyped 31 tagging SNPs in a approximately 110 kb region at 11q13 in a Swedish case-control study (Cancer of the Prostate in Sweden), including 2,899 cases and 1,722 controls. We found evidence of prostate cancer association for the previously implicated SNPs including rs10896449, which we termed locus 1. In addition, multiple SNPs on the centromeric side of the region, including rs12418451, were also significantly associated with prostate cancer risk (termed locus 2). The two groups of SNPs were separated by a recombination hotspot. We then evaluated these two representative SNPs in an additional approximately 4,000 cases and approximately 3,000 controls from three study populations and confirmed both loci at 11q13. In the combined allelic test of all four populations, P = 4.0 x 10(-11) for rs10896449 at locus 1 and P = 1.2 x 10(-6) for rs12418451 at locus 2, and both remained significant after adjusting for the other locus and study population. The prostate cancer association at these two 11q13 loci was unlikely confounded by prostate-specific antigen (PSA) detection bias because neither SNP was associated with PSA levels in controls. Unlike locus 1, in which no known gene is located, several putative mRNAs are in close proximity to locus 2. Additional confirmation studies at locus 2 and functional studies for both loci are needed to advance our knowledge on the etiology of prostate cancer.
Peroxisomal Metabolism of Propionic Acid and Isobutyric Acid in Plants (2007)

The subcellular sites of branched-chain amino acid metabolism in plants have been controversial, particularly with respect to valine catabolism. Potential enzymes for some steps in the valine catabolic pathway are clearly present in both mitochondria and peroxisomes, but the metabolic functions of these isoforms are not clear. The present study examined the possible function of these enzymes in metabolism of isobutyryl-CoA and propionyl-CoA, intermediates in the metabolism of valine and of odd-chain and branched-chain fatty acids. Using (13)C NMR, accumulation of beta-hydroxypropionate from [2-(13)C]propionate was observed in seedlings of Arabidopsis thaliana and a range of other plants, including both monocots and dicots. Examination of coding sequences and subcellular targeting elements indicated that the completed genome of A. thaliana likely codes for all the enzymes necessary to convert valine to propionyl-CoA in mitochondria. However, Arabidopsis mitochondria may lack some of the key enzymes for metabolism of propionyl-CoA. Known peroxisomal enzymes may convert propionyl-CoA to beta-hydroxypropionate by a modified beta-oxidation pathway. The chy1-3 mutation, creating a defect in a peroxisomal hydroxyacyl-CoA hydrolase, abolished the accumulation of beta-hydroxyisobutyrate from exogenous isobutyrate, but not the accumulation of beta-hydroxypropionate from exogenous propionate. The chy1-3 mutant also displayed a dramatically increased sensitivity to the toxic effects of excess propionate and isobutyrate but not of valine. (13)C NMR analysis of Arabidopsis seedlings exposed to [U-(13)C]valine did not show an accumulation of beta-hydroxypropionate. No evidence was observed for a modified beta-oxidation of valine. (13)C NMR analysis showed that valine was converted to leucine through the production of alpha-ketoisovalerate and isopropylmalate. These data suggest that peroxisomal enzymes for a modified beta-oxidation of isobutyryl-CoA and propionyl-CoA could function for metabolism of substrates other than valine.
The Anti-Inflammatory Activity of HMGB1 A Box Is Enhanced When Fused with C-Terminal Acidic Tail (2010)

HMGB1, composed of the A box, B box, and C tail domains, is a critical proinflammatory cytokine involved in diverse inflammatory diseases. The B box mediates proinflammatory activity, while the A box alone acts as a specific antagonist of HMGB1. The C tail contributes to the spatial structure of A box and regulates HMGB1 DNA binding specificity. It is unknown whether the C tail can enhance the anti-inflammatory effect of A box. In this study, we generated fusion proteins consisting of the A box and C tail, in which the B box was deleted and the A box and C tail were linked either directly or by the flexible linker sequence (Gly4Ser)3. In vitro and in vivo experiments showed that the two fusion proteins had a higher anti-inflammatory activity compared to the A box alone. This suggests that the fused C tail enhances the anti-inflammatory effect of the A box.
Distributed Coverage Control for a Multi-Robot Team in a Non-Convex Environment (2009)

International audience
Molecular determinants of macrophage tropism and viral persistence: importance of single amino acid changes in the polymerase and glycoprotein of lymphocytic choriomeningitis virus (1993)

This study documents that the immunosuppressive lymphocytic choriomeningitis virus (LCMV) variant, clone 13, shows a specific predilection for enhanced infection of macrophages both in vitro and in vivo and that single amino acid changes in the viral polymerase and glycoprotein are responsible for macrophage tropism. The growth difference seen between variant clone 13 and the parental Armstrong strain was specific for macrophages, since both clone 13 and Armstrong grew equally well in fibroblasts and neither isolate infected lymphocytes efficiently. Complete sequencing of the clone 13 genome, along with genetic analysis, showed that a single amino acid change in the polymerase (K-->Q at position 1079) was the major determinant of virus yield in macrophages. This was proven unequivocally by comparing the sequences of parental and reassortant viruses, which were identical at all loci except for the single mutation in the polymerase gene. This finding was further strengthened by showing that reversion at this site back to lysine (Q-->K) resulted in loss of macrophage tropism. In addition, an independently derived macrophage-tropic variant of LCMV, clone 28b, had a K-->N mutation at the same position. Thus, these results show that substitution of the positively charged amino acid K with a neutral amino acid (either Q or N) at residue 1079 of the polymerase resulted in enhanced viral replication in macrophages. In addition to the polymerase change, a mutation in the glycoprotein was also associated with macrophage tropism. This single amino acid change in the glycoprotein (F-->L at position 260) did not affect virus yield per macrophage but was critical in determining the number of macrophages infected. Our previous studies have shown that the same two mutations in the polymerase and glycoprotein are essential for establishing a chronic infection in adult mice. Since the same mutations confer macrophage tropism and ability to persist in vivo, these studies provide compelling evidence that infection of macrophages is a critical determinant of viral persistence and immune suppression.
Translation Eukaryotic Initiation Factor 4G Recognizes a Specific Structural Element within the Internal Ribosome Entry Site of Encephalomyocarditis Virus RNA (1998)

A complex of eukaryotic initiation factors (eIFs) 4A, 4E, and 4G (collectively termed eIF4F) plays a key role in recruiting mRNAs to ribosomes during translation initiation. The site of ribosomal entry onto most mRNAs is determined by interaction of the 5'-terminal cap with eIF4E; eIFs 4A and 4G may facilitate ribosomal entry by modifying mRNA structure near the cap and by interacting with ribosome-associated factors. eIF4G recruits uncapped encephalomyocarditis virus (EMCV) mRNA to ribosomes without the involvement of eIF4E by binding directly to the approximately 450-nucleotide long EMCV internal ribosome entry site (IRES). We have used chemical and enzymatic probing to map the eIF4G binding site to a structural element within the J-K domain of the EMCV IRES that consists of an oligo(A) loop at the junction of three helices. The oligo(A) loop itself is not sufficient to form stable complexes with eIF4G since alteration of its structural context abolished its interaction with eIF4G. Addition of wild type or trans-dominant mutant forms of eIF4A to binary IRES.eIF4G complexes did not further alter the pattern of chemical/enzymatic modification of the IRES.