gebhart/patrepeval huggingface dataset:
The von Willebrand factor-binding protein (vWbp) of Staphylococcus aureus is a coagulase (2004)

Staphylococcus aureus encodes a secreted von Willebrand factor-binding protein (vWbp) of 482 amino acids. The N-terminal part of this protein is homologous to staphylocoagulase and therefore we investigated whether vWbp has coagulating activity. Recombinant vWbp was shown to coagulate human and porcine plasma efficiently, but was less active against plasma from other species. The coagulation efficiency was concentration dependent, and could be inhibited by specific antibodies against vWbp. Furthermore, the species-specific coagulation by vWbp depended on the interaction with prothrombin. This interaction also resulted in specific cleavage of vWbp, releasing the C-terminal part from the coagulating domain.
Large‐Scale N‐Ethyl‐N‐Nitrosourea Mutagenesis of Mice – from Phenotypes to Genes (2000)

The most important tool for obtaining insight into the function of genes is the use of mutant model organisms. Homologous recombination in embryonic stem cells allows the systematic production of mouse mutants for any gene that has been cloned. Gene trap strategies have been designed to interrupt even unknown genes which are tagged by the inserted vector and can be characterised structurally and functionally. Complementary to such ‘gene‐driven’ approaches, ‘phenotype‐driven’ approaches are necessary to identify new genes or gene products through a search for mutants with specific defects, uncovering the function of genetic pathways in physiological and pathological processes. Mutagenesis using the alkylating agent N‐ethyl‐N‐nitrosourea (ENU) is a powerful approach for the production of such mouse mutants. Since ENU induces mainly point mutations in premeiotic spermatogonia, this strategy allows the production of multiple alleles of a particular gene, which is pivotal for a fine tuned analysis of its function.
Candidate Source of Flux Noise in SQUIDs: Adsorbed Oxygen Molecules (2015)

A major obstacle to using superconducting quantum interference devices (SQUIDs) as qubits is flux noise. We propose that the heretofore mysterious spins producing flux noise could be O_{2} molecules adsorbed on the surface. Using density functional theory calculations, we find that an O_{2} molecule adsorbed on an α-alumina surface has a magnetic moment of ~1.8 μ_{B}. The spin is oriented perpendicular to the axis of the O-O bond, the barrier to spin rotations is about 10 mK. Monte Carlo simulations of ferromagnetically coupled, anisotropic XY spins on a square lattice find 1/f magnetization noise, consistent with flux noise in Al SQUIDs.
Sub Graph Approach In Iterative Sum-Product Algorithm (2006)

A new scheduling algorithm to the iterative sum-product algorithm, which is called sub-graph scheduling, will be presented in this paper. The propesed algorithm provides a schedule which has a higher convergence rate than the iterative sum-product algorithm while keeping the complexity of one iteration withot degrading the performance. Our method also gives an explanation to the fact that turbo decoders have faster convergence rate than LDPC decoders.
Lint, a C Program Checker (1978)

Lint is a command which examines C source programs, detecting a number of bugs and obscurities. It enforces the type rules of C more strictly than the C compilers. It may also be used to enforce a number of portability restrictions involved in moving programs between different machines and/or operating systems. Another option detects a number of wasteful, or error prone, constructions which nevertheless are, strictly speaking, legal. Lint accepts multiple input files and library specifications, and checks them for consistency. The separation of function between lint and the C compilers has both historical and practical rationale. The compilers turn C programs into executable files rapidly and efficiently. This is possible in part because the compilers do not do sophisticated type checking, especially between separately compiled programs. Lint takes a more global, leisurely view of the program, looking much more carefully at the compatibilities. This document discusses the use of lint...
Preparation of soluble murine IL-6 receptor and anti-murine IL-6 receptor antibodies (1991)

Starting with a previously isolated cDNA clone encoding murine IL-6R, a stable transformed Chinese hamster ovary cell line constitutively expressing soluble murine IL-6R (smIL-6R) has been established. The smIL-6R was purified to homogeneity by sequential filtration and chromatography of culture medium. The smIL-6R augmented the sensitivity of M1 cells to IL-6 in their growth inhibition in a dose-response manner. Rat hybridomas producing mAb specific to murine IL-6R were also established. One of the clones, RS13, produced IgG2a isotype that was capable of inhibiting IL-6 activity. ELISA for the quantitation of smIL-6R was established, which could detect smIL-6R in a quantity as low as 1 ng/ml.
Association between shear stress, angiogenesis, and VEGF in skeletal muscles in vivo. (2001)

Higher capillary shear stress with prazosin than with stimulation may upregulate VEGF expression in the early stages of treatment. Greater proliferation of capillaries preceding a higher proportion of VEGF-positive capillaries in stimulated muscles, in the presence of a modest increase in shear stress, suggests that angiogenesis was initiated by other factors in addition to shear stress.
Human cyclophilin B: a second cyclophilin gene encodes a peptidyl-prolyl isomerase with a signal sequence. (1991)

We report the cloning and characterization of a cDNA encoding a second human cyclosporin A-binding protein (hCyPB). Homology analyses reveal that hCyPB is a member of the cyclophilin B (CyPB) family, which includes yeast CyPB, Drosophila nina A, and rat cyclophilin-like protein. This family is distinguished from the cyclophilin A (CyPA) family by the presence of endoplasmic reticulum (ER)-directed signal sequences. hCyPB has a hydrophobic leader sequence not found in hCyPA, and its first 25 amino acids are removed upon expression in Escherichia coli. Moreover, we show that hCyPB is a peptidyl-prolyl cis-trans isomerase which can be inhibited by cyclosporin A. These observations suggest that other members of the CyPB family will have similar enzymatic properties. Sequence comparisons of the CyPB proteins show a central, 165-amino acid peptidyl-prolyl isomerase and cyclosporin A-binding domain, flanked by variable N-terminal and C-terminal domains. These two variable regions may impart compartmental specificity and regulation to this family of cyclophilin proteins containing the conserved core domain. Northern blot analyses show that hCyPB mRNA is expressed in the Jurkat T-cell line, consistent with its possible target role in cyclosporin A-mediated immunosuppression.
High-content Analysis of Antibody Phage-display Library Selection Outputs Identifies Tumor Selective Macropinocytosis-dependent Rapidly Internalizing Antibodies (2014)

Many forms of antibody-based targeted therapeutics, including antibody drug conjugates, utilize the internalizing function of the targeting antibody to gain intracellular entry into tumor cells. Ideal antibodies for developing such therapeutics should be capable of both tumor-selective binding and efficient endocytosis. The macropinocytosis pathway is capable of both rapid and bulk endocytosis, and recent studies have demonstrated that it is selectively up-regulated by cancer cells. We hypothesize that receptor-dependent macropinocytosis can be achieved using tumor-targeting antibodies that internalize via the macropinocytosis pathway, improving potency and selectivity of the antibody-based targeted therapeutic. Although phage antibody display libraries have been utilized to find antibodies that bind and internalize to target cells, no methods have been described to screen for antibodies that internalize specifically via macropinocytosis. We hereby describe a novel screening strategy to identify phage antibodies that bind and rapidly enter tumor cells via macropinocytosis. We utilized an automated microscopic imaging-based, High Content Analysis platform to identify novel internalizing phage antibodies that colocalize with macropinocytic markers from antibody libraries that we have generated previously by laser capture microdissection-based selection, which are enriched for internalizing antibodies binding to tumor cells in situ residing in their tissue microenvironment (Ruan, W., Sassoon, A., An, F., Simko, J. P., and Liu, B. (2006) Identification of clinically significant tumor antigens by selecting phage antibody library on tumor cells in situ using laser capture microdissection. Mol. Cell. Proteomics. 5, 2364-2373). Full-length human IgG molecules derived from macropinocytosing phage antibodies retained the ability to internalize via macropinocytosis, validating our screening strategy. The target antigen for a cross-species binding antibody with a highly active macropinocytosis activity was identified as ephrin type-A receptor 2. Antibody-toxin conjugates created using this macropinocytosing IgG were capable of potent and receptor-dependent killing of a panel of EphA2-positive tumor cell lines in vitro. These studies identify novel methods to screen for and validate antibodies capable of receptor-dependent macropinocytosis, allowing further exploration of this highly efficient and tumor-selective internalization pathway for targeted therapy development.
Influenza Virus Matrix Protein Is the Major Driving Force in Virus Budding (2000)

To get insights into the role played by each of the influenza A virus polypeptides in morphogenesis and virus particle assembly, the generation of virus-like particles (VLPs) has been examined in COS-1 cell cultures expressing, from recombinant plasmids, different combinations of the viral structural proteins. The presence of VLPs was examined biochemically, following centrifugation of the supernatants collected from transfected cells through sucrose cushions and immunoblotting, and by electron-microscopic analysis. It is demonstrated that the matrix (M1) protein is the only viral component which is essential for VLP formation and that the viral ribonucleoproteins are not required for virus particle formation. It is also shown that the M1 protein, when expressed alone, assembles into virus-like budding particles, which are released in the culture medium, and that the recombinant M1 protein accumulates intracellularly, forming tubular structures. All these results are discussed with regard to the roles played by the virus polypeptides during virus assembly.
Transcriptional activation induced in macrophages by Toll‐like receptor (TLR) ligands: from expression profiling to a model of TLR signaling (2004)

Toll-like receptors (TLR) sense microbial compounds and bridge innate and adaptive immunity by activation of antigen-presenting cells. TLR-induced signaling via intracellular adaptor molecules, including MyD88 and TRIF, drives transcriptional activation of genes including pro-inflammatory cytokines and cell activation markers. To globally assess the activation programs triggered by individual TLR in macrophages, we used microarray-based gene expression profiling of the murine macrophage cell line RAW264.7. Here we describe that the TLR4 ligand LPS more strongly modulates gene expression compared to ligands for TLR 2, 3, 7, and 9. Taking advantage of the known dependency of TLR on given adaptor molecules, we operationally define sets of MyD88 and TRIF "private" genes. We conclude with a TLR signaling model that incorporates both negative and synergistic interactions of MyD88- and TRIF-controlled signaling pathways as deduced from the microarray data presented.
Neuroprotective actions of noradrenaline: effects on glutathione synthesis and activation of peroxisome proliferator activated receptor delta (2007)

The endogenous neurotransmitter noradrenaline (NA) can protect neurons from the toxic consequences of various inflammatory stimuli, however the exact mechanisms of neuroprotection are not well known. In the current study, we examined neuroprotective effects of NA in primary cultures of rat cortical neurons. Exposure to oligomeric amyloid beta (Abeta) 1-42 peptide induced neuronal damage revealed by increased staining with fluorojade, and toxicity assessed by LDH release. Abeta-dependent neuronal death did not involve neuronal expression of the inducible nitric oxide synthase 2 (NOS2), since Abeta did not induce nitrite production from neurons, LDH release was not reduced by co-incubation with NOS2 inhibitors, and neurotoxicity was similar in wildtype and NOS2 deficient neurons. Co-incubation with NA partially reduced Abeta-induced neuronal LDH release, and completely abrogated the increase in fluorojade staining. Treatment of neurons with NA increased expression of gamma-glutamylcysteine ligase, reduced levels of GSH peroxidase, and increased neuronal GSH levels. The neuroprotective effects of NA were partially blocked by co-treatment with an antagonist of peroxisome proliferator activated receptors (PPARs), and replicated by incubation with a selective PPARdelta (PPARdelta) agonist. NA also increased expression and activation of PPARdelta. Together these data demonstrate that NA can protect neurons from Abeta-induced damage, and suggest that its actions may involve activation of PPARdelta and increases in GSH production.
The BCL11 gene family: involvement of BCL11A in lymphoid malignancies (2001)

Many malignancies of mature B cells are characterized by chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus on chromosome 14q32.3 and result in deregulated expression of the translocated oncogene. t(2;14)(p13;q32.3) is a rare event in B-cell malignancies. In contrast, gains and amplifications of the same region of chromosome 2p13 have been reported in 20% of extranodal B-cell non-Hodgkin lymphomas (B-NHL), in follicular and mediastinal B-NHL, and in Hodgkin disease (HD). It has been suggested that REL, an NF-kappaB gene family member, mapping within the amplified region, is the pathologic target. However, by molecular cloning of t(2;14)(p13;q32.3) from 3 cases of aggressive B-cell chronic lymphocytic leukemia (CLL)/immunocytoma, this study has shown clustered breakpoints on chromosome 2p13 immediately upstream of a CpG island located about 300 kb telomeric of REL. This CpG island was associated with a Krüppel zinc finger gene (BCL11A), which is normally expressed at high levels only in fetal brain and in germinal center B-cells. There were 3 major RNA isoforms of BCL11A, differing in the number of carboxy-terminal zinc fingers. All 3 RNA isoforms were deregulated as a consequence of t(2;14)(p13;q32.3). BCL11A was highly conserved, being 95% identical to mouse, chicken, and Xenopus homologues. BCL11A was also highly homologous to another gene (BCL11B) on chromosome 14q32.1. BCL11A coamplified with REL in B-NHL cases and HD lymphoma cell lines with gains and amplifications of 2p13, suggesting that BCL11A may be involved in lymphoid malignancies through either chromosomal translocation or amplification.
Triene prostaglandins: Prostacyclin and thromboxane biosynthesis and unique biological properties (1979)

Platelets enzymatically convert prostaglandin H(3) (PGH(3)) into thromboxane A(3). Both PGH(2) and thromboxane A(2) aggregate human platelet-rich plasma. In contrast, PGH(3) and thromboxane A(3) do not. PGH(3) and thromboxane A(3) increase platelet cyclic AMP in platelet-rich plasma and thereby: (i) inhibit aggregation by other agonists, (ii) block the ADP-induced release reaction, and (iii) suppress platelet phospholipase-A(2) activity or events leading to its activation. PGI(3) (Delta(17)-prostacyclin; synthesized from PGH(3) by blood vessel enzyme) and PGI(2) (prostacyclin) exert similar effects. Both compounds are potent coronary relaxants that also inhibit aggregation in human platelet-rich plasma and increase platelet adenylate cyclase activity. Radioactive eicosapentaenoate and arachidonate are readily and comparably acylated into platelet phospholipids. In addition, stimulation of prelabeled platelets with thrombin releases comparable amounts of eicosapentaenoate and arachidonate, respectively. Although eicosapentaenoic acid is a relatively poor substrate for platelet cyclooxygenase, it appears to have a high binding affinity and thereby inhibits arachidonic acid conversion by platelet cyclooxygenase and lipoxygenase. It is therefore possible that the triene prostaglandins are potential antithrombotic agents because their precursor fatty acids, as well as their transformation products, PGH(3), thromboxane A(3), and PGI(3), are capable of interfering with aggregation of platelets in platelet-rich plasma.
Scattering Suppression and High-Mobility Effect of Size-Quantized Electrons in Ultrafine Semiconductor Wire Structures (1980)

Transport properties of electrons confined in ultrafine wire structures are studied theoretically. The scattering probability of such size-quantized electrons is calculated for Coulomb potential and is shown to be suppressed drastically because of the one-dimensional nature of the electronic motion in the wire. Mobilities are estimated to be well beyond 106 cm2/Vs for a properly-designed GaAs wire at low temperatures. The feasibility of preparing such ultrafine structures with and without ultrafine lithography is discussed.
Findings of the WMT 2019 Shared Task on Parallel Corpus Filtering for Low-Resource Conditions (2019)

Following the WMT 2018 Shared Task on Parallel Corpus Filtering, we posed the challenge of assigning sentence-level quality scores for very noisy corpora of sentence pairs crawled from the web, with the goal of sub-selecting 2% and 10% of the highest-quality data to be used to train machine translation systems. This year, the task tackled the low resource condition of Nepali-English and Sinhala-English. Eleven participants from companies, national research labs, and universities participated in this task.
NF- k appa B regulates IL-1 beta transcription through a consensus NF- k appa B binding site and a nonconsensus CRE-like site. (1994)

In these studies, we show that NF-kappa B induces transcription from the human pro-IL-1 beta (IL-1 beta) gene. A recombinant plasmid pIL-1(-4000)-CAT, containing 4 kb of the IL-1 beta gene upstream regulatory sequence was transactivated by the p65 subunit of NF-kappa B or by treatment of the cells with a combination of NF-kappa B inducers including LPS, PMA, and dibutyryl cyclic AMP (L+P+C) in U937 cells. Coexpression of p65 with L+P+C treatment led to a synergistic response, whereas coexpression of the I kappa B alpha/MAD-3 protein, in place of p65, blocked L+P+C induction. A series of 5' deletion mutants of the IL-1 beta promoter were used to define two p65 response regions: region I located between -2800 to -2720 bp and region II located between -512 and -133 bp. Electrophoretic mobility shift assays confirmed that NF-kappa B-like proteins could bind to two consensus binding sites in region II. A site-specific mutation in only one of these NF-kappa B sites (-296/-286 bp) caused a specific loss of induction by p65 or L+P+C. A cyclic AMP response element (CRE) site (-2761/-2753 bp) in region I has been shown previously to be critical for L+P+C induction. Mutation of the CRE in an enhancerless test plasmid containing two copies of region I blocked transactivation by p65. Likewise, coexpression of I kappa B alpha inhibited CRE-dependent L+P+C induction of the wild-type counterpart. These data show that NF-kappa B regulates a nonconsensus CRE site in addition to the consensus binding site at -296/-286 bp and suggest that NF-kappa B may play multiple roles in the induction of IL-1 beta transcription.
Primary Renal Cell Carcinoma in a Transplanted Kidney: Genetic Evidence of Recipient Origin (2009)

We report the first case of a grafted-kidney RCC whose recipient's cell origin has been proved by microsatellite analysis. An origin from the recipient's kidney or bone marrow stem cells is proposed as the more plausible hypothesis.
Design and Antimicrobial Action of Purine Analogues That Bind Guanine Riboswitches (2009)

Riboswitches are structured RNA domains that can bind directly to specific ligands and regulate gene expression. These RNA elements are located most commonly within the noncoding regions of bacterial mRNAs, although representatives of one riboswitch class have been discovered in organisms from all three domains of life. In several Gram-positive species of bacteria, riboswitches that selectively recognize guanine regulate the expression of genes involved in purine biosynthesis and transport. Because these genes are involved in fundamental metabolic pathways in certain bacterial pathogens, guanine-binding riboswitches may be targets for the development of novel antibacterial compounds. To explore this possibility, the atomic-resolution structure of a guanine riboswitch aptamer from Bacillus subtilis was used to guide the design of several riboswitch-compatible guanine analogues. The ability of these compounds to be bound by the riboswitch and repress bacterial growth was examined. Many of these rationally designed compounds are bound by a guanine riboswitch aptamer in vitro with affinities comparable to that of the natural ligand, and several also inhibit bacterial growth. We found that one of these antimicrobial guanine analogues (6-N-hydroxylaminopurine, or G7) represses expression of a reporter gene controlled by a guanine riboswitch in B. subtilis, suggesting it may inhibit bacterial growth by triggering guanine riboswitch action. These studies demonstrate the utility of a three-dimensional structure model of a natural aptamer to design ligand analogues that target riboswitches. This approach also could be implemented to design antibacterial compounds that specifically target other riboswitch classes.
Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver (2002)

Using flow cytometry and single cell-based assays, we prospectively identified hepatic stem cells with multilineage differentiation potential and self-renewing capability. These cells could be clonally propagated in culture where they continuously produced hepatocytes and cholangiocytes as descendants while maintaining primitive stem cells. When cells that expanded in vitro were transplanted into recipient animals, they morphologically and functionally differentiated into hepatocytes and cholangiocytes with reconstitution of hepatocyte and bile duct structures. Furthermore, these cells differentiated into pancreatic ductal and acinar cells or intestinal epithelial cells when transplanted into pancreas or duodenal wall. These data indicate that self-renewing pluripotent stem cells persist in the developing mouse liver and that such cells can be induced to become cells of other organs of endodermal origin under appropriate microenvironment. Manipulation of hepatic stem cells may provide new insight into therapies for diseases of the digestive system.