gebhart/patrepeval huggingface dataset:
Effect of recombinant factor VIIa on the hemostatic defect in dogs with hemophilia A, hemophilia B, and von Willebrand disease. (1989)

Recombinant factor VIIa (rF.VIIa) is a two-chain procoagulant enzyme (Mr, approximately 50,000) active only when complexed with tissue factor in the extrinsic clotting system. We administered human rF.VIIa to hemophilic and von Willebrand disease (vWD) dogs to determine its hemostatic effectiveness and survival in the circulation. Hemophilia A dogs lacking factor VIII demonstrated an immediate increase in plasma rF. VIIa and prompt stoppage of hemorrhage at bleeding time (BT) sites. In seven studies in two dogs, the range of dose of rF. VIIa was 50-220 micrograms/kg, with an apparent 7- to 11-fold increase in plasma factor VII and a mean recovery in plasma of 34%. The t1/2 was 2.8 +/- 0.5 hr. The BT was normalized except in an animal given the minimum dose. In four studies in two hemophilia B dogs lacking factor IX, BT was normalized. The elevation in plasma factor VII was by a factor of 8-30, with a mean recovery of rF.VIIa in plasma of 44%. In two studies in a homozygous vWD dog lacking von Willebrand factor, which is needed for platelet function, BT was not corrected even though large doses of rF. VIIa were given. The human rF. VIIa protein was immunogenic for dogs. These studies indicate that factor VIIa corrects the hemostatic defect in dogs with hemophilia A and B, diseases primarily of the intrinsic clotting system, but does not correct the hemostatic defect in vWD.
A manual nanoscale method for protein crystallization (2003)

To overcome one of the major hurdles in three-dimensional crystal structure determination - the requirement for large quantities of purified material to grow crystals - crystallization methodologies have been developed that require only a total of 2-5 microl of a concentrated macromolecular solution to screen more than 100 conditions. These procedures employ a circular slide containing an array of 25 wells designed for crystallization setups in the nanolitre volume range. These 'crystallization slides' fit into the wells of standard crystallization trays. These nanoscale crystallization approaches have been used to reproducibly obtain well diffracting crystals of three proteins, two that are being actively studied (glycerol kinase and NADH peroxidase) and one test protein (lysozyme), using only 40-350 microg (0.04-0.35 mg) of proteins to screen 100 conditions. These nanolitre crystallization methods are easily adapted for the typical laboratory, without the requirement of robotics or expensive equipment.
Flucytosine: Correlation between Toxicity and Pharmacokinetic Parameters (2000)

Flucytosine (5-fluorocytosine, 5-FC) is a systemic antimycotic drug the major toxicities of which are bone marrow depression and hepatotoxicity. The purpose of this observational and retrospective study was to assess a possible relationship between toxicity and 5-FC pharmacokinetics within a group of 53 intensive care unit patients. The presented results reveal that thrombocytopenia is associated with a decreased 5-FC clearance and that the thrombocyte nadir is linearly related to the 5-FC clearance. Furthermore, patients experiencing 5-FC levels exceeding 100 mg 5-FC/l were found to be at a higher risk of developing thrombocytopenia and hepatotoxicity as compared to those not exceeding this level.
Effect of New Oral Antidiabetic Agent CS-045 on Glucose Tolerance and Insulin Secretion in Patients with NIDDM (1991)

CS-045 is effective in improving glucose tolerance without stimulation of insulin secretion in NIDDM, suggesting an effect in improving insulin sensitivity.
Clinicopathological Analysis of Papillary Thyroid Cancer withPIK3CAAlterations in a Middle Eastern Population (2007)

A higher incidence of PIK3CA alterations and the possible synergistic effect of PIK3CA alterations and BRAF mutations suggest their major role in Middle Eastern PTC tumorigenesis and argue for therapeutic targeting of PI3K/AKT and MAPK pathways.
Signal Regulatory Proteins Negatively Regulate Immunoreceptor-dependent Cell Activation (1999)

Signal regulatory proteins of the alpha subtype (SIRPalpha) are ubiquitous molecules of the immunoglobulin superfamily that negatively regulate protein tyrosine kinase receptor-dependent cell proliferation. Their intracytoplasmic domain contains four motifs that resemble immunoreceptor tyrosine-based inhibition motifs (ITIMs) and that, when tyrosyl-phosphorylated, recruit cytoplasmic SH2 domain-bearing protein tyrosine phosphatases (SHPs). ITIMs are borne by molecules that negatively regulate cell activation induced by receptors bearing immunoreceptor tyrosine-based activation motifs (ITAMs). Because SIRPalpha are coexpressed with ITAM-bearing receptors in hematopoietic cells, we investigated whether SIRPalpha could negatively regulate ITAM-dependent cell activation. We found SIRPalpha transcripts in human mast cells, and we show that a chimeric molecule having the transmembrane and intracytoplasmic domains of SIRPalpha could inhibit IgE-induced mediator secretion and cytokine synthesis by mast cells. Inhibition required that the SIRPalpha chimera was coaggregated with ITAM-bearing high affinity IgE receptors (FcepsilonRI). It was correlated with the tyrosyl phosphorylation of the SIRPalpha chimera and the recruitment of SHP-1 and SHP-2. The phosphorylation of FcepsilonRI ITAMs was decreased; the mobilization of intracellular Ca(2+) and the influx of extracellular Ca(2+) were reduced, and the activation of the mitogen-activated protein kinases Erk1 and Erk2 was abolished. SIRPalpha can therefore negatively regulate not only receptor tyrosine kinase-dependent cell proliferation but also ITAM-dependent cell activation.
Inhibition of Anchorage-Independent Growth of Human Melanoma Cells by a Monoclonal Antibody to a Chondroitin Sulfate Proteoglycan<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref> (1983)

Anchorage-independent growth of tumor cells constitutes a phenotype highly associated with malignant transformation and appears to be important in the ultimate event of tumor metastasis, i.e., secondary tumor colonization. The role of a specific, melanoma-associated chondroitin sulfate proteoglycan population in anchorage-independent growth was assessed. Melanoma cells cultured in soft agar containing monoclonal antibody (mAb) 9.2.27, which recognizes such molecules on the surface of these cells, showed a 67-74% specific decrease in their colony formation. In contrast, neither mouse myeloma IgG nor monoclonal anti-HLA-A,B,C antibody (W6/32) had any effect on colony formation of the melanoma cells grown in soft agar. Human melanoma cells cultured in the presence of mAb 9.2.27 or W6/32 did not exhibit any changes in their DNA or protein synthetic metabolism. These findings suggest that 9.2.27-defined chondroitin sulfate proteoglycans on the surface of human melanoma cells may be involved in cell--cell interaction important in anchorage-independent growth.
Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis (2006)

The newer 5-ASA preparations were superior to placebo and tended towards therapeutic benefit over SASP. However, considering their relative costs, a clinical advantage to using the newer 5-ASA preparations in place of SASP appears unlikely. This review updates the existing review of oral 5-aminosalicylic acid for induction of remission in ulcerative colitis which was published in the Cochrane Library (Issue 1, 2006).
Deep Biaffine Attention for Neural Dependency Parsing (2016)

In this paper, we present our approach for Multilingual Open Information Extraction. Our sequence labeling based approach builds only on Universal Dependency representation to capture OpenIE’s regularities and to perform Cross-lingual Multilingual OpenIE. We propose a new two-stage pipeline model for sequence labeling, that first identifies all the arguments of the relation and only then classifies them according to their most likely label. This paper also introduces a new benchmark evaluation for French. Experimental Evaluation shows that our approach achieves the best results in the available Benchmarks (English, French, Spanish and Portuguese).
Uptake of Hydrophilic Solutes Through Plant Leaves: Current State of Knowledge and Perspectives of Foliar Fertilization (2009)

The definitive version is available at:&#13;\n&#13;\nhttp://www.informaworld.com/smpp/title~content=t713400911
Water Injection in IC - SI Engines to Control Detonation and to Reduce Pollutant Emissions (2003)

&lt;div class="htmlview paragraph"&gt;In this paper the effects of water injection in the intake pipe of a single-cylinder standard CFR engine are investigated from an experimental viewpoint. Research was carried out at AGIP Petroli and ISAB ERG Refineries of Priolo Gargallo (SR).&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;Tests were performed according to ASTM Research and Motor Method. Water was supplied by a continuous and pulsed injection system. The engine was fed with low Octane Number (O.N.) base gasoline (cheap products, intermediate of refinery processes). The water to fuel mass flow rate ratio was varied in the range 0 to 2.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;Measurements of O.N. have shown that water injection virtually increases the water/fuel mixture O.N. and that it is possible to obtain a correct run feeding the engine with a low octane number fuel. The pollutant emissions measurements confirm the effectiveness of water injection in reducing the engine environmental impact.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;In conclusion results have shown that water injection really represents a way to avoid detonation and to control NO&lt;sub&gt;x&lt;/sub&gt; formation in SI engines.&lt;/div&gt;
Minimally Invasive Torque Sensor for Tendon-Driven Robotic Hands (2008)

The purpose of this paper is to present preliminary results on the use of a torque sensor based on a Bragg grating for torque control applications of tendon-driven mechanisms. Owing to the minimally invasive nature of optical fibres, one of the most promising applications can be the integration of the sensor into anthropomorphic robotic hands for accurate impedance or compliance control. In fact, the sensing element of the proposed torque sensor can be easily bonded directly to the tendon following its natural routing with a significantly reduced invasiveness with respect to conventional sensors. These are usually based on strain gauges, which are cumbersome and require additional mechanical components and interfaces in order to provide the necessary measurement, while the Bragg sensor is embedded into the optical fibre whose typical diameter is about 125 mum which allows its integration into the tendon itself. The experimental results presented here have been obtained on a simple test-bench realized by using off-the-shelf and cheap components conceived to demonstrate the potentiality of the sensor and its effectiveness in an actual compliance control scheme.
The Notch pathway in ovarian carcinomas and adenomas (2005)

Elements of the Notch pathway regulate differentiation; we investigated the expression of such elements in epithelial ovarian tumours. A total of 32 ovarian tumour samples (17 adenocarcinomas, three borderline tumours, 12 adenomas), two human ovarian cancer (A2780, OVCAR3), and one ovarian surface (IOSE 144) cell lines were analysed. The expression of Notch pathway elements was assessed by RT-PCR, real-time PCR (Notch 1), and by immunoblots (Notch 1 extracellular domain (EC), HES1). The proliferation and colony formation of A2780 cells were measured after stable transfection with activated Notch 1 (intracellular domain). Jagged 2, Delta-like-1, Manic Fringe, and TSL1 were expressed more frequently in adenocarcinomas whereas Deltex, Mastermind, and Radical Fringe were more frequent in adenomas. Quantitative PCR revealed decreased Notch 1 mRNA in ovarian adenocarcinomas compared with adenomas. The expression of Notch 1-EC protein was similar in benign and malignant tumours. HES1 protein was strongly expressed in 18/19 ovarian cancers and borderline tumours but not in adenomas. Transfecting A2780 cells with active Notch 1-IC resulted in a proliferative and colony formation advantage compared to mock transfected cells. Thus, Notch pathway elements are expressed in ovarian epithelial tumours and some of them are differentially expressed between adenomas and carcinomas. The Notch pathway could be a target for the development of therapies for ovarian cancer.
Monoamine oxidases in major depressive disorder and alcoholism (2012)

Monoamine oxidases play an integral role in brain function. Both monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) regulate neurochemistry by degrading monoamine neurotransmitters (serotonin, dopamine, and norepinephrine). Any alteration in MAO levels can have devastating effects on the brain and behavior by lowering or raising neurotransmitter levels and producing toxic reactive oxygen species. In this review article, MAO is examined in terms of function and genetic organization, with special focus on recent discoveries related to the transcriptional regulation of MAO. In recent studies, transcriptional regulation involves a repressor protein, R1, for MAO-A and an activator protein, KLF11 (a Krüppel-like factor; also referred to as transforming growth factor-beta early inducible gene 2, TIEG2), for both MAO-A and MAO-B, by binding to Sp/KLF sites in the core promoters of MAO and regulating MAO gene expression. Furthermore, KLF11 may influence MAO-B expression and augment glyceraldehyde-3 phosphate dehydrogenase (GAPDH) to upregulate MAO-B transcription upon exposure to ethanol. Finally, we review recent progress in MAO research and highlight the roles that MAOs play in several psychiatric conditions, including chronic stress, major depressive disorder and alcohol dependence. Further research in this area is needed to better understand MAOs, their transcription factors and signaling pathways in psychiatric illnesses in order to develop new strategies for pharmacological advancement.
A Y526Q Mutation in the Newcastle Disease Virus HN Protein Reduces Its Functional Activities and Attenuates Virus Replication and Pathogenicity (2009)

The hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) is a multifunctional protein that plays a crucial role in virus infectivity. In this study, using the mesogenic strain Beaudette C (BC), we mutated three conserved amino acids thought to be part of the binding/catalytic active site in the HN protein. We also mutated five additional residues near the proposed active site that are nonconserved between BC and the avirulent strain LaSota. The eight recovered NDV HN mutants were assessed for effects on biological activities. While most of the mutations had surprisingly little effect, mutation at conserved residue Y526 reduced the neuraminidase, receptor binding, and fusion activities and attenuated viral virulence in eggs and young birds.
Functional Rescue of Mutant Human Cystathionine β-Synthase by Manipulation of Hsp26 and Hsp70 Levels in Saccharomyces cerevisiae (2008)

Many human diseases are caused by missense substitutions that result in misfolded proteins that lack biological function. Here we express a mutant form of the human cystathionine beta-synthase protein, I278T, in Saccharomyces cerevisiae and show that it is possible to dramatically restore protein stability and enzymatic function by manipulation of the cellular chaperone environment. We demonstrate that Hsp70 and Hsp26 bind specifically to I278T but that these chaperones have opposite biological effects. Ethanol treatment induces Hsp70 and causes increased activity and steady-state levels of I278T. Deletion of the SSA2 gene, which encodes a cytoplasmic isoform of Hsp70, eliminates the ability of ethanol to restore function, indicating that Hsp70 plays a positive role in proper I278T folding. In contrast, deletion of HSP26 results in increased I278T protein and activity, whereas overexpression of Hsp26 results in reduced I278T protein. The Hsp26-I278T complex is degraded via a ubiquitin/proteosome-dependent mechanism. Based on these results we propose a novel model in which the ratio of Hsp70 and Hsp26 determines whether misfolded proteins will either be refolded or degraded.
Estrogen receptors in canine mammary tumors. (1982)

The presence of estrogen receptor in 67 canine mammary lesions was correlated with pathological features of the disease. All tissue specimens were analyzed for estrogen receptor content by a sucrose gradient ultracentrifugation method previously used in analyzing human breast cancer cytosols. Pathological features of the tissues were assessed by a veterinary pathologist without knowledge of results of estrogen receptor analysis. Sixty-two (92.5%) of the tissue samples analyzed were classified as epithelial neoplastic lesions, and 38 of these (61.3%), including 24 adenocarcinomas, were estrogen receptor for positive (i.e., estrogen receptor concentration equal to or greater than 10 fmol/mg cytosol protein). All five of the nonepithelial neoplastic lesions were estrogen receptor negative. Canine and human breast cancers share common histological types and have similar biological behavior. If a significant percentage of canine mammary cancer is also estrogen dependent, the dog may be a useful model for hormonal studies and for the development of models of endocrine therapy for human breast cancer.
Direct Cardiac NMR Imaging of Heart Wall and Blood Flow Velocity (1984)

Nuclear magnetic resonance (NMR) imaging is used to produce in the same scan both anatomical and functional information of the heart and great vessels. A method is described to generate velocity images by the use of phase shifts for moving spins induced by imaging gradients under electrocardiogram (ECG) synchronized imaging conditions. The influence of the different gradients is discussed together with methods to obtain velocity information for each gradient direction separately. The results, obtained with a 0.14 T resistive NMR scanner and normal volunteers, show the spatial velocity distribution in the aorta and heart walls in color scale images. The feasibility of velocity calculations is demonstrated and some applications are given. The present results indicate the possibility of quantitative flow and motion analysis with ECG synchronized NMR imaging.
Autosomal dominant polycystic kidney disease: pathophysiology and treatment (2006)

Autosomal dominant polycystic disease (ADPKD) is one of the most common monogenic disorders, and globally is the third most common cause of end-stage kidney disease. Until recently, the causes of this disease remained obscure. However, the past decade has seen enormous advances in the understanding of the pathophysiology and genetics of this condition, and recent studies have suggested the possibility of specific treatment for slowing cyst growth. This review attempts to address three central questions: (i) how cysts are created; (ii) how mutated gene products give rise to cysts; and (iii) the prospects for treatment.

Cysts usually develop from the collecting duct,1,,2 and are highly focal in nature, only developing in a very small proportion of nephrons. They generally increase in size and number throughout life, and encroach on normal renal tissue, causing macrophage infiltration, neovascularization, progressive fibrosis and a slow deterioration in renal function.3,,4 The disease only reaches the stage of chronic renal failure or end-stage renal disease in the fourth or fifth decade in the case of autosomal dominant polycystic disease type 1 (PKD1), or a decade later in the case of autosomal dominant polycystic disease type 2 (PKD2),5 in approximately 50% of patients.

Cysts are originally connected to the mother tubule, but eventually the connection closes off, and the cysts can then only enlarge by a process of increased proliferation of mural epithelial cells and tubular secretion. In ADPKD, these cells undergo a remarkable phenotypic change, from the usual non-proliferative and reabsorptive phenotype of collecting duct principal cells, to a secretory and proliferative phenotype; this process has been extensively investigated by Grantham and coworkers.6–10 They initially microdissected cysts from polycystic kidneys, and suspended them in a hydrated collagen gel. The growth of the cysts could then be measured by … 

Address correspondence to Dr J. Rapoport, Department of Nephrology & Hypertension, Kaplan Medical Center, POB 1, Rehovot 76100, Israel. e-mail: jayson_r{at}clalit.org.il
CD4+ T cell-independent DNA vaccination against opportunistic infections (2005)

Depletion or dysfunction of CD4+ T lymphocytes profoundly perturbs host defenses and impairs immunogenicity of vaccines. Here, we show that plasmid DNA vaccination with a cassette encoding antigen (OVA) and a second cassette encoding full-length CD40 ligand (CD40L), a molecule expressed on activated CD4+ T lymphocytes and critical for T cell helper function, can elicit significant titers of antigen-specific immunoglobulins in serum and Tc1 CD8+ T cell responses in CD4-deficient mice. To investigate whether this approach leads to CD4+ T cell-independent vaccine protection against a prototypic AIDS-defining infection, Pneumocystis (PC) pneumonia, we used serum from mice vaccinated with PC-pulsed, CD40L-modified DCs to immunoprecipitate PC antigens. Kexin, a PC antigen identified by this approach, was used in a similar DNA vaccine strategy with or without CD40L. CD4-deficient mice receiving DNA vaccines encoding Kexin and CD40L showed significantly higher anti-PC IgG titers as well as opsonic killing of PC compared with those vaccinated with Kexin alone. Moreover, CD4-depleted, Kexin-vaccinated mice showed a 3-log greater protection in a PC challenge model. Adoptive transfer of CD19+ cells or IgG to SCID mice conferred protection against PC challenge, indicating a role of humoral immunity in the protection. The results of these studies show promise for CD4-independent vaccination against HIV-related or other opportunistic pathogens.
Relationship between Activation Energy and Bottleneck Size for Li+ Ion Conduction in NASICON Materials of Composition LiMM‘(PO4)3; M, M‘ = Ge, Ti, Sn, Hf (1998)

The activation energy involved in the motion of Li+ ions along the conduction channels of the NASICON framework has been determined from electrical conductivity measurements in samples of composition LiM2(PO4)3 and LiMM‘(PO4)3, where M and M‘ are Ge, Ti, Sn, and Hf, all compounds belonging to space group R3̄c. Two lithium sites, M1 and M2, inside the channels, can be distinguished. The sites are connected through triangular bottlenecks of oxygen atoms, and the size of the bottleneck has been estimated from refined and simulated structures for each composition. The plot of activation energy vs bottleneck size shows two regimes: for sizes up to 2.04 Å the activation energy decreases steeply, but above 2.04 Å the activation energy is almost constant. These regimes are discussed on the basis of the effective Li+ ionic radius for the compounds analyzed.