gebhart/patrepeval huggingface dataset:
Diagnosis and treatment of inherited factor X deficiency (2008)

Factor X is a vitamin K-dependent, liver-produced serine protease that serves a pivotal role in coagulation as the first enzyme in the common pathway to fibrin formation. Inherited factor X deficiency is a rare autosomal recessive bleeding disorder that is estimated to occur in 1:1,000,000 individuals up to 1:500 carriers. Several international registries of FX-deficient patients have greatly expanded the knowledge of clinical phenotype. A proposed classification of severity is based on FX:C activity measurements: an FX:C measurement <1% is severe, an FX:C measurement of 1-5% is moderate and an FX:C measurement of 6-10% is mild. Levels above 20% are infrequently associated with bleeding and heterozygotes are usually asymptomatic. Among patients with FX:C levels <10%, unlike moderate or severe haemophilia A and B, mucocutaneous bleeding symptoms such as epistaxis and menorrhagia occur in the majority. In addition, patients with moderate-severe deficiency may have symptoms similar to that of haemophilia A and B, including haemarthrosis, intracranial haemorrhage, and gastrointestinal bleeding. Genotype characterization may offer important clues about clinical prognosis. More than 80 mutations of the F10 gene have been identified, most of which are missense mutations. There is no specific FX replacement product yet readily available, but fresh frozen plasma and prothrombin complex concentrates can be used for treatment of bleeding symptoms and preparation for surgery.
Compact electro-optic modulator on silicon-on-insulator substrates using cavities with ultra-small modal volumes (2007)

We experimentally demonstrate a micron-size electro-optic modulator using a high-index-contrast silicon Fabry-Pérot resonator cavity. This compact device consists of a 1-D cavity formed within a single mode silicon channel waveguide and an embedded p-i-n junction on a silicon-oninsulator platform. The entire device is 6.0 microns in length. We demonstrate modulation depths as large as 5.87 dB at speeds of 250 Mbps limited only by fabrication imperfections, with optimized theoretical speeds of several Gbps.
A New Method of DNA Sequencing Using Deoxynucleoside α-Thiotriphosphates (1986)

A new procedure for determining DNA nucleotide sequences is reported. In the first step of the method, four DNAs, each separately substituted with a different deoxynucleoside phosphorothioate in place of the corresponding monophosphate, are prepared by template-directed polymerization catalyzed by DNA polymerase. In the second step, these DNAs are subjected to stringent exonuclease III treatment, which produces only fragments terminating with a phosphorothioate internucleotide linkage. These can then be separated by standard gel electrophoresis techniques and the sequence can be read directly as in presently used sequencing methods.
Site Occupancies by Iron in Nontronites (2002)

Abstract Twelve nontronites and two ferruginous smectites have been characterized with respect to Fe 3+ occupancy of tetrahedral sites. The techniques used were near infrared, Fe-K X-ray absorption near-edge and X-ray absorption fine-structure spectroscopies, along with two X-ray diffraction techniques. The results show that calculations of the structural formulae of many nontronites should be adjusted to include Fe 3+ in tetrahedral sites. The nontronite from Spokane County, Washington, (∼44% Fe 2 O 3 ) is essentially an end-member with its non-siliceous tetrahedral sites occupied by Fe 3+ . Samples with chemical compositions similar to Garfield nontronite (∼36.5% Fe 2 O 3 ) may have small amounts (&lt;5% of total Fe 3+ ) of tetrahedral Fe 3+ . Tetrahedral Fe 3+ is unlikely to be present in samples containing less than ∼34% Fe 2 O 3 .
Evaluación sanitaria de alimentos no tradicionales que se venden sin receta (2009)

Los suplementos nutricionales, productos naturales, y alimentos funcionales, entre otros similares en propositos, son opciones puestas a disposicion de los consumidores preocupados por el logro de una dieta equilibrada, nutritiva y saludable. A pesar de la presencia en el mercado de estos “alimentos no tradicionales”, y el consumo que se hace de ellos, no existe informacion util sobre ellos con vistas al acto del registro sanitario como paso previo para la libre venta y comercializacion. El Registro sanitario de Cuba, adscrito al INHA Instituto de Nutricion e Higiene de los Alimentos, esta obligado por ley a establecer las pautas necesarias a los efectos del asentamiento y registro. Durante el bienio 2007-2008 se presentaron solicitudes de registro de 135 alimentos no tradicionales, 20 (14.8%) de ellos de produccion nacional. La tasa de aprobacion fue del 97.8%, comportamiento superior al del bienio anterior. El etiquetado deficiente del producto, la insuficiente informacion sobre las dosis de los nutrientes contenidos en el mismo, y la pobre informacion tecnica, se revelaron como las no-conformidades mas comunmente encontradas durante los procesos de evaluacion y registro. El perfeccionamiento de la actividad del registro de los alimentos no tradicionales ha resultado en un cuerpo programatico-regulatorio unico, un ordenamiento del proceso de solicitud y registro, y una tasa superior de aprobacion de tales productos.
Theoretical analysis of channel drop tunneling processes (1999)

We investigate general channel drop tunneling processes using both analytic theory and first-principles simulations. These tunneling processes occur when two one-dimensional continuums are brought into close proximity with a resonator system that supports localized states. Propagating states can be transferred between the continuums through the resonator system. We show that the transport properties are intricately related to the symmetries of the resonant states. Complete transfer can be achieved by manipulating the symmetries of the system, and by forcing an accidental degeneracy between states with different symmetries. In addition, the line shape of the transfer spectrum can be engineered by varying the number of localized states in the resonator system. The theoretical analysis is confirmed by first-principles simulations of transport properties in a two-dimensional photonic crystal.
Comparison of Photodynamic Targets in a Carcinoma Cell Line and Its Mitochondrial DNA-Deficient Derivative (2000)

The relative contribution, to cell death, of photodynamic damage to respiratory proteins (known targets of photodynamic therapy with many photosensitizers) and other cellular sites was examined. The models were a human ovarian carcinoma cell line 2008, and its mitochondrial DNA-deficient derivative ET3, which lacks several key respiratory protein subunits. Phototoxicity was compared in the two cell lines with photosensitizers that localized to different cellular compartments. Photosensitizers included Victoria Blue BO (VBBO; mitochondria); Photofrin with a short incubation, (plasma membrane) or a long incubation (intracellular membranes including mitochondria); and Nile Blue A (NBA; lysosomes). Photosensitizer content and localization did not differ between the 2008 and ET3 cells. For sensitizers without a primary mitochondrial localization (NBA and Photofrin with a short incubation), there was no significant difference between 2008 and ET3 toxicity. Consistent with a mitochondrial localization of VBBO and independence from respiratory-chain damage, ET3 cells were less susceptible than 2008 to both dark- and light-activated VBBO-mediated damage. Statistical analysis of the data demonstrated minimal photobleaching of VBBO and a significant difference between the phototoxicity curves of ET3 and 2008. For Photofrin with a long incubation, dark- and phototoxicity effects were similar for both cell lines. Inhibition of respiratory enzymes is thus only a minor component of Photofrin-mediated (long incubation) phototoxicity in these cell lines and is overwhelmed by more significant damage elsewhere, whereas it is a major but not the exclusive element of death mediated by VBBO.
Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes (2001)

Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide with biologic effects that include regulation of hematopoietic stem cell development, extracellular matrix remodeling, and inflammatory cytokine generation. To delineate the potential role of VEGF in patients with myelodysplastic syndrome (MDS), VEGF protein and receptor expression and its functional significance in MDS bone marrow (BM) were evaluated. In BM clot sections from normal donors, low-intensity cytoplasmic VEGF expression was detected infrequently in isolated myeloid elements. However, monocytoid precursors in chronic myelomonocytic leukemia (CMML) expressed VEGF in an intense cytoplasmic pattern with membranous co-expression of the Flt-1 or KDR receptors, or both. In situ hybridization confirmed the presence of VEGF mRNA in the neoplastic monocytes. In acute myelogenous leukemia (AML) and other MDS subtypes, intense co-expression of VEGF and one or both receptors was detected in myeloblasts and immature myeloid elements, whereas erythroid precursors and lymphoid cells lacked VEGF and receptor expression. Foci of abnormal localized immature myeloid precursors (ALIP) co-expressed VEGF and Flt-1 receptor, suggesting autocrine cytokine interaction. Antibody neutralization of VEGF inhibited colony-forming unit (CFU)-leukemia formation in 9 of 15 CMML and RAEB-t patient specimens, whereas VEGF stimulated leukemia colony formation in 12 patients. Neutralization of VEGF activity suppressed the generation of tumor necrosis factor-alpha and interleukin-1beta from MDS BM-mononuclear cells and BM-stroma and promoted the formation of CFU-GEMM and burst-forming unit-erythroid in methylcellulose cultures. These findings indicate that autocrine production of VEGF may contribute to leukemia progenitor self-renewal and inflammatory cytokine elaboration in CMML and MDS and thus provide a biologic rationale for ALIP and its adverse prognostic relevance in high-risk MDS.
Human Immunodeficiency Virus Type 1-Induced Macrophage Gene Expression Includes the p21 Gene, a Target for Viral Regulation (2005)

In contrast to CD4+ T cells, human immunodeficiency virus type 1 (HIV-1)-infected macrophages typically resist cell death, support viral replication, and consequently, may facilitate HIV-1 transmission. To elucidate how the virus commandeers the macrophage's intracellular machinery for its benefit, we analyzed HIV-1-infected human macrophages for virus-induced gene transcription by using multiple parameters, including cDNA expression arrays. HIV-1 infection induced the transcriptional regulation of genes associated with host defense, signal transduction, apoptosis, and the cell cycle, among which the cyclin-dependent kinase inhibitor 1A (CDKN1A/p21) gene was the most prominent. p21 mRNA and protein expression followed a bimodal pattern which was initially evident during the early stages of infection, and maximum levels occurred concomitant with active HIV-1 replication. Mechanistically, viral protein R (Vpr) independently regulates p21 expression, consistent with the reduced viral replication and lack of p21 upregulation by a Vpr-negative virus. Moreover, the treatment of macrophages with p21 antisense oligonucleotides or small interfering RNAs reduced HIV-1 infection. In addition, the synthetic triterpenoid and peroxisome proliferator-activated receptor gamma ligand, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), which is known to influence p21 expression, suppressed viral replication. These data implicate p21 as a pivotal macrophage facilitator of the viral life cycle. Moreover, regulators of p21, such as CDDO, may provide an interventional approach to modulate HIV-1 replication.
Instruction Issue Logic in Pipelined Supercomputers (1984)

Basic principles and design tradeoffs for control of pipelined processors are first discussed. We concentrate on register-register architectures like the CRAY-1 where pipeline control logic is localized to one or two pipeline stages and is referred to as "instruction issue logic." Design tradeoffs are explored by giving designs for a variety of instruction issue methods that represent a range of complexity and sophistication. These vary from the CRAY-1 issue logic to a version of Tomasulo's algorithm, first used in the IBM 360/91 floating point unit. Also studied are Thornton's "scoreboard" algorithm used on the CDC 6600 and an algorithm we have devised. To provide a standard for comparison, all the issue methods are used to implement the CRAY-1 scalar architecture. Then, using a simulation model and the Lawrence Livermore Loops compiled with the CRAY Fortran compiler, performance results for the various issue methods are given and discussed.
Induction of ob Gene Expression by Corticosteroids Is Accompanied by Body Weight Loss and Reduced Food Intake (1995)

Genetic studies in mice have identified the ob gene product as a potential signaling factor regulating body weight homeostasis and energy balance. It is suggested that modulation of ob gene expression results in changes in body weight and food intake. Glucocorticoids are shown to have important metabolic effects and to modulate food intake and body weight. In order to test the hypothesis that these metabolic effects of glucocorticoids are linked to changes in the expression of the ob gene, ob mRNA levels were evaluated in rats treated with different glucocorticosteroids at catabolic doses and correlated to the kinetics of changes in body weight gain and food intake. Results from time course experiments demonstrate that adipose tissue ob gene expression is rapidly induced by glucocorticosteroids. This induction is followed by a concordant decrease in body weight gain and food consumption. These data suggest that the catabolic effects of corticosteroids on body weight mass and food intake might be mediated by changes in ob expression. Modulation of ob expression may therefore constitute a mechanism through which hormonal, pharmacological, or other factors control body weight homeostasis.
Taxanes: A New Class of Antitumor Agents (1995)

Taxanes belong to a new group of antineoplastic agents with a novel mechanism of action for a cytotoxic drug. They promote microtubule assembly and stabilize the microtubules. Paclitaxel, the first agent in this group to become available, was isolated from the Pacific yew, Taxus brevifolia, in 1971. In preclinical and clinical studies, paclitaxel and its semisynthetic analog docetaxel exhibit significant antitumor activity. This review deals with the physicochemical properties, pharmacology, and results of preclinical and clinical trials of the taxanes.
Molecular Design of Liquid Crystalline Brush-Like Block Copolymers for Magnetic Field Directed Self-Assembly: A Platform for Functional Materials (2014)

We report on the development of a liquid crystalline block copolymer with brush-type architecture as a platform for creating functional materials by magnetic-field-directed self-assembly. Ring-opening metathesis of <i>n</i>-alkyloxy cyanobiphenyl and polylactide (PLA) functionalized norbornene monomers provides efficient polymerization yielding low polydispersity block copolymers. The mesogenic species, spacer length, monomer functionality, brush-chain length, and overall molecular weight were chosen and optimized to produce hexagonally packed cylindrical PLA domains which self-assemble and align parallel to an applied magnetic field. The PLA domains can be selectively removed by hydrolytic degradation resulting in the production of nanoporous films. The polymers described here provide a versatile platform for scalable fabrication of aligned nanoporous materials and other functional materials based on such templates.
Reduction of Intraocular Pressure and Glaucoma Progression (2002)

The Early Manifest Glaucoma Trial is the first adequately powered randomized trial with an untreated control arm to evaluate the effects of IOP reduction in patients with open-angle glaucoma who have elevated and normal IOP. Its intent-to-treat analysis showed considerable beneficial effects of treatment that significantly delayed progression. Whereas progression varied across patient categories, treatment effects were present in both older and younger patients, high- and normal-tension glaucoma, and eyes with less and greater visual field loss.
Interaction and Solvation Energies of Nonpolar DNA Base Analogues and Their Role in Polymerase Insertion Fidelity (1999)

Although DNA polymerase fidelity has been mainly ascribed to Watson-Crick hydrogen bonds, two nonpolar isosteres for thymine (T) and adenine (A)--difluorotoluene (F) and benzimidazole (Z) --effectively mimic their natural counterparts in polymerization experiments with pol I (KF exo-) [JC Morales and ET Kool. Nature Struct Biol, 5, 950-954, 1998]. By ab initio quantum chemical gas phase methods (HF/6-31G* and MP2/6-31G**) and a solvent phase method (CPCM-HF/6-31G**), we find that the A-F interaction energy is 1/3 the A-T interaction energy in the gas phase and unstable in the solvent phase. The F-Z and T-Z interactions are very weak and T-Z is quite unstable in the solvent. Electrostatic solvation energy calculations on F, Z and toluene yield that Z is two times, and F and toluene are five times, less hydrophilic than the natural bases. Of the new "base-pairs" (F-Z, T-Z, and F-A), only F-A formed an A-T-like arrangement in unconstrained optimizations. F-Z and T-Z do not freely form planar arrangements, and constrained optimizations show that large amounts of energy are required to make these pairs fit the exact A-T geometry, suggesting that the polymerase does not require all bases to conform to the exact A-T geometry. We discuss a model for polymerase/nucleotide binding energies and investigate the forces and conformational range involved in the polymerase geometrical selection.
Homodimers but not monomers of Rituxan (chimeric anti-CD20) induce apoptosis in human B-lymphoma cells and synergize with a chemotherapeutic agent and an immunotoxin (2001)

In 1997, a chimeric anti-CD20 monoclonal antibody (mAb) (Rituxan) was approved for the treatment of low-grade/follicular B-cell lymphoma. Rituxan has a long half-life and low immunogenicity, and it mediates effector function. Rituxan induces apoptosis in some tumor cell lines in vitro. Previous studies with mAbs that react with neoplastic B cells have demonstrated that homodimers of immunoglobulin G ([IgG](2)) often inhibit cell growth more effectively than their monomeric (IgG)(1) counterparts. In this study, the ability of IgG or F(ab')(2) homodimers vs monomers of Rituxan were compared for their ability to inhibit the growth of several different B-lymphoma cell lines in vitro. It was found that homodimers of Rituxan had superior antigrowth activity in vitro and that F(ab')(2) homodimers were the most active. Homodimers, but not monomers, of Rituxan induced both apoptosis and necrosis of several B-cell lymphoma lines in vitro; the inhibition of cell growth was not dependent upon the presence of Fc receptors or upon 10-fold or greater differences in the density of CD20 on the target cells. Rituxan homodimers, compared with monomers, also rendered drug-resistant CD20(+) B-lymphoma cells more sensitive to chemotherapeutic agents and synergized with an anti-CD22 immunotoxin in vitro.
Characterisation of an outer membrane protein of Moraxella catarrhalis (1997)

To elucidate potential vaccine antigens, Moraxella catarrhalis outer membrane proteins (OMPs) were studied. We have previously shown an OMP to be a target for human IgG and have now further characterised this OMP which appears to have a molecular mass of 84 kDa and to be distinct from the 81-kDa OMP, CopB. Human transferrin was shown to bind the 84-kDa OMP alone. N-terminal sequencing of this OMP and purified M. catarrhalis transferrin binding protein B (TbpB) revealed homology both with each other and with the TbpB of Haemophilus influenzae and Neisseria meningitidis. Adsorption of human anti-serum with purified TbpB from two M. catarrhalis strains abolished or reduced binding of IgG to the 84-kDa OMP from three M. catarrhalis isolates. IgG binding to CopB was unaffected. It is clear that the 84-kDa OMP is distinct from CopB and is a likely homologue of TbpB.
A BeepBeep ranging system on mobile phones (2007)

The demo, BeepBeep, shows a high-accuracy acoustic-based ranging system without relaying on any pre-planned infrastructure or inter-device time synchronization. Moreover, the BeepBeep is a pure software-based solution and readily applicable to many low-cost sensor platforms and to most commercial-off-the-shelf mobile devices. Our demo using two common cell phones shows that BeepBeep can achieve average two centimeters accuracy within a range of more than ten meters.
Bone Morphogenic Protein Antagonists Are Coexpressed With Bone Morphogenic Protein 4 in Endothelial Cells Exposed to Unstable Flow In Vitro in Mouse Aortas and in Human Coronary Arteries (2007)

The present results suggest that ECs coexpress BMP antagonists along with BMP4 in an attempt to minimize the inflammatory response by oscillatory shear stress as part of a negative feedback mechanism. The balance between the agonist, BMP4, and its antagonists may play an important role in the overall control of inflammation and atherosclerosis.
Substrate specificities of catalytic fragments of protein tyrosine phosphatases (HPTPβ, LAR, and CD45) toward phosphotyrosylpeptide substrates and thiophosphotyrosylated peptides as inhibitors (1993)

The transmembrane PTPase HPTP beta differs from its related family members in having a single rather than a tandemly duplicated cytosolic catalytic domain. We have expressed the 354-amino acid, 41-kDa human PTP beta catalytic fragment in Escherichia coli, purified it, and assessed catalytic specificity with a series of pY peptides. HPTP beta shows distinctions from the related LAR PTPase and T cell CD45 PTPase domains: it recognizes phosphotyrosyl peptides of 9-11 residues from lck, src, and PLC gamma with Km values of 2, 4, and 1 microM, some 40-200-fold lower than the other two PTPases. With kcat values of 30-205 s-1, the catalytic efficiency, kcat/Km, of the HPTP beta 41-kDa catalytic domain is very high, up to 5.7 x 10(7) M-1 s-1. The peptides corresponding to PLC gamma (766-776) and EGFR (1,167-1,177) phosphorylation sites were used for structural variation to assess pY sequence context recognition by HPTP beta catalytic domain. While exchange of the alanine residue at the +2 position of the PLC gamma (Km of 1 microM) peptide to lysine or aspartic acid showed little or no effect on substrate affinity, replacement by arginine increased the Km 35-fold. Similarly, the high Km value of the EGFR pY peptide (Km of 104 microM) derives largely from the arginine residue at the +2 position of the peptide, since arginine to alanine single mutation at the -2 position of the EGFR peptide decreased the Km value 34-fold to 3 microM. Three thiophosphotyrosyl peptides have been prepared and act as substrates and competitive inhibitors of these PTPase catalytic domains.