gebhart/patrepeval huggingface dataset:
Reduced bleeding events with subcutaneous administration of recombinant human factor IX in immune-tolerant hemophilia B dogs (2003)

Intravenous administration of recombinant human factor IX (rhFIX) acutely corrects the coagulopathy in hemophilia B dogs. To date, 20 of 20 dogs developed inhibitory antibodies to the xenoprotein, making it impossible to determine if new human FIX products, formulations, or methods of chronic administration can reduce bleeding frequency. Our goal was to determine whether hemophilia B dogs rendered tolerant to rhFIX would have reduced bleeding episodes while on sustained prophylactic rhFIX administered subcutaneously. Reproducible methods were developed for inducing tolerance to rhFIX in this strain of hemophilia B dogs, resulting in a significant reduction in the development of inhibitors relative to historical controls (5 of 12 versus 20 or 20, P <.001). The 7 of 12 tolerized hemophilia B dogs exhibited shortened whole blood clotting times (WBCTs), sustained detectable FIX antigen, undetectable Bethesda inhibitors, transient or no detectable antihuman FIX antibody titers by enzyme-linked immunosorbent assay (ELISA), and normal clearance of infused rhFIX. Tolerized hemophilia B dogs had 69% reduction in bleeding frequency in year 1 compared with nontolerized hemophilia B dogs (P =.0007). If proven safe in human clinical trials, subcutaneous rhFIX may provide an alternate approach to prophylactic therapy in selected patients with hemophilia B.
The cAMP response element binding protein, CREB, is a potent inhibitor of diverse transcriptional activators (1993)

Cyclic AMP response element binding protein (CREB) activates transcription of cAMP response element (CRE)-containing promoters following an elevation of intracellular cAMP. Here we show that CREB and the highly related protein ATF-1 are also potent transcription inhibitors. Strikingly, CREB inhibits transcription of multiple activators, whose DNA-binding domains and activation regions are unrelated to one another. Inhibition requires that the CREB dimerization and DNA-binding domains are intact. However, inhibition is not dependent upon the presence of a CRE in the promoter, and does not involve heterodimer formation between CREB and the activator. The ability of an activator protein to inhibit transcription in such a promiscuous fashion has not been previously reported.
A Laminar-Flow, Water-Based Condensation Particle Counter (WCPC) (2005)

A new water-based condensation particle counter (WCPC) is presented.The WCPC is a thermally diffusive, laminar flow instrument.Condensational enlargement is achieved through the introduction of a saturated airflow into a "growth tube" with wetted walls held at a temperature higher than that of the entering flow.An unsheathed, 1 L/min instrument utilizing this principle has been evaluated with various aerosols.The particle size detected with an efficiency of 50% is at or below 4.8 nm for particles sampled from vehicular emissions or ambient air, and for various laboratorygenerated inorganic salts.The cut point is higher for the organic materials tested, ranging from 8 nm to 30 nm depending on the compound and purity level.An empirically determined dead-time correction factor is applied to the coincidence correction, which allows extension of the single-count mode to higher concentrations.The counting efficiencies for 80 nm oil and salt aerosols are equal, and above 97% for concentrations approaching 10 5 cm -3 .When subject to a step-fucntion change in input concentration the time required to attain 90% of the final value, including a 0.5 s lag, is 1.3 s.The corresponding exponential time constant is 0.35 s.The WCPC evaluated here is marketed as the TSI Model 3785.
Human artificial chromosomes generated by modification of a yeast artificial chromosome containing both human alpha satellite and single-copy DNA sequences (1999)

A human artificial chromosome (HAC) vector was constructed from a 1-Mb yeast artificial chromosome (YAC) that was selected based on its size from among several YACs identified by screening a randomly chosen subset of the Centre d'Etude du Polymorphisme Humain (CEPH) (Paris) YAC library with a degenerate alpha satellite probe. This YAC, which also included non-alpha satellite DNA, was modified to contain human telomeric DNA and a putative origin of replication from the human beta-globin locus. The resultant HAC vector was introduced into human cells by lipid-mediated DNA transfection, and HACs were identified that bound the active kinetochore protein CENP-E and were mitotically stable in the absence of selection for at least 100 generations. Microdissected HACs used as fluorescence in situ hybridization probes localized to the HAC itself and not to the arms of any endogenous human chromosomes, suggesting that the HAC was not formed by telomere fragmentation. Our ability to manipulate the HAC vector by recombinant genetic methods should allow us to further define the elements necessary for mammalian chromosome function.
An iC3b Receptor on Candida albicans: Structure, Function, and Correlates for Pathogenicity (1988)

Heretofore, the existence of membrane receptors for biologically active fragments of mammalian complement proteins has been confined to mammalian cells, where these receptors serve to protect the host by triggering multiple aspects of the phagocytic response to microbial invasion. In this study, we show that surface receptors for the C3 fragment iC3b are present on the yeast Candida albicans, where they promote the pathogenicity of this organism by inhibiting phagocytosis. These receptors share homology with the alpha-chain, but not with the beta-chain, of neutrophil receptors for iC3b, as determined by the binding of monoclonal antibodies, and are induced by mycelial transformation of the yeast and by high concentrations of glucose. Blockade of these receptors by monoclonal antibodies significantly augments phagocytosis for those strains studied. By binding iC3b noncovalently, these receptors impair phagocytic uptake of C. albicans by human polymorphonuclear leukocytes.
The Role of Angiotensin Receptors in Cardiovascular Diseases (1997)

As an antihypertensive regimen, angiotensin I-converting enzyme (ACE) inhibition appears to have an antiproliferative cardiovascular effect that is not caused by blood pressure reduction alone. On the other hand, ACE inhibition has been shown to induce neocapillarization in hypertrophied myocardium. The possible mechanisms behind these beneficial cardiovascular effects of ACE inhibition are the suppression of angiotensin II formation and the potentiation of bradykinin. Angiotensin II receptor antagonism appears to have a similar antiproliferative effect on myocardium and vascular smooth muscle as ACE inhibition. This suggests that the antiproliferative action of both regimens is due only to the reduction of the pressor and growth effects of angiotensin II, or that both regimens have an additional, similarly effective antiproliferative action. Recently, knowledge about angiotensin II receptors has almost exponentially expanded. The two main classes of angiotensin II receptors, type 1 and 2 (AT1 and AT2), have been shown to belong to the same receptor family. However, their signal transduction and function seem to differ totally. The function and signal transduction of AT1 are to a large extent known. All the well-known physiological and pathophysiological effects of angiotensin II have been attributed to AT1. On the other hand, AT2 has quite recently been shown to mediate antiproliferation and differentiation at least in some tissues and cells, e.g. in vascular endothelial cells and some cells of neuronal origin. This review highlights the recent findings on angiotensin II receptors, and discusses the mechanisms behind the beneficial cardiovascular effects of interfering with the renin-angiotensin system.
Amino acid catabolism in cheese-related bacteria: selection and study of the effects of pH, temperature and NaCl by quadratic response surface methodology (2001)

The findings of this work contribute to the knowledge about the amino acid catabolic enzymes in order to improve cheese ripening.
Prognostic Factors in Autologous Stem Cell Transplantation for Multiple Myeloma: An EBMT Registry Study (1994)

Autologous bone marrow- and blood progenitor cell transplantation was performed in 130 patients with multiple myeloma in 16 European centers between 1986 and 1993. At the time of follow-up, 77 patients were alive and 53 were dead. Complete remission after transplantation was obtained in 47% of all patients. The actuarial survival at 65 months was 28%. The median duration of relapse-free survival among patients who were in complete remission after transplantation was 29 months. The following factors were predictive for longer survival and freedom of progression in a univariate analysis: Male sex, age less than 45 years, a low serum-beta-2-microglobulin value at diagnosis, prior administration of only one treatment regimen, response on conventional chemotherapy immediately pretransplant and the use of a preparative regimen including melphalan. The last factor, in addition to stage I disease at diagnosis, male sex and responsive disease immediately pretransplant, were also demonstrated as independent predictive variables for longer survival in a multivariate analysis. Progression-free survival was significantly better for patients who were in complete remission after transplantation, as compared to those with persisting signs of disease. We conclude that high-dose chemo-radiotherapy with autologous stem cell transplantation can induce long-term responses, primarily in younger, male patients with chemotherapy-responsive early disease. High-dose melphalan, as single drug or in combination, appeared to be superior to other regimens. The chance of being persistently disease-free seemed to be greatest for patients being in complete remission already before the transplantation.
Megalin-Mediated Transcytosis of Thyroglobulin by Thyroid Cells is a Calmodulin-Dependent Process (2000)

Megalin, a multiligand receptor expressed on the apical surface of thyroid cells, mediates transepithelial transport (transcytosis) of thyroglobulin (Tg) across thyrocytes, resulting in diversion of Tg from the lysosomal pathway and reduction of the extent of thyroid hormone release from internalized Tg molecules. The calcium regulatory protein calmodulin facilitates some forms of transcytosis. Here we investigated the role of calmodulin in megalin-mediated transcytosis of Tg by thyroid cells. For this purpose, we studied the effect of calmodulin antagonists on Tg transcytosis by Fisher rat thyroid cells (FRTL-5), an established, differentiated thyroid cell line. FRTL-5 cells were cultured on permeable filters in the upper chamber of dual chambered devices, with megalin expression exclusively on the upper surface. Unlabeled Tg was added to the upper chamber at 37 degrees C, and transcytosed Tg was detected by enzyme-linked immunosorbent assay (ELISA) in fluids collected 1 hour later from the lower chamber. To study the role of calmodulin in Tg transcytosis, cells were preincubated with one of two calmodulin antagonists, either trifluoperazine or W7. Both antagonists markedly reduced transcytosis of Tg by FRTL-5 cells. These inhibitory effects and those of a monoclonal antimegalin antibody were not additive, indicating that calmodulin acts on the megalin-mediated pathway. Furthermore, trifluoperazine increased the extent of triiodothyronine (T3) release from exogenously added Tg by FRTL-5 cells, indicating that Tg transported in the calmodulin-dependent, megalin-mediated pathway, bypasses the lysosomal pathway.
The use of ustekinumab in autoimmune disease (2010)

Ustekinumab has shown significant efficacy in the treatment of chronic plaque psoriasis in Phase III studies, and promising results in Phase II studies in psoriatic arthritis. Efficacy has been shown in Crohn's disease only in non-responders to infliximab. Ustekinumab did not show benefit in the treatment of multiple sclerosis.
Single-Particle Model for a Lithium-Ion Cell: Thermal Behavior (2010)

The single-particle model presented by Santhanagopalan et al. [ J. Power Sources , 156 , 620 (2006)] is extended to include an energy balance. The temperature dependence of the solid phase diffusion coefficient of the lithium in the intercalation particles, the electrochemical reaction rate constants, and the open circuit potentials (OCPs) of the positive and negative electrodes are included in the model. The solution phase polarization is approximated using a nonlinear resistance, which is a function of current and temperature. The model is used to predict the temperature and voltage profiles in a lithium-ion cell during galvanostatic operations. The single-particle thermal model is validated by comparing the simulated voltage and temperature profiles to the results obtained using a distributed porous electrode model. The simulation results from the single-particle thermal model also show good agreement with experimental voltage data obtained from lithium-ion pouch cells under different discharge rates (C/33, C/2 and C) at different temperatures (15, 25, 35, and ).
Smoking by family members and friends and electroniccigaretteuse in adolescence: A systematic review and metaanalysis (2018)

The present meta-analysis suggests that smoking by family members and friends is significantly associated with increased probability of e-cigarette use in adolescents.
Isolation and Sequence of a Novel Human Chondrocyte Protein Related to Mammalian Members of the Chitinase Protein Family (1996)

We describe the isolation of a novel protein from the conditioned medium of human articular cartilage chondrocytes in primary culture. This 39-kDa protein has the N-terminal sequence YKL, which we have termed YKL-39. The 1434-nucleotide sequence of the YKL-39 cDNA predicts a 385-residue initial translation product and a 364-residue mature YKL-39. The amino acid sequence of YKL-39 is most closely related to YKL-40, followed by macrophage chitotriosidase, oviductal glycoprotein, and macrophage YM-1. All five proteins share significant sequence identity with bacterial chitinases and have the probable structure of an (alphabeta)8 barrel. YKL-39 lacks the active site glutamate, which is essential for the activity of chitinases, and as expected has no chitinase activity. The highest level of YKL-39 mRNA expression is seen in chondrocytes, followed by synoviocytes, lung, and heart. YKL-39 accounts for 4% of the protein in chondrocyte-conditioned medium, prostromelysin accounts for 17%, and YKL-40 accounts for 33%. In contrast to YKL-40, YKL-39 is not a glycoprotein and does not bind to heparin.
Design method and stress analysis on bioprosthetic heart valve (2007)

This paper reports the geometrical design method of bioprosthetic heart valve and stress distribution of leaflets with different shapes based on the theory of Membrane and finite element analysis method. According to Membrane theories, we construct the geometrical parametric model of bioprosthetic heart valve to achieve the efficiency of the natural heart valves of human. Combining traditional design theories and modern design methods, we create the paraboloid, spherical curved surfaces in accordance with the geometrical equations in the appropriate frame ordinal. Based on the stress analysis of two kinds of curved surfaces, we take turns to create relative inverse conic curved surfaces which satisfy the actual condition. Meanwhile, the space positions of boundary curves and important points are determined by the intersected curves and axis of revolution. Geometrical design and the Finite Element analysis could provide direct and useful information for the bioprosthetic-heart-valve designer.The experimental result of the finite element analysis reveal that the force distribution of sphere valves leaflets is comparatively reasonable. We also find that paraboloid valves leaflets have such obvious features of stress concentration and non-uniform force distribution. Therefore, mechanical properties of spherical valves leaflets are superior to those of paraboloid valves leaflets.
GERp95, a Membrane-associated Protein that Belongs to a Family of Proteins Involved in Stem Cell Differentiation (1999)

A panel of mAbs was elicited against intracellular membrane fractions from rat pancreas. One of the antibodies reacted with a 95-kDa protein that localizes primarily to the Golgi complex or the endoplasmic reticulum (ER), depending on cell type. The corresponding cDNA was cloned and sequenced and found to encode a protein of 97.6 kDa that we call GERp95 (Golgi ER protein 95 kDa). The protein copurifies with intracellular membranes but does not contain hydrophobic regions that could function as signal peptides or transmembrane domains. Biochemical analysis suggests that GERp95 is a cytoplasmically exposed peripheral membrane protein that exists in a protease-resistant complex. GERp95 belongs to a family of highly conserved proteins in metazoans and Schizosaccharomyces pombe. It has recently been determined that plant and Drosophila homologues of GERp95 are important for controlling the differentiation of stem cells (Bohmert et al., 1998; Cox et al., 1998; Moussian et al., 1998). In Caenorhabditis elegans, there are at least 20 members of this protein family. To this end, we have used RNA interference to show that the GERp95 orthologue in C. elegans is important for maturation of germ-line stem cells in the gonad. GERp95 and related proteins are an emerging new family of proteins that have important roles in metazoan development. The present study suggests that these proteins may exert their effects on cell differentiation from the level of intracellular membranes.
Interactive television: new genres, new format, new content (2005)

The aim of this paper is to discuss some of the main issues associated with interactive genres, formats and content in the context of interactive television (ITV). First, a set of new forms or categorizations of ITV will be presented. Second, the suite of interactive genres, formats and applications that currently constitutes ITV will be introduced and discussed. And third, some general conclusions concerning interactivity, television and the interactive user/viewer will be drawn.
Comparative Economics Of Deep Drilling In Anadarko Basin (1979)

Abstract In the Anadarko Basin, well development costs increase exponentially with depth. Average porosities for both sandstone and carbonate reservoirs decrease with depth in a predictable manner. Normal pressure and temperature gradients and a general porosity-water saturation relationship can be used to establish gas in place for reservoir rock at various depths. Recoveries can be calculated using typical permeability versus porosity data. A base case with 10 feet of net sandstone pay at a depth of 10,000 feet was used for comparative purposes. A 0.15 probability of this case yields an expected discounted cash flow rate of return of 15%. At depths of 15,000, 20,000 and 25,000 feet, sandstone pay thicknesses of 29, 89 and 297 feet are required to match the base case in terms of volume of gas in place per dollar spent. If recovery rates are considered, these thicknesses must be increased to 34, 128 and 670 feet respectively, to maintain a 15% rate of return. Similar relationships are indicated for carbonate reservoirs. Introduction The purpose of this paper was to compare economic for wells in the Anadarko Basin for depths varying from 10,000 to 25,000 feet. Because of the low incidence ooil occurrence below 10,000 feet, only gas wells were considered. For comparative purposes, economics for a base case gas well at a depth of 10,000 feet were run. Economics were then calculated for gas wells at depths of 15,000, 20,000 and 25,000 feet. The following data were used:constant gas price, gas gravity and operating expenseexisting Anadarko Basin data correlating porosity with depthnormal temperature and pressure gradientsgeneral variations in water saturation and permeability with porosity Pay thicknesses were varied to maintain constant economics at depths of 10,000 to 25,000 feet. Economics were considered both from the standpoint of maintaining a constant cost per Mcf of gas in place and also a constant cost per discounted Mcf of gas recovered. For this paper, the term "discounted Mcf" refers to the gas volume which is derived from projecting production rates with a deliverability model projecting production rates with a deliverability model and discounting those predicted volumes of gas with 15% present value factors. This approach considers both recovery efficiency and the present value concept of money. BASE CASE For this case, the following data were used:10,000 ft depth10 ft sandstone pay400 acre drainage area0.65 gas gravity (no condensate)4340 psia original pressure207 degrees F reservoir temperature12% porosity27% water saturation0.5 md permeability-4 skin factor215 psia pipeline pressure$475,000 producing well cost (1/3 equipment;2/3 intangibles)$380,000 dry hole cost$2.07/Mcf gas price$20/day operating expense50% tax rate (federal income, production and ad valorem taxes)3/16 royalty20 year double declining balance depreciation
The clinical utility of inhibiting CD28‐mediated costimulation (2009)

This volume covers many topics in the field of T-cell costimulation. The need for such a volume is testament to the growth of the field. From its beginning as a concept in the 1980s, we have now progressed to the point where many molecules now have functionally defined roles in T-cell costimulation. In addition, the field has progressed 'from bench to bedside'. Abatacept [cytotoxic T-lymphocyte antigen-4 (CTLA-4)-immunoglobulin (Ig) (CTLA-4-Ig)], an inhibitor of CD28-mediated T-cell costimulation, was approved for the treatment of moderate-to-severe rheumatoid arthritis in 2006 by the Food and Drug Administration and in 2007 by the European Medicines Agency. This chapter first presents a personal historical perspective on the early basic studies on the elucidation of the CD28/B7 T-cell costimulatory pathway and the discovery of CTLA-4-Ig. We next present an overview of studies of CTLA-4-Ig in preclinical animal studies. The material discussed in these first two sections is selective rather than exhaustive; their purpose is to provide context for the final section, a summary of human clinical studies performed with abatacept.
New Tool for Metabolic Pathway Engineering in Escherichia coli : One-Step Method To Modulate Expression of Chromosomal Genes (2005)

A simple and highly efficient method was developed to produce a library of Escherichia coli clones that express a particular chromosomal gene at a wide range of expression levels. The basic strategy was to replace all or part of the upstream region of a coding sequence containing the elements involved in its expression (promoter, operator, gene coding for a regulator, ribosome binding site, and start codon) with a PCR-generated library of expression cassettes.