gebhart/patrepeval huggingface dataset:
TNF? potentiates IFN?-induced cell death in oligodendrocyte progenitors (1998)

Oligodendrocytes in multiple sclerosis brain may be under a direct attack by proinflammatory cytokines, particularly tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma). In this study, we have examined the in vitro cytotoxic effects of the two cytokines, individually and in combination, on oligodendrocyte lineage cells using morphological criteria, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction assay (MTT), terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL), and agarose-gel electrophoretic analysis of fragmented DNA. IFNgamma exerted a dose-dependent cytotoxic effect on cultured CG4 cells, an oligodendrocyte progenitor cell line, and in primary cultures of purified oligodendrocyte progenitors. TNFalpha, while by itself being only mildly toxic, greatly potentiated the cytotoxicity of IFNgamma. The cytokine effects were developmentally modified in that their cytotoxic and cooperative effects became less evident in more differentiated cells. A cell-permeable peptide inhibitor (i.e., z-VAD.fmk) of caspases partially suppressed apoptotic changes elicited by the cytokine combination in CG4 cells but not in primary oligodendrocytes. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis of mRNA prepared from cytokine-treated cultures revealed an increased expression of the death receptor, Fas. The results suggest particular vulnerability of oligodendrocyte progenitors to a combination of TNFalpha and IFNgamma involving an activation of the cell death program.
Glycation of proteins as a source of superoxide. (1988)

For the monitoring of diabetes mellitus, the concentration of serum glycated proteins is currently measured by a colorimetric reaction using the dye nitroblue tetrazolium. As this reduction may depend on superoxide ions (O2-), we checked whether glycated proteins were capable of generating O2- in vitro. We incubated ferricytochrome c with glucose, fructose, 1-deoxy-1-morpholino-D-fructose (an analog of the 1-desoxy-1-amino-fructose radical found in glycated proteins) and glycated proteins prepared from diabetic blood serum. We found that these substances, except free glucose, were all able to generate O2- not only at alkaline pH, but even at pH 7.4 with a slower rate. The possibility of O2- formation from glycated proteins may explain some long term complications of diabetes mellitus.
Molecular characterization of the Bacillus anthracis main S‐layer component: evidence that it is the major cell‐associated antigen (1997)

Bacillus anthracis, the aetiological agent of anthrax, is a Gram-positive spore-forming bacterium. The cell wall of vegetative cells of B. anthracis is surrounded by an S-layer. An array remained when sap, a gene described as encoding an S-layer component, was deleted. The remaining S-layer component, termed EA1, is chromosomally encoded. The gene encoding EA1 (eag) was obtained on two overlapping fragments in Escherichia coli and shown to be continuous to the sap gene. The EA1 amino acid sequence, deduced from the eag nucleotide sequence, shows classical S-layer protein features (no cysteine, only 0.1% methionine, 10% lysine, and a weakly acidic pl). Similar to Sap and other Gram-positive surface proteins, EA1 has three 'S-layer-homology' motifs immediately downstream from a signal peptide. Single- and double-disrupted mutants were constructed. EA1 and Sap were co-localized at the cell surface of the wild-type bacilli. However, EA1 was more tightly bound than Sap to the bacteria. Electron microscopy studies and in vivo experiments with the constructed mutants showed that EA1 constitutes the main lattice of the B. anthracis S-layer, and is the major cell-associated antigen.
Improved Arene Fluorination Methodology for I(III) Salts (2010)

The use of low polarity aromatic solvents (benzene or toluene) and/or the removal of inorganic salts results in dramatically improved yields of fluorinated arenes from diaryliodonium salts. This methodology is shown to "scale down" to the conditions used typically for radiotracer synthesis.
<title>High-flexibility scalable image coding</title> (2003)

This paper presents a new, highly flexible, scalable image coder based on a Matching Pursuit expansion. The dictionary of atoms is built by translation, rotation and anisotropic refinement of gaussian functions, in order to efficiently capture edges in natural images. In the same time, the dictionary is invariant under isotropic scaling, which interestingly leads to very simple spatial resizing operations. It is shown that the proposed scheme compares to state-of-the-art coders when the compressed image is transcoded to a lower (octave-based) spatial resolution. In contrary to common compression formats, our bit-stream can moreover easily and efficiently be decoded at any spatial resolution, even with irrational re-scaling factors. In the same time, the Matching Pursuit algorithm provides an intrinsically progressive stream. This worthy feature allows for easy rate filtering operations, where the least important atoms are simply discarded to fit restrictive bandwidth constraints. Our scheme is finally shown to favorably compare to state-of-the-art progressive coders for moderate to quite important rate reductions.
Inhibition of poly(ADP-ribose)polymerase stimulates extrachromosomal homologous recombination in mouse Ltk- fibroblasts (1999)

Poly(ADP-ribose)polymerase (PARP) is an abundant nuclear enzyme activated by DNA breaks. PARP is generally believed to play a role in maintaining the integrity of the genome in eukaryote cells via anti-recombinogenic activity by preventing inappropriate homologous recombination reactions at DNA double-strand breaks. While inhibition of PARP reduces non-homologous recombination, at the same time it stimulates sister chromatid exchange and intrachromosomal homologous recombination. Here we report that the inhibition of PARP with 100 microg/ml (0.622 mM) 1,5-isoquinolinediol results in an average 4.6-fold increase in the frequency of extrachromosomal homologous recombination between two linearized plasmids carrying herpes simplex virus thymidine kinase genes inactivated by non-overlapping mutations, in mouse Ltk-fibroblasts. These results are in disagreement with the previously reported observation that PARP inhibition had no effect on extrachromosomal homologous recombination in Ltk-cells.
Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis (2009)

The disposition of infliximab in patients with moderately to severely active ulcerative colitis, unlike in rheumatoid arthritis, was not affected by coadministration of immunomodulators and corticosteroids but was related to formation of antibodies to infliximab and, notably, to serum albumin levels.
Oxaliplatin: A Review in the Era of Molecularly Targeted Therapy (2011)

Oxaliplatin lends itself to further clinical research in combination with molecularly targeted therapy.
Unbounded Transactional Memory (2006)

Transactional memory should be virtualized to support transactions of arbitrary footprint and duration. The unbounded transactional memory (UTM) architecture achieves high performance in the common case of small transactions, without sacrificing correctness in large transactions.
BEK and FLG, two receptors to members of the FGF family, are amplified in subsets of human breast cancers. (1991)

Tumor DNA samples from 387 breast carcinomas have been investigated for amplification of BEK and FLG genes, both of which have been shown to code for cell surface receptors to FGFs. BEK and FLG were found amplified in 11.5 and 12.7% of breast tumors respectively. Statistical analysis, performed on the subset of 297 primary cancers without presurgical therapy, showed for BEK a trend of preferential amplification in patients above 50 years (P = 0.055), whereas amplification of FLG could significantly be correlated with nodal involvement (P = 0.032) and seemed prevalent in steroid hormones receptor positive tumors. Since the same tumors were previously analysed for the amplification of MYC, ERBB2 and HST/INT2/BCL1 possible associations with BEK and FLG amplifications were looked for. BEK was found significantly correlated with MYC and FLG with HST/INT2/BLC1. The amplification of these two FGF receptor genes may therefore represent additional steps in the molecular phenotyping of breast cancer.
Nitric oxide inhibits indoleamine 2,3-dioxygenase activity in interferon-gamma primed mononuclear phagocytes. (1994)

Indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase are part of the anti-tumor and antimicrobial activities of mononuclear phagocytes induced by interferon-gamma (IFN gamma). As IDO is a heme-containing enzyme and NO, the product of nitric oxide synthase-initiated arginine degradation, is a regulator of heme enzymes, we investigated whether NO is capable of modulating IDO activity in IFN gamma-primed mononuclear phagocytes. Authentic NO gas or the NO-generating compound, diethylamine dinitric oxide adduct, dose-dependently inhibited IDO activity in cell lysates prepared from IFN gamma-primed human peripheral blood mononuclear cells, as assessed by the ascorbate/methylene blue assay for IDO. In contrast, neither nitrite nor nitrate affected IDO activity. Exposure of intact IFN gamma-primed human peripheral blood mononuclear cells or monocyte-derived macrophages to any of the NO-generating compounds, sodium nitroprusside, glyceryl trinitrate, S-nitroso-N-acetylpenicillamine, or diethylamine dinitric oxide adduct, resulted in inhibition of both the consumption of tryptophan from and formation of its metabolite, kynurenine, in the culture medium. The observed inhibition of IDO activity was not due to toxicity of the NO generators and was abrogated by the co-addition of oxyhemoglobin, an antagonist of NO function. Comparable concentrations of nitrite or nitrate did not inhibit IDO activity in intact cells. In contrast to human cells, addition of IFN gamma to murine macrophages, cultured in complete RPMI 1640 medium, readily induced nitric oxide synthase. Others have reported that such treatment does not induce IDO activity in these cells. However, induction of IDO activity was observed in murine macrophages when the synthesis of reactive nitrogen species was inhibited, by using arginine-free medium and/or the nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine. Together, these results demonstrate that both exogenous and endogenous NO inhibit IDO activity and that oxidative arginine and tryptophan metabolism in IFN gamma-primed mononuclear phagocytes are functionally related. Our study thereby provides an insight into how these cells may regulate some of their antimicrobial and anti-tumor activities.
Strain sensing using photocurrent generated by photoactive P3HT-based nanocomposites (2012)

Many sensor technologies commonly used for structural health monitoring (SHM) still suffer from high energy demand, large form factors and weight, and indirect damage detection. These constraints limit the application of these sensor systems for SHM of various space, aeronautical, mechanical and civil structures. In this study, a self-sensing thin film fabricated from poly(3-hexylthiophene) (P3HT) and multi-walled carbon nanotubes (MWNTs) is proposed for strain sensing. Unique to this nanocomposite is its ability to generate a photocurrent in response to light illumination, and it will be shown that the magnitude of the generated photocurrent scales with the level of applied strain. First, two types of P3HT-based sample sets with and without MWNTs have been prepared by spin coating. Second, current?voltage measurements have been used for characterizing electrode response due to applied strains. Lastly, strain sensing characterization tests have been conducted, where thin film generated photocurrent has been measured during applied cyclic tensile strains. The nanocomposites? strain sensitivity, linearity and sensing range have been analyzed and compared. The results show that these P3HT-based thin films can be used for photocurrent-based strain sensing. These films do not require an external power source, have small form factors and can directly measure structural strains.
Muscle function and protein metabolism after initiation of eccentric contraction-induced injury (1995)

This study was designed to determine the relationship between skeletal muscle function and protein metabolism after initiation of eccentric contraction-induced injury. Mouse anterior crural muscles were injured in vivo, and then either immediately or 3, 6, 24, 48, 72, 120, or 336 h after injury muscles were isolated and studied for indexes of muscle function, injury, phagocyte infiltration, and protein metabolism. A group of mice were administered anti-polymorphonuclear cell and anti-macrophage antisera in an attempt to reduce phagocytic infiltration into injured muscle. Force production in extensor digitorum longus muscles was reduced 55% immediately after injury induction and did not recover significantly until 120 h postinjury (28% below baseline). However, rates of protein degradation were not elevated until 48 h postinjury (60% above normal) and were not correlated with the changes in force production (r = -0.37; P = 0.24). Phagocytic infiltration was evident 24-120 h postinjury and was correlated with the elevated protein degradation rates (r = 0.75; P < 0.01). Protein synthesis rates began to increase approximately 48 h after injury was induced and were elevated by 83% 5 days postinjury. Fourteen days after injury, muscle protein degradation and synthesis rates had returned to normal, as well as specific force production, and phagocytic infiltration was not detected. However, muscle mass, protein content, and absolute force production were lower than normal. Antisera-treated mice were rendered neutropenic, but there was no difference in any variable measured between muscles from these mice and muscles from normal mice.
β-Galactosidase Tablets in the Treatment of Lactose Intolerance in Pediatrics (1990)

Lactose-intolerant children manifest diminished or nonexistent intestinal lactase activity, resulting in flatulence, abdominal pain, and diarrhea. To assess the hydrolytic capability of lactase-containing tablets taken immediately before oral lactose challenge, we studied 18 children previously identified as being lactose intolerant and having no underlying organic gastrointestinal disease. Subjects had a mean (+/- SEM) age of 11.4 +/- 3.4 years; 72% were male. At time of the study, lactase-containing tablets or placebo tablets were ingested (double-blind) immediately before drinking a solution of lactose. Breath samples were obtained for hydrogen analysis at 30-minute intervals during a 2-hour period, and clinical symptoms were monitored. In lactose-intolerant patients, hydrogen production was significantly greater following placebo (maximum hydrogen excretion, approximately 60 ppm) compared with lactase-containing tablets (maximum hydrogen excretion, 7 ppm). Increased hydrogen production was associated with clinical symptoms including abdominal pain (89% of subjects following placebo ingestion), bloating (83%), diarrhea (61%), and flatulence (44%). These results indicate, therefore, that coingestion of lactose and lactase-containing tablets significantly reduces both breath hydrogen excretion and clinical symptoms associated with lactose intolerance.
Hemodynamic parameters to guide fluid therapy (2011)

The clinical determination of the intravascular volume can be extremely difficult in critically ill and injured patients as well as those undergoing major surgery. This is problematic because fluid loading is considered the first step in the resuscitation of hemodynamically unstable patients. Yet, multiple studies have demonstrated that only approximately 50% of hemodynamically unstable patients in the intensive care unit and operating room respond to a fluid challenge. Whereas under-resuscitation results in inadequate organ perfusion, accumulating data suggest that over-resuscitation increases the morbidity and mortality of critically ill patients. Cardiac filling pressures, including the central venous pressure and pulmonary artery occlusion pressure, have been traditionally used to guide fluid management. However, studies performed during the past 30 years have demonstrated that cardiac filling pressures are unable to predict fluid responsiveness. During the past decade, a number of dynamic tests of volume responsiveness have been reported. These tests dynamically monitor the change in stroke volume after a maneuver that increases or decreases venous return (preload) and challenges the patients' Frank-Starling curve. These dynamic tests use the change in stroke volume during mechanical ventilation or after a passive leg raising maneuver to assess fluid responsiveness. The stroke volume is measured continuously and in real-time by minimally invasive or noninvasive technologies, including Doppler methods, pulse contour analysis, and bioreactance.
IgG subclass distribution of antibody responses to protein and polysaccharide mycobacterial antigens in leprosy and tuberculosis patients (1998)

Immunoenzymatic assays were developed for the measurement of antibodies against mycobacterial lipoarabinomannan (LAM), a cell-free proteic extract (CFX) of Mycobacterium leprae, and the 38-kD protein antigen of M. tuberculosis. Sera from 108 leprosy patients, belonging to all clinical-immunological forms of the spectrum, and 81 patients with localized or disseminated tuberculosis (TB) were tested for antibodies of the four IgG subclasses. Standard calibration curves were used to allow comparisons between results of different isotypes and specificities. Mean concentrations of total IgG antibodies were higher in the overall leprosy population than in TB patients. In leprosy, levels of anti-CFX increased from tuberculoid toward lepromatous forms, with a clear switch from IgG1 to IgG2 subclass predominance. A similar IgG1 to IgG2 conversion was observed in anti-LAM antibodies, although total levels of anti-LAM were similar in patients with tuberculoid and lepromatous forms. In TB, antibodies against polysaccharide and protein antigens were both predominantly of IgG1 subclass, whatever the patient's clinical status, although lower in disseminated forms, probably due to concomitant HIV infection. A hypergammaglobulinaemia was also found in most leprosy and TB patients. In TB this was due to increased IgG1 and IgG3, especially in HIV co-infected patients. Based on the current knowledge of the influence of T cell-secreted cytokines on human immunoglobulin isotype expression, these results do not fit with a putative role of Th1 (such as found in TB and tuberculoid leprosy (TT)) and Th2 (such as found in leprosy lepromatous (LL) leprosy) environment in the isotypy of antibody responses in mycobacterial infections. Nor do variations of isotypy according to pathological conditions seem to be related to the biochemical nature of antigens, since antibodies to LAM and protein antigens had comparable evolutions of their subclass distribution. Other factors are to be investigated in order to understand better the significance and possible roles of antibodies in mycobacterial diseases.
New Avenues of Exploration for Erythropoietin (2005)

Discovery that the hormone erythropoietin (EPO) and its receptor play a significant biological role in tissues outside of the hematopoietic system has fueled significant interest in EPO as a novel cytoprotective agent in both neuronal and vascular systems. Erythropoietin is now considered to have applicability in a variety of disorders that include cerebral ischemia, myocardial infarction, and chronic congestive heart failure. Erythropoietin modulates a broad array of cellular processes that include progenitor stem cell development, cellular integrity, and angiogenesis. As a result, cellular protection by EPO is robust and EPO inhibits the apoptotic mechanisms of injury, including the preservation of cellular membrane asymmetry to prevent inflammation. As the investigation into clinical applications for EPO that maximize efficacy and minimize toxicity progresses, a deeper appreciation for the novel roles that EPO plays in the brain and heart and throughout the entire body should be acquired.
Chromatography in a Bed of Spheres (1979)

Abstract A computationally efficient method is presented for calculating the combined effects of intraparticle diffusion, interphase mass-transfer resistance, and fluid-phase axial dispersion for chromatography in a column of uniform regularly packed spheres. The method uses an extension of the generalized Sturm-Liouville theory of Ramkrishna and Amundson to adapt the Taylor-Gill-Subramanian dispersion analysis to two-phase systems. The primary utility of the analysis is to determine the importance of diffusional transients and to obtain asymptotic limiting behavior for very long columns. Simple closed-form solutions are given for this limiting condition. Our analysis suggests that the transients neglected in presently used lumped-parameter analyses are in fact often small, especially for small packing diameter and low flow rates. In addition, the Glueckauf and Coates approximation for internal diffusional resistance is found to be a valid asymptotic limit. However, conditions do arise in practice where transients should be considered.
Block copolymers as nanoscopic templates (2000)

Block copolymers self-assemble into well-ordered, microphase separated morphologies having dimensions on the molecular scale. The key to the use of these nanoscopic structures lies in controlling the spatial orientation of the morphology, particularly in thin films. The preferential interactions of the segments of the blocks with interfaces forces an alignment of the morphology parallel to the interface. Here we describe the use of controlled interfacial interactions and electric fields to manipulate the orientation of the morphology and subsequent steps towards the generation of nanoporous templates as scaffolds for nanoscopic structures.
Chemoselective approaches to the preparation of peptide dendrimers and branched artificial proteins using unprotected peptides as building blocks. (1995)

Peptide dendrimers such as Multiple Antigen Peptides (MAPs) are artificial proteins with branched architectures. They hold promise in biochemical and biomedical applications such as synthetic vaccines, serodiagnostics and intracellular delivery of peptides. We have shown that a new design of MAPs containing lipidated built-in adjuvant can be delivered by oral administration to elicit systemic and mucosal immunoglobulins as well as cytotoxic T-lymphocytes. For synthetic vaccines, it is desirable to obtain highly homogeneous preparations. To provide the precision and chemical unambiguity of this class of artificial proteins, we have devised several chemoselective approaches by thiol and carbonyl chemistries to facilitate their synthesis using unprotected peptide segments as building blocks and ligating them to the core matrix. This paper describes the methods of preparation, comparative studies of stability, and presents results of the preparation of antigens containing preformed multiple disulfides.
Generic Drug Product Development (2010)

Introduction to Generic Drug Development Leon Shargel and Izzy Kanfer Active Pharmaceutical Ingredients Edward Cohen and Lih-Yang Lin Analytical Methods Development and Validation Nicholas Cappuccino Experimental Formulation Development Izzy Kanfer, Peter H.R. Persicaner, and Roderick B. Walker Scale-up, Technology Transfer and Validation Salah U. Ahmed, Venkatesh Naini, and Dilip Wadgaonker Product Stability Pranab K. Bhattacharyya Quality Control and Quality Assurance Loren Gelber and Joan Janulis Drug Product Performance, In Vitro Pradeep Sathe, Larry Ouderkirk, Ajaz Hussain, and Lawrence X.Yu ANDA Regulatory Approval Process Timothy W. Ames, Karen A. Bernard, Beth Fabian Fritsch, Koung Lee, Aida L. Sanchez, Krista M. Scardina, and Martin Shimer Bioequivalence and Drug Product.