gebhart/patrepeval huggingface dataset:
Calcium Handling in Human Embryonic Stem Cell-Derived Cardiomyocytes (2008)

The objective of the current study was to characterize calcium handling in developing human embryonic stem cell-derived cardiomyocytes (hESC-CMs). To this end, real-time polymerase chain reaction (PCR), immunocytochemistry, whole-cell voltage-clamp, and simultaneous patch-clamp/laser scanning confocal calcium imaging and surface membrane labeling with di-8-aminonaphthylethenylpridinium were used. Immunostaining studies in the hESC-CMs demonstrated the presence of the sarcoplasmic reticulum (SR) calcium release channels, ryanodine receptor-2, and inositol-1,4,5-trisphosphate (IP3) receptors. Store calcium function was manifested as action-potential-induced calcium transients. Time-to-target plots showed that these action-potential-initiated calcium transients traverse the width of the cell via a propagated wave of intracellular store calcium release. The hESC-CMs also exhibited local calcium events ("sparks") that were localized to the surface membrane. The presence of caffeine-sensitive intracellular calcium stores was manifested following application of focal, temporally limited puffs of caffeine in three different age groups: early-stage (with the initiation of beating), intermediate-stage (10 days post-beating [dpb]), and late-stage (30-40 dpb) hESC-CMs. Calcium store load gradually increased during in vitro maturation. Similarly, ryanodine application decreased the amplitude of the spontaneous calcium transients. Interestingly, the expression and function of an IP3-releasable calcium pool was also demonstrated in the hESC-CMs in experiments using caged-IP3 photolysis and antagonist application (2 microM 2-Aminoethoxydiphenyl borate). In summary, our study establishes the presence of a functional SR calcium store in early-stage hESC-CMs and shows a unique pattern of calcium handling in these cells. This study also stresses the importance of the functional characterization of hESC-CMs both for developmental studies and for the development of future myocardial cell replacement strategies. Disclosure of potential conflicts of interest is found at the end of this article.
The Scientific Rediscovery of a Precious Ancient Chinese Herbal Regimen: Cordyceps sinensis Part II (1998)

Cordyceps sinensis (Berk.) Sacc. is a time-honored tonic food and herbal medicine in China, where recent research has shown that many of its traditional uses may be viewed from the basis of pharmacological activities. The ongoing exploration of C. sinensis in its wild form and cultured, fermented mycelial products derived from it, are reviewed from English and Chinese literature. Part II concludes the series with a review of C. sinensis in preclinical in vitro and in vivo studies, and open-label and double-blinded clinical trials on the respiratory, renal, hepatic, cardiovascular, immunologic, and nervous systems, and its effects on cancer, glucose metabolism, inflammatory conditions, and toxicological studies. In Part I, which appeared in the Fall 1998 issue of this journal (4(3):289-303), we discussed the effects of C. sinensis on antisenescence, endocrine and sexual functions, atherosclerosis, hyperlipidemia, and free radicals.
Helicobacter pyloriEradication with Doxycycline—Metronidazole—Bismuth Subcitrate Triple Therapy (1992)

Triple therapy containing tetracycline HCl is currently among the most efficient combination therapies for eradication of Helicobacter pylori. Substitution of doxycycline for tetracycline HCl offers advantages of less frequent dosing and extrarenal excretion. In this study patients with duodenal ulcer or non-ulcer dyspepsia positive for H. pylori were randomized to either doxycycline or tetracycline HCl triple therapy in conjunction with bismuth subcitrate and metronidazole. Of the 34 patients taking doxycycline, only 22 (65%) achieved H. pylori eradication at the 4-week rebiopsy, compared with 36 of 39 (92%) taking tetracycline HCl (p = 0.004). We conclude that doxycycline-containing triple therapy is less effective for H. pylori eradication and offers no clinical advantage over tetracycline HCl-containing triple therapy.
Reconstruction of divergence‐free velocity fields from cine 3D phase‐contrast flow measurements (2012)

Three-dimensional phase-contrast velocity vector field mapping shows great potential for clinical applications; however measurement inaccuracies may limit the utility and robustness of the technique. While parts of the error in the measured velocity fields can be minimized by background phase estimation in static tissue and magnetic field monitoring, considerable inaccuracies remain. The present work introduces divergence-reduction processing of 3D phase-contrast flow data based on a synergistic combination of normalized convolution and divergence-free radial basis functions. It is demonstrated that this approach effectively addresses erroneous flow for image reconstructions from both fully sampled and undersampled data. Using computer simulations and in vivo data acquired in the aorta of healthy subjects and a stenotic valve patient it is shown that divergence arising from measurement imperfections can be reduced by up to 87% resulting in improved vector field representations. Based on the results obtained it is concluded that integration of the divergence-free condition into postprocessing of vector fields presents an efficient approach to addressing flow field inaccuracies.
Surface modification of wood fibers using maleic anhydride and isocyanate as coating components and their performance in polystyrene composites (1991)

Abstract The effect of surface modification of various wood fibers [e.g. woodflour and chemithermomechanical pulp (CTMP) of hardwood aspen, and woodflour of softwood spruce] by precoating with only maleic anhydride (MA) and/or poly[methylene (polyphenyl isocyanate)] (PMPPIC) in the presence of benzoyl peroxide (BPO) on the mechanical performance of modified fiber-filled polystyrene (PS 201 and PS 525) composites has been studied. The effects of the concentration of fiber, MA, PMPPIC, and BPO on the mechanical properties of the composites have also been evaluated. As opposed to unmodified fiber-filled composites, most of the mechanical properties of the modified fiber-filled composites increased with an increase in the concentration of BPO, MA, and/or PMPPIC up to a certain limit, and then either decreased or levelled off. The properties improved even more when both MA and PMPPIC were used as compared with the use of only one of them. The optimum concentrations of BPO, MA, PMPPIC, and fiber vary according to the wood species, the nature of the fiber, and the type of polystyrene. Compared with woodflour, CTMP is believed to be by far the best as far as the mechanical properties of the modified fiber-filled composites are concerned. Keywords: Surface modificationwood fiberpolystyrenethermoplastic compositesmaleic anhydrideisocyanateinterfacial bondmechanical properties
APPLICATION OF EXACT SOLUTIONS OF SOME ELLIPTIC EQUATIONS FOR GENERATION OF TWO- AND MULTI- DIMENSIONAL ANALYTICAL GRIDS (2002)

Abstract. Now algebraic approaches to construction of grids are rapidly developing (B-spline, transfinite interpolation etc.) [1, 2]. Their advantage appears in the possibility of fast construction of grids. Traditional approaches based on a numerical solution of differential equations give, as a rule, best grids, but demand much more time for their construction. Especially it is right in calculation of flows in moving boundaries. In present work, the new method of grid construction based on an analytical solution of some system of elliptic differential equations is suggested. It combines a speed of the algebraic approach with quality of the elliptical approach. In suggested method, the functions which map computational space to physical one (mapping-functions, MF), are obtained in exact form. It allows to receive analytical expressions for metric coefficients and, thereby, completely eliminate errors of their numerical calculation. The method of control of some relevant grid properties is also suggested. The idea of quality control of the obtained grid is based on application of analytical solutions of a boundary value problem for the class of higher order equations. As MF remain analytical, method does not increase grid construction time. The offered grids have some advantage in comparison to conformal ones, where the MF have no sufficient functional arbitrariness. The obtained results are illustrated by examples. Key words. Analytical grids, mapping-functions, Laplace’s equation 1. Introduction. The
Directional copper deposition using dc magnetron self-sputtering (1998)

A directional copper deposition process has been developed that uses a dc magnetron source operating in self-sputtering mode. The process is performed at 10−5 Torr range pressure where a “long throw” approach can be utilized without discharge enhancement or mechanical collimation due to a very long mean free path of sputtered species. Magnetron sputtering conditions at which the contact hole filling is promoted and substantially enhanced by the self-sputtering process are illustrated and compared to standard sputtering (i.e., short throw, mTorr pressure) in the presence of argon. The experimental parameters of the new process have been explored by depositing Cu on patterned Si wafers with trenches and contact holes of various aspect ratios.
Mesenchymal stem/progenitor cells promote the reconstitution of exogenous hematopoietic stem cells in Fancg−/− mice in vivo (2009)

Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow failure and complex congenital anomalies. Although mutations in FA genes result in a characteristic phenotype in the hematopoietic stem/progenitor cells (HSPCs), little is known about the consequences of a nonfunctional FA pathway in other stem/progenitor cell compartments. Given the intense functional interactions between HSPCs and the mesenchymal microenvironment, we investigated the FA pathway on the cellular functions of murine mesenchymal stem/progenitor cells (MSPCs) and their interactions with HSPCs in vitro and in vivo. Here, we show that loss of the murine homologue of FANCG (Fancg) results in a defect in MSPC proliferation and in their ability to support the adhesion and engraftment of murine syngeneic HSPCs in vitro or in vivo. Transplantation of wild-type (WT) but not Fancg(-/-) MSPCs into the tibiae of Fancg(-/-) recipient mice enhances the HSPC engraftment kinetics, the BM cellularity, and the number of progenitors per tibia of WT HSPCs injected into lethally irradiated Fancg(-/-) recipients. Collectively, these data show that FA proteins are required in the BM microenvironment to maintain normal hematopoiesis and provide genetic and quantitative evidence that adoptive transfer of WT MSPCs enhances hematopoietic stem cell engraftment.
Immobilization of Arginase on Hollow Fiber Hemodialyzer (1981)

The enzyme arginase, purified from bovine liver, was covalently immobilized by the glutaraldehyde method to the inner surface of Cuprophan hollow fibers of a conventional hemodialyzer with a surface 1.3 m3. The yield of the process was 0.3 microgram/cm2 of active enzyme at physiological pH. The immobilization method did not adversely affect the physical and mechanical properties of hollow fibers neither their hemocompatibility. After sterilization with ethylene oxide, the bioreactor was able to metabolize five liters of 50 microM arginine solution at pH 7.4, in six hours.
H5N1 influenza: A protean pandemic threat (2004)

Infection with avian influenza A virus of the H5N1 subtype (isolates A/HK/212/03 and A/HK/213/03) was fatal to one of two members of a family in southern China in 2003. This incident was preceded by lethal outbreaks of H5N1 influenza in waterfowl, which are the natural hosts of these viruses and, therefore, normally have asymptomatic infection. The hemagglutinin genes of the A/HK/212/03-like viruses isolated from humans and waterfowl share the lineage of the H5N1 viruses that caused the first known cases of human disease in Hong Kong in 1997, but their internal protein genes originated elsewhere. The hemagglutinin of the recent human isolates has undergone significant antigenic drift. Like the 1997 human H5N1 isolates, the 2003 human H5N1 isolates induced the overproduction of proinflammatory cytokines by primary human macrophages in vitro, whereas the precursor H5N1 viruses and other H5N1 reassortants isolated in 2001 did not. The acquisition by the viruses of characteristics that enhance virulence in humans and waterfowl and their potential for wider distribution by infected migrating birds are causes for renewed pandemic concern.
Growth and differentiation of an embryonal carcinoma cell line (C145b) (1979)

Several cell and tumour lines were isolated from a single-embryo-derived teratocarcinoma and their karyotypes and differentiation in adult hosts recorded. The majority of cells contained normal karyotypes by banding. The cells were injected into blastocysts and although they sometimes colonized the yolk sac, they never colonized the embryo. Thus the possession of a normal karyotype is not a sufficient condition for embryo colonization. The loss of growth capacity was investigated by studying differentiation and tumourigenicity in a variety of circumstances. The change in appearance from an EC cell morphology to a big flat cell in culture leads to retardation of growth in adult hosts. When EC cells are injected into a blastocyst, the ability to grow progressively both in culture and in adult hosts is lost.
TXU (Anti-CD7)-Pokeweed Antiviral Protein as a Potent Inhibitor of Human Immunodeficiency Virus (1998)

We have evaluated the clinical potential of TXU (anti-CD7)-pokeweed antiviral protein (PAP) immunoconjugate (TXU-PAP) as a new biotherapeutic anti-human immunodeficiency virus (anti-HIV) agent by evaluating its anti-HIV type 1 (anti-HIV-1) activity in vitro, as well as in a surrogate human peripheral blood lymphocyte-severe combined immunodeficient (Hu-PBL-SCID) mouse model of human AIDS. The present report documents in a side-by-side comparison the superior in vitro anti-HIV-1 activity of TXU-PAP compared to the activities of zidovudine, 2',3'-didehydro-2',3'-dideoxythymidine, unconjugated PAP, and B53-PAP, an anti-CD4-PAP immunoconjugate. Notably, TXU-PAP elicited potent anti-HIV activity in the Hu-PBL-SCID mouse model of human AIDS without any side effects and at doses that were very well tolerated by cynomolgus monkeys. Furthermore, plasma samples from TXU-PAP-treated cynomolgus monkeys showed potent anti-HIV-1 activity in vitro.
High doses of cyclophosphamide, etoposide and total body irradiation followed by autologous stem cell transplantation in the management of patients with chronic myelogenous leukemia. (1994)

Eighteen patients with chronic myelogenous leukemia (CML) in chronic (9 patients) or advanced phases (9 patients) underwent autologous bone marrow transplantation (BMT) with a preparative regimen using high doses of cyclophosphamide, etoposide and total body irradiation (CY-VP16-TBI): cyclophosphamide 60 mg/kg daily on days 1 and 2; VP16 250 mg/m2 twice daily on days 1-3 and TBI 1020 cGy in six fractionated doses on days 5-7. Autologous marrow cells were reinfused on day 8. Three of the 8 patients in late chronic phase Philadelphia (Ph) chromosome-positive CML (37%) achieved a cytogenetic response, with Ph suppression to 25%, 29% and 44% Ph-positive metaphases, respectively, and lasting for 11, 1 and 3 months, respectively. The median duration of chronic phase following BMT was 26+ months (range 2-33+ months). One patient with Ph-negative, BCR-rearranged, chronic phase CML had a decrease of the BCR-rearranged band to 10% of pretreatment levels, which persisted for 6 months. None of the 9 patients with advanced CML phases (5 in second chronic, 1 in blastic, 3 in accelerated) achieved meaningful cytogenetic responses. Their median survival was 7 months from the time of BMT. Toxicities were mostly related to myelosuppression, particularly thrombocytopenia. Febrile episodes developed in 16 patients (89%). Treatment-related deaths occurred in 2 patients (11%). In summary, autologous BMT using a TBI-containing regimen had acceptable toxicity. Future investigations will evaluate the additional benefit of purged autologous stem cell transplantation in patients with chronic phase CML.
Setting Behavior and in Vitro Bioactivity of Hydroxyapatite/Calcium Sulfate Cements (2002)

The transformation of calcium sulfate hemihydrate into gypsum via reaction with water has been used for many years to produce materials for bone augmentation. In this work, a mixture of CaSO4·1/2H2O and hydroxyapatite was prepared, and its behavior as cement was studied and compared with that of pure calcium sulfate hemihydrate. The setting process was monitored with Gillmore needles, X-ray diffraction, and differential scanning calorimetry. The utilization of the mixture allows one to prepare homogeneous pastes with better manipulation characteristics than pure calcium sulfate hemihydrate. The workability and setting time of the hydroxyapatite-containing cements are higher than those of pure CaSO4·1/2H2O. The different techniques employed allow us to relate the initial setting time with the chemical transformation of the calcium sulfate hemihydrate into calcium sulfate dihydrate. The biphasic specimens show an improved bioactivity response compared to pure hydroxyapatite or gypsum when soaked in a simulated body fluid.
Breast cancer selective gene expression and therapy mediated by recombinant adenoviruses containing the DF3/MUC1 promoter. (1995)

The high molecular weight mucin-like glycoprotein, DF3 (MUC1), is overexpressed in the majority of human breast cancers. Here we demonstrate that replication defective recombinant adenoviral vectors, containing the DF3 promoter (bp -725 to +31), can be used to express beta-galactosidase (Ad.DF3-betagal) and the herpes simplex virus thymidine kinase (HSV-tk) gene (Ad.Df3-tk) in DF3 positive breast carcinoma cell lines. In vivo experiments using breast tumor implants in nude mice injected with Ad.DF3-betagal demonstrated that expression of the beta-galactosidase gene is limited to DF3-positive breast cancer xenografts. Moreover, in an intraperitoneal breast cancer metastases model, we show that i.p. injection of Ad.DF3-tk followed by GCV treatment results in inhibition of tumor growth. These results demonstrate that utilization of the DF3 promoter in an adenoviral vector can confer selective expression of heterologous genes in breast cancer cells in vitro and in vivo.
Crystallographic and Biophysical Analysis of a Bacterial Signal Peptidase in Complex with a Lipopeptide-based Inhibitor (2004)

We report here the crystallographic and biophysical analysis of a soluble, catalytically active fragment of the Escherichia coli type I signal peptidase (SPase Delta2-75) in complex with arylomycin A2. The 2.5-A resolution structure revealed that the inhibitor is positioned with its COOH-terminal carboxylate oxygen (O45) within hydrogen bonding distance of all the functional groups in the catalytic center of the enzyme (Ser90 O-gamma, Lys145 N-zeta, and Ser88 O-gamma) and that it makes beta-sheet type interactions with the beta-strands that line each side of the binding site. Ligand binding studies, calorimetry, fluorescence spectroscopy, and stopped-flow kinetics were also used to analyze the binding mode of this unique non-covalently bound inhibitor. The crystal structure was solved in the space group P4(3)2(1)2. A detailed comparison is made to the previously published acyl-enzyme inhibitor complex structure (space group: P2(1)2(1)2) and the apo-enzyme structure (space group: P4(1)2(1)2). Together this work provides insights into the binding of pre-protein substrates to signal peptidase and will prove helpful in the development of novel antibiotics.
Investigating the association between BRAFV600E and methylation in sporadic colon cancer (2012)

Aberrant methylation of CpG island promoters is a frequent observation in cancer and is known to affect many genes, including tumour suppressor genes. Genes with methylated promoters are usually repressed and inactive, and there is good evidence that most genes that become methylated in cancer are already repressed in the normal tissues from which tumours arise. However, the methylation of some genes appears to arise at previously active loci, suggesting either a stochastic epigenetic event or that these genes are somehow predisposed to becoming methylated. The DNA mismatch repair gene MLH1 is expressed in normal colonic epithelial cells but methylated and down-regulated in some sporadic mismatch repair-deficient colon tumours. These tumours are almost invariably associated with the simultaneous methylation of multiple cancer-specific loci, termed the CpG island methylator phenotype (CIMP) and an activating mutation of BRAF (V600E), raising the possibility that a hypermethylator phenotype may arise in cancer in direct association with a specific genetic alteration. The possibility that MLH1-deficiency caused BRAF mutation was discounted as genetic deficiency of MLH1 is not associated with BRAFV600E. I explored the possibility that BRAFV600E might induce MLH1 methylation but found no evidence in support of this. I then focused on factors that might mediate CIMP gene methylation, of which MLH1 methylation is known to be a part. Bioinformatic analysis of the genes methylated in BRAFV600E colon tumours indicated a significant enrichment in binding sites for the transcription factor MAZ (MYC-associated zinc finger protein). I hypothesised that loss of MAZ might lead to MLH1 down-regulation and its subsequent methylation. In this thesis I provide evidence that both MAZ and MLH1 expression are deregulated during normal colonic epithelial differentiation. The down-regulation of MAZ by RNA interference led to a reduction in MLH1 expression and methylation of its promoter. I speculate that MLH1 methylation may be associated with BRAF mutation because transformation by BRAFV600E allows progenitor cells to undergo a degree of differentiation whilst maintaining their malignant proliferation. I speculate that it is during this process of differentiation that MLH1 becomes susceptible to methylation.
DNA glycosylase activities for thymine residues oxidized in the methyl group are functions of the AlkA enzyme in Escherichia coli. (1994)

The alkA gene of Escherichia coli encodes a DNA glycosylase involved in base excision repair of DNA alkylation damage. In an attempt to define the reactions of the AlkA enzyme with methylated DNA, we discovered that the enzyme released substantial amounts of radioactivity from [methyl-3H]thymidine-labeled DNA even without any exposure of the DNA to methylating agents. The excised material was identified by chromatography as two different oxidized derivatives of thymine, 5-hydroxymethyluracil and 5-formyluracil. These products are formed in such DNA by one and two consecutive decays, respectively, of the tritiums of the labeled methyl group. Kinetic analysis showed that both the apparent Km and Vmax values for 5-formyluracil removal are within the same range as found for 3-methyladenine removal, suggesting that this catalytic property of AlkA is also significant under in vivo conditions. Removal of 5-hydroxymethyluracil proceeds at a rate that is 1-3 orders of magnitude slower. Since both 5-formyluracil and 5-hydroxymethyluracil are major products formed in DNA by exposure to ionizing radiation, these results implicate the alkA gene function also in the repair of oxidative DNA damage. Neither of the two other enzymes involved in the repair of oxidative DNA damage in E. coli, i.e. endonuclease III and formamidopyrimidine DNA glycosylase, has any affinity for oxidized unsaturated pyrimidines in DNA.
Protective effect of n‐3 polyunsaturated fatty acid on primary culture of rat hepatocytes (2006)

EPA has a direct protective effect on rat hepatocytes, which is in agreement with the clinical efficacy of EPA in PBC patients.