gebhart/patrepeval huggingface dataset:
Conventional cytogenetics in myelofibrosis: literature review and discussion (2009)

The clinical phenotype of myelofibrosis (MF) is recognized either de novo (primary) or in the setting of polycythemia vera (post-PV) or essential thrombocythemia (post-ET). Approximately one-third of patients with primary MF (PMF) present with cytogenetic abnormalities; the most frequent are del(20q), del(13q), trisomy 8 and 9, and abnormalities of chromosome 1 including duplication 1q. Other less frequent lesions include -7/del(7q), del(5q), del(12p), +21 and der(6)t(1;6)(q21;p21.3). In general, cytogenetic abnormalities are qualitatively similar among PMF, post-ET MF and post-PV MF although their individual frequencies may differ. Based on prognostic effect, cytogenetic findings in MF are classified as either 'favorable' or 'unfavorable'. The former include normal karyotype or isolated del(20q) or del(13q) and the latter all other abnormalities. Unfavorable cytogenetic profile in both PMF and post-PV/ET MF confers an independent adverse effect on survival; it is also associated with higher JAK2V617F mutational frequency. In addition to their prognostic value, cytogenetic studies in MF ensure diagnostic exclusion of other myeloid neoplasms that are sometimes associated with bone marrow fibrosis (e.g. BCR-ABL1-positive or PDGFRB-rearranged) and also assist in specific treatment selection (e.g. lenalidomide therapy is active in MF associated with del(5q).
Efficacy of Tilmicosin Phosphate (PulmotilR Premix) in Feed for the Treatment of a Clinical Outbreak of Actinobacillus pleuropneumoniae Infection in Growing-Finishing Pigs (2001)

A double-blind randomized clinical trial was carried out to investigate the efficacy of tilmicosin (Pulmotil premix) for the treatment of a clinical outbreak of Actinobacillus pleuropneumoniae infection in growing-finishing pigs. The effects of tilmicosin administration in the feed at 400 mg/kg and an injection therapy of clinically diseased pigs with long-acting oxytetracycline (Terramycine LA) at 20 mg/kg bodyweight were compared. Both groups, totalling 147 pigs, were compared during a medication period of 15 days and a post-medication period of 11 days by means of different clinical and performance parameters. During the medication period, the tilmicosin group showed a significant advantage with respect to the number of new disease cases (P < 0.01), and a non-significant advantage regarding the number of removed pigs (P = 0.16), the number of sick pigs that recovered (P = 0.27) and the time to recovery (P = 0.42). During the post-medication period, the pigs of the tilmicosin group showed numerical non-significant benefits (P > 0.05) with respect to the clinical parameters. During the overall study period (26 days), the average daily gain and the feed conversion ratio were both significantly (P < 0.01) better in pigs from the tilmicosin group compared with pigs from the oxytetracycline group. This study demonstrated that in-feed medication of tilmicosin at a dosage of 400 mg/kg is efficacious for the treatment of a clinical respiratory disease outbreak of A. pleuropneumoniae infection in growing-finishing pigs. Compared with oxytetracycline injection of clinically diseased pigs, the tilmicosin treatment is particularly beneficial in the prevention of new disease cases while increasing or maintaining the performance of the pigs.
Coagulation Factors VII and X Induce Ca2+ Oscillations in Madin-Darby Canine Kidney Cells Only When Proteolytically Active (1996)

We have recently reported that the activated serine protease and blood coagulation Factor VII (FVIIa) can induce Ca2+ oscillations in Madin-Darby canine kidney cells. We now demonstrate a similar response by Madin-Darby canine kidney cells to the active coagulation Factor X (FXa), which is also a serine protease and a substrate of the tissue factor (TF).FVIIa complex in the initiation of the coagulation cascade. The phosphatidyl inositol-specific phospholipase C inhibitor U73122 inhibited the signals elicited by both FVIIa and FXa. Lack of sensibility to the tyrosine kinase inhibitors herbimycin A, genistein, and the tyrphostin AG18 and discordance between TF expression and FVIIa responsiveness argued against TF acting as a cytokine-like receptor, with tyrosine kinase-mediated activation by FVIIa. As demonstrated using the protease inhibitor benzamidine and by specific active site inhibition with 1,5-dansyl-Glu-Gly-Arg chloromethyl ketone, both FVIIa and FXa lost their ability to elicit a calcium response when devoid of their proteolytic activity. Consistent with this, the native (zymogen) form of Factor X did not induce Ca2+ transients. Homologous but not heterologous inhibition of FVIIa- and FXa-evoked Ca2+ signals by 1,5-dansyl-Glu-Gly-Arg chloromethyl ketone-inactivated FVIIa and FXa suggested that each factor had its own specific cell surface anchoring receptor. The two coagulation factors did not show homologous desensitization as seen for thrombin stimulation. Studies with hirudin excluded involvement of the established activation pathway through thrombin itself. Lack of desensitization of the response to FVIIa or FXa by thrombin ruled out any involvement of proteinase activated receptor-1 (PAR-1), the thrombin receptor. We speculate that FXa and FVIIa may work via a receptor (possibly common) analogous to PAR-1 or its functional homologue PAR-2. Although TF is essential for the FVIIa-induced signaling event, its role in the phosphatidyl inositol-specific phospholipase C-mediated Ca2+ signal may be in anchoring FVIIa to the cell surface rather than in transmembrane signal mediation.
A programmable multi-channel stimulator for array electrodes in transcutaneous electrical stimulation (2011)

Transcutaneous electrical stimulation (TES) has been applied to restore or maintain the muscle activity of paralyzed patients who suffer from spinal cord injuries and related neural impairments for several decades. In this paper, a portable and low-cost versatile stimulator for multichannel TES applications is described. The microcontroller-based programmable stimulator with four bipolar output channels send arbitrarily specified electrical pulses to the element in the electrode array for enabling the complex schemes of muscles. The amplitude and phase of each pulse in the stimulus sequence are independently variable, and the four channels are independently programmable, allowing a wide variety of stimulus patterns. We also designed an output circuit that can provide bi-phasic, voltage-regulated, charge-balanced outputs while avoiding the electrochemical erosion of electrode due to charge accumulation. The proposed stimulator has provided an opportunity for further study of a potential novel electrical stimulator with closed-loop stimulation paradigm suitable for a variety of FES applications, both for experimental and clinical studies.
Yeast Mating and Image-Based Quantification of Spatial Pattern Formation (2014)

Communication between cells is a ubiquitous feature of cell populations and is frequently realized by secretion and detection of signaling molecules. Direct visualization of the resulting complex gradients between secreting and receiving cells is often impossible due to the small size of diffusing molecules and because such visualization requires experimental perturbations such as attachment of fluorescent markers, which can change diffusion properties. We designed a method to estimate such extracellular concentration profiles in vivo by using spatiotemporal mathematical models derived from microscopic analysis. This method is applied to populations of thousands of haploid yeast cells during mating in order to quantify the extracellular distributions of the pheromone α-factor and the activity of the aspartyl protease Bar1. We demonstrate that Bar1 limits the range of the extracellular pheromone signal and is critical in establishing α-factor concentration gradients, which is crucial for effective mating. Moreover, haploid populations of wild type yeast cells, but not BAR1 deletion strains, create a pheromone pattern in which cells differentially grow and mate, with low pheromone regions where cells continue to bud and regions with higher pheromone levels and gradients where cells conjugate to form diploids. However, this effect seems to be exclusive to high-density cultures. Our results show a new role of Bar1 protease regulating the pheromone distribution within larger populations and not only locally inside an ascus or among few cells. As a consequence, wild type populations have not only higher mating efficiency, but also higher growth rates than mixed MATa bar1Δ/MATα cultures. We provide an explanation of how a rapidly diffusing molecule can be exploited by cells to provide spatial information that divides the population into different transcriptional programs and phenotypes.
Method to Prepare Ternary Methanol Electro-Oxidation Catalysts for Direct Methanol Fuel Cell Applications (2017)

In this work ternary methanol electro-oxidation catalysts based on mesoporous carbon (MC) were prepared by a novel approach for direct methanol fuel cell applications. Platinum (Pt), ruthenium (Ru) along with oxides of iron, cobalt and nickel were used as the active component in the electrocatalyst. A novel approach was used to prepare Pt-Ru/Fe2O3-MC, Pt-Ru/CoO-MC and PtRu/NiO-MC methanol electro-oxidation catalysts by synthesizing high surface area Fe2O3-MC, CoO-MC and NiO-MC and then followed by impregnation with Pt-Ru. The synthesized metal oxides and catalysts were characterized using FESEM, BET surface area, FT-IR and XRD. The prepared Fe2O3-MC, CoO-MC and NiO-MC showed large pore volume of 0.72–1.46 cm3/g and high surface area of 686–1589 m2/g, which enabled high dispersion of the Pt-Ru nanoparticles. These catalysts have been tested for methanol electro-oxidation activity by electrochemical techniques. The highest catalyst activity of 12.36 mA/mg has been found for the Pt-Ru/NiO-MC, which is higher than the commercial Pt-Ru/C (E-TEK) catalyst. The measured catalytic activity decreased in the order: Pt-Ru/NiO-MC &gt; Pt-Ru/CoO-MC &gt; Pt-Ru/Fe2O3-MC &gt; Pt-Ru/C (E-TEK). In addition, Moreover, these prepared catalyst samples also showed good stability, Moreover, these catalysts are fairly stable, which is similar to the commercial catalyst.
N-Acetylcysteine Inhibits Latent HIV Expression in Chronically Infected Cells (1991)

The progression of the human immunodeficiency virus (HIV) infection from its early latent (asymptomatic) stage to active, late-stage acquired immunodeficiency syndrome (AIDS) apparently begins with the production of inflammatory cytokines that stimulate the expression and replication of the latent virus. We have shown that N-acetylcysteine, a cysteine precursor that is converted intracellularly into glutathione, blocks cytokine-stimulated HIV replication in an acutely infected T-cell line and in acutely infected peripheral blood mononuclear cells from normal individuals. In this report, we show that N-acetylcysteine also inhibits stimulated HIV expression in chronically infected monocyte and T-cell lines which are used as models for latent infection in AIDS. Furthermore, we show that N-acetylcysteine blocks viral production in monocyte cell lines more effectively than it blocks viral production in T cells. Since monocytes are a major reservoir for HIV in infected individuals, these results suggest that N-acetylcysteine may slow the change from latency to the later stages of AIDS in HIV-infected individuals.
Fish diet, fish oil and docosahexaenoic acid rich oil lower fasting and postprandial plasma lipid levels. (1996)

These results show that both fasting and postprandial triglyceride concentrations can be decreased with moderate intakes of long-chain n-3 fatty acids either from a fish diet or fish oil and that also pure DHA has a hypotriglyceridemic effect.
Increased removal of beta-very low density lipoproteins after ethinyl estradiol is associated with increased mRNA levels for hepatic lipase, lipoprotein lipase, and the low density lipoprotein receptor in Watanabe heritable hyperlipidemic rabbits. (1991)

The mechanism by which ethinyl estradiol (EE) decreases the concentration of lipids in the d less than 1.019 g/ml fraction (beta-very low density lipoprotein [beta-VLDL]) of homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits was studied. Treatment with EE increased the activity of hepatic lipase (HL) twofold to threefold in postheparin plasma and in liver biopsies. Postheparin plasma and adipose tissue lipoprotein lipase (LPL) activities were also increased twofold to fourfold after EE. The effects of EE on HL and LPL activities were associated with a threefold to sixfold elevation in liver HL mRNA and a fourfold elevation in adipose tissue LPL mRNA steady-state levels, pointing to an effect of EE on HL and LPL gene transcription. EE also increased liver low density lipoprotein (LDL) receptor mRNA levels threefold to fivefold. These results suggest a concerted action of LPL, HL, and the LDL receptor in the removal of beta-VLDL in homozygous WHHL rabbits with a defective LDL receptor. In addition, the content of apolipoprotein E in the d less than 1.019 g/ml fraction changed toward normal after EE. Because the remaining particles contained apolipoprotein B-100 almost exclusively, it is likely that apolipoprotein E-containing beta-VLDLs are preferentially removed. This may be the result of the increased activity of LPL and HL influencing the conformation of apolipoprotein E on the beta-VLDL particle in such a way that it is directly removed from the circulation, possibly by the induced LDL receptor.
New CsI/a-Si 17" x 17" x-ray flat-panel detector provides superior detectivity and immediate direct digital output for general radiography systems (1998)

A new 17' X 17' immediate direct digital flat panel detector has been developed to fit the needs of General Radiography. After reviewing a few key aspects of the General Radiography needs (X-ray energy range and associated measurement conditions, system integration and system operation), we describe the new detector Cesium Iodide/Amorphous Silicon based technology, and give measurement results (MTF, DQE stability). We compare the new detector performance to existing technologies (film/screen combination, storage phosphor devices) and also to other flat panel solutions (Selenium). We conclude that the CsI/a-Si technology is now the best suited one in order to fit the needs of General Radiography, this means all kinds of examinations (chest, abdomen, bones, extremities. . .) which have been up to now done using films.
Transforming growth factor beta inhibits formation of osteoclast-like cells in long-term human marrow cultures. (1988)

Transforming growth factor beta (TGF-beta), a polypeptide present in abundant amounts in bone matrix, was examined for its effects on osteoclast formation by using a human bone marrow culture system in which multinucleated cells (MNCs) with osteoclast characteristics form. TGF-beta strongly inhibited MNC formation at concentrations as low as 1 ng/ml. TGF-beta also completely suppressed the effects of osteotropic factors known to stimulate MNC formation. The inhibitory effect of TGF-beta on osteoclast-like cell formation was more pronounced during the first week of culture, which corresponds to the period of proliferation of mononuclear osteoclast precursors. To examine whether the inhibitory effects of TGF-beta on MNC formation could be due to inhibition of the granulocyte/macrophage progenitor cell [colony-forming unit granulocyte/macrophage (CFU-GM)], the probable precursor for MNC, we tested the effects of TGF-beta on CFU-GM formation in presence of a source of colony-stimulating factor. Unexpectedly, TGF-beta at concentrations (0.1-1 ng/ml) that were inhibitory for MNC formation enhanced day 7 CFU-GM colony formation. This increase in CFU-GM colony formation seen in cultures containing TGF-beta resulted from significantly more granulocytic colonies being formed in the cultures, suggesting that TGF-beta may induce CFU-GM to differentiate preferentially to cells of the granulocytic lineage. Differentiation of CFU-GM to granulocytes rather than osteoclast precursors in response to TGF-beta would result in inhibition of MNC formation by depleting the precursor pool for MNC. These data suggest that inhibition of osteoclast-like cell formation by TGF-beta may be an important mechanism of control of local bone resorption.
Every Breath You Take: The Impact of Environment on Resident Memory CD8 T Cells in the Lung (2014)

Resident memory T cells (TRM) are broadly defined as a population of T cells, which persist in non-lymphoid sites long-term, do not re-enter the circulation, and are distinct from central memory T cells (TCM) and circulating effector memory T cells (TEM). Recent studies have described populations of TRM cells in the skin, gut, lungs, and nervous tissue. However, it is becoming increasingly clear that the specific environment in which the TRM reside can further refine their phenotypical and functional properties. Here, we focus on the TRM cells that develop following respiratory infection and reside in the lungs and the lung airways. Specifically, we will review recent studies that have described some of the requirements for establishment of TRM cells in these tissues, and the defining characteristics of TRM in the lungs and lung airways. With continual bombardment of the respiratory tract by both pathogenic and environmental antigens, dynamic fluctuations in the local milieu including homeostatic resources and niche restrictions can impact TRM longevity. Beyond a comprehensive characterization of lung TRM cells, special attention will be placed on studies, which have defined how the microenvironment of the lung influences memory T cell survival at this site. As memory T cell populations in the lung airways are requisite for protection yet wane numerically over time, developing a comprehensive picture of factors which may influence TRM development and persistence at these sites is important for improving T cell-based vaccine design.
Epitaxial growth and characterization of zinc-blende gallium nitride on (001) silicon (1992)

GaN films have been epitaxially grown onto (001) Si by electron cyclotron resonance microwave-plasma-assisted molecular-beam epitaxy, using a two-step growth process, in which a GaN buffer is grown at relatively low temperatures and the rest of the film is grown at higher temperatures. This method of film growth was shown to lead to good single-crystalline β-GaN and to promote lateral growth resulting in smooth surface morphology. The full width at half-maximum of the x-ray rocking curve in the best case was found to be 60 min. Optical-absorption measurements indicate that the band gap of β-GaN is 3.2 eV and the index of the refraction below the absorption edge is 2.5. Conductivity measurements indicate that the films may have a carrier concentration below 1017 cm−3.
Panitumumab and cetuximab epitope mapping and in vitro activity (2008)

14536 Background: Panitumumab, a fully human monoclonal antibody against epidermal growth factor receptor (EGFR), has anti- tumor activity as monotherapy in both preclinical models and clinical trials. The objective of this study was to identify the epitope on EGFR for panitumumab and compare it to that of cetuximab, a chimeric anti-EGFR Ab. Methods: The extracellular domain of EGFR (amino acids 1–618) and domains I, II, III, IV individually were expressed to determine the domain on EGFR that was necessary for panitumumab binding. Chromatography was used to compare the binding affinity of panitumumab vs cetuximab. By flow cytometry and amino acid replacement scanning, the critical residues involved in panitumumab and cetuximab binding for EGFR were determined. Using diffraction data from the panitumumab Fab’2 and published data for cetuximab, crystal structure models of EGFR and the residues determined to be critical for panitumumab or cetuximab binding were built. To evaluate in vitro activity, A549 NSCLC cells were treated with 20μg/ml of panitumumab or cetuximab for 1 hour prior to a 15-minute stimulation with known EGFR ligands (TGF-α, amphiregulin, epiregulin, HB-EGF, betacellulin, and EGF). Inhibition of ligand-induced phosphorylation of EGFR was determined using a specific anti-pEGFR (pY1068) antibody. Results: Truncation analysis by flow cytometry narrowed the binding epitopes of panitumumab and cetuximab to domain III of EGFR. Point mutations revealed that amino acids 349, 355, 412, and 438 were critical for panitumumab and cetuximab binding. A 2.9 Angstrom crystal structure of the panitumumab Fab’2 was solved. Models of the panitumumab-EGFR and cetuximab-EGFR complexes were generated and predicted that the CDRs for both light and heavy chains would be proximal to domain III of EGFR. From in vitro studies, panitumumab and cetuximab can inhibit receptor activation of all known EGFR ligands in A549 NSCLC tumor cells. Conclusion: Panitumumab and cetuximab bind to comparable surface exposed amino acids in domain III of EGFR and inhibit all known EGFR ligands, resulting in inhibition of receptor activation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Inc. Amgen Inc.
A Store-operated Calcium Channel in Drosophila S2 Cells (2004)

Using whole-cell recording in Drosophila S2 cells, we characterized a Ca(2+)-selective current that is activated by depletion of intracellular Ca2+ stores. Passive store depletion with a Ca(2+)-free pipette solution containing 12 mM BAPTA activated an inwardly rectifying Ca2+ current with a reversal potential >60 mV. Inward currents developed with a delay and reached a maximum of 20-50 pA at -110 mV. This current doubled in amplitude upon increasing external Ca2+ from 2 to 20 mM and was not affected by substitution of choline for Na+. A pipette solution containing approximately 300 nM free Ca2+ and 10 mM EGTA prevented spontaneous activation, but Ca2+ current activated promptly upon application of ionomycin or thapsigargin, or during dialysis with IP3. Isotonic substitution of 20 mM Ca2+ by test divalent cations revealed a selectivity sequence of Ba2+ > Sr2+ > Ca2+ >> Mg2+. Ba2+ and Sr2+ currents inactivated within seconds of exposure to zero-Ca2+ solution at a holding potential of 10 mV. Inactivation of Ba2+ and Sr2+ currents showed recovery during strong hyperpolarizing pulses. Noise analysis provided an estimate of unitary conductance values in 20 mM Ca2+ and Ba2+ of 36 and 420 fS, respectively. Upon removal of all external divalent ions, a transient monovalent current exhibited strong selectivity for Na+ over Cs+. The Ca2+ current was completely and reversibly blocked by Gd3+, with an IC50 value of approximately 50 nM, and was also blocked by 20 microM SKF 96365 and by 20 microM 2-APB. At concentrations between 5 and 14 microM, application of 2-APB increased the magnitude of Ca2+ currents. We conclude that S2 cells express store-operated Ca2+ channels with many of the same biophysical characteristics as CRAC channels in mammalian cells.