gebhart/patrepeval huggingface dataset:
Vaccinia Virus-Mediated Inhibition of Type I Interferon Responses Is a Multifactorial Process Involving the Soluble Type I Interferon Receptor B18 and Intracellular Components (2008)

Poxviruses such as virulent vaccinia virus (VACV) strain Western Reserve encode a broad range of immune modulators that interfere with host responses to infection. Upon more than 570 in vitro passages in chicken embryo fibroblasts (CEF), chorioallantois VACV Ankara (CVA) accumulated mutations that resulted in highly attenuated modified vaccinia virus Ankara (MVA). MVA infection of mice and of dendritic cells (DC) induced significant type I interferon (IFN) responses, whereas infection with VACV alone or in combination with MVA did not. These results implied that VACV expressed an IFN inhibitor(s) that was functionally deleted in MVA. To further characterize the IFN inhibitor(s), infection experiments were carried out with CVA strains isolated after 152 (CVA152) and 386 CEF passages (CVA386). Interestingly, neither CVA152 nor CVA386 induced IFN-alpha, whereas the latter variant did induce IFN-beta. This pattern suggested a consecutive loss of inhibitors during MVA attenuation. Similar to supernatants of VACV- and CVA152-infected DC cultures, recombinantly expressed soluble IFN decoy receptor B18, which is encoded in the VACV genome, inhibited MVA-induced IFN-alpha but not IFN-beta. In the same direction, a B18R-deficient VACV variant triggered only IFN-alpha, confirming B18 as the soluble IFN-alpha inhibitor. Interestingly, VACV infection inhibited IFN responses induced by a multitude of different stimuli, including oligodeoxynucleotides containing CpG motifs, poly(I:C), and vesicular stomatitis virus. Collectively, the data presented show that VACV-mediated IFN inhibition is a multistep process involving secreted factors such as B18 plus intracellular components that cooperate to efficiently shut off systemic IFN-alpha and IFN-beta responses.
[Insulin secretion and insulin resistance in type II diabetes. Relation to fatty acid composition of serum phospholipids]. (1990)

Non-obese middle-aged men (n = 21) in an early stage after manifestation of Type 2 diabetes mellitus, and free of signs of atherosclerotic complications, when compared with an age-, weight- and sex-matched control group (n = 14), were found to show: 1. a decrease in linoleic acid content and increase in polyunsaturated elongated forms of n-6 and n-3 families fatty acids in serum phospholipids; 2. fasting hyperinsulinemia and impaired dynamics of insulin secretion after glucose load; 3. insulin resistance due to both receptor and postreceptor defect. Under physiologic conditions (i.e., in the control group), the drop in linoleic acid content and the rise in saturated fatty acids were associated with increased insulin secretion, and decrease in maximal insulin action. The nature of the changes in fatty acid pattern, the decrease in linoleic acid in particular, resembles findings made in persons who died middle-aged from serious complications of atherosclerosis. Combined with the relationship between the fatty acid composition of lipids and insulin secretion and action, our findings suggest a common metabolic defect of atherosclerosis and Type 2 diabetes which is probably insulin resistance in glucose metabolism.
Human Bodies, Computer Music (2002)

The author considers the absence of the artist's body in electronic music, a missing element that he finds crucial to the success of any work of art. In reviewing the historical development of electronic music from musique concrÈte to analog and then digital synthesizers, the author finds that the attainment of increased control and flexibility has coincided with the reduction of identifiable bodily involvement by the performer. He contrasts this trend with the highly physical intervention and manipulation, first practiced with atypical electronic instruments such as the theremin, subsequently introduced to the electric guitar by Jimi Hendrix and his followers, and then to vinyl by turntable artists. He concludes that the tension between body and machine in music, as in modern life itself, can only exist as an experience to examine and criticize and not as a problem to resolve.
Un estiu de pelegrinatges (2010)

This study provided an opportunity for cab drivers to describe their perspectives on reasons why their occupation was associated with a high risk for cardiovascular disease. The Go-Alongs contributed to the understanding of the social and environmental context that characterized cardiovascular risks in this occupation.
A Single Tyrosine of the Interleukin-9 (IL-9) Receptor Is Required for STAT Activation, Antiapoptotic Activity, and Growth Regulation by IL-9 (1996)

Interleukin-9 (IL-9), a T-cell-derived cytokine, interacts with a specific receptor associated with the IL-2 receptor gamma chain. In this report, we analyze the functional domains of the human IL-9 receptor transfected into mouse lymphoid cell lines. Three different functions were examined: growth stimulation in factor-dependent pro-B Ba/F3 cells, protection against dexamethasone-induced apoptosis, and Ly-6A2 induction in BW5147 lymphoma cells. The results indicated that a single tyrosine, at position 116 in the cytoplasmic domain, was required for all three activities. In addition, we observed that human IL-9 reduced the proliferation rate of transfected BW5147 cells, an effect also dependent on the same tyrosine. This amino acid was necessary for IL-9-mediated tyrosine phosphorylation of the receptor and for STAT activation but not for IRS-2/4PS activation or for JAK1 phosphorylation, which depended on a domain closer to the plasma membrane. We also showed that JAK1 was constitutively associated with the IL-9 receptor. Activated STAT complexes induced by IL-9 were found to contain STAT1, STAT3, and STAT5 transcription factors. Moreover, sequence homologies between human IL-9 receptor tyrosine 116 and tyrosines (of other receptors activating STAT3 and STAT5 were observed. Taken together, these data indicate that a single tyrosine of the IL-9 receptor, required for activation of three different STAT proteins, is necessary for distinct activities of this cytokine, including proliferative responses.
Condensed heteroaromatic ring systems. VII Synthesis of thienopyridines, thienopyrimidines, and furopyridines from o-substituted N-heteroarylacetylenes. (1986)

the cross-coupling reaction of 2-chloro-3-iodo- and 4-chloro-3-iodopyridines with phenylacetylene in the presence of dichlorobis(triphenylphosphine)palladium occurred at the 3-position. The 3-ethynylpyridines containing an adjacent chloro group were convertible to thienopyridines by traatment with sodium hydrosulfide. Similarly, various thieno[2, 3-d]pyrimidines were synthesized from 4-chloro-5-iodopuyrimidines. One-step synthesis of furopyridines by the palladium-catalyzed reaction of iodohydroxypyridines with terminal acetylenes is also described.
Uremic toxicity of indoxyl sulfate. (2010)

Indoxyl sulfate, a uremic toxin, is accumulated in the serum of chronic kidney disease (CKD) patients. A part of the dietary protein-derived tryptophan is metabolized into indole by tryptophanase in intestinal bacteria. Indole is absorbed into the blood from the intestine, and is metabolized to indoxyl sulfate in the liver. Indoxyl sulfate is normally excreted into urine. In CKD, however, an inadequate renal clearance of indoxyl sulfate leads to its elevated serum levels. The oral adsorbent AST-120 reduces the serum levels of indoxyl sulfate by adsorbing indole in the intestines and stimulating its excretion into feces. I have proposed a protein metabolite theory by which endogenous protein metabolites such as indoxyl sulfate play a significant role in the progression of CKD. A progressive decline in the glomerular filtration rate leads to increased serum levels of endogenous protein metabolites such as indoxyl sulfate, and to the adverse effects of their overload on the remnant nephrons. Indoxyl sulfate stimulates progressive both tubulointerstitial fibrosis and glomerular sclerosis by increasing the expression of transforming growth factor-beta1, a tissue inhibitor of metalloproteinase-1 and proalpha1 (I) collagen, leading to a further loss of nephrons. AST-120 delays the progression of CKD by removing serum indoxyl sulfate. Moreover, indoxyl sulfate induces oxidative stress in tubular cells, mesangial cells, vascular smooth muscle cells, endothelial cells and osteoblasts as well as stimulating aortic calcification in hypertensive rats, it is also involved in the progression of CKD, cardiovascular disease (CVD) and osteodystrophy. Thus, the removal of indoxyl sulfate by AST-120 ameliorates the progression of not only CKD, but also of CVD and osteodystrophy.
Membrane‐associated transcripts in Arabidopsis; their isolation and characterization by DNA microarray analysis and bioinformatics (2006)

Membrane-associated, integral membrane and secreted proteins are of key importance in many cellular processes. For most of the 28,952 predicted proteins in Arabidopsis, the actual subcellular localization has not been demonstrated experimentally. So far, their potential membrane-association has been deduced from algorithms that predict transmembrane domains and signal peptides. However, the comprehensiveness and accuracy of these algorithms is still limited. The majority of membrane-associated and secreted proteins is synthesized on membrane-bound polysomes. Therefore, the isolation and characterization of mRNA associated with membrane-bound polysomes offers an experimental tool for the genome-wide identification of these proteins. Here we describe an efficient method to isolate mRNA from membrane-bound polysomes and report on the validation of the method to enrich for transcripts encoding membrane-associated and secreted proteins. The sensitivity and reproducibility of the isolation method was investigated by DNA microarray analysis. Pearson correlations between transcript levels obtained from three replicate isolations showed that the method is highly reproducible. A significant enrichment for mRNAs encoding proteins containing predicted transmembrane domains and signal peptides was observed in the membrane-bound polysomal fraction. In this fraction, 301 transcripts were classified by gene ontologies as 'cellular component unknown', and potentially encode previously unrecognized secreted or membrane-associated proteins.
CD4+CD25high Regulatory Cells in Human Peripheral Blood (2001)

Thymectomy in mice on neonatal day 3 leads to the development of multiorgan autoimmune disease due to loss of a CD(+)CD25(+) T cell regulatory population in their peripheral lymphoid tissues. Here, we report the identification of a CD4(+) population of regulatory T cells in the circulation of humans expressing high levels of CD25 that exhibit in vitro characteristics identical with those of the CD4(+)CD25(+) regulatory cells isolated in mice. With TCR cross-linking, CD4(+)CD25(high) cells did not proliferate but instead totally inhibited proliferation and cytokine secretion by activated CD4(+)CD25(-) responder T cells in a contact-dependent manner. The CD4(+)CD25(high) regulatory T cells expressed high levels of CD45RO but not CD45RA, akin to the expression of CD45RB(low) on murine CD4(+)CD25(+) regulatory cells. Increasing the strength of signal by providing either costimulation with CD28 cross-linking or the addition of IL-2 to a maximal anti-CD3 stimulus resulted in a modest induction of proliferation and the loss of observable suppression in cocultures of CD4(+)CD25(high) regulatory cells and CD4(+)CD25(-) responder cells. Whereas higher ratios of CD4(+)CD25(high) T cells are required to suppress proliferation if the PD-L1 receptor is blocked, regulatory cell function is shown to persist in the absence of the PD-1/PD-L1 or CTLA-4/B7 pathway. Thus, regulatory CD4 T cells expressing high levels of the IL-2 receptor are present in humans, providing the opportunity to determine whether alterations of these populations of T cells are involved in the induction of human autoimmune disorders.
Evidence for a close link between the thyroid hormone transport system and the aromatic amino acid transport system T in erythrocytes. (1990)

The transport of [125I]triiodothyronine ([125I]T3) and [3H]tryptophan ([3H]Trp) by washed rat erythrocytes was studied at 25 degrees C in the presence of leucine in order to block the neutral amino acid transport system L. Eadie-Hofstee plots of initial velocity data gave the following values of Km (micromolar) and Vmax (nanomole/min/10(8) cells): 0.122 +/- 0.007 and 0.140 +/- 0.021 for T3, and 558 +/- 28 and 17.4 +/- 2.3 for Trp (n = 5). The Trp transport system in rat erythrocytes is similar to the human erythrocyte aromatic amino acid-specific system T described by Rosenberg et al. (Rosenberg, R., Young, J. D., and Ellory, J. C. (1980) Biochim. Biophys. Acta 598, 375-384). Unlabeled aromatic amino acids (e.g. Trp, phenylalanine, tyrosine) competitively inhibited [125I]T3 uptake and unlabeled iodothyronine analogues (e.g. T3, D-T3, thyroxine, thyronine) competitively inhibited [3H]Trp uptake. The inhibition constants of these competitors measured with each labeled substrate were highly correlated. N-Ethylmaleimide irreversibly inhibited T3 and Trp transport and each substrate protected the transport system of the other from inactivation by N-ethylmaleimide. The Vmax of T3 and Trp transport by human erythrocytes were 500 and 120 times lower, respectively, than those of rat erythrocytes (0.30 and 126 pmol/min/10(8) cells, respectively). The T3 and Trp transport activities of sheep erythrocytes were undetectable. These results indicate that T3 and Trp either share a common multi-specific transport system or are transported by closely linked systems which interact in the erythrocyte membrane.
Characterization of interaction between DNA and 4',6-diamidino-2-phenylindole by optical spectroscopy (1987)

We have examined the interaction between 4',6-diamidino-2-phenylindole (DAPI) and DNA using flow linear dichroism (LD), circular dichroism (CD), and fluorescence techniques. We show the presence of two spectroscopically distinct binding sites at low binding ratios with saturation values of 0.025 and 0.17, respectively. In both sites DAPI is bound with its long axis approximately parallel to the grooves of the DNA helix. Resolution of CD spectra shows that an exciton component is present at higher binding ratios, which we attribute to the interaction of two accidentally close-lying DAPI molecules. We also find evidence that DAPI, at least in the high-affinity site, binds preferentially to AT-rich regions. From the spectroscopic results, supported by structural considerations, we can completely exclude that DAPI is bound to DNA by intercalation. Binding geometries and site densities are consistent with a location of DAPI in the grooves of DNA, with the high-affinity site most probably in the minor groove.
The effect of chitosan on corneal wound healing. (1987)

Chitosan, a suspected inducer of vascular endothelium regeneration, was applied topically to the eyes of rabbits after they had sustained central corneal wounds. The rabbits were given chitosan tid for seven days in one experimental set and for 14, 17, and 21 days in subsequent sets. For all time sets, there were no apparent statistical differences in corneal wound tensile strength between the chitosan-treated eyes and control eyes.
Quantitative Analysis of Debranched Amylopectin by HPAEC-PAD with a Postcolumn Enzyme Reactor (1997)

Abstract The chain-length distribution of debranched amylopectin was analyzed by using high performance anion-exchange chromatography with an amyloglucosidase (AMG) reactor and a pulsed amperometric detector (HPAEC-ENZ-PAD). The effects of reactor length, reactor temperature, and additional a-amylase reactor were studied. Results showed that a 2 mm i.d. x 23 mm AMG reactor at 25%°C was sufficient to convert HPAEC-separated amylodextrins to glucose; the PAD response for the hydrolyzed amylodextrins of different chain-length was consistent, and quantitative results were achieved. With this enzymatic treatment, amylodextrin with DP up to 77 was detected for a debranched tapioca amylopectin sample. The chain-length distribution profile of debranched tapioca amylopectin showed three fractions with peak DPs 48± 1 (Fl), 19 (F2a), and 12 (F2b).
Restoration of Tight Junction Structure and Barrier Function by Down-Regulation of the Mitogen-activated Protein Kinase Pathway in Ras-transformed Madin-Darby Canine Kidney Cells (2000)

In the Madin-Darby canine kidney epithelial cell line, the proteins occludin and ZO-1 are structural components of the tight junctions that seal the paracellular spaces between the cells and contribute to the epithelial barrier function. In Ras-transformed Madin-Darby canine kidney cells, occludin, claudin-1, and ZO-1 were absent from cell-cell contacts but were present in the cytoplasm, and the adherens junction protein E-cadherin was weakly expressed. After treatment of the Ras-transformed cells with the mitogen-activated protein kinase kinase (MEK1) inhibitor PD98059, which blocks the activation of mitogen-activated protein kinase (MAPK), occludin, claudin-1, and ZO-1 were recruited to the cell membrane, tight junctions were assembled, and E-cadherin protein expression was induced. Although it is generally believed that E-cadherin-mediated cell-cell adhesion is required for tight junction assembly, the recruitment of occludin to the cell-cell contact area and the restoration of epithelial cell morphology preceded the appearance of E-cadherin at cell-cell contacts. Both electron microscopy and a fourfold increase in the transepithelial electrical resistance indicated the formation of functional tight junctions after MEK1 inhibition. Moreover, inhibition of MAPK activity stabilized occludin and ZO-1 by differentially increasing their half-lives. We also found that during the process of tight junction assembly after MEK1 inhibition, tyrosine phosphorylation of occludin and ZO-1, but not claudin-1, increased significantly. Our study demonstrates that down-regulation of the MAPK signaling pathway causes the restoration of epithelial cell morphology and the assembly of tight junctions in Ras-transformed epithelial cells and that tyrosine phosphorylation of occludin and ZO-1 may play a role in some aspects of tight junction formation.
Reflection-mode x-ray powder diffraction cell for in situ studies of electrochemical reactions (2004)

The design and operation of an electrochemical cell for reflection-mode powder x-ray diffraction experiments are discussed. The cell is designed for the study of electrodes that are used in rechargeable lithium batteries. It is designed for assembly in a glove box so that air-sensitive materials, such as lithium foil electrodes and carbonate-based electrolytes with lithium salts, can be used. The cell uses a beryllium window for x-ray transmission and electrical contact. A simple mechanism for compressing the electrodes is included in the design. Sample results for the cell are shown with a Cu Kα source and a position-sensitive detector.
Long-Term Disuse Osteoporosis Seems Less Sensitive to Bisphosphonate Treatment Than Other Osteoporosis (2005)

RIS treatment reduces cortical bone loss at periosteal and endocortical surfaces caused by long-term immobilization, thus partially conserving tissue mechanical properties. This modest effect contrasts with more dramatic actions of the bisphosphonate in other osteoporoses. Our results suggest that risedronate impairs osteoclastic function but cannot completely overcome the intense stimulus for osteoclast recruitment during prolonged disuse.
Sugars and Desiccation Tolerance in Seeds (1988)

Soluble sugars have been shown to protect liposomes and lobster microsomes from desiccation damage, and a protective role has been proposed for them in several anhydrous systems. We have studied the relationship between soluble sugar content and the loss of desiccation tolerance in the axes of germinating soybean (Glycine max L. Merr. cv Williams), pea (Pisum sativum L. cv Alaska), and corn (Zea mays L. cv Merit) axes. The loss of desiccation tolerance during imbibition was monitored by following the ability of seeds to germinate after desiccation following various periods of preimbibition and by following the rates of electrolyte leakage from dried, then rehydrated axes. Finally, we analyzed the soluble sugar contents of the axes throughout the transition from desiccation tolerance to intolerance. These analyses show that sucrose and larger oligosaccharides were consistently present during the tolerant stage, and that desiccation tolerance disappeared as the oligosaccharides were lost. The results support the idea that sucrose may serve as the principal agent of desiccation tolerance in these seeds, with the larger oligosaccharides serving to keep the sucrose from crystallizing.
Drug Evaluations Anti-infectives: Nevirapine: A review of its development, pharmacological profile and potential for clinical use (1996)

Nevirapine, a dipyridodiazepinone, is the prototypic member of a class of antiretroviral compounds referred to as nonnucleoside reverse transcriptase inhibitors. Nevirapine is a potent and selective noncompetitive inhibitor of the reverse transcriptase enzyme, an important therapeutic target for the treatment of HIV-1 infection. The activity of nevirapine does not compete with template or nucleoside triphosphates, nor does it inhibit HIV-2 reverse transcriptase or any of the human DNA polymerases. In completed clinical studies, nevirapine has demonstrated antiretroviral activity both as monotherapy and in combination with nucleoside analogues. When administered with zidovudine or the combination zidovudine/didanosine, the antiviral effect has been profound and sustained. A favourable antiviral effect and CD4+ lymphocyte response has been demonstrated in both adults and children, in patients experienced and naive to antiretroviral therapy as well as in those with baseline resistance to zidovudine. Nevirapine has a favourable pharmacokinetic profile, becomes widely distributed throughout body tissues including the central nervous system, and is active in the adult at an oral dose of 200 mg administered twice daily after a two week lead-in dose of 200 mg per day. There are no significant drug-drug interactions noted with the nucleoside reverse transcriptase inhibitors; however, because nevirapine induces cytochrome P450 isoenzymes, the currently used protease inhibitors may undergo more rapid rates of metabolism. Other commonly used drugs, such as ketoconazole, dapsone, rifampin, rifabutin and trimethoprim-sulfamethoxazole, appear not to be significantly affected. Resistance to nevirapine is rapid when administered as a monotherapy but this is altered and made less clinically relevant when nevirapine is given in combination with one or more of the nucleosides. Nevirapine has a safety profile that does not overlap with other antiretroviral therapies, the most common treatment-limiting reaction being rash. Nevirapine is an active antiretroviral agent with excellent biodistribution and good potential for use in combination with other antiretrovirals across the spectrum of HIV disease as well as in selected populations.