gebhart/patrepeval huggingface dataset:
Identification of small molecule inhibitors of hypoxia-inducible factor 1 transcriptional activation pathway. (2002)

Hypoxia-inducible factor 1 (HIF-1) is a master regulator of the transcriptional response to oxygen deprivation. HIF-1 has been implicated in the regulation of genes involved in angiogenesis [e.g., vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase] and anaerobic metabolism (e.g., glycolytic enzymes). HIF-1 is essential for angiogenesis and is associated with tumor progression. In addition, overexpression of HIF-1 alpha has been demonstrated in many common human cancers. Therefore, HIF-1 is an attractive molecular target for development of novel cancer therapeutics. We have developed a cell-based high-throughput screen for the identification of small molecule inhibitors of the HIF-1 pathway. We have genetically engineered U251 human glioma cells to stably express a recombinant vector in which the luciferase reporter gene is under control of three copies of a canonical hypoxia-responsive element (U251-HRE). U251-HRE cells consistently expressed luciferase in a hypoxia- and HIF-1-dependent fashion. We now report the results of a pilot screen of the National Cancer Institute "Diversity Set," a collection of approximately 2000 compounds selected to represent the greater chemical diversity of the National Cancer Institute chemical repository. We found four compounds that specifically inhibited HIF-1-dependent induction of luciferase but not luciferase expression driven by a constitutive promoter. In addition, these compounds inhibited hypoxic induction of VEGF mRNA and protein expression in U251 cells. Interestingly, three compounds are closely related camptothecin analogues and topoisomerase (Topo)-I inhibitors. We show that concomitant with HIF-1 and VEGF inhibition, the activity of the Topo-I inhibitors tested is associated with induction of cyclooxygenase 2 mRNA expression. The luciferase-based high-throughput screen is a feasible tool for the identification of small molecule inhibitors of HIF-1 transcriptional activation. In addition, our results suggest that altered Topo-I function may be associated with repression of HIF-1-dependent induction of gene expression.
Alemtuzumab in Previously Treated Chronic Lymphocytic Leukemia Patients Who Also Had Received Fludarabine (2002)

Alemtuzumab has significant activity in poor-prognosis, fludarabine-treated CLL patients. However, because of a relatively high incidence of opportunistic infections accompanying profound lymphopenia, future protocols should include mandatory prophylaxis.
Argon laser treatment of trichiasis. (1986)

This paper presents the application of argon laser in the treatment of trichiasis. The technique involves the destruction of the follicles of the abnormal cilia. A beam of 50- to 200-micron spot size, 0.1- to 0.2 second time, and 1,000 to 1,200 mW power is used under local anesthesia. This method proved safe, convenient, precise, and effective in 11 cases. The technique is most suitable when a few fine cilia are involved, but repeated treatment may be required for more and thicker eyelashes. The follow-up period in this study varied from a minimum of four months to a maximum of nine months.
Plasma adiponectin before and after kidney transplantation (2012)

The role of plasma adiponectin (ADPN) in patients with impaired kidney function and following kidney transplantation (Tx) is debated. We aimed to: (i) determine whether pretransplant ADPN level is an independent risk factor for deterioration of glucose tolerance including development of new-onset diabetes mellitus after Tx, (ii) describe which parameters that influence the ADPN concentration before and after Tx. Fifty-seven nondiabetic kidney allograft recipients and 40 nondiabetic uraemic patients were included. The Tx group was examined at baseline and 3 and 12 months after Tx. The uraemic control group was examined twice, separated by 12 months. ADPN levels declined significantly following Tx (P < 0.0001), while estimated glomerular filtration rate (eGFR) increased (P < 0.0005). eGFR, BMI and insulin sensitivity index were independently associated with ADPN in a multivariate regression analysis, whereas an ordinal logistic regression analysis revealed no predictive characteristic of ADPN for aggravation of the glucose tolerance after Tx. In conclusion, kidney transplantation is accompanied by a significant reduction in ADPN concentration. Several factors determine the ADPN concentration before and after Tx including kidney function, insulin resistance, use of immunosuppressive agents and BMI. Pretransplant ADPN level did not predict development of new-onset diabetes mellitus or even deterioration of the glucose tolerance following Tx.
An endoplasmic reticulum-retained herpes simplex virus glycoprotein H is absent from secreted virions: evidence for reenvelopment during egress (1996)

Although it is generally accepted that one of the first steps of herpesvirus egress is the acquisition of an envelope by nucleocapsids budding into the inner nuclear membrane, later events in the pathway are not well understood. We tested the hypothesis that the virus then undergoes de-envelopment, followed by reenvelopment at membranes outside the endoplasmic reticulum (ER), by constructing a recombinant virus in which the expression of an essential glycoprotein, gH, is restricted to the inner nuclear membrane-ER by means of the ER retention motif, KKXX. This targeting signal conferred the predicted ER localization properties on gH in recombinant virus-infected cells, and gH and gL polypeptides failed to become processed to their mature forms. Cells infected with the recombinant virus released particles with 100-fold less infectivity than those released by cells infected with the wild-type parent virus, yet the number of enveloped virus particles released into the medium was unaltered. These particles contained normal amounts of gD and VP16 but did not contain detectable amounts of gH, and these data are consistent with a model of virus exit whereby naked nucleocapsids in the cytoplasm acquire their final envelope from a subcellular compartment other than the ER-inner nuclear membrane.
Ylides by the desilylation of .alpha.-silyl onium salts (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleYlides by the desilylation of .alpha.-silyl onium saltsEdwin Vedejs and Frederick G. WestCite this: Chem. Rev. 1986, 86, 5, 941–955Publication Date (Print):October 1, 1986Publication History Published online1 May 2002Published inissue 1 October 1986https://pubs.acs.org/doi/10.1021/cr00075a014https://doi.org/10.1021/cr00075a014research-articleACS PublicationsRequest reuse permissionsArticle Views855Altmetric-Citations148LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Further Investigations of High-Order Ambisonics and Wavefield Synthesis for Holophonic Sound Imaging (2003)

This convention paper has been reproduced from the author&amp;apos;s advance manuscript, without editing, corrections, or consideration by the Review Board. The AES takes no responsibility for the contents. Additional papers may be obtained by sending request
A prospective randomised double-blind study of functional outcome and range of flexion following total knee replacement with the NexGen standard and high flexion components (2007)

Modifications in the design of knee replacements have been proposed in order to maximise flexion. We performed a prospective double-blind randomised controlled trial to compare the functional outcome, including maximum knee flexion, in patients receiving either a standard or a high flexion version of the NexGen legacy posterior stabilised total knee replacement. A total of 56 patients, half of whom received each design, were assessed pre-operatively and at one year after operation using knee scores and analysis of range of movement using electrogoniometry. For both implant designs there was a significant improvement in the function component of the knee scores (p < 0.001) and the maximum range of flexion when walking on the level, ascending and descending a slope or stairs (all p < 0.001), squatting (p = 0.020) and stepping into a bath (p = 0.024). There was no significant difference in outcome, including the maximum knee flexion, between patients receiving the standard and high flexion designs of this implant.
Colony-stimulating factors regulate the development of multinucleated osteoclasts from recently replicated cells in vitro. (1987)

Osteoclasts mediate the process of bone resorption. However, little is known about the mechanisms that regulate the formation of either osteoclasts or osteoclast precursors. In contrast, colony-stimulating factors (CSFs) are well-known to regulate the formation of myeloid cells and their precursors. Because osteoclasts and myeloid cells may originate from a common stem cell, we examined the effects of two CSFs, granulocyte-macrophage CSF (GM-CSF) and interleukin 3 (IL-3), on bone resorption, osteoclast formation, and the incorporation of recently replicated nuclei into the osteoclasts of mouse bone cultures. CSFs had little effect on the formation rate of osteoclasts or their resorptive activity but significantly decreased the percentage of recently replicated osteoclast progenitor cell nuclei present in the osteoclasts of bones treated with parathyroid hormone. GM-CSF also increased the number of myeloid cells in the marrow space of the cultures and the percentage of these cells derived from recently replicated progenitors. These results demonstrate that GM-CSF and IL-3 can regulate the development of osteoclasts from recently replicated precursor cells in cultured fetal mouse long bones. However, the mechanisms by which CSFs influence osteoclast formation are difficult to determine from these studies because markers for the osteoclast progenitor and precursor do not exist. These data also provide evidence that the differentiation of osteoclast progenitors is regulated by different factors at different points in their ontogeny.
CD4 is a critical component of the receptor for human herpesvirus 7: interference with human immunodeficiency virus. (1994)

In this study, we demonstrate that the glycoprotein CD4, a member of the immunoglobulin superfamily, is a critical component of the receptor for human herpesvirus 7 (HHV-7), a recently discovered T-lymphotropic human herpesvirus. A selective and progressive downregulation of the surface membrane expression of CD4 was observed in human CD4+ T cells in the course of HHV-7 infection. Various murine monoclonal antibodies to CD4 and the recombinant soluble form of human CD4 caused a dose-dependent inhibition of HHV-7 infection in primary CD4+ T lymphocytes. Moreover, radiolabeled HHV-7 specifically bound to cervical carcinoma cells (HeLa) expressing human CD4. A marked carcinoma cells (HeLa) expressing human CD4. A marked reciprocal interference was observed between HHV-7 and human immunodeficiency virus (HIV), the retrovirus that causes the acquired immunodeficiency syndrome and also uses CD4 as a receptor. Previous exposure of CD4+ T cells to HHV-7 dramatically interfered with infection by both primary and in vitro-passaged HIV-1 isolates. Reciprocally, persistent infection with HIV-1 or treatment with the soluble form of gp120, the CD4-binding envelope glycoprotein of HIV-1, rendered CD4+ T cells resistant to HHV-7 infection. These data indicate that CD4 is critically involved in the receptor mechanism for HHV-7. The antagonistic effect between HHV-7 and HIV could be exploited to devise therapeutic approaches to AIDS.
5α‐androst‐16‐ene‐3‐one:—Compound responsible for taint in boar fat (1968)

Abstract The volatile compounds stripped from boar, hog and gilt fats under conditions of high vacuum and elevated temperature have been subjected to gas chromatographic and olfactory analysis. The compound primarily responsible for the taint of boar fat has been isolated and identified by mass spectrometry as 5α‐androst‐16‐ene‐3‐one. It has an unpleasant odour of perspiration and is detectable in most boars of 200 lb live‐weight and over but not in hogs or gilts.
Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs (2014)

Hematopoietic stem cell (HSC)-based gene therapy holds promise for the cure of many diseases. The field is now moving toward the use of lentiviral vectors (LVs) as evidenced by 4 successful clinical trials. These trials used vesicular-stomatitis-virus-G protein (VSV-G)-LVs at high doses combined with strong cytokine-cocktail stimulation to obtain therapeutically relevant transduction levels; however, they might compromise the HSC character. Summarizing all these disadvantages, alternatives to VSV-G-LVs are urgently needed. We generated here high-titer LVs pseudotyped with a baboon retroviral envelope glycoprotein (BaEV-LVs), resistant to human complement. Under mild cytokine prestimulation to preserve the HSC characteristics, a single BaEV-LV application at a low dose, resulted in up to 90% of hCD34(+) cell transduction. Even more striking was that these new BaEV-LVs allowed, at low doses, efficient transduction of up to 30% of quiescent hCD34(+) cells, whereas high-dose VSV-G-LVs were insufficient. Importantly, reconstitution of NOD/Lt-SCID/γc(-/-) (NSG) mice with BaEV-LV-transduced hCD34(+) cells maintained these high transduction levels in all myeloid and lymphoid lineages, including early progenitors. This transduction pattern was confirmed or even increased in secondary NSG recipient mice. This suggests that BaEV-LVs efficiently transduce true HSCs and could improve HSC-based gene therapy, for which high-level HSC correction is needed for life-long cure.
Endothelial Programmed Death-1 Ligand 1 (PD-L1) Regulates CD8 + T-Cell–Mediated Injury in the Heart (2007)

Myocardial PD-L1, mainly localized on endothelium, is critical for control of immune-mediated cardiac injury and polymorphonuclear leukocyte inflammation.
Neuroprotective Effects of Creatine in a Transgenic Mouse Model of Huntington's Disease (2000)

Huntington's disease (HD) is a progressive neurodegenerative illness for which there is no effective therapy. We examined whether creatine, which may exert neuroprotective effects by increasing phosphocreatine levels or by stabilizing the mitochondrial permeability transition, has beneficial effects in a transgenic mouse model of HD (line 6/2). Dietary creatine supplementation significantly improved survival, slowed the development of brain atrophy, and delayed atrophy of striatal neurons and the formation of huntingtin-positive aggregates in R6/2 mice. Body weight and motor performance on the rotarod test were significantly improved in creatine-supplemented R6/2 mice, whereas the onset of diabetes was markedly delayed. Nuclear magnetic resonance spectroscopy showed that creatine supplementation significantly increased brain creatine concentrations and delayed decreases in N-acetylaspartate concentrations. These results support a role of metabolic dysfunction in a transgenic mouse model of HD and suggest a novel therapeutic strategy to slow the pathological process.
Protein Extraction from Solid Tissue (2010)

Maximal extraction and solubilization of protein from diseased or healthy tissue is important to make the whole protein complement available for proteomic analysis. It also helps to maximize reproducibility and to minimize waste. Minimal degradation of the protein amino acid backbone or dephosphorylation is essential to preserve the analytical utility of the extract. Containment of the sample is important to minimize the risk of contamination to and from the sample. The proposed standard protocol for protein extraction and solubilization can result in 98% solubilization of brain tissue, corresponding to about 100 μg protein per mg tissue wet weight, by a frozen disintegration/SDS-based solubilization method: Tissue is crushed in the frozen state in a cryotube by shaking with a sterile steel ball. The crushing is followed by the extraction and solubilization in 2% SDS for 10 min, at 70°C, in a volume corresponding to ten times the tissue wet weight, with shaking. The containment in a cryotube helps to prevent contamination. The treatment with SDS sample buffer can inhibit protease and phosphatase activity. The resulting protein extracts can be used for SDS PAGE, 2-D PAGE, Western blotting, ESI-MS, and ELISA. The proposed standard protocol has the potential to find wide application where protein extraction, solubilization, identification, and quantitation from cryopreserved clinical samples are desirable.
Binding mode analysis of 3-(4-benzoyl-1-methyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamide: a new synthetic histone deacetylase inhibitor inducing histone hyperacetylation growth inhibition and terminal cell differentiation (2002)

The binding mode of 3-(4-aroyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamides 1a−c, belonging to a recently reported class of synthetic histone deacetylase (HDAC) inhibitors (Massa, S.; et al. J. Med. Chem. 2001, 44, 2069−2072), into the new modeled HDAC1 catalytic core is presented, and enzyme/inhibitor interactions are discussed. HDAC1 X-ray coordinates were obtained by virtual “mutation” of those of histone deacetylase-like protein, a bacterial HDAC homologue. In in vitro antimaize HD2 as well as antimouse HDAC1 assay, compounds 1a−c showed inhibitory activities in the low micromolar range. Similarly, 1a−c are endowed with anti-HDAC activity in vivo:  on mouse A20 cells, 1a−c induced histone hyperacetylation leading to a highly increased acetylation level of H4 as compared to control histones. Results obtained with acid−urea−triton polyacrylamide gel electrophoresis have been confirmed by Western Blot experiments. Finally, compound 1a, chosen as a representative member of this class of HDAC inhibitors, result...
Artificial Polypeptide Scaffold for Protein Immobilization (2005)

An artificial polypeptide scaffold composed of surface anchor and protein capture domains was designed and expressed in vivo. By using a mutant E. coli phenylalanyl−tRNA synthetase, the photoreactive amino acid para-azidophenylalanine was incorporated into the surface anchor domain. Octyltrichlorosilane-treated surfaces were functionalized with this polypeptide by spin coating and photocrosslinking. The resulting protein films were shown to immobilize recombinant proteins through association of coiled coil heterodimer.
The Adipokine Lipocalin 2 Is Regulated by Obesity and Promotes Insulin Resistance (2007)

Lcn2 is an adipokine with potential importance in insulin resistance associated with obesity.
Human Tamm-Horsfall glycoprotein: urinary and plasma levels in normal subjects and patients with renal disease determined by a fully validated radioimmunoassay (1985)

A recently developed, simple and sensitive radioimmunoassay has been used to examine 24 h excretion and plasma levels of Tamm-Horsfall glycoprotein (THG) in normal subjects, stone formers and patients with stable chronic renal disease. In normal subjects THG excretion ranged from 22 to 66 mg/24 h, with no sex difference and no correlation with creatinine clearance or body surface area. There was no correlation between 24 h THG excretion and urine volume, pH or osmolality, excretion of Na+, K+ or Ca2+ or free-water clearance. There was a small significant correlation between plasma THG concentration and urinary THG excretion. A good correlation was obtained between the THG/creatinine ratio in 24 h and random samples. This made possible the use of random samples to establish a reference range for THG excretion of 0.15-0.50 micrograms/ml of creatinine clearance which did not depend on sex or age. The excretion rate of THG in stone formers was generally within the reference range. It was not significantly different in those who were hypercalciuric or in those taking thiazides. In patients with chronic renal disease there was a good correlation between 24 h THG excretion, plasma THG concentration and creatinine clearance. The range of excretion of THG per ml of creatinine clearance was greater than in normal subjects, independent of the type of renal disease and unrelated to proteinuria. In patients with glomerulonephritis the excretion of THG per ml of creatinine clearance was significantly higher in those with well-preserved tubules compared with those with tubular atrophy.
Staphylococcus aureus Strain DU4916 -- an Atypical Methicillin-resistant Isolate? (1974)

SUMMARY: Staphylococcus aureus strain du4916 was examined for linkage of markers. No ‘curing’ action due to treatment with acridine dyes was demonstrated. The genes for penicillinase production and metal-ion resistance (borne by a plasmid of 20 × 106 daltons), tetracycline resistance (a plasmid of 2·9 × 106), streptomycin resistance (a chromosomal gene) and methicillin resistance (of uncertain locus) were separately transduced to recipients. No linkage of methicillin resistance with enterotoxin B, haemolysins, pigment, or a gene that suppresses inducible resistance to erythromycin was demonstrated. These data are consistent with the hypothesis that all methicillin-resistant strains of S. aureus have a common and relatively recent origin.
TLR-Independent and P2X7-Dependent Signaling MediateAluRNA-Induced NLRP3 Inflammasome Activation in Geographic Atrophy (2013)

NF-κB and P2X7 are critical signaling intermediates in Alu RNA-induced inflammasome priming and RPE degeneration. These molecules are novel targets for rational drug development for geographic atrophy.
[An analysis on need and demand for dental service in urban residents of Beijing]. (2000)

A substantial discrepancy is found between oral disease presence and demand for dental service. The levels of demand are also irrational. The large potential demand is caused by both receiver and provider's factors. At last, the future demand for dental care is forecasted under three hypothesis.
BCG-induced resistance in Trypanosoma cruzi experimental infections. (1981)

Administration of BCG induced in mice a clear resistance to a challenge infection with bloodstream trypomastigotes from two Trypanosoma cruzi strains. This finding represents a further demonstration that cell mediated immunity plays a definite role in the immune response in experimental Chagas' disease. "In vitro" experiments have shown that BCG-activated mouse macrophages are able to inhibit the development of T. cruzi intracellular stages, although no microbicidal effect could be detected. The controversial results on BCG effect in T. cruzi infections reported in the literature had been reviewed and discussed.