gebhart/patrepeval huggingface dataset:
Analysis of EPC‐1 growth state–dependent expression, specificity, and conservation of related sequences (1995)

The transcript for EPC-1 (early population doubling level (PDL) cDNA-1) is induced under conditions of growth arrest due to density-dependent contact inhibition and/or serum deprivation in early-passage but not in senescent WI-38 fibroblasts. We have characterized the EPC-1 transcript with respect to its cell-cycle regulation, tissue specificity, and interspecies conservation of related genomic sequences. In low density, quiescent (serum-deprived), early-passage fibroblasts that are stimulated to proliferate with fresh serum, steady-state EPC-1 transcript levels are steadily reduced until they reach a basal level approximately 24 h after stimulation. However, when early-passage fibroblasts are made quiescent by both serum deprivation and density-dependent contact inhibition and then stimulated with serum, steady-state EPC-1 transcript levels remain relatively constant throughout a 36 h period following serum stimulation. Senescent WI-38 cells (> 95% life span completed) do not express EPC-1 under these conditions. We show that differences in the regulation of EPC-1 transcript levels in early-passage cells are due to differences in growth state rather than changes in cell density or contact. We also show that expression of the EPC-1 transcript is limited to specific cell types and that related genomic sequences are found in all mammalian species examined as well as in the chicken.
Glycogen Synthase Kinase-3β Inhibition Preserves Hematopoietic Stem Cell Activity and Inhibits Leukemic Cell Growth (2008)

Ex vivo expansion of cord blood cells generally results in reduced stem cell activity in vivo. Glycogen synthase kinase-3beta (GSK-3beta) regulates the degradation of beta-catenin, a critical regulator of hematopoietic stem cells (HSCs). Here we show that GSK-3beta inhibition activates beta-catenin in cord blood CD34(+) cells and upregulates beta-catenin transcriptional targets c-myc and HoxB4, both known to regulate HSC self-renewal. GSK-3beta inhibition resulted in delayed ex vivo expansion of CD34(+) cells, yet enhanced the preservation of stem cell activity as tested in long-term culture with bone marrow stroma. Delayed cell cycling, reduced apoptosis, and increased adherence of hematopoietic progenitor cells to bone marrow stroma were observed in these long-term cultures treated with GSK-3beta inhibitor. This improved adherence to stroma was mediated via upregulation of CXCR4. In addition, GSK-3beta inhibition preserved severe combined immunodeficiency (SCID) repopulating cells as tested in the nonobese diabetic/SCID mouse model. Our data suggest the involvement of GSK-3beta inhibition in the preservation of HSC and their interaction with the bone marrow environment. Methods for the inhibition of GSK-3beta may be developed for clinical ex vivo expansion of HSC for transplantation. In addition, GSK-3beta inhibition suppressed leukemic cell growth via the induction of apoptosis mediated by the downregulation of survivin. Modulators of GSK-3beta may increase the range of novel drugs that specifically kill leukemic cells while sparing normal stem cells.
Effect of Testosterone Replacement Therapy on Prostate Tissue in Men With Late-Onset Hypogonadism (2006)

These preliminary data suggest that in aging men with late-onset hypogonadism, 6 months of TRT normalizes serum androgen levels but appears to have little effect on prostate tissue androgen levels and cellular functions. Establishment of prostate safety for large populations of older men undergoing longer duration of TRT requires further study. Trial Registration clinicaltrials.gov Identifier: NCT00161304.
Aligned Carbon Nanotube Films: Production and Optical and Electronic Properties (1995)

Carbon nanotube material can now be produced in macroscopic quantities. However, the raw material has a disordered structure, which restricts investigations of both the properties and applications of the nanotubes. A method has been developed to produce thin films of aligned carbon nanotubes. The tubes can be aligned either parallel or perpendicular to the surface, as verified by scanning electron microscopy. The parallel aligned surfaces are birefringent, reflecting differences in the dielectric function along and normal to the tubes. The electrical resistivities are anisotropic as well, being smaller along the tubes than perpendicular to them, because of corresponding differences in the electronic transport properties.
Expression of the P-protein of the human hepatitis B virus in a vaccinia virus system and detection of the nucleocapsid-associated P-gene product by radiolabelling at newly introduced phosphorylation sites (1992)

Hepatitis B virus (HBV) contains a particle-associated DNA polymerase/reverse transcriptase activity encoded by the P (pol) open reading frame. Due to its low abundance, the corresponding protein has so far escaped direct detection and structural analysis. As a first step to overcome these difficulties, a series of recombinant vaccinia viruses was constructed and used for the synthesis in human hepatoma cells of both the authentic full length protein and of its functional domains. Pulse chase experiments demonstrated that the P-proteins had very short half lives in striking contrast to the viral core protein expressed in parallel with the same system. No evidence was obtained for a specific proteolytic processing of the P-protein as occurring with retroviral pol gene products. Overexpression of P-protein by recombinant vaccinia viruses was then employed to develop a highly sensitive detection method based on the in vitro phosphorylation of newly introduced target sites for protein kinase A. The usefulness of this method was demonstrated in the analysis of encapsidated P-gene products that were transiently expressed from an appropriately modified HBV genome. The results obtained indicate that the P-protein acts unprocessed, at least during the initial steps of nucleocapsid assembly and reverse transcription, and that a fraction of the P-protein molecules is linked as such to the viral DNA. Direct detection of the hepadnaviral P-protein by in vitro phosphorylation should greatly facilitate future analyses on P-protein structure and function.
The Evolution of Concepts of Opioid Receptors (1988)

The early evolution of concepts of endogenous opioids and multiple opioid receptors had its inception in a concerted program to develop safe, nonaddicting substitutes for opiates (see Eddy, 1973). This endeavor was initiated by the Bureau of Social Hygiene and subsequently supported by the United States Public Health Service under the auspices of the National Research Council. An empiric approach was taken in which a large number of chemicals, synthesized by University-based chemists and the pharmaceutical industry, were examined for their pharmacologic effects, particularly their analgesic activity and their abuse potential. Although heroin and morphine addiction were the initial driving force of this endeavor, the economic gains associated with the marketing of a less-addicting analgesic became the most important factor of the pharmaceutical industries large synthetic effort. From a societal perspective, however, the economics of drug abuse is by far the most important economic factor, since drug abuse costs the United States well over $100 billion dollars a year. The search for safer and less-abusable analgesics has not been entirely successful. The evolution of ideas concerning multiple opioid receptors and endogenous opioid transmitters is still active.
Differential Normalization of Mucosal Interleukin-8 and Interleukin-6 Activity afterHelicobacter pyloriEradication (1998)

There is differential resolution of mucosal infiltration with neutrophils and mononuclear cells following successful Helicobacter pylori eradication. We investigated the effects of H. pylori eradication on mucosal interleukin-8 (IL-8) and IL-6 activity in relation to the resolution of H. pylori-associated gastritis. Eighty-one duodenal ulcer patients with H. pylori infection received dual- or triple-treatment eradication therapy, and mucosal biopsy specimens obtained at the initial and follow-up endoscopic examinations were cultured in vitro for 24 h. The levels of IL-8 and IL-6 were measured by enzyme-linked immunosorbent assays. In the 42 patients in whom H. pylori eradication failed, there was little change in the numbers of neutrophils and mononuclear cells infiltrating the mucosa and in IL-8 and IL-6 activity. In the 39 patients in whom H. pylori was eradicated, there was normalization both in the numbers of infiltrating neutrophils and in mucosal IL-8 activity, which was evident within 1 month following therapy. In contrast, there was a gradual resolution of mononuclear cell infiltration over a 6-month period, accompanied by a gradual normalization in IL-6 levels. Addition of H. pylori to cultures of mucosal tissues induced a significant increase in IL-8 activity in both uninfected control subjects and patients from whom H. pylori was eradicated. However, this introduction yielded a significant increase in IL-6 activity only in the latter group. This study indicates a dichotomy in the changes of mucosal IL-8 and IL-6 activity after H. pylori eradication. The rapid normalization of IL-8 after H. pylori eradication and the ability of H. pylori cells to stimulate IL-8 in control tissues indicate that IL-8 induction is a part of the innate (nonimmune) responses to this organism. In contrast, the results of experiments analyzing IL-6 activity in cultured mucosal tissues suggest that the gradual resolution of mucosal IL-6 activity and mononuclear infiltration after successful eradication observed in vivo may reflect gradually diminishing residual immune responses against H. pylori.
Temporal and Spatial Expression Profiles of BMP Receptors and Noggin During BMP-2-Induced Ectopic Bone Formation (2003)

In the BMP group, expression of BMPR-1A, -2, and Noggin mRNA and protein was enhanced 2-4 days after implantation in undifferentiated mesenchymal cells and regenerating muscle fibers located close to the BMP-retaining implants. On day 7, the expression was also observed in cartilage cells, and after day 14, in the osteoblastic cells around bone tissue. The level of expression peaked at day 4 after implantation and persisted at a much lower level during the bone forming process. No significant expression of BMPR-1B was detected at the mRNA and protein levels during the bone-forming reaction. In the BMP free control groups, a mild enhancement of BMPR-2 expression was also noted around the implant, but this was not observed for BMPR-1A, -1B, or Noggin. Upregulated expression of BMPR-1A, -2, and Noggin in undifferentiated mesenchymal cells and regenerating muscle fibers occurs during the early phase of BMP-2-induced bone formation. The coordinate expression of these positive and negative regulators of BMP signaling points to a potential regulatory mechanism for bone induction.
SMART, a simple modular architecture research tool: Identification of signaling domains (1998)

Accurate multiple alignments of 86 domains that occur in signaling proteins have been constructed and used to provide a Web-based tool (SMART: simple modular architecture research tool) that allows rapid identification and annotation of signaling domain sequences. The majority of signaling proteins are multidomain in character with a considerable variety of domain combinations known. Comparison with established databases showed that 25% of our domain set could not be deduced from SwissProt and 41% could not be annotated by Pfam. SMART is able to determine the modular architectures of single sequences or genomes; application to the entire yeast genome revealed that at least 6.7% of its genes contain one or more signaling domains, approximately 350 greater than previously annotated. The process of constructing SMART predicted (i) novel domain homologues in unexpected locations such as band 4.1-homologous domains in focal adhesion kinases; (ii) previously unknown domain families, including a citron-homology domain; (iii) putative functions of domain families after identification of additional family members, for example, a ubiquitin-binding role for ubiquitin-associated domains (UBA); (iv) cellular roles for proteins, such predicted DEATH domains in netrin receptors further implicating these molecules in axonal guidance; (v) signaling domains in known disease genes such as SPRY domains in both marenostrin/pyrin and Midline 1; (vi) domains in unexpected phylogenetic contexts such as diacylglycerol kinase homologues in yeast and bacteria; and (vii) likely protein misclassifications exemplified by a predicted pleckstrin homology domain in a Candida albicans protein, previously described as an integrin.
Paraboloid electronic eye cameras using deformable arrays of photodetectors in hexagonal mesh layouts (2010)

We report on a type of digital camera that uses a hexagonal array of silicon photodetectors on a substrate whose surface has parabolic curvature. This elliptical paraboloid shape closely matches the image surface formed by a simple, planoconvex lens. The hexagonal arrangement provides high area coverage with an approximately circular peripheral view. Details of the design strategies and underlying features of the mechanics and optics are described. Full imaging with these parabolic cameras and comparison to planar layouts reveals improved uniformity of illumination and focus across a wide field of view.
The Biosynthesis of Cyclopropanated Mycolic Acids in Mycobacterium tuberculosis (1995)

The major mycolic acid produced by Mycobacterium tuberculosis contains two cis-cyclopropanes in the meromycolate chain. The gene whose product cyclopropanates the proximal double bond was cloned by homology to a putative cyclopropane synthase identified from the Mycobacterium leprae genome sequencing project. This gene, named cma2, was sequenced and found to be 52% identical to cma1 (which cyclopropanates the distal double bond) and 73% identical to the gene from M. leprae. Both cma genes were found to be restricted in distribution to pathogenic species of mycobacteria. Expression of cma2 in Mycobacterium smegmatis resulted in the cyclopropanation of the proximal double bond in the alpha 1 series of mycolic acids. Coexpression of both cyclopropane synthases resulted in cyclopropanation of both centers, producing a molecule structurally similar to the M. tuberculosis alpha-dicyclopropyl mycolates. Differential scanning calorimetry of purified cell walls and mycolic acids demonstrated that cyclopropanation of the proximal position raised the observed transition temperature by 3 degrees C. These results suggest that cyclopropanation contributes to the structural integrity of the cell wall complex.
Phosphate transport by capillaries of the blood-brain barrier. (1992)

3P8Capillaries were isolated from bovine brain cortex and used for phosphate transport studies.The influx of phosphate through capillary membranes was studied by incubation with [32Pi]phosphate followed by a rapid filtration technique.Phosphate uptake by brain capillaries was mediated by a saturable high-affinity system which is independent of the sodium concentration in the incubation medium.The apparent half-saturation constant (K,) and maximal influx (VmaX) were estimated to 160 g~ and 0.37 nmol/mg protein/30 s.Transport was inhibited by the phosphate analogues arsenate and phosphonoformic acid with apparent inhibition constants of 5 and 11 mM, respectively.The metabolic inhibitors cyanide and ouabain had no effect on the transport activity.Competition experiments showed that phosphate uptake was inhibited up to 41% by various anions (pyruvate, acetate, citrate, glutamate, and sulfate).In addition, phosphate uptake was significantly decreased by two selective inhibitors of anionic exchangers, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid.Chloride was not a substrate of the phosphate carrier as the replacement of external chloride, by nitrate, thiocyanate, or gluconate, did not increase phosphate transport.Aminohippuric acid and N'-methylnicotinamide, two specific substrates of anionic and cationic drug exchangers, did not compete with the phosphate carrier of cerebral capillaries.However, trans-stimulation with bicarbonate increased phosphate transport by 28%, and this stimulation was inhibited by 1 m M 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, suggesting that the carrier of the cerebral capillaries could exchange phosphate with bicarbonate.The plasma membrane of endothelial cells of cerebral capillaries forms a continuous barrier between blood and brain interstitium.These endothelial cells are sealed together by tight junctions and do not possess fenestrations or transendothelial channels (1,2).Brain capillaries also contain a large number of mitochondria and are able to metabolize a variety of substrates (3, 4).This specialized endothelium regulates the movement of solutes between blood and brain.This is accomplished through carrier-mediated transport systems for hexoses, monocarboxylic acids, amino acids, nucleosides, purines, and amines (5).Active transport pumps in the endothe-
Dioxiranes: synthesis and reactions of methyldioxiranes (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDioxiranes: synthesis and reactions of methyldioxiranesRobert W. Murray and Ramasubbu JeyaramanCite this: J. Org. Chem. 1985, 50, 16, 2847–2853Publication Date (Print):August 1, 1985Publication History Published online1 May 2002Published inissue 1 August 1985https://pubs.acs.org/doi/10.1021/jo00216a007https://doi.org/10.1021/jo00216a007research-articleACS PublicationsRequest reuse permissionsArticle Views8857Altmetric-Citations548LEARN 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
Evaluation of commercially available acridinium ester-labeled chemiluminescent DNA probes for culture identification of Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, and Histoplasma capsulatum (1993)

Four commercially available acridinium ester-labeled DNA probes directed against rRNA were evaluated for their ability to identify Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, and Cryptococcus neoformans in culture. rRNA was extracted by sonication of 1- to 2-mm2 portions of cultures of fungi in two chaotropic reagents with glass beads. Following a heat inactivation step, the extracts were hybridized in solution with probes specific for each pathogen. The acridinium ester reporter moiety of nonhybridized probe was selectively hydrolyzed, and chemiluminescence of specific DNA:RNA hybrids was quantitated in relative light units with a luminometer. A positive identification required a relative light unit value of > or = 50,000. Sensitivity and specificity of the probes were determined by probing cultures of the respective pathogenic fungi (target) and nontarget fungi. Both mycelial and yeast forms of the dimorphic fungi (B. dermatitidis and H. capsulatum) were tested. For B. dermatitidis, sensitivity and specificity were 87.8 and 100%, respectively (74 target and 219 nontarget fungi tested). For C. immitis, sensitivity and specificity were 99.2 and 100%, respectively (122 target and 164 nontarget fungi tested). For H. capsulatum, sensitivity and specificity were 100 and 100%, respectively (86 target and 154 nontarget fungi tested). For C. neoformans, sensitivity and specificity were 97 and 100%, respectively (100 target and 230 nontarget fungi tested). For B. dermatitidis, C. immitis, and C. neoformans, repeat testing increased the respective sensitivities to 97.3, 100, and 100%. The high sensitivities and specificities of the probes, the relatively short time (less than 1 h) required to perform the assay, and the availability of standardized reagent kits make the acridinium ester-labeled DNA probes well suited to laboratories in need of a rapid method to identify these fungal pathogens. Further, use of the probes to identify pathogenic fungi as soon as colonies appear on primary recovery media significantly shortens the time to reporting.
Two populations of splenic dendritic cells detected with M342, a new monoclonal to an intracellular antigen of interdigitating dendritic cells and some B lymphocytes (1992)

A monoclonal has been isolated that labels an intracellular antigen in dendritic cells and some B cells. The M342 hamster immunoglobulin was selected because it stained cells in the periarterial sheaths of spleen, the deep cortex of lymph node, and the thymic medulla--the same regions in which one finds interdigitating cells, the presumptive in situ counterparts of isolated lymphoid dendritic cells. M342 labeled an antigen within granules of isolated dendritic cells, but only in cells that had been cultured for a day and not in fresh isolates. This extends recent findings that most freshly isolated spleen dendritic cells are located in the periphery of the white pulp nodule and may serve as precursors for the periarterial pool of interdigitating cells, the site for M342 staining in situ. By electron microscopic immunolabeling, the M342 antigen was found exclusively in a type of multivesicular body. M342 staining was not found in mononuclear phagocytes from blood and peritoneal cavity. Peritoneal B cells expressed M342+ granules, and upon appropriate stimulation splenic B cells developed reactive granules as well. We conclude that M342 is a strong marker for interdigitating cells. Its existence reveals intracellular specializations in the vacuolar system of antigen-presenting cells including subsets of dendritic cells.
Bayesian Multi-object Tracking Using Motion Context from Multiple Objects (2015)

Online multi-object tracking with a single moving camera is a challenging problem as the assumptions of 2D conventional motion models (e.g., first or second order models) in the image coordinate no longer hold because of global camera motion. In this paper, we consider motion context from multiple objects which describes the relative movement between objects and construct a Relative Motion Network (RMN) to factor out the effects of unexpected camera motion for robust tracking. The RMN consists of multiple relative motion models that describe spatial relations between objects, thereby facilitating robust prediction and data association for accurate tracking under arbitrary camera movements. The RMN can be incorporated into various multi-object tracking frameworks and we demonstrate its effectiveness with one tracking framework based on a Bayesian filter. Experiments on benchmark datasets show that online multi-object tracking performance can be better achieved by the proposed method.