gebhart/patrepeval huggingface dataset:
GPR56 Regulates VEGF Production and Angiogenesis during Melanoma Progression (2011)

Angiogenesis is a critical step during cancer progression. The VEGF is a major stimulator for angiogenesis and is predominantly contributed by cancer cells in tumors. Inhibition of the VEGF signaling pathway has shown promising therapeutic benefits for cancer patients, but adaptive tumor responses are often observed, indicating the need for further understanding of VEGF regulation. We report that a novel G protein-coupled receptor, GPR56, inhibits VEGF production from the melanoma cell lines and impedes melanoma angiogenesis and growth, through the serine threonine proline-rich segment in its N-terminus and a signaling pathway involving protein kinase Cα. We also present evidence that the two fragments of GPR56, which are generated by autocatalyzed cleavage, played distinct roles in regulating VEGF production and melanoma progression. Finally, consistent with its suppressive roles in melanoma progression, the expression levels of GPR56 are inversely correlated with the malignancy of melanomas in human subjects. We propose that components of the GPR56-mediated signaling pathway may serve as new targets for antiangiogenic treatment of melanoma.
A DNA Aptamer That Binds Adenosine and ATP (1995)

We have used in vitro selection to isolate adenosine/ATP-binding DNA sequences from a pool of approximately 2 x 10(14) different random-sequence single-stranded DNA molecules. One of these aptamers has been characterized and binds adenosine in solution with a dissociation constant of 6 +/- 3 microM. Experiments with ATP analogs indicate that functional groups on both the base and the sugar of ATP are involved in the ligand/aptamer interaction. The binding domain of this aptamer was localized to a 42 base sequence by deletion analysis. A pool of mutagenized versions of this sequence was then synthesized and screened for functional adenosine binding sequences; comparison of the selected variants revealed two highly conserved guanosine-rich regions, two invariant adenosine residues, and two regions of predominantly Watson--Crick covariation. This data led us to propose a model of the ATP-binding DNA structure which is based on a stable framework composed of two stacked G-quartets. The two highly conserved adenosine residues may stack between the top G-quartet and the two short stems, forming a pocket in which the adenosine or ATP ligand binds. Site-directed mutagenesis, base analog substitution studies, and the design of highly divergent but functional sequences provide support for this model.
Isolation and Characterization of Adenoviruses Persistently Shed from the Gastrointestinal Tract of Non-Human Primates (2009)

Adenoviruses are important human pathogens that have been developed as vectors for gene therapies and genetic vaccines. Previous studies indicated that human infections with adenoviruses are self-limiting in immunocompetent hosts with evidence of some persistence in adenoid tissue. We sought to better understand the natural history of adenovirus infections in various non-human primates and discovered that healthy populations of great apes (chimpanzees, bonobos, gorillas, and orangutans) and macaques shed substantial quantities of infectious adenoviruses in stool. Shedding in stools from asymptomatic humans was found to be much less frequent, comparable to frequencies reported before. We purified and fully sequenced 30 novel adenoviruses from apes and 3 novel adenoviruses from macaques. Analyses of the new ape adenovirus sequences (as well as the 4 chimpanzee adenovirus sequences we have previously reported) together with 22 complete adenovirus genomes available from GenBank revealed that (a) the ape adenoviruses could clearly be classified into species corresponding to human adenovirus species B, C, and E, (b) there was evidence for intraspecies recombination between adenoviruses, and (c) the high degree of phylogenetic relatedness of adenoviruses across their various primate hosts provided evidence for cross species transmission events to have occurred in the natural history of B and E viruses. The high degree of asymptomatic shedding of live adenovirus in non-human primates and evidence for zoonotic transmissions warrants caution for primate handling and housing. Furthermore, the presence of persistent and/or latent adenovirus infections in the gut should be considered in the design and interpretation of human and non-human primate studies with adenovirus vectors.
Silent GABAASynapses during Flurazepam Withdrawal Are Region-Specific in the Hippocampal Formation (1997)

Whole-cell patch-clamp recordings were made from CA1 pyramidal and dentate gyrus granule cells (GCs) in hippocampal slices to assess the effects of withdrawal from chronic flurazepam (FRZ) treatment on the function of synaptic GABAA receptors. In slices from control rats, acute perfusion of FRZ (30 microM) increased the monoexponential decay time constant of miniature IPSCs (mIPSCs) in CA1 and GCs (from 3.4 +/- 0.6 to 7.6 +/- 2.1 msec and from 4.2 +/- 0. 6 to 7.1 +/- 1.8 msec, respectively) but did not change their mean conductance, 10-90% rise time, or frequency of occurrence. Withdrawal (2-5 d) from chronic in vivo FRZ treatment (40-110 mg/kg per day, per os) resulted in a dramatic loss of mIPSCs in CA1 neurons. On day 5 of withdrawal, no mIPSCs could be recorded in 40% of CA1 pyramidal cells. In the remaining 60% of the neurons, mIPSCs had a reduced mean conductance (from 0.78 +/- 0.12 nS in vehicle-treated controls to 0.31 +/- 0.05 nS) and a diminished frequency of occurrence (from 20.7 +/- 7.9 to 4.1 +/- 0.6 Hz). We have estimated that >80% of GABAA synapses on CA1 pyramidal cells had become silent, whereas at still-active synapses the number of functional GABAA receptor channels decreased by 60%. This reduction rapidly reverted to control levels on day 6 of withdrawal. FRZ withdrawal did not alter mIPSC properties in GCs. Our results are consistent with the hypothesis that chronic benzodiazepine treatment leads to a reduced number of functional synaptic GABAA receptors in a region-specific manner that may stem from differences in the subunit composition of synaptic GABAA receptors.
Modulation of doxorubicin cytotoxicity by ethacrynic acid (1996)

Energy-dependent membrane efflux pumps have been implicated in mediating resistance to doxorubicin (DOX). Membrane-transport mechanisms distinct from P-glycoprotein, capable of transporting DOX and glutathione conjugates have been reported in human cells. Since glutathione-conjugate-forming compounds may be candidates for modulating the cytotoxicity of certain anti-neoplastic agents transported by such transport mechanism, the present studies were performed (i) to determine whether ethacrynic acid, a glutathione-conjugate-forming diuretic, can increase DOX cytotoxicity, and (ii) to study the kinetics of DOX transport and its inhibition by the glutathione conjugate of ethacrynic acid (EA-SG) in the H69 human small-cell-lung-cancer cell line and 2 derived DOX-resistant sublines. Our results indicate that more than one DOX transport mechanism may exist in these cell lines, and that glutathione conjugates may be useful for modulating the cytotoxic effects of DOX. © 1996 Wiley-Liss, Inc.
Background Review and Current Concepts of Reperfusion Injury (1990)

We define the concept of reperfusion injury, and we present a background chronology of experimental work supporting and questioning this concept. We identify several new influences, such as current clinical interest in thrombolytic therapy for acute ischemia of heart and brain and the growing recognition of endothelium as a regulator of homeostasis. We propose that these influences will encourage a reexamination of reperfusion injury as a factor in the ultimate outcome of tissue exposed to reversible ischemia. We briefly discuss the major mechanisms presently implicated in reperfusion injury--loss of calcium homeostasis, free radical generation, leukocyte-mediated injury, and acute hypercholesterolemia.
PCR in a silicon microstructure (1994)

Devices for performing polymerase chain reactions (PCR) have been developed for use with photolithographed silicon. Microchambers capable of holding between 5.0 and 10 microL of PCR reagents were constructed by etching specific areas of rectangular silicon chips (17 x 15 mm), which were then capped with Pyrex glass. These silicon devices (PCRChips), which were etched to depths of 40-80 microns, permitted free flow of fluids in the microchannels and microchambers. Access to the microchambers was through holes in the silicon. Thermal cycling of the PCR reagents was achieved by placing the disposable PCRChip in a small holder containing a computer-controlled Peltier heater-cooler. Successful amplification was demonstrated by electrophoresis of products in agarose gel containing ethidium bromide, and the migration of the product was compared with that obtained in a commercially available thermal cycler. The thermal characteristics of the silicon, coupled with the high surface area to volume ratio in the new devices, are particularly advantageous features for amplification by PCR.
Convolutional neural network-based image representation for visual loop closure detection (2015)

Deep convolutional neural networks (CNN) have recently been shown in many computer vision and pattern recognition applications to outperform by a significant margin state-of-the-art solutions that use traditional hand-crafted features. However, this impressive performance is yet to be fully exploited in robotics. In this paper, we focus one specific problem that can benefit from the recent development of the CNN technology, i.e., we focus on using a pre-trained CNN model as a method of generating an image representation appropriate for visual loop closure detection in SLAM (simultaneous localization and mapping). We perform a comprehensive evaluation of the outputs at the intermediate layers of a CNN as image descriptors, in comparison with state-of-the-art image descriptors, in terms of their ability to match images for detecting loop closures. The main conclusions of our study include: (a) CNN-based image representations perform comparably to state-of-the-art hand-crafted competitors in environments without significant lighting change, (b) they outperform state-of-the-art competitors when lighting changes significantly, and (c) they are also significantly faster to extract than the state-of-the-art hand-crafted features even on a conventional CPU and are two orders of magnitude faster on an entry-level GPU.
Insulin activation of acetyl-CoA carboxylase accompanied by inhibition of the 5'-AMP-activated protein kinase. (1992)

The activity of acetyl-CoA carboxylase (ACC), a rate-limiting enzyme of fatty acid biosynthesis and malonyl-CoA production, can be regulated by several mechanisms, including multisite covalent phosphorylation, both in vitro and in intact cells. Evidence has been presented by others to indicate that a 5'-AMP-activated protein kinase (AMPK) is likely the major regulatory kinase active on ACC. While insulin is known to activate ACC in several cell types, accompanied by changes in ACC phosphorylation, the mechanism underlying this activation has been obscure. In the present study, we have examined, in Fao hepatoma cells, the effects of insulin on ACC and AMPK activity, the latter measured with a synthetic peptide corresponding to one of the phosphorylation sites on ACC for AMPK. Our results show that insulin leads to inhibition of kinase activity prior to the onset of ACC activation; the peak of maximal kinase inhibition (approximately 35% at 10 min) is seen to precede the onset of ACC activation (20 min). The inhibition of kinase activity due to insulin is observed both in the absence and presence of varying stimulating concentrations of added 5'-AMP. Both kinase inhibition and ACC activation display similar insulin sensitivity (A50 0.3 nM). Preservation of this insulin-induced kinase inhibition requires the presence of protein phosphatase inhibitors in the cell lysis buffer, suggesting that AMPK itself might be regulated by insulin-stimulated changes in kinase phosphorylation. Taken together, these data are consistent with the hypothesis that the 5'-AMP-activated protein kinase is a regulated component of the insulin signal transduction pathway and may be the major target for insulin regulation of ACC.
Effects of heparan sulfate removal on attachment and reattachment of fibroblasts and endothelial cells (1986)

Human skin fibroblasts and calf aorta endothelial cells were grown as tissue culture monolayers in the presence of [35S]sulfate in order to label the glycosaminoglycan portions of proteoglycans for investigation of their role in cell attachment. The [35S]glycosaminoglycans were then selectively removed from the cell monolayers by the addition of various glycosaminoglycan-degrading enzymes. As previously described, in contrast to trypsin treatment none of these enzymes removed any cells from the culture plates. Incubation with a preparation from Flavobacterium heparinum left only small stubs of [35S]glycosaminoglycans on the cell monolayers, indicating that all the cell-surface proteoheparan [35S]sulfate and proteochondroitin [35S]sulfate was accessible to this enzyme preparation. The treatment did not change the amount or time of incubation with trypsin necessary for release of the cells from the monolayers. Thus, cell attachment was not weakened by removal of heparan sulfate or chondroitin sulfate. In contrast, neither fibroblasts nor endothelial cells in suspension would reattach in the presence of the F. heparinum preparation while reattachment occurred readily in the presence of chondroitin ABC lyase. This provides evidence that heparan sulfate, but not chondroitin sulfate, is involved in the process of cell attachment even though neither is necessary for maintaining attachment.
Monoclonal B-cell response to diphtheria toxoid: evidence for cross-reactive epitopes. (1987)

Our previous studies on the human specific B- and T-cell responses against diphtheria toxoid (DT) had shown that the B- and T-cell antigenic determinants were mostly assembled topographic sites with large intra-molecular cross-reactivities. In order to characterize further the B-cell responses against DT, and to investigate these cross-reactivities, we have produced 54 murine monoclonal antibodies (moAbs) against the native DT. Determination of their antigenic specificity showed that 25 moAbs recognized conformational determinants on the native DT, 20 moAbs reacted against the A fragment (DTA) of the toxin, and nine moAbs reacted with at least three distinct highly purified CNBr peptides of the B fragment (DTB); some of them simultaneously recognized two or three purified CNBr peptides of DTB. As shown by cross-inhibition studies, the epitopes cross-reacting with those moAbs were distinct. Previously described sequence data indicated that these epitopes were not induced by repetitive amino-acid sequences. Finally, a cross-reactive idiotype was shared by moAbs specific for the CB1 and the CB3 peptides of DTB. Altogether, these data indicate that anti-DT moAbs are mostly directed against conformational determinants, and may cross-react with several DTB CNBr peptides.
Total Synthesis of the Pseudopterane (.+-.)-Kallolide B (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal Synthesis of the Pseudopterane (.+-.)-Kallolide BJames A. Marshall, Eli M. Wallace, and Paul S. CoanCite this: J. Org. Chem. 1995, 60, 4, 796–797Publication Date (Print):February 1, 1995Publication History Published online1 May 2002Published inissue 1 February 1995https://pubs.acs.org/doi/10.1021/jo00109a007https://doi.org/10.1021/jo00109a007research-articleACS PublicationsRequest reuse permissionsArticle Views802Altmetric-Citations141LEARN 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-AlertscloseSupporting Info (3)»Supporting Information Supporting Information Get e-Alerts
Verification of the omni wedge technique (1998)

The optimal field shape achieved using a multileaf collimator (MLC) often requires collimator rotation to minimize the adverse effects of the scalloped dose distribution the leaf steps produce. However, treatment machines are designed to deliver wedged fields parallel or perpendicular to the direction of the leaves. An analysis of cases from our clinic showed that for 25% of the wedged fields used to treat brain and lung tumors, the wedge direction and optimal MLC orientation differed by 20 degrees or more. The recently published omni wedge technique provides the capability of producing a wedged field with orientation independent of the orientation of the collimator. This paper presents a comparison of the three-dimensional (3D) dose distributions of the omni wedged field with distributions of wedged fields produced using both the universal and dynamic wedge techniques. All measurements were performed using film dosimetry techniques. The omni wedge generated fields closely matched the conventional wedged fields. Throughout 95% of the irradiated volume (excluding the penubra), the dose distribution of the omni wedged field ranged from +5.5 to -3.5 +/- 1.5% of that of the conventionally wedged fields. Calculation of the omni wedged field is as accurate as conventional wedged field calculation when using a 3D treatment planning systems. For two-dimensional treatment planning systems, where one must assume that the omni wedged field is identical to a conventional field, the calculated field and the delivered field differs by a small amount.
Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants. (1985)

Conditioned medium from cultured bovine aortic endothelial cells contains an inactive plasminogen activator inhibitor (PAI). This latent PAI can be "activated" with denaturants. For example, less than 0.01 units/microliter of PAI activity was detected in untreated conditioned medium, but medium treated with sodium dodecyl sulfate (1.7 mM), guanidine HCl (4 M), urea (12 M) or KSCN (6 M) contained 0.9, 1.9, 0.8, and 0.5 units/microliter, respectively. This effect was dose-dependent with respect to the particular reagent used, and the same concentration of reagent which induced PAI activity also stimulated the ability of a component in conditioned medium to form sodium dodecyl sulfate-stable complexes with exogenously added plasminogen activators. Neither activity was stimulated by extensive dialysis or by treatment with NaCl (5 M), Na2SO4 (2.8 M), or dicetyl phosphate (0.1%). Analysis of treated and untreated conditioned medium by gel filtration revealed that the latent and active PAIs migrated with apparent Mr values of 30,000 and 50,000, respectively. Thus, "activation" is associated with an increase in the apparent Mr of the molecule. These observations suggest that activation does not result from the removal of either a small dialyzable component from the medium, or of a large Mr component that is bound to the latent PAI. Other possible mechanisms of activation are discussed. We recently isolated an active PAI from bovine endothelial cells (van Mourik, J.A., Lawrence, D.A., and Loskutoff, D.J. (1984) J. Biol. Chem. 259, 14914-14921). Monospecific antiserum to this active PAI selectivity immunoprecipitated the latent PAI from conditioned medium. These results indicate that the two PAIs are immunologically related and suggest that the latent form is converted into the active form by the sodium dodecyl sulfate present during the purification.
Identification of a promoter for the vegetative insecticidal protein-encoding genevip3LBfromBacillus thuringiensis (2005)

The expression of vip3LB, one of the vegetative insecticidal protein-encoding genes of Bacillus thuringiensis, was studied at the transcriptional level. By primer extension analysis, we have identified, for the first time, the transcription start point of vip3-type gene. Upstream from vip3LB transcription start point, was found a nucleotide sequence partially homologous to the consensus sequence for the E sigma(E) holoenzyme of B. subtilis. Thus, it was strongly suggested that the identified vip3 promoter was under the control of sigma(35)-like enzyme, the B. thuringiensis homolog of sigma(E). The transcriptional activity from the promoter was detected at the vegetative stage of growth starting at mid-log phase as well as during the middle stage of sporulation.
Surface antigens of melanomas and melanocytes defined by mouse monoclonal antibodies: specificity analysis and comparison of antigen expression in cultured cells and tissues. (1985)

Mouse monoclonal antibodies (mAb) detecting 13 distinct systems of surface antigens on cultured melanocytes and melanomas were tested for reactivity with panels of (a) normal and malignant cultured cells; (b) normal adult and fetal tissues; and (c) specimens of metastatic melanoma and other tumor types. The objectives of this study were to compare antigen expression in cultured versus noncultured cells, to develop a panel of mAbs that identify subsets of melanomas, and to provide requisite information about antibody specificity in preparation for the use of antibodies in the diagnosis, imaging, and therapy of melanoma. Five of the melanoma surface antigens have been well characterized biochemically [GD3, chondroitin sulfate proteoglycan, HLA Class II antigens, glycoprotein of molecular weight 130,000 (gp130), and glycoprotein Mr 95,000/protein Mr 97,000 (gp95/p97)]. Three antigens have been related to melanocyte differentiation (HLA Class II, M111/M231, and M144), and six provide additional markers for subsets of cultured melanomas. mAb R24 reacts with the disialoganglioside GD3, a predominant ganglioside on cultured melanoma cells and other cells of neuroectodermal origin. A high proportion of melanoma, astrocytoma, and sarcoma tissue specimens were GD3+. In normal tissues, reactivity of mAb R24 was restricted to melanocytes, neuronal and glial cells in the central nervous system, parotid gland, adrenal medullary cells, and rare cells in the connective tissue. mAb B5 detects a chondroitin sulfate proteoglycan that is expressed by most melanoma and astrocytoma cell lines and by cultured melanocytes. Most of the melanoma and astrocytoma specimens were B5+, whereas other tumor types tested were B5-. mAb 13-17, which detects a monomorphic determinant of HLA Class II antigens, reacted with melanomas, and with a variety of other cancers, but not with normal skin melanocytes. There is considerable variability in the expression of GD3 and HLA Class II antigens in individual melanoma specimens; cotyping for these two antigens showed no evidence for coordinate expression. mAb L101 detects gp130 and mAb L235 detects gp95, antigens that are strongly expressed on a broad range of cultured cell types. In contrast to their wide distribution on cultured cells, gp130 expression in tissues was generally restricted to a subset of melanomas and some normal cells, and gp95 was detected on only a small number of melanomas. mAb M111/mAb M231 and mAb M144 define intermediate and late stage differentiation markers of cultured melanocytes and melanomas.(ABSTRACT TRUNCATED AT 400 WORDS)