gebhart/patrepeval huggingface dataset:
Neurogenic responses mediated by vanilloid receptor‐1 (TRPV1) are blocked by the high affinity antagonist, iodo‐resiniferatoxin (2003)

(1) Stimulation of the vanilloid receptor-1 (TRPV1) results in the activation of nociceptive and neurogenic inflammatory responses. Poor specificity and potency of TRPV1 antagonists has, however, limited the clarification of the physiological role of TRPV1. (2) Recently, iodo-resiniferatoxin (I-RTX) has been reported to bind as a high affinity antagonist at the native and heterologously expressed rat TRPV1. Here we have studied the ability of I-RTX to block a series of TRPV1 mediated nociceptive and neurogenic inflammatory responses in different species (including transfected human TRPV1). (3) We have demonstrated that I-RTX inhibited capsaicin-induced mobilization of intracellular Ca(2+) in rat trigeminal neurons (IC(50) 0.87 nM) and in HEK293 cells transfected with the human TRPV1 (IC(50) 0.071 nM). (4) Furthermore, I-RTX significantly inhibited both capsaicin-induced CGRP release from slices of rat dorsal spinal cord (IC(50) 0.27 nM) and contraction of isolated guinea-pig and rat urinary bladder (pK(B) of 10.68 and 9.63, respectively), whilst I-RTX failed to alter the response to high KCl or SP. (5) Finally, in vivo I-RTX significantly inhibited acetic acid-induced writhing in mice (ED(50) 0.42 micro mol kg(-1)) and plasma extravasation in mouse urinary bladder (ED(50) 0.41 micro mol kg(-1)). (6) In in vitro and in vivo TRPV1 activated responses I-RTX was approximately 3 log units and approximately 20 times more potent than capsazepine, respectively. This high affinity antagonist, I-RTX, may be an important tool for future studies in pain and neurogenic inflammatory models.
Synthetic peptides representing T-cell epitopes act as carriers in pneumococcal polysaccharide conjugate vaccines (1995)

Improvement of antibody responses to polysaccharides through their linkage to proteins is thought to be mediated by protein-specific T helper (Th) cells. To investigate whether the carrier protein of a conjugate could be substituted by a Th epitope, Streptococcus pneumoniae type 17F polysaccharide (PS) was bromoacetylated and coupled to different peptides via their carboxy-terminal cysteines. Two peptides, one from the mycobacterial 65-kDa heat shock protein (hsp65) and the other from influenza virus hemagglutinin, are well-known Th epitopes. Two other peptides were selected from the pneumolysin sequence by Th epitope prediction methods; one of them was synthesized with cysteine either at the carboxy or the amino terminus. Three conjugates consistently elicited in mice anti-PS immunoglobulin M (IgM) and IgG responses that were not observed upon immunization with derivatized PS without peptide. The same conjugates induced no anti-PS antibody responses in athymic (nu/nu) mice, whereas clear responses were elicited in euthymic (nu/+) controls, demonstrating the thymus-dependent character of these conjugates. Only the three conjugates inducing anti-PS responses were capable of eliciting antipeptide antibodies. One of the immunogenic conjugates was studied in more detail. It induced significant protection and an anti-PS IgG response comprising all subclasses. On the basis of these results and proliferation studies with peptide and conjugate-primed cells, it is concluded that linkage of Th epitopes to PS in the right orientation enhances its immunogenicity in a thymus-dependent manner. Future possibilities for using peptides as carriers for inducing antibody responses to poorly immunogenic saccharide antigens are discussed.
Toward a Shared Vision for Cancer Genomic Data (2016)

This FAIRsharing record describes: The National Cancer Institute’s (NCI’s) Genomic Data Commons (GDC) is a data sharing The National Cancer Institute's Genomic Data Commons (GDC) was created to promote precision medicine in oncology. It supports the import and standardization of genomic and clinical data from cancer research programs. The GDC contains NCI-generated data from some of the largest and most comprehensive cancer genomic datasets, including The Cancer Genome Atlas (TCGA) and Therapeutically Applicable Research to Generate Effective Therapies (TARGET). For the first time, these datasets have been harmonized using a common set of bioinformatics pipelines, so that the data can be directly compared. As a growing knowledge system for cancer, the GDC also enables researchers to submit data, and harmonizes these data for import into the GDC.
Superoxide-forming NADPH oxidase preparation of pig polymorphonuclear leucocyte (1982)

A phagocytic vesicle fraction with high NADPH-dependent superoxide-forming activity was obtained in large quantity from pig blood polymorphonuclear leucocytes, phagocytosing oil droplets in the presence of cyanide. The activity of the homogenate of the phagocytosing cells was 40 times that of the resting cells, and 70% of the activity in the homogenate was recovered in the phagocytic vesicle fraction. Essentially all of the superoxide-forming activity was extracted by repeated extraction with a mixture containing deoxycholate and Tween 20. The extract had a superoxide-forming activity of 1 mumol/min per mg of protein with NADPH, and one-fifth of this with NADH, Km values being similar to those of the vesicle fraction (40 microM for NADPH and 400 microM for NADH). A stoichiometric relationship of 1:2 for NADPH oxidation and superoxide formation was obtained, in agreement with the reaction NADPH +2O2 leads to NADP+ + 2O2 -. + H+. The activity of the extract was enhanced 2-fold by the addition of FAD, suggesting that the flavin is a component of the enzyme system. The Km value for FAD was 0.077 microM. The activities in both vesicle fraction and extract were labile even on refrigeration, but could be kept for several months at -70 degrees C.
Optical Systems for <i>in Vivo</i> Molecular Imaging of Cancer (2003)

Progress toward a molecular characterization of cancer would have important clinical benefits; thus, there is an important need to image the molecular features of cancer in vivo. In this paper, we describe a comprehensive strategy to develop inexpensive, rugged and portable optical imaging systems for molecular imaging of cancer, which couples the development of optically active contrast agents with advances in functional genomics of cancer. We describe initial results obtained using optically active contrast agents to image the expression of three well known molecular signatures of neoplasia: including over expression of the epidermal growth factor receptor (EGFR), matrix metallo-proteases (MMPs), and oncoproteins associated with human papillomavirus (HPV) infection. At the same time, we are developing inexpensive, portable optical systems to image the morphologic and molecular signatures of neoplasia noninvasively in real time. These real-time, portable, inexpensive systems can provide tools to characterize the molecular features of cancer in vivo.
The effects of endocrine therapy on plasma steroids in prostatic carcinoma patients. (1984)

Plasma testosterone (T), 5 alpha-dihydrotestosterone (DHT), T/DHT ratio, estrone (E1), estradiol (E2), E2/T ratio and 17-hydroxyprogesterone (17-OH-P) were measured in 70 patients with prostatic carcinoma (PCA) (T34, N01, M01), after endocrine therapy including: steroidal estrogens (polyestradiol phosphate = Estradurin monthly in injections of 80 mg; estradiol - 17 beta: 5 mg/d), nonsteroidal synthetic estrogens (DES: 5 mg/d; chlorotrianisene = TACE: 24 mg/d; DES-diphosphate = Honvan: 360 mg/d), orchidectomy and their combinations. All these forms of treatment lowered T, DHT, T/DHT ratio and 17-OH-P, the maximal suppression being observed after castration. No further decrease of the mentioned parameters was achieved by estrogen treatment of castrated patients, as compared with castration alone. In the noncastrated patients, steroidal estrogens were less effective than nonsteroidal ones, in terms of lowering T, DHT and T/DHT ratio. Significant decreases in estrone (p less than 0.05) and estradiol (p less than 0.01) levels were observed after nonsteroidal estrogen treatment and castration respectively, and extremely high values of circulating estrogens were found after steroidal estrogen administration.
In vitro antiviral activity of penciclovir, a novel purine nucleoside, against duck hepatitis B virus (1994)

The in vitro antihepadnavirus activities of the purine nucleoside analogs ganciclovir (9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine) and penciclovir [9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine; BRL 39123] were compared in primary duck hepatocyte cultures congenitally infected with the duck hepatitis B virus (DHBV). Both compounds inhibited DHBV DNA replication to a comparable extent during continuous short-term treatment of the cultures. However penciclovir was more active both during longer-term continuous treatment (50% inhibitory concentrations: penciclovir, 0.7 +/- 0.1 microM; ganciclovir, 4.0 +/- 0.2 microM) and in washout experiments (50% inhibitory concentrations: penciclovir, 3.0 +/- 0.4 microM; ganciclovir, 46 +/- 1.5 microM) designed to compare the persistence of inhibitory activity after removal of the extracellular compound. The effects on viral protein synthesis were similar to the effects on viral DNA replication. These data suggest that penciclovir or its oral form, famciclovir, may have clinical utility in the treatment of chronic hepatitis B virus infection.
"Plug and play" single chip controllers for variable speed induction motor drives in white goods and HVAC systems (2002)

Variable speed performance has become increasingly important for appliances in the home due to the increased emphasis on energy efficiency. Three phase inverters driving conventional induction motors under simple V/f scalar control offer continuously variable speed performance but until recently the total system cost has precluded the use of such solutions in white goods and HVAC systems. This paper describes the architecture and features of a new family of easy to use low-cost PWM controllers which were developed and launched by GPS in 1997.
Treatment of Breast and Lung Cancer Cells with a N-7 Benzyl Guanosine Monophosphate Tryptamine Phosphoramidate Pronucleotide (4Ei-1) Results in Chemosensitization to Gemcitabine and Induced eIF4E Proteasomal Degradation (2013)

The development of cancer and fibrotic diseases has been shown to be highly dependent on disregulation of cap-dependent translation. Binding protein eIF4E to N(7)-methylated guanosine capped mRNA has been found to be the rate-limiting step governing translation initiation, and therefore represents an attractive target for drug discovery. Our group has found that 7-benzyl guanosine monophosphate (7Bn-GMP) is a potent antagonist of eIF4E cap binding (K(d) = 0.8 μM). Recent X-ray crystallographic studies have revealed that the cap-dependent pocket undergoes a unique structural change in order to accommodate the benzyl group. Unfortunately, 7Bn-GMP is not cell permeable. Recently, we have prepared a tryptamine phosphoramidate prodrug of 7Bn-GMP, 4Ei-1, and shown that it is a substrate for human histidine triad nucleotide binding protein (hHINT1) and inhibits eIF4E initiated epithelial-mesenchymal transition (EMT) by Zebra fish embryo cells. To assess the intracellular uptake of 4Ei-1 and conversion to 7Bn-GMP by cancer cells, we developed a sensitive assay using LC-ESI-MS/MS for the intracellular quantitation of 4Ei-1 and 7Bn-GMP. When incubated with the breast cancer cell line MDA-231 or lung cancer cell lines H460, H383 and H2009, 4Ei-1 was found to be rapidly internalized and converted to 7Bn-GMP. Since oncogenic mRNAs are predicted to have the highest eIF4E requirement for translation, we carried out chemosensitization studies with 4Ei-1. The prodrug was found to chemosensitize both breast and lung cancer cells to nontoxic levels of gemcitabine. Further mechanistic studies revealed that the expressed levels of eIF4E were substantially reduced in cells treated with 4Ei-1 in a dose-dependent manner. The levels of eI4E could be restored by treatment with the proteasome inhibitor MG-132. Taken together, our results demonstrate that 4Ei-1 is likely to inhibit translation initiation by eIF4E cap binding by both antagonizing eIF4E cap binding and initiating eIF4E proteasomal degradation.
Analysis and compensation of nonlinearities in digital transmission systems (1988)

The compensation of channel nonlinearities in digital radio communication systems is considered. A discrete system with memory, inserted between the source and the modulator, is designed with the aim of providing an equivalent channel with a distortionless linear part and no nonlinearities up to a given order. This design is based on a Volterra series model of the channel and on the theory of pth-order inverse systems. Since the compensator design is based on a mathematical model of the channel, the problem of model identification is considered. A modeling technique is described that uses computer simulation and orthogonal Volterra series. Several examples show the performance of this class of compensators.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Efficient traffic splitting on commodity switches (2015)

Traffic often needs to be split over multiple equivalent backend servers, links, paths, or middleboxes. For example, in a load-balancing system, switches distribute requests of online services to backend servers. Hash-based approaches like Equal-Cost Multi-Path (ECMP) have low accuracy due to hash collision and incur significant churn during update. In a Software-Defined Network (SDN) the accuracy of traffic splits can be improved by crafting a set of wildcard rules for switches that better match the actual traffic distribution. The drawback of existing SDN-based traffic-splitting solutions is poor scalability as they generate too many rules for small rule-tables on switches. In this paper, we propose Niagara, an SDN-based traffic-splitting scheme that achieves accurate traffic splits while being extremely efficient in the use of rule-table space available on commodity switches. Niagara uses an incremental update strategy to minimize the traffic churn given an update. Experiments demonstrate that Niagara (1) achieves nearly optimal accuracy using only 1.2%--37% of the rule space of the current state-of-art, (2) scales to tens of thousands of services with the constrained rule-table capacity and (3) offers nearly minimum churn.
Chrome and Zinc Contaminants Removal from Silicon (100) Surfaces by Remote Plasma Cleaning Techniques (2001)

Removal of Cr and Zn impurities on Si surfaces using remote plasma H 2 was investigated. Si surfaces were contaminated intentionally with low-purity acetone. To determine the optimum process conditions, remote plasma H 2 cleaning was conducted for various rf powers and plasma exposure times. After remote plasma H 2 cleaning, Si surfaces were analyzed by total X-ray reflection fluorescence (TXRF), surface photovoltage (SPV) and atomic force microscopy (AFM). The concentrations of Cr and Zn impurities were reduced by more than a factor of 2 and the minority carrier lifetime increased. Also the root-mean-square (RMS) roughness decreased by more than 30% after the remote plasma H 2 cleaning. TXRF analysis results show that remote plasma H 2 cleaning is effective in eliminating Cr and Zn impurities from the Si surface only if it is performed under optimum process conditions. AFM analysis results also show that remote plasma H 2 cleaning causes no damage to the Si surface. Cr and Zn impurities on the Si substrate are considered to be contaminated as forms of hydroxides, silioxides and oxides on chemical oxides formed during intentional chemical contamination. The removal mechanism of Cr and Zn impurities using remote plasma H 2 treatments is proposed for the lift-off during the removal of underlying chemical oxides.
Refractive index variations in proton-bombared fused silica (1974)

The variations in the refractive index of fused silica upon bombardment by protons are determined as a function of depth, in an optical fiber geometry, by techniques of interference microscopy. The index profiles clearly distinguish between the ionization and nuclear stopping regions, and the magnitude of the index change for both is presented as a function of incident flux. Significant differences in the dose dependence and the annealing properties of the two regions are found.
Tat Protein Induces Human Immunodeficiency Virus Type 1 (HIV-1) Coreceptors and Promotes Infection with both Macrophage-Tropic and T-Lymphotropic HIV-1 Strains (1998)

Chemokine receptors CCR5 and CXCR4 are the primary fusion coreceptors utilized for CD4-mediated entry by macrophage (M)- and T-cell line (T)-tropic human immunodeficiency virus type 1 (HIV-1) strains, respectively. Here we demonstrate that HIV-1 Tat protein, a potent viral transactivator shown to be released as a soluble protein by infected cells, differentially induced CXCR4 and CCR5 expression in peripheral blood mononuclear cells. CCR3, a less frequently used coreceptor for certain M-tropic strains, was also induced. CXCR4 was induced on both lymphocytes and monocytes/macrophages, whereas CCR5 and CCR3 were induced on monocytes/macrophages but not on lymphocytes. The pattern of chemokine receptor induction by Tat was distinct from that by phytohemagglutinin. Moreover, Tat-induced CXCR4 and CCR5 expression was dose dependent. Monocytes/macrophages were more susceptible to Tat-mediated induction of CXCR4 and CCR5 than lymphocytes, and CCR5 was more readily induced than CXCR4. The concentrations of Tat effective in inducing CXCR4 and CCR5 expression were within the picomolar range and close to the range of extracellular Tat observed in sera from HIV-1-infected individuals. The induction of CCR5 and CXCR4 expression correlated with Tat-enhanced infectivity of M- and T-tropic viruses, respectively. Taken together, our results define a novel role for Tat in HIV-1 pathogenesis that promotes the infectivity of both M- and T-tropic HIV-1 strains in primary human leukocytes, notably in monocytes/macrophages.
A new structure type in polyoxoanion chemistry: synthesis and structure of the V5O143- anion (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA new structure type in polyoxoanion chemistry: synthesis and structure of the V5O143- anionV. W. Day, Walter G. Klemperer, and O. M. YaghiCite this: J. Am. Chem. Soc. 1989, 111, 12, 4518–4519Publication Date (Print):June 1, 1989Publication History Published online1 May 2002Published inissue 1 June 1989https://pubs.acs.org/doi/10.1021/ja00194a068https://doi.org/10.1021/ja00194a068research-articleACS PublicationsRequest reuse permissionsArticle Views803Altmetric-Citations86LEARN 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 (1)»Supporting Information Supporting Information Get e-Alerts
Lactone, 19. Mitt. Zur Struktur und Pharmakologie γ‐lactonverbrückter Diphenylalkylamine (1988)

Abstract Die γ‐lactonverbrückten Diphenylethyl‐bis‐pentylamine 1–5 wurden am isolierten Ileum des Meerschweinchens untersucht. 2–5 weisen nichtkompetitive bzw. kompetitive H 1 ‐antagonistische und parasympatholytische Aktivität auf. Sie sind Jedoch den offenkettigen Analoga mit Ausnahme der parasympatholytischen Aktivität von 3a im Vergleich zu 8a unterlegen. Zur Diskussion der Stereochemie und der Struktur‐Wirkungs‐Beziehungen dieser Lactone wird die Röntgenstrukturanalyse von 3a herangezogen.
Soluble receptor-mediated selective inhibition of VEGFR and PDGFRβ signaling during physiologic and tumor angiogenesis (2008)

The simultaneous targeting of both endothelial cells and pericytes via inhibition of VEGF receptor (VEGFR) and PDGFbeta receptor (PDGFRbeta) signaling, respectively, has been proposed to enhance the efficacy of antiangiogenic tumor therapy. Clinical and preclinical modeling of combined VEGFR and PDGFRbeta signaling inhibition, however, has used small molecule kinase inhibitors with inherently broad substrate specificities, precluding detailed examination of this hypothesis. Here, adenoviral expression of a soluble VEGFR2/Flk1 ectodomain (Ad Flk1-Fc) in combination with a soluble ectodomain of PDGFRbeta (Ad sPDGFRbeta) allowed highly selective inhibition of these pathways. The activity of Ad sPDGFRbeta was validated in vitro against PDGF-BB and in vivo with near-complete blockade of pericyte recruitment in the angiogenic corpus luteum, resulting in prominent hemorrhage, thus demonstrating an essential function for PDGF signaling during ovarian angiogenesis. Combination therapy with Ad PDGFRbeta and submaximal doses of Ad Flk1-Fc produced modest additive antitumor effects; however, no additivity was observed with maximal VEGF inhibition in numerous s.c. models. Notably, VEGF inhibition via Ad Flk1-Fc was sufficient to strongly suppress tumor endothelial and pericyte content as well as intratumoral PDGF-B mRNA, obscuring additive Ad sPDGFRbeta effects on pericytes or tumor volume. These studies using highly specific soluble receptors suggest that additivity between VEGFR and PDGFRbeta inhibition depends on the strength of VEGF blockade and appears minimal under conditions of maximal VEGF antagonism.