gebhart/patrepeval huggingface dataset:
Synthesis, Gastrointestinal Prokinetic Activity and Structure-Activity Relationships of Novel N-((2-(Dialkylamino)ethoxy)benzyl)benzamide Derivatives. (1992)

Novel N-[[dialkylamino)ethoxy]benzyl]benzamide derivatives (II-1-51), derived from the structural modification of metoclopramide (I), were synthesized and examined for their pharmacological activities. Among them, N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide (II-34) which exhibited well balanced gastrointestinal prokinetic and antiemetic activities was selected as a new type of gastrointestinal prokinetic agent.
Protein Kinase C α Expression Is Required for Heparin Inhibition of Rat Smooth Muscle Cell Proliferation in Vitro and in Vivo (1996)

Heparin is a complex glycosaminoglycan that inhibits vascular smooth muscle cell (SMC) growth in vitro and in vivo. To define the mechanism by which heparin exerts its antiproliferative effects, we asked whether heparin interferes with the activity of intracellular protein kinase C (PKC). The membrane-associated intracellular PKC activity increased following stimulation of cultured rat SMCs with fetal calf serum and was suppressed by heparin in a time- and dose-dependent manner. Heparin acted through a selective inhibition of the PKC-alpha since preincubation of the cells with a 20-mer phosphorothioate PKC-alpha antisense oligodeoxynucleotide (ODN) eliminated the heparin effect. In vivo, following balloon injury of the rat carotid artery, particulate fraction PKC content increased with a time course and to an extent comparable with the observed changes in vitro. Heparin, administered at the time of injury or shortly thereafter, inhibited the activity of the particulate PKC and suppressed the in situ phosphorylation of an 80-kDa myristoylated alanine-rich protein kinase C substrate (MARCKS), a substrate of PKC. The topical application of the phosphorothioate antisense ODN selectively suppressed the expression of the PKC-alpha isoenzyme in vivo but did not affect injury-induced myointimal proliferation. Topical application of the ODN also eliminated the antiproliferative activity of heparin. These results therefore suggest that heparin might block SMC proliferation by interfering with the PKC pathway through a selective direct inhibition of the PKC-alpha isoenzyme.
Targeting the Neurokinin Receptor 1 with Aprepitant: A Novel Antipruritic Strategy (2010)

The high response rate in patients with therapy refractory pruritus suggests that the NKR1 antagonist aprepitant may indeed exhibit antipruritic effects and may present a novel, effective treatment strategy based on pathophysiology of chronic pruritus. The results are promising enough to warrant confirming the efficacy of NKR1 antagonists in a randomized, controlled clinical trial.
Ein Rechenverfahren von Verbundträgern mit Stegöffnungen ‐ Teil 2 (2003)

Abstract Ein Ingenieurmodell zur Berechnung der Tragfähigkeit von Verbundträgern mit Stegöffnungen wurde mit Anwendung des Traglastverfahrens hergeleitet. Die Herleitung erfolgte unter Ausnutzung der Gleichgewichtsbedingungen und ist leicht nachvollziehbar. Einige Beispiele wurden mit dem Rechenmodell berechnet. Dabei lassen sich die Tragfähigkeit und Tragverhalten anschaulich darstellen.
Targeting antigen to CD19 on B cells efficiently activates T cells (2005)

CD19 is a B cell-surface molecule that participates as an important regulatory signaling complex for antigen bound at the surface by Ig. Triggering of CD19 through its linkage with CD21 amplifies signals transduced through the Src family kinases and modulates B cell differentiation in response to antigen. This study examines the kinetics of antigen uptake and processing of antigen directly targeted to the CD19 protein on purified B cells. We have demonstrated that the antigen internalized within minutes through CD19 forms a cap at the B cell surface and can be found within lysosomes in the cytoplasm in 90 min. B cells acquiring antigen via CD19 express elevated levels of B7-1 and B7-2 co-stimulatory molecules. Moreover, antigen-anti-CD19 complexes administered intravenously bind B cells in vivo and activate antigen-specific T cells more efficiently than non-specific uptake and in a manner similar to antigen taken up through surface IgM on B cells. This work illustrates an important and previously unrecognized mechanism for targeting proteins to B lymphocytes for antigen presentation and activation of CD4 T cells.
Rapid, noncontact optical figuring of aspheric surfaces with plasma-assisted chemical etching (1990)

This paper presents results on figuring aspheric optical surfaces by Plasma Assisted Chemical Etching (PACE) demonstrating rapid, predictable convergence to the final figure. The figuring data shows better than 95% convergence of the final figure in a single operation for large spatial errors (on the order of the plasma tool size and larger) and a high efficiency for correcting errors much smaller than the tool size (mid-spatial frequency range). Automated correction of arbitrary figure errors are made from surface metrology data. This technology can be scaled from small optics, millimeters in diameter, to large optics, meters in diameter. A PACE production capability is first being developed for relatively small optics, up to 12" diameter, that can have an anamorphic shape. The central feature of PACE is control of material removal regardless of surface shape. In addition, it is capable of high removal rates for a polishing process, one to two orders of magnitude larger than conventional pitch polishing. Thus, PACE can be used for figure generation as well as final figure correction. PACE intrinsically smoothes while removing material leaving a virgin surface free of process related contamination and subsurface damage.
Oxidative Preparation of 9-Hydroxytetracyclines (1966)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxidative Preparation of 9-HydroxytetracyclinesP. ShuCite this: J. Am. Chem. Soc. 1966, 88, 19, 4529–4530Publication Date (Print):October 1, 1966Publication History Published online1 May 2002Published inissue 1 October 1966https://pubs.acs.org/doi/10.1021/ja00971a056https://doi.org/10.1021/ja00971a056research-articleACS PublicationsRequest reuse permissionsArticle Views81Altmetric-Citations8LEARN 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
Platinum Deposited Nitrogen-Doped Vertically Aligned Carbon Nanofibers as Methanol Tolerant Catalyst for Oxygen Reduction Reaction with Improved Durability (2021)

Nitrogen doping in carbon materials can modify the employed carbon material’s electronic and structural properties, which helps in creating a stronger metal-support interaction. In this study, the role of nitrogen doping in improving the durability of Pt catalysts supported on a three-dimensional vertically aligned carbon nanofiber (VACNF) array towards oxygen reduction reaction (ORR) was explored. The nitrogen moieties present in the N-VACNF enhanced the metal-support interaction and contributed to a reduction in the Pt particle size from 3.1 nm to 2.3 nm. The Pt/N-VACNF catalyst showed better durability when compared to Pt/VACNF and Pt/C catalysts with similar Pt loading. DFT calculations validated the increase in the durability of the Pt NPs with an increase in pyridinic N and corroborated the molecular ORR pathway for Pt/N-VACNF. Moreover, the Pt/N-VACNF catalyst was found to have excellent tolerance towards methanol crossover.
Development of NIR Fluorescent Dyes Based on Si–rhodamine for in Vivo Imaging (2012)

We have developed a series of novel near-infrared (NIR) wavelength-excitable fluorescent dyes, SiR-NIRs, by modifying the Si-rhodamine scaffold to obtain emission in the range suitable for in vivo imaging. Among them, SiR680 and SiR700 showed sufficiently high quantum efficiency in aqueous media. Both antibody-bound and free dye exhibited high tolerance to photobleaching in aqueous solution. Subcutaneous xenograft tumors were successfully visualized in a mouse tumor model using SiR700-labeled anti-tenascin-C (TN-C) antibody, SiR700-RCB1. SiR-NIRs are expected to be useful as labeling agents for in vivo imaging studies including multicolor imaging, and also as scaffolds for NIR fluorescence probes.
Rat mast cells permeabilized with ATP secrete histamine in response to calcium ions buffered in the micromolar range. (1981)

1. Rat mast cells with ATP (0.5-4 micro M) in the absence of divalent cations (so that almost all the ATP is present as ATP4-) became permeable to normally impermeant aqueous solutes, added extracellularly. These include the stable complexes Co HEDTA and Ca EDTA, and 6-carboxyfluorescein but not inulin. At 4 micro M-ATP4- the space accessible to Ca EDTA is 89% of that occupied by 3H2O. 2. The kinetics of solute entry are regulated by the concentration of ATP4-. 3. Ca2+, buffered in the range 1-10 micro M with HEDTA, causes histamine secretion from mast cells that have been rendered permeable with ATP4-. The extent of secretion increases as the concentration of ATP4- is raised from 3 to 5 micro M. With extracellular Ca2+ present as physiological (millimolar) concentrations, the effect of increasing ATP4- through this range is to inhibit secretion. 4. The rates of histamine secretion and of 32P-metabolite leakage from 32P-prelabelled cells in the presence of micromolar concentrations of Ca2+, were compared. The kinetics of both processes are regulated by the concentration of ATP4-, but not Ca2+.
Human Leukocyte Interferon for the Treatment of Herpes Zoster in Patients with Cancer (1978)

We tested the effect of human leukocyte interferon on early localized herpes zoster infections in three placebo-controlled, randomized double-blind trials involving 90 patients with cancer. There were no significant differences in pretreatment severity of infection or nature of underlying disease in the groups. Higher dosages of more purified interferon in the second and third trials produced a significant (P≤0.01) decrease in cutaneous dissemination. No dissemination occurred in those receiving the highest dosage (5.1 X 105 U per kilogram per day) (P≤0.025). The number of days of new-vesicle formation in the primary dermatome decreased (mean, 2.3 days, P≤0.05) in this group. Treated patients had a trend toward less acute pain, and significantly (P≤0.05) diminished severity of post-herpetic neuralgia, at the two highest dosage levels. Visceral complications were six times less frequent in interferon recipients. High-dosage interferon appeared effective in limiting cutaneous dissemination, visceral complications and progression within the primary dermatome. (N Engl J Med 298:981–987, 1978)
Synthesis and properties of an oligodeoxynucleotide modified with a pyrene derivative at the 5'-phosphate (1992)

The synthesis of an oligonucleotide (ODN) modified with pyrene (pyr) on the 5'-phosphate is described. The ODN and pyrene are joined through a linker composed of four methylene groups. Modification of the oligonucleotide was effected via condensation of the 2-cyanoethyl N,N-diisopropylphosphoramidite of 4-(1-pyrenyl)butanol (pyr-m4OPAm, 2) with the 5'-OH of an ODN. This derivative is suitable for incorporation into automated solid-phase DNA synthesis and was attached to the 5' terminus of the DNA chain through a phosphodiester linkage. The properties of the 5'-(pyr-m4)d(T)15 (3) and the duplex it formed with d(A)15 were investigated by fluorescence and absorbance spectroscopy. The pyrene fluorescence in the modified duplex was quenched 96.3% relative to an identical concentration of free 4-(1-pyrenyl)butanol. The ultraviolet spectrum of the 5'-(pyr-m4)-d(T)15 and 5'-(pyr-m4)-d(T)15-d-(A)15 modified duplex, in the 320-360-nm region, was red-shifted 6 nm relative to the free 4-(1-pyrenyl)-butanol. The Tm values of the unmodified and modified duplexes at 0.1 M NaCl were 34.9 and 41.9 degrees C, respectively. The pyrene-induced stabilization corresponds to a free energy change (delta delta G degrees) of -2.6 kcal/mol.
HLA A2 restricted HIV specific mucosal and systemic immunity induced with secreted heat shock protein gp96‐Ig (2008)

Heat shock protein gp96 is the primary chaperone of the endoplasmic reticulum and a natural adjuvant for priming the innate and adaptive immune system. We have generated a secreted gp96‐fusion protein (gp96‐Ig) that mediated strong, antigen specific CD8‐CTL expansion in vivo. The aim of this study was to generate and test gp96‐Ig secreting and HIV‐antigen expressing cells as vaccines for HIV. Murine NIH‐3T3 or human 293 cells were co‐transfected with gp96‐Ig and HIVgag‐gfp cDNAs. To ensure high level of expression of HIV antigen transfected cells were sorted for gag‐gfp+ cells and level of gp96‐Ig secretion was determined by ELISA. We used H2Dd‐HLA A2 transgenic mice and immunize them with 3T3‐HIV‐gag‐gfp‐gp96‐Ig. The frequency of the murine gag‐specific CD8 CTL response was quantified with HLA A2 tetramers loaded with HIV‐gag‐peptide (SLYNTVATL). HLA A2 tetramer specific CD8 cells were found in the peripheral blood, spleen, peritoneal cavity as well as at mucosal sites (Peyer's Patches, intraepithelial compartment and lamina propria) within five days after intraperitoneal injection of 3T3‐HIV‐gag‐gfp‐gp96‐Ig. Our results imply that allogeneic cells secreting gp96‐Ig with associated HIV gag‐peptides work well as vaccines and are inducing both mucosal and systemic immunity. This study was supported by NIH/NIAID grants AI073234 and AI068515
Suppression of adenovirus type 5 E1A‐mediated transformation and expression of the transformed phenotype by caffeic acid phenethyl ester (CAPE) (1991)

Viral transformation and DNA-transfection assays were employed to investigate the differential toxic effect of caffeic acid phenethyl ester (CAPE), an extract of the honeybee hive product propolis, on adenovirus type 5 (Ad5)-transformed cloned rat embryo fibroblast (CREF) cells. CAPE inhibited, in a dose-dependent manner, both de novo and carcinogen-enhanced transformation of CREF cells by H5hr1, the cold-sensitive (cs) host-range mutant of Ad5. CAPE had a selective inhibitory effect on Ad5-induced transformation when a wild-type (wt) Ad5 E1A gene or a cs Ad5 E1A gene (at 37 degrees C, but not at 32 degrees C) was cotransfected into CREF cells with a dominant-acting bacterial hygromycin-resistance gene. A requirement for the expression of Ad5 E1A-encoded mRNAs and transforming proteins and sensitivity to CAPE was demonstrated using CREF cells stably transformed by a cs Ad5 E1A gene and an Ad5 E1A gene under the transcriptional control of a mouse mammary tumor virus promoter. To distinguish between the effects of the two Ad5 E1A-encoded proteins of 289 amino acids (aa) and 243 aa, CREF cells were stably transformed with cDNAs encoding either the 13S or the 12S E1A mRNA. CREF cells expressing the 13S E1A-encoded 289-aa protein were more sensitive to the growth-suppressing effect of CAPE than cells producing only the 12S E1A-encoded 243-aa protein. However, the growth-suppressing and toxic effects of CAPE were greatest in cells expressing both E1A-encoded transforming proteins. Analysis of the effect of CAPE on E1A and beta-actin gene expression in wt and cs E1A and H5hr1-transformed CREF cells indicated that low levels of CAPE, which were growth suppressive, did not selectively suppress E1A expression. These results demonstrated that cellular changes induced in CREF cells by the 13S E1A-encoded 289-aa protein of Ad5, when expressed alone or in combination with the 12S E1A-encoded 243-aa protein, rendered transformed cells sensitive to the growth-suppressing and toxic effects of CAPE.
Detection Methodology Based on Target Molecule-Induced Sequence-Specific Binding to a Single-Stranded Oligonucleotide (2012)

We have recently developed a mix-and-read format homogeneous antigen peptide based assay for detection of the antibodies (Tian, L.; Heyduk, T. Anal. Chem. 2009, 81, 5218-5225) that employed for target detection a simple biophysical mechanism of target antibody induced annealing between two complementary oligonucleotides attached to the antigen peptide. In this work, we propose and experimentally validate an alternative variant of this assay format in which target antibody binding to antigen peptide-oligonucleotide conjugate produces a complex with high sequence-specific binding affinity to a single-stranded capture oligonucleotide. This new assay format can be used for preparing various solid-surface based assays by immobilizing the capture oligonucleotide. This assay design is not limited to antibody detection. We demonstrate that it can also be employed for detecting proteins or pathogenic bacteria using oligonucleotide-labeled antibodies as target recognition elements. Preparation of these solid-surface based assays is simplified because all interactions with the solid surfaces are mediated by well-understood oligonucleotide-oligonucleotide interactions and because of the relative ease of immobilizing oligonucleotides on various solid surfaces. These unique aspects of the assay design also allow microarray-style multiplexing that could be most useful for multiplexed antibody profiling for diagnosis and analysis of cancer, autoimmune, and infectious diseases.
A composite complexity measure for component-based systems (2011)

The increasing importance of software measurement has led to design and development of new software measures. Controlling and minimizing software complexity is the most important objective of each software development paradigm because it affects all other software quality attributes like reusability, reliability, testability, maintainability etc. For this purpose, a number of software complexity measures have been reported to quantify different aspects of complexity. Component-based software development (CBSD) is an evolving paradigm where emphasis is laid on reuse of existing components and effective designing of new components. As the development of component-based software is rising, more and more complexity metrics are being developed for the same. In this paper, we have attempted to design a composite complexity measure to quantify important aspects of complexity of a component-based system. The proposed measure takes into account two major complexities of a component-based system : one due to individual component and the other due to its interaction with other components. Individual component complexity may arise due to size of a component, type and nesting level of control structures present in code component. Component's interaction complexity may be due to its interface with other components. Graph theoretic notions and concept of weights have been used to illustrate interaction among software components and to compute complexity. The proposed measure has been applied to four cases chosen for present study and yields quiet encouraging results which may further help in controlling the complexity of component-based systems so as to minimize both integration and maintenance efforts.
T-cell exhaustion in the tumor microenvironment (2015)

T-cell exhaustion was originally identified during chronic infection in mice, and was subsequently observed in humans with cancer. The exhausted T cells in the tumor microenvironment show overexpressed inhibitory receptors, decreased effector cytokine production and cytolytic activity, leading to the failure of cancer elimination. Restoring exhausted T cells represents an inspiring strategy for cancer treatment, which has yielded promising results and become a significant breakthrough in the cancer immunotherapy. In this review, we overview the updated understanding on the exhausted T cells in cancer and their potential regulatory mechanisms and discuss current therapeutic interventions targeting exhausted T cells in clinical trials.
Human T‐cell leukemia virus type I: Pseudotype neutralization of Japanese And American isolates with human and rabbit sera (1985)

CCC/2M, CCC/10Y and CCC/MT-2 cat kidney cells producing Japanese isolates of human T-cell leukemia virus type I (HTLVs) and HOS/PL human osteosarcoma cells producing an American isolate of HTLV were infected with vesicular stomatitis virus (VSV) to prepare VSV pseudotypes bearing envelope antigens of HTLVs. VSV propagated in CCC/2M cells contained plaque-forming fractions that were not neutralized by treatment with anti-VSV serum alone: VSV pseudotypes bearing envelope antigens of HTLV2M and CCC cat endogenous virus were formed by infection of CCC/2M cells with VSV. Japanese HTLV2M, HTLV10Y and HTLVMT-2 and American HTLVPL pseudotypes were neutralized by sera of Japanese, American and British patients with ATL. Each serum, including the serum of the patient from whom HTLV2M or HTLV10Y had been derived, gave similar antibody titers against Japanese and American HTLV pseudotypes. The HTLV pseudotypes were also neutralized by rabbit serum raised against HTLVMT-2. A rabbit antiserum against the C-terminal half of the HTLV env protein produced in E. coli also neutralized Japanese and American HTLV pseudotypes. Thus, VSV pseudotype analyses indicated that envelope antigens of HTLVs represent a single serotype worldwide. The env protein produced in E. coli may be used to raise neutralizing antibody against HTLVs.
Mutagenesis of the potato ADPglucose pyrophosphorylase and characterization of an allosteric mutant defective in 3-phosphoglycerate activation. (1996)

ADPglucose pyrophosphorylase (glucose-1-phosphate adenylyltransferase; ADP:alpha-D-glucose-1-phosphate adenylyltransferase, EC 2.7.7.27) catalyzes a key regulatory step in alpha-glucan synthesis in bacteria and higher plants. We have previously shown that the expression of the cDNA sequences of the potato tuber large (LS) and small (SS) subunits yielded a functional heterotetrameric enzyme capable of complementing a mutation in the single AGP (glgC) structural gene of Escherichia coli. This heterologous complementation provides a powerful genetic approach to obtain biochemical information on the specific roles of LS and SS in enzyme function. By mutagenizing the LS cDNA with hydroxylamine and then coexpressing with wild-type SS in an E. coli glgC- strain, >350 mutant colonies were identified that were impaired in glycogen production. One mutant exhibited enzymatic and antigen levels comparable to the wild-type recombinant enzyme but required 45-fold greater levels of the activator 3-phosphoglycerate for maximum activity. Sequence analysis identified a single nucleotide change that resulted in the change of Pro-52 to Leu. This heterologous genetic system provides an efficient means to identify residues important for catalysis and allosteric functioning and should lead to novel approaches to increase plant productivity.