gebhart/patrepeval huggingface dataset:
Kinematic Optimization of a Modified Helical Gear Train (1997)

A mathematical model of a modified helical gear train (MHGT), manufactured with a practical hobbing machine using a curved-template guide, and which takes considerations of center-distance variation and axial misalignment into account, is developed. Tooth contact analysis (TCA) and kinematic errors of a MHGT due to mis-assembly are investigated. A multiple optimization method is applied to reduce the level of MHGT kinematic errors, and to investigate optimal gear tooth modifications. Computer simulation programs for TCA and optimization are also developed. Two numerical examples are presented to illustrate the kinematic optimization of the proposed helical gear train. The results of this study are most helpful in designing and analyzing a MHGT.
Incretin Receptors for Glucagon-Like Peptide 1 and Glucose-Dependent Insulinotropic Polypeptide Are Essential for the Sustained Metabolic Actions of Vildagliptin in Mice (2007)

These findings illustrate that although GLP-1 and GIP receptors represent the dominant molecular mechanisms for transducing the glucoregulatory actions of DPP4 inhibitors, prolonged DPP4 inhibition modulates the expression of genes important for lipid metabolism independent of incretin receptor action in vivo.
A Single Specific Amino Acid Residue in Peptide Antigens Is Sufficient to Activate Memory CTL: Potential Role of Cross-Reactive Peptides in Memory T Cell Maintenance (1999)

In the present study, we examined the structural requirements of peptide Ags for productive interactions with the TCR of CTL. For this purpose, we used as a model a previously identified immunodominant epitope that represents the target of EBV-specific HLA-A11-restricted CTL responses. By the use of peptides having minimal sequence homology with the wild-type epitope, we demonstrated that it is possible to selectively expand and reactivate memory CTL precursors without triggering the lytic mechanisms of wild-type specific effectors. In fact, stimulation of PBL from EBV-seropositive donors by polyalanine analogues, sharing only the putative TCR contact residue with the natural epitope, exclusively induced clonal expansion and reactivation of EBV-specific memory CTL precursors. Interestingly, these polyalanine peptides failed to trigger the cytotoxic function of CTLs specific for the wild-type viral epitope. This clearly indicates that reactivation of memory CTL precursors and triggering of the cytotoxic function have different requirements. The same phenomenon was observed using as stimulators naturally occurring peptides carrying the appropriate TCR contact residue. These data strongly suggest that cross-reactive peptides may play an important role in the expansion and reactivation of CTL clones from the memory T cell pool, and may be involved in long-term maintenance of T cell memory.
Catalytic subunit of cAMP‐dependent protein kinase is essential for cAMP‐mediated mammalian gene expression (1988)

Cyclic AMP-stimulated mRNA levels in cultured rat hepatocytes were inhibited by three different inhibitors of cAMP-dependent protein kinase activity: (i) Rp-cAMPS, a cAMP analog with a sulfur substitution at the equatorial oxygen of the cyclic monophosphate; (ii) H8, an isoquinoline sulfonamide derivative; and (iii) PKI, a 20-amino acid synthetic peptide of the Walsh protein kinase inhibitor. These inhibitors specifically blocked the cAMP-stimulated increase in mRNA for tyrosine aminotransferase and phosphoenolpyruvate carboxykinase; they had no effect on the level of albumin mRNA which is not cAMP regulated. These results provide functional evidence that kinase activity involving protein phosphorylation is required in cAMP-mediated gene expression in mammalian cells.
High-Temperature Reliability Assessment of 4H-SiC Vertical-Channel JFET Including Forward Bias Stress (2009)

In this work, we report the most recent reliability results of the 1200-V SiC vertical-channel JFETs (VJFETs) under reverse and forward bias of the gate-source diode at temperatures up to 200 °C. The preliminary results indicate that continuous forward bias stress of the gate-source diode at 200 °C for 112 hours produced no observable change in the forward conduction or transient or reverse blocking characteristics of the vertical-channel JFET. This preliminary result suggests that devices based on this structure, such as the enhancement-mode (normally off) SiC VJFET, may not be effected by the recombination enhanced defect creation process and the associated increase in on-resistance, related to body-diode conduction in the SiC DMOSFET and the SiC lateral-channel depletion-mode JFET. Since the vertical-channel JFET has no body diode, no degradation is possible from the reverse conduction mode of operation.
A study of tobacco carcinogenesis. 17. Tobacco-specific nitrosamines: occurrence, formation, carcinogenicity, and metabolism (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA study of tobacco carcinogenesis. 17. Tobacco-specific nitrosamines: occurrence, formation, carcinogenicity, and metabolismStephen S. Hecht, Chi-Hong B. Chen, and Dietrich HoffmannCite this: Acc. Chem. Res. 1979, 12, 3, 92–98Publication Date (Print):March 1, 1979Publication History Published online1 May 2002Published inissue 1 March 1979https://pubs.acs.org/doi/10.1021/ar50135a003https://doi.org/10.1021/ar50135a003research-articleACS PublicationsRequest reuse permissionsArticle Views213Altmetric-Citations40LEARN 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
Direct determination of creatine kinase equilibrium constants with creatine or cyclocreatine as substrate (1989)

The equilibrium constants of two reactions catalyzed by rabbit muscle creatine kinase with creatine or cyclocreatine as substrate were determined by 31P-NMR. The value of the equilibrium constant with creatine as substrate was 172.10(7) M(-1) in agreement with previous work (Veech, R.L., Lawson, J.W.R., Cornell, W. and Krebs, H.A. (1979) J. Biol. Chem 254, 6538-6547). The value with cyclocreatine was 5.62.10(7) M(-1) and the ratio of the two constants is 30.6. It was possible to determine the ratio of the two equilibrium constants in a reaction mixture containing both substrates since it was found that the 31P resonances of P-creatine and P-cyclocreatine were well resolved. The ratio of K1/K2 determined in such experiments was 34.6, of the same order as previously reported by Annesley and Walker (Annesley, T.M. and Walker, J.B. (1977) Biochem. Biophys. Res. Commun. 74, 185-190).
Gene Set Enrichment Analyses Revealed Several Affected Pathways in Niemann-Pick Disease Type C Fibroblasts (2007)

Niemann-pick type C (NPC) disease is characterized by endosomal and lysosomal accumulation of lipids, impaired tubulovesicular trafficking, and neurodegeneration leading to premature death. Current treatment options are limited to mainly symptomatic treatments. Thus, new and efficient drug targets are needed, and therefore we performed a Gene Set Enrichment Analysis (GSEA) on NPC and healthy fibroblasts to identify globally affected pathways in NPC that could serve as targets for later drug discovery programs. Cell lines were characterized by analyzing cellular concentrations of cholesterol, its precursors and metabolites, as well as cellular plant sterol levels. Gene expression analyses were performed with Sentrix Human-8 Expression BeadChips, analyzing 23,000 transcripts. Pathway analysis of the expression data was performed using the GSEA method. Twenty-seven upregulated and 33 downregulated pathways emerged as globally affected in the GSEA analysis. These pathways included, for example, mitochondrial pathway, caspase cascade, as well as prostaglandin and leukotriene metabolism. Based on the present results and earlier published data, anti-inflammatory and antiapoptotic treatment could be beneficial in NPC.
Highly Active, Air-Stable Palladium Catalysts for the C−C and C−S Bond-Forming Reactions of Vinyl and Aryl Chlorides:  Use of Commercially Available [(t-Bu)2P(OH)]2PdCl2, [(t-Bu)2P(OH)PdCl2]2, and [[(t-Bu)2PO···H···OP(t-Bu)2]PdCl]2 as Catalysts (2002)

Air-stable palladium complexes [(t-Bu)(2)P(OH)](2)PdCl(2), [(t-Bu)(2)P(OH)PdCl(2)](2), and [[(t-Bu)(2)PO...H...OP((t-Bu)(2)]PdCl](2) serve as efficient catalysts for a variety of cross-coupling reactions of vinyl and aryl chlorides with arylboronic acids, arylzinc reagents, and thiols to yield the corresponding styrene derivatives, biaryls, and thioethers. (31)P NMR and mechanistic studies argue that the phosphinous acid ligands in the complexes can be deprotonated in the presence of a base to yield an electron-rich anionic species, which is likely a catalyst intermediate, and dimeric [[(t-Bu)(2)PO...H...OP((t-Bu)(2)]PdCl](2) was isolated and cystallographically characterized. These anionic complexes are anticipated not only to accelerate the rate-determining oxidative addition of aryl chlorides but also to stabilize the palladium complexes in the catalytic cycle.
Pharmacological Characterization of Itch-Associated Response Induced by Repeated Application of Oxazolone in Mice (2010)

We investigated pharmacological characteristics of the itch-associated response to chronic dermatitis induced by 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (oxazolone) repeated application in mice. Application of an oxazolone challenge to mice with oxazolone-induced chronic dermatitis evoked severe and transient scratching behavior for up to 1h. Thereafter, mild and continuous scratching behavior was observed for at least 8 h. Both severe and continuous scratching behaviors were suppressed by the opioid-receptor antagonist naltrexone, but not by the H(1) histamine-receptor antagonist fexofenadine, 5-hydroxytryptamine-2 (5-HT(2))-receptor antagonist methysergide, NK(1)-receptor antagonist LY303870, cyclooxygenase inhibitor indomethacin, or the platelet-activating factor-receptor antagonist YM264. The severe scratching behavior was suppressed by the 5-lipoxygenase inhibitor zileuton and leukotriene B(4)-receptor antagonist ONO-4057, but not by the cysteinyl leukotriene-receptor antagonist montelukast. The continuous scratching behavior was suppressed by pretreatment with the non-selective muscarinic acetylcholine-receptor antagonist atropine and M(3) muscarinic acetylcholine-receptor antagonist darifenacin. These results suggest that leukotriene B(4) receptor and M(3) muscarinic acetylcholine receptor are involved in the itch-associated response induced by repeated application of oxazolone in mice.
Abstract 2725: Preclinical development of an Fc-enhanced anti-B7-H3 monoclonal antibody with potent anti-tumor activity (2012)

Abstract Antigens that are tumor-specific or over-expressed on cancer cells represent opportunities for developing target-specific antibody-based therapeutics. Utilizing a non-target-biased intact cell-based immunization approach, we have generated greater than 1600 mAbs to cell-surface proteins that are expressed on cancer cells. A subset of the mAbs exhibit differential reactivity to tumor cells compared to normal cells. One of the differentially expressed proteins identified was B7-H3 (also referred to as CD276). B7-H3 is a member of the B7 family of immune regulatory proteins. Over-expression of B7-H3 has been correlated with disease severity and outcome in a growing number of cancer types, and several lines of evidence support a functional role for B7-H3 in cancer. In this report we describe the development of a humanized anti-B7-H3 mAb, designated MGA271, which bears an engineered Fc domain that imparts enhanced antibody-dependent cellular cytotoxicity (ADCC) through increased affinity for the human activating Fc-gamma receptor IIIA (CD16A) and decreased affinity for the human inhibitory Fc-gamma receptor IIB (CD32B). MGA271 displays strong reactivity to multiple tumors including kidney, prostate, pancreatic, breast, colon, gastric and ovarian cancer as well as melanoma, but limited reactivity toward normal human tissues. Independently of the donor's CD16A genotype, MGA271 mediates ADCC in vitro against human tumor cell lines representing these tumor types, as well as to human lung and gastrointestinal cell lines that exhibit properties of cancer stem cells. MGA271 exhibits potent anti-tumor activity toward B7-H3-expressing tumor xenografts in mice knocked-out for the murine CD16 gene and transgenic for the low affinity allele of human CD16A. Single- and repeat-dose toxicology studies were carried out in cynomolgus monkeys and no significant test article-related safety findings were observed. Taken together, these data support the clinical development of MGA271 for the treatment of patients who have B7-H3-expressing cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2725. doi:1538-7445.AM2012-2725
Blocking Java applets at the firewall (2002)

This paper explores the problem of protecting a site on the Internet against hostile external Java applets while allowing trusted internal applets to run. With careful implementation, a site can be made resistant to current Java security weaknesses as well as those yet to be discovered. In addition, we describe a new attack on certain sophisticated firewalls that is most effectively realized as a Java applet.
Modulation of TNF Release by Choline Requires α7 Subunit Nicotinic Acetylcholine Receptor-Mediated Signaling (2008)

The alpha7 subunit-containing nicotinic acetylcholine receptor (alpha7nAChR) is an essential component in the vagus nerve-based cholinergic anti-inflammatory pathway that regulates the levels of TNF, high mobility group box 1 (HMGB1), and other cytokines during inflammation. Choline is an essential nutrient, a cell membrane constituent, a precursor in the biosynthesis of acetylcholine, and a selective natural alpha7nAChR agonist. Here, we studied the anti-inflammatory potential of choline in murine endotoxemia and sepsis, and the role of the alpha7nAChR in mediating the suppressive effect of choline on TNF release. Choline (0.1-50 mM) dose-dependently suppressed TNF release from endotoxin-activated RAW macrophage-like cells, and this effect was associated with significant inhibition of NF-kappaB activation. Choline (50 mg/kg, intraperitoneally [i.p.]) treatment prior to endotoxin administration in mice significantly reduced systemic TNF levels. In contrast to its TNF suppressive effect in wild type mice, choline (50 mg/kg, i.p.) failed to inhibit systemic TNF levels in alpha7nAChR knockout mice during endotoxemia. Choline also failed to suppress TNF release from endotoxin-activated peritoneal macrophages isolated from alpha7nAChR knockout mice. Choline treatment prior to endotoxin resulted in a significantly improved survival rate as compared with saline-treated endotoxemic controls. Choline also suppressed HMGB1 release in vitro and in vivo, and choline treatment initiated 24 h after cecal ligation and puncture (CLP)-induced polymicrobial sepsis significantly improved survival in mice. In addition, choline suppressed TNF release from endotoxin-activated human whole blood and macrophages. Collectively, these data characterize the anti-inflammatory efficacy of choline and demonstrate that the modulation of TNF release by choline requires alpha7nAChR-mediated signaling.
Energetics of cooperative binding of oligonucleotides with discrete dimerization domains to DNA by triple helix formation. (1993)

Cooperativity in oligonucleotide-directed sequence-specific recognition of DNA by triple helix formation can be enhanced by the addition of discrete dimerization domains. The equilibrium association constants for cooperative binding of oligonucleotides that dimerize by Watson-Crick hydrogen bonds and occupy adjacent sites on double helical DNA by triple helix formation have been measured by quantitative affinity cleavage titration. For two oligonucleotides that bind unique neighboring 11-bp and 15-bp sites on double helical DNA, and dimerize by formation of an 8-bp Watson-Crick mini-helix, the free energy of binding is -8.0 and -9.7 kcal.mol-1, respectively, and the cooperative energy of interaction is -2.3 kcal.mol-1 (1 kcal = 4.18 kJ). The energetics of this artificial nucleic acid cooperative intermolecular assembly can mimic naturally occurring cooperative protein-DNA systems, such as the phage lambda repressor.
William J. McAuley, Applied Research in Gerontology, Van Nostrand Reinhold Company, New York1987, 158 pp., £23.95, ISBN 0 422 26468 2. (1988)

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Transport and Storage of Faeces for Bacteriological Examination (1971)

Summary. The survival of bacteria in specimens of human faeces transported and stored at different temperatures was examined quantitatively. No significant losses of bacteroides, bifidobacteria, viridans streptococci, Streptococcus salivarius , enterococci, enterobacteria, and clostridia were observed when 10% (w/v) suspensions of faeces in broth containing 10% (v/v) of glycerol were frozen for one month at −25, −78 or −196°; lactobacilli showed significant losses at −196°; veillonellae showed significant losses at −25°. At −12° veillonellae and enterobacteria showed significant losses. Most bacteria survived well for 24 h in undiluted faeces sent by post.
Intraoperative near-infrared spectroscopy for evaluating hepatic venous outflow in living-donor right lobe liver1 (2003)

Intraoperative NIRS enables quantification of the extent of congestion in the anterior segment after implantation of a right lobe liver graft and even enables prediction of such congestion at the phase of ex vivo perfusion.
Multi-Axis Controlled Ultraprecision Machining and Measurement (2009)

Demands of micro aspheric optical components such as lenses and mirrors are increasing for installing to the digital devices. As the devices become to be more compact and complicated, the molds shapes of lens and mirrors would become more difficult to be machined and measured. In this study, multi-axis controlled ultra precision machining/grinding and on-machine measurement technologies are developed for manufacturing of the complicated and micro molds. In this paper, the next four technologies are focused: (1) micro fresnel grinding, (2) Micro lens array grinding, (3) Ultrasonic vibration assisted polishing, and (4) Contact type of multi axis controlled on-machine measuring system.
Optical spectroscopy of high dielectric contrast 3D photonic crystals (2001)

Spectroscopy was performed along three distinct crystallographic axes of a high refractive index contrast photonic crystal and the spectra were compared with theoretical calculations. Deep dips were observed in the experimental spectra at 2.1 and 3.2 μm and predicted by calculations. The photonic crystal was prepared through melt-imbibing of selenium into a self-assembled face-centered-cubic colloidal crystal template.
The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice (1978)

The pathogenicity for mice of two mutants of herpes simplex virus (type 1 and type 2), which fail to induce thymidine kinase, were compared with their respective parent strains. The mutants were much less virulent than the parents following either intracerebral or peripheral inoculation. The replication of the virus at the site of inoculation and its progression into the nervous system were studied. Following a very large inoculum in the ear, the type 1 mutant was found to establish a latent infection in the cervical dorsal root ganglia. Mice inoculated intracerebrally with small doses of the mutant viruses were solidly immune to challenge with lethal doses of the parent strain.
ODYSSEY MONO: Effect of Alirocumab 75 Mg Subcutaneously Every 2 Weeks As Monotherapy Versus Ezetimibe Over 24 Weeks (2015)

ABSTRACT Alirocumab is a fully human monoclonal antibody to PCSK9. The ODYSSEY MONO study was the first alirocumab Phase III study to test a previously unused dose of 75 mg subcutaneously every 2 weeks in a population on no lipid-lowering therapy. A total of 103 patients were randomly assigned to alirocumab starting at 75 mg subcutaneously every 2 weeks or ezetimibe 10 mg per os every day with alirocumab dose uptitration at 12 weeks based on achieved LDL-cholesterol level at week 8 and followed to week 24. At the week-24 primary end point, the alirocumab intent-to-treat group showed a 47.2% (least square [LS] mean) reduction in LDL-cholesterol compared with a 15.6% (LS mean) reduction with ezetimibe (LS mean difference of 31.6%; p < 0.0001). Safety parameters and adverse events were similar between the two groups.
Structure and Function of Syk Protein-Tyrosine Kinase (2001)

Non-receptor type of protein-tyrosine kinase Syk contains 2 Src homology 2 (SH2) domains in tandem and multiple autophosphorylation sites. Syk is activated upon binding of tandem SH2 domains to immunoreceptor tyrosine-based activating motif (ITAM) and plays an essential role in lymphocyte development and activation of immune cells. Syk is critical for tyrosine phosphorylation of multiple proteins which regulate important pathways leading from the receptor, such as Ca(2+) mobilization and mitogen-activated protein kinase (MAPK) cascades. Recent findings reveal that expression of Syk appears to be involved in a wide variety of cellular functions and pathogenesis of malignant cancer. These observations have demonstrated that Syk is a key molecule that controls multiple physiological functions in cells.
Reversible, Band-Gap-Selective Protonation of Single-Walled Carbon Nanotubes in Solution (2003)

In acidic solution between pH 6 and 2.5, protons react reversibly and selectively in the presence of preadsorbed oxygen at the sidewall of aqueous dispersed single-walled carbon nanotubes suspended in sodium dodecyl sulfate. This reactive complex, which protonates the nanotube sidewall, reversibly diminishes absorption intensity, fluorescent emission, and resonant Raman scattering intensity. The results document the first evidence of electronic selectivity with metallic nanotubes reacting initially near neutral pH, followed by successive protonation of nanotubes with increasing band gap as the solution is increasingly acidified. Preadsorption of molecular oxygen is shown to play a critical role in the interaction, and its desorption kinetics is followed using UV irradiation. The role of the charged electric double layer of the surfactant is discussed. This chemistry, which proceeds under relatively mild conditions, holds promise for separating nanotubes by metal and semiconducting types.