gebhart/patrepeval huggingface dataset:
Biologic Significance of Disulfide Bonds in Human IgE Molecules (1975)

Abstract E myeloma protein, PS, was reduced in different concentrations of dithiothreitol (DTT) for 1 hr followed by alkylation with 14C-iodoacetamide. The affinity of the reduced-alkylated molecules for target cells was evaluated by their ability 1) to sensitize primate skin in a reversed P-K reaction, 2) to sensitize human basophils in a reversed-type histamine release and 3) to block passive sensitization with reaginic antibody. Antibody-ε0 antibody was employed for reversed type reactions to avoid participation of cellbound normal IgE in the reactions. The sensitizing activity of IgE did not change following reduction in 1 mM DTT, which split inter-heavy-light chain disulfide bond. The activity of IgE significantly diminished after reduction in 2 mM DTT followed by alkylation. This treatment resulted in the cleavage of two intra-ε-chain disulfide bonds, which are present between the hinge and the Fd portion of the molecules. The reduced-alkylated protein was capable of sensitizing primate skin and human basophils, however, a much higher concentration of the reduced-alkylated protein than the native protein was required for passive sensitization. The optimal sensitization period for the reversed P-K reaction was 3 hr with the reduced-alkylated protein. The protein had the ability to block passive sensitization with reaginic antibody. The reduced-alkylated protein and the native protein were labeled with 125I, and binding of these proteins with human basophils was examined by autoradiography. The results showed that affinity of the reduced-alkylated protein for basophils was less than that of native protein. Since the disulfide bonds split by 2 mM DTT were not included in the Fc portion of the molecule, the Fc fragment was obtained from the reduced-alkylated protein and was tested for affinity for basophils. It was found that the Fc fragment had higher affinity than the reduced-alkylated protein. Recovery of the affinity by papain digestion strongly suggested that cleavage of disulfide bonds in the Fab portion of the molecules induced conformational changes in the Fc portion which is involved in binding to the target cells. Reduction of IgE with 10 mM DTT followed by alkylation resulted in cleavage of 5 disulfide bonds, which is accompanied by a loss of both sensitizing and blocking activities. The fifth disulfide bond which was cleaved by 10 mM DTT, but not by 2 mM DTT, appears to be an inter-heavy chain disulfide bond in the Fc portion of the ε-chains. Neither ε1 nor ε2 determinants in the Fc portion of ε-chains were degraded by this treatment.
Determinants of antithrombin consumption in cardiac operations requiring cardiopulmonary bypass (2004)

Antithrombin (AT) is a natural anticoagulant that is consumed during cardiac operations with cardiopulmonary bypass (CPB). This study is an observational trial aimed at identifying the factors determining the magnitude of the AT consumption during cardiac operations. Two hundred and fifty consecutive adult patients undergoing cardiac operations with CPB were admitted to the study. Preoperative and intraoperative variables were tested with respect to their role in determining AT activity at the end of the operation. At a univariate analysis, eight predictors of AT activity at the end of the operation have been identified: preoperative AT activity; age; diabetes on medication; preoperative haematocrit value; preoperative dialysis; combined operation; CPB duration; lowest temperature on CPB. A multivariate predictive model was created, and five factors remained as independent predictors of AT activity at the end of the operation: preoperative AT activity (p = 0.001); age (p = 0.015); combined operation (p = 0.014); diabetes (p = 0.013) and CPB duration (p = 0.001). On this basis, predictive tables of AT consumption have been established for different combinations of risk factors.
Excitonic Aharonov-Bohm effect in isotopically pureG70e/Siself-assembled type-II quantum dots (2010)

We report on a magnetophotoluminescence study of isotopically pure $^{70}\text{G}\text{e}/\text{Si}$ self-assembled type-II quantum dots. Oscillatory behaviors attributed to the Aharonov-Bohm effect are simultaneously observed for the emission energy and intensity of excitons subject to an increasing magnetic field. When the magnetic flux penetrates through the ringlike trajectory of an electron moving around each quantum dot, the ground state of an exciton experiences a change in its angular momentum. Our results provide the experimental evidence for the phase coherence of localized electron wave functions in group-IV Ge/Si self-assembled quantum structures.
Passively Q-Switched Microchip Lasers for Environmental Monitoring (1996)

The need exists for sensors capable of measuring soil, groundwater, and airborne pollutants without laborious sample collection and analysis. Single-wavelength transmission, differential absorption, laser-induced fluorescence (LIF), stimulated Raman scattering, and laser-induced breakdown spectroscopy (LIBS) are all highly sensitive methods for providing quantitative values of concentrations of chemical species. These optical techniques have been proven to provide high sensitivity and chemical selectivity for a large number of the materials on the EPA’s priority pollutant list.
Arginase Inhibition Reverses Endothelial Dysfunction, Pulmonary Hypertension, and Vascular Stiffness in Transgenic Sickle Cell Mice (2016)

Arginase inhibition improves NO bioavailability and thereby attenuates systemic and pulmonary vascular endothelial dysfunction in transgenic mice with SCD. Therefore, arginase is a potential therapeutic target in the treatment of cardiovascular dysfunction in SCD.
Expression Compilation of Several Putative Cancer Stem Cell Markers by Primary Ovarian Carcinoma (2010)

Cancer stem cells (CSCs) or tumor initiating cells are rare cells that are able to establish a tumor or metastasis. Identification of those CSCs is, however, cumbersome even in established cell lines. Several cancer stem cell markers were reported to be expressed by ovarian cancer. Those cancer stem cells are gifted with lower vulnerability to irradiation and cytostatic drugs explaining the high incidence of recurrence after treatment. A variety of different cancer stem cell markers were described for epithelial tumors. Also, cancer cell lines were assessed for stem cell markers with no common denominator. The expression of CD24, CD44, CD117, CD133, ABCG2, ALDH was determined for cells from 22 patients. Ovarian cancer cells were collected from ascites. Part of the tumor cells were analyzed immediately and stained for the above mentioned cancer stem cell markers. The remainder of the cells was cultured for several weeks using standard stem cell culture conditions. We observed a large variety in expression of putative stem cell markers for primary tumors. After two weeks of culture spheres were seen in several cultures, indicative for cancer stem cells, though not all patients’ cells were able to form spheres. Our data show for the first time the heterogeneity in marker display in primary tumors. Also for the cultured cells stem cell markers were determined. None of the stem cell markers was expressed by all patients’ cells. No correlation with tumor type was demonstrated. The complexity of expression challenges the isolation of cancer stem cells
Discovery of the Potent and Selective M1 PAM-AgonistN-[(3R,4S)-3-Hydroxytetrahydro-2H-pyran-4-yl]-5-methyl-4-[4-(1,3-thiazol-4-yl)benzyl]pyridine-2-carboxamide (PF-06767832): Evaluation of Efficacy and Cholinergic Side Effects (2016)

It is hypothesized that selective muscarinic M1 subtype activation could be a strategy to provide cognitive benefits to schizophrenia and Alzheimer's disease patients while minimizing the cholinergic side effects observed with nonselective muscarinic orthosteric agonists. Selective activation of M1 with a positive allosteric modulator (PAM) has emerged as a new approach to achieve selective M1 activation. This manuscript describes the development of a series of M1-selective pyridone and pyridine amides and their key pharmacophores. Compound 38 (PF-06767832) is a high quality M1 selective PAM that has well-aligned physicochemical properties, good brain penetration and pharmacokinetic properties. Extensive safety profiling suggested that despite being devoid of mAChR M2/M3 subtype activity, compound 38 still carries gastrointestinal and cardiovascular side effects. These data provide strong evidence that M1 activation contributes to the cholinergic liabilities that were previously attributed to activation of the M2 and M3 receptors.
Transition-state modeling with empirical force fields (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTransition-state modeling with empirical force fieldsJohn E. Eksterowicz and K. N. HoukCite this: Chem. Rev. 1993, 93, 7, 2439–2461Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://pubs.acs.org/doi/10.1021/cr00023a006https://doi.org/10.1021/cr00023a006research-articleACS PublicationsRequest reuse permissionsArticle Views1047Altmetric-Citations148LEARN 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
Spectral Efficiency of Multi-Antenna Index Modulation (2021)

Index modulation emits information through the index of the activated component of a vector signal as well as the value of the activated component. Indexing could occur across antennas, subcarriers, or other degrees of freedom. When index modulation is applied to antennas, it is known as spatial modulation. Earlier bounds or estimates for the spectral efficiency of spatial modulation have been too loose for determining the parameters of coding and modulation, which are important in practice. Furthermore, the best bounds formerly available did not effectively elucidate the relationship of spatial modulation capacity with SIMO and MIMO capacity at low- and high-SNR. The present work develops novel, tighter bounds on the spectral efficiency of spatial modulation. Specifically, for a 4 × 2 antenna configuration at 8 bits/slHz, our results are 2dB tighter than the best bounds available in the literature.
Tumor Necrosis Factor-Like Weak Inducer of Apoptosis-Induced Neurodegeneration (2004)

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor (TNF) family of cytokines. It has proangiogenic and proinflammatory properties in vivo and induces cell death in tumor cell lines. TWEAK effects are mediated by the membrane receptor Fn14. In a systematic search for genes regulated in a murine stroke model with the tag-sequencing technique massively parallel signature sequencing, we have identified TWEAK as an induced gene. After 24 hr of focal cerebral ischemia in vivo or oxygen glucose deprivation in primary cortical neurons, both TWEAK and its receptor Fn14 were significantly upregulated. TWEAK induced cell death in primary neurons. Transfection of a nuclear factor (NF)-kappaB-luciferase fusion gene demonstrated that TWEAK stimulated transcriptional activity of NF-kappaB through Fn14 and the IkappaB kinase. Inhibition of NF-kappaB reduced TWEAK-stimulated neuronal cell death, suggesting that NF-kappaB mediates TWEAK-induced neurodegeneration at least in part. Intraperitoneal injection of a neutralizing anti-TWEAK antibody significantly reduced the infarct size after 48 hr of permanent cerebral ischemia. In summary, our data show that TWEAK induces neuronal cell death and is involved in neurodegeneration in vivo.
Microparticles Locally Deliver Active Interleukin‐1 Receptor Antagonist In Vivo (2018)

Despite significant research in therapeutic protein delivery, localized and sustained delivery of active therapeutic proteins remains a challenge. Delivery is a particular challenge for therapeutic proteins with a short half-life. Herein, localized delivery of interleukin-1 receptor antagonist (IL-1Ra) by mineral coated microparticles (MPs) is assessed in a healing rat medial collateral ligament (MCL). The local tissue concentration and systemic serum concentration of IL-1Ra, the anti-inflammatory activity of IL-1Ra delivered with MPs, and whether IL-1Ra loaded MPs (IL-1Ra MPs) are immunogenic in a healing ligament are also examined. IL-1Ra MPs significantly increase the local concentration of IL-1Ra compared to soluble IL-1Ra at 7 and 14 days after treatment but do not elevate the systemic concentration of IL-1Ra at these time points, indicating localized delivery of IL-1Ra. IL-1Ra MPs significantly reduce inflammation caused by the MPs themselves, indicating the IL-1Ra is active. Finally, IL-1Ra MPs do not induce a foreign body response and decrease the immunogenicity of human IL-1Ra in a healing rat MCL. Overall, mineral coated microparticles have the ability to locally deliver active therapeutic proteins for an extended period of time.
Poly(3,4-alkylenedioxythiophene)-Based Supercapacitors Using Ionic Liquids as Supporting Electrolytes (2002)

A series of dual conducting polymer based type I supercapacitors were constructed using poly(3,4-propylenedioxythiophene) and poly(3,4-ethylenedioxythiophene) as electrode couples. The switching speeds and cycle lifetimes of these supercapacitors were compared using two types of supporting electrolytes; lithium bis(trifluoromethanesulfonyl)imide and 1-ethyl-3-methyl-1-H-imidazolium bis(trifluoromethanesulfonyl)imide (a room temperature molten salt). The results indicate that supercapacitors using 1-ethyl-3-methyl-1-H-imidazolium bis(trifluoromethanesulfonyl)imide as the supporting electrolyte have cycle lifetimes superior to supercapacitors using lithium bis(trifluoromethanesulfonyl)imide as the supporting electrolyte. © 2002 The Electrochemical Society. All rights reserved.
Abstract 1166: APOBEC deaminases compete with tobacco smoking mutagenesis and affect age at onset of lung cancer (2023)

Abstract APOBEC enzymes are part of the innate immunity and are responsible for restricting viruses and retroelements by deaminating cytosine residues. Most solid tumors harbor different levels of somatic mutations attributed to the off-target activities of APOBEC3A (A3A) and/or APOBEC3B (A3B). However, how APOBEC3A/B interact with exogenous mutagenic processes in shaping tumor development is largely unknown. Here, by combining deep whole-genome sequencing with multi-omics profiling of 309 lung cancers from smokers with detailed tobacco smoking information, we identify two subtypes defined by low (LAS) and high (HAS) APOBEC mutagenesis. LAS are enriched for A3B-like mutagenesis and KRAS mutations, whereas HAS for A3A-like mutagenesis and TP53 mutations. Unlike APOBEC3A, APOBEC3B expression is strongly associated with an upregulation of the base excision repair pathway. Hypermutation by unrepaired A3A and tobacco smoking mutagenesis combined with TP53-induced genomic instability can trigger senescence, apoptosis, and cell regeneration, as indicated by telomere shortening, high expression of pulmonary healing signaling pathway and stemness markers in HAS. The expected association of tobacco smoking exposure with genomic/epigenomic changes are not observed in HAS, a plausible consequence of frequent cell senescence or apoptosis. HAS tumors have slower clonal expansion and older age at onset compared to LAS, particularly in heavy smokers, consistent with high proportions of newly generated, unmutated cells in HAS. These findings show how heterogeneity in mutational burden across competing mutational processes and cell types contributes to tumor development, with important clinical implications. Citation Format: Tongwu Zhang, Jian Sang, Phuc H. Hoang, Wei Zhao, Jennifer Rosenbaum, Leszek J. Klimczak, John McElderry, Alyssa Klein, Christopher Wirth, Erik N. Bergstrom, Marcos Díaz-Gay, Raviteja Vangara, Amy Hutchinson, Scott M. Lawrence, Nathan Cole, Bin Zhu, Teresa M. Przytycka, Jianxin Shi, Neil E. Caporaso, Robert Homer, Angela C. Pesatori, Dario Consonni, Stephen J. Chanock, David C. Wedge, Dmitry A. Gordenin, Ludmil B. Alexandrov, Reuben S. Harris, Maria Teresa Landi. APOBEC deaminases compete with tobacco smoking mutagenesis and affect age at onset of lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1166.
Focusing and amplification of electromagnetic waves by time reversal in an leaky reverberation chamber (2010)

In this article, time reversal is used to generate high power microwave pulses from a low power arbitrary wave generator. We use a reverberation chamber with an aperture on the front face and we take advantage of the pulse compression property of time reversal. High amplitude peaks are generated outside the chamber thanks to the long spreading time of the signals inside. We study the amplitude of this peak and the width of the focal spot with respect to the different experimental parameters. A gain of 18 dB compared to a directive antenna of the same aperture is obtained.
Smallpox Vaccination Does Not Elevate Systemic Levels of Prothrombotic Proteins Associated with Ischemic Cardiac Events (2005)

During the recent smallpox vaccination campaigns, ischemic cardiac complications were observed after vaccination. To examine a possible association between the smallpox vaccine and postvaccination ischemic events, we investigated alterations in levels of prothrombotic proteins (plasminogen activator inhibitor type 1 [PAI-1] and soluble CD40 ligand [sCD40L]) in recently vaccinated individuals.Vaccinia-naive (cohort N; aged 18-32 years) and vaccinia-experienced (cohort E; aged 33-49 years) healthy adults were vaccinated with a 1 : 5 dilution of the Aventis Pasteur smallpox vaccine. Plasma levels of PAI-1 and sCD40L were measured in 30 subjects (cohort N, n=15; cohort E, n=15) at baseline and twice after vaccination (between days 7 and 9 and between days 26 and 30).Baseline mean PAI-1 levels significantly differed between cohorts N and E (P=.04). Within each exposure cohort, mean PAI-1 levels did not significantly change after vaccination. Baseline sCD40L levels did not differ between cohorts N and E. In cohort N, sCD40L levels significantly decreased after vaccination but returned to baseline levels within 1 month. Vaccination did not significantly alter levels of sCD40L in cohort E.Levels of PAI-1 and sCD40L did not significantly increase after smallpox vaccination. Vaccine-induced alterations in levels of these prothrombotic proteins do not appear to play a role in ischemic events observed after smallpox vaccination.
Contrast-Enhanced Ultrasound Angiogenesis Imaging by Mutual Information Analysis for Prostate Cancer Localization (2016)

An improved PCa localization method can possibly lead to better grading and staging of tumors, and support focal-treatment guidance. Moreover, future employment of the method in other types of angiogenic cancer can be considered.
Improved Measurement of the Angular Power Spectrum of Temperature Anisotropy in the Cosmic Microwave Background from Two New Analyses of BOOMERANG Observations (2003)

We report the most complete analysis to date of observations of the cosmic microwave background (CMB) obtained during the 1998 flight of BOOMERANG. We use two quite different methods to determine the angular power spectrum of the CMB in 20 bands centered at l = 50-1000, applying them to ~50% more data than has previously been analyzed. The power spectra produced by the two methods are in good agreement with each other and constitute the most sensitive measurements to date over the range 300 &lt; l &lt; 1000. The increased precision of the power spectrum yields more precise determinations of several cosmological parameters than previous analyses of BOOMERANG data. The results continue to support an inflationary paradigm for the origin of the universe, being well fitted by a ~13.5 Gyr old, flat universe composed of approximately 5% baryonic matter, 30% cold dark matter, and 65% dark energy, with a spectral index of initial density perturbations ns ~ 1.
Issues important for rational COMT inhibition. (2000)

Levodopa is the most efficacious drug in the symptomatic treatment of Parkinson's disease. However, exogenously administered levodopa is extensively metabolized in the periphery by aromatic amino acid decarboxylase (AAAD) and catechol-O-methyltransferase (COMT) so that only 1% of an administered dose gains access to the brain. Even when levodopa is co-administered with an inhibitor of AAAD such as benserazide or carbidopa, the bulk (90%) of levodopa is converted by COMT to the therapeutically inactive 3-O-methyldopa. Two COMT inhibitors, tolcapone and entacapone, have recently been introduced as adjuncts to levodopa to further inhibit peripheral levodopa metabolism and thereby enhance brain levodopa availability. This paper reviews the pharmacokinetics, dosing schedule, peripheral and central effects, and safety profile of these agents.
(29) MCP Treatment Makes Delayed Application of Ethoxyquin Effective in Control of Superficial Scald of `d'Anjou' Pears (2005)

Superficial scald of `d'Anjou' pears usually develops after storage of 2 months or longer. MCP application controls scald; however, fruit lose their ripening capacity if the dosage is &gt;30 ppb, but lower dosages cannot control scald substantially. In this study, fruit treated with or without 25 ppb MCP within 2 d after harvest were stored at –1 °C for up to 5 months. After 1, 7, 30, or 70 d of storage, part of the fruit were pulled from storage and treated with 1000 ppm ethoxyquin line spray and immediately returned to the storage, left untreated as non-ethoxyquin control. Incidence of superficial scald along with the concentrations of α-farnesene and conjugated trienes (CTs), and the ripening capacity of fruit were investigated after 3, 4, and 5 months storage. All fruit ripened properly within 7 d of conditioning at room temperature regardless of treatments. Both of MCP or ethoxyquin-1d (ethoxyquin was applied after 1 day storage at –1 °C) alone controlled scald for only 3 months; however, MCP + ethoxyquin controlled scald for 5 months, whenever ethoxyquin was applied between 1 to 70 d after storage. Thus, with 25 ppb MCP treatment, which is simple, with rapid and mass treatment available, a delayed application (up to 70 d) of ethoxyquin becomes effective to control scald. Furthermore, the later application of ethoxyquin within 70 d after MCP treatment, the less incidence of scald was observed. Scald is caused by the CTs oxidation products of α-farnesene. MCP and ethoxyquin inhibited accumulation of CTs of fruit peel by different mechanisms. MCP inhibited the production by influencing ethylene production through control of α-farnesene synthesis; however, ethoxyquin worked by inhibiting the oxidation of α-farnesene to the CTs.
Simulation and Fabrication of a New System For Vibration Energy Harvesting (2005)

International audience
ChemInform Abstract: One Hundred Years of Vitamins — A Success Story of the Natural Sciences (2013)

Abstract Review: 316 refs.