gebhart/patrepeval huggingface dataset:
Molecular effects of recombinant human interleukin-11 in the HLA-B27 rat model of inflammatory bowel disease. (1998)

Recombinant human interleukin-11 (rhIL-11) is a pleiotropic cytokine with effects on multiple cell types. In addition to thrombopoietic activity, rhIL-11 has demonstrated anti-inflammatory activity in vitro and in vivo. rhIL-11 treatment reduces clinical signs and histologic lesions of colitis in transgenic rats expressing the human major histocompatibility complex (MHC) Class I allele, HLA-B27. We have investigated the effects of rhIL-11 at the molecular and cellular level in this model of inflammatory bowel disease. RT-PCR analysis of colonic RNA revealed that treatment with rhIL-11 down-regulated expression of proinflammatory cytokines including TNF-alpha, IL-1beta, and IFN-gamma. rhIL-11 also reduced the level of myeloperoxidase activity in the cecum indicating reduced inflammation. After stimulation in vitro with anti-CD3 antibody, spleen cell cultures derived from rhIL-11-treated rats produced less IFN-gamma, TNF-alpha, and IL-2 than cultures derived from vehicle-treated rats. These molecular and cellular effects correlated with amelioration of disease as measured by stool character and histologic lesion scores. These findings suggest that rhIL-11 acts to reduce inflammation through modulation of multiple proinflammatory mediators including products of activated T cells. This study has identified pharmacodynamic markers of rhIL-11 anti-inflammatory activity in vivo and supports rhIL-11 therapy to treat inflammatory bowel disease.
Vesicle associated membrane protein (VAMP)‐7 and VAMP‐8, but not VAMP‐2 or VAMP‐3, are required for activation‐induced degranulation of mature human mast cells (2008)

Mediator release from mast cells (MC) is a crucial step in allergic and non-allergic inflammatory disorders. However, the final events in response to activation leading to membrane fusion and thereby facilitating degranulation have hitherto not been analyzed in human MC. Soluble N-ethyl-maleimide-sensitive factor attachment protein receptors (SNARE) represent a highly conserved family of proteins that have been shown to mediate intracellular membrane fusion events. Here, we show that mature MC isolated from human intestinal tissue express soluble N-ethylmaleide sensitive factor attachment protein (SNAP)-23, Syntaxin (STX)-1B, STX-2, STX-3, STX-4, and STX-6 but not SNAP-25. Furthermore, we found that primary human MC express substantial amounts of vesicle associated membrane protein (VAMP)-3, VAMP-7 and VAMP-8 and, in contrast to previous reports about rodent MC, only low levels of VAMP-2. Furthermore, VAMP-7 and VAMP-8 were found to translocate to the plasma membrane and interact with SNAP-23 and STX-4 upon activation. Inhibition of SNAP-23, STX-4, VAMP-7 or VAMP-8, but not VAMP-2 or VAMP-3, resulted in a markedly reduced high-affinity IgE receptor-mediated histamine release. In summary, our data show that mature human MC express a specific pattern of SNARE and that VAMP-7 and VAMP-8, but not VAMP-2, are required for rapid degranulation.
cDNA cloning for mouse thymocyte-activating molecule. A multifunctional ecto-dipeptidyl peptidase IV (CD26) included in a subgroup of serine proteases. (1992)

Thymocyte-activating molecule (THAM) was initially characterized as a developmentally regulated, dimeric cell-surface molecule capable of activating mouse thymocytes and T lymphocytes upon monoclonal antibody (mAb)-mediated cross-linking. We recently obtained structural evidence indicating that this molecule is the mouse homologue of the human T cell-activating ectoenzyme CD26 (dipeptidyl peptidase IV, DPP IV). We describe here the cloning and the characterization of THAM cDNA. Two clones (3.3 and 2.8 kilobases) were isolated. THAM-3.3 cDNA contains an open reading frame of 2,280 nucleotides that encodes a protein of 760 amino acids having a calculated size of 87,500 Da. Complete N-glycosylation at each of the nine potential sites would result in a mature 110,000-Da molecule. Protein sequence comparisons revealed a significant homology (in particular in the COOH-terminal domain) between THAM and the rat or human DPP IV or the yeast dipeptidyl aminopeptidase B molecules (92, 85, and 30% sequence identity, respectively). Structural comparison of serine proteases (i.e. acyl-amino acid hydrolase or prolyl endopeptidase) with the most conserved domain of THAM identified a stretch of 200 amino acids containing a putative catalytic triad arranged in a novel topological order (Ser-624, Asp-702, and His-734) thereby defining a subfamily of nonclassical serine proteases. Expression of THAM during thymus ontogeny was found to be mainly regulated at the transcriptional level as determined by RNase protection assay. To investigate directly some of the functions which have been ascribed to DPP IV, we transfected an ovalbumin/Aq-reactive, THAM- T hybridoma cell line with THAM-3.3 cDNA. The resultant transfectants acquired (i) DPP IV enzymatic activity that precisely paralleled the density of surface-expressed THAM; (ii) an Mr = 115,000 (reduced) and 110,000/128,000 (nonreduced) molecule that could be immunoprecipitated by the THAM-specific mAb H194-112; and (iii) the capacity of being triggered by this mAb to release interleukin-2. These data indicate that a single cDNA species can encode a multifunctional molecule (e.g. activation signal-transducing structure and ectopeptidase), the heterodimeric state of which very likely results from a differential post-translational modification of the same protein core.
Joint Super-Resolution and Array Interpolation for MIMO Radar Virtual Arrays (2018)

Multiple-input multiple-output (MIMO) radars offer increased angular resolutions compared to conventional radars, based on a virtual enlargement of the physical antenna array by means of digital signal processing. In this paper, we show that the angular resolution of MIMO radars can be further increased by combining MIMO processing with an array extrapolation method based on Burg's algorithm. Moreover, we demonstrate that Burg's algorithm is also able to interpolate missing virtual antenna elements caused by failure of physical receive antennas. Measurements conducted with Hensoldt's compact 3D MIMO radar demonstrator serve as a basis to validate our findings.
Pharmacokinetics, Methionine Depletion, and Antigenicity of Recombinant Methioninase in Primates (2004)

Pharmacokinetics, methionine depletion, antigenicity, and toxicity of recombinant methioninase (rMETase), which has shown efficacy in achieving cell kill in a broad range of human tumor models, were examined in macaque monkeys. Dose-ranging studies at 1000, 2000, and 4000 units/kg i.v. identified the 4000 units/kg dose as able to reduce plasma methionine to an undetectable level (less than 0.5 microM) by 30 min, and the level so remained for 8 h. Pharmacokinetic analysis showed that rMETase was eliminated with a T(1/2) of 2.49 h. A 2-week i.v. administration of 4000 units/kg every 8 h/day for 2 weeks resulted in a steady-state depletion of plasma methionine to less than 2 microM. The only manifest toxicity was decreased food intake and slight weight loss. Serum albumin and red cell values declined transiently during treatment, which may be related to extensive blood sampling. Re-challenge on day 28 resulted in anaphylactic shock and death in one animal. Subsequent pretreatment with hydrocortisone prevented the anaphylactic reaction, although vomiting was frequently observed. Re-challenge was carried out at days 66, 86, and 116. Anti-rMETase antibodies (at 10(-3)) were found after the first challenge, and these increased to 10(-6) after the fourth challenge and decreased to 10(-2) by 2 months post therapy. The main rMETase antibody was IgG, and although it has some in vitro features of being a neutralizing antibody, each challenge dose was effective in depleting plasma methionine levels. Thus, rMETase was able to effectively deplete plasma methionine levels with minimal toxicity in a primate model. These data provide the bases for alteration by polyethyleneglycol conjugation (PEGylation) of the enzyme to increase its duration of effect and reduce its immunogenicity.
Breast Cancer Risk in Postmenopausal Women Using Estrogen-Only Therapy (2006)

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DNA-Based Magnetic Nanoparticle Assembly Acts as a Magnetic Relaxation Nanoswitch Allowing Screening of DNA-Cleaving Agents (2002)

Monodisperse magnetic nanoparticles conjugated with complementary oligonucleotide sequences self-assemble into stable magnetic nanoassemblies resulting in a decrease of the spin-spin relaxation times (T2) of neighboring water protons. When these nanoassemblies are treated with a DNA cleaving agent, the nanoparticles become dispersed, switching the T2 of the solution back to original values. These qualities render the developed nanoparticles and their nanoassemblies as magnetic relaxation switches capable of screening for DNA-cleaving compounds by magnetic resonance methods such as MRI and NMR.
Duchenne's muscular dystrophy: animal models used to investigate pathogenesis and develop therapeutic strategies (2003)

Duchenne's muscular dystrophy (DMD) is a lethal childhood disease caused by mutations of the dystrophin gene, the protein product of which, dystrophin, has a vital role in maintaining muscle structure and function. Homologues of DMD have been identified in several animals including dogs, cats, mice, fish and invertebrates. The most notable of these are the extensively studied mdx mouse, a genetic and biochemical model of the human disease, and the muscular dystrophic Golden Retriever dog, which is the nearest pathological counterpart of DMD. These models have been used to explore potential therapeutic approaches along a number of avenues including gene replacement and cell transplantation strategies. High-throughput screening of pharmacological and genetic therapies could potentially be carried out in recently available smaller models such as zebrafish and Caenorhabditis elegans. It is possible that a successful treatment will eventually be identified through the integration of studies in multiple species differentially suited to addressing particular questions.
Psoralen synthesis. Improvements in furano ring formation. Application to the synthesis of 4,5',8-trimethylpsoralen (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPsoralen synthesis. Improvements in furano ring formation. Application to the synthesis of 4,5',8-trimethylpsoralenDean R. Bender, John E. Hearst, and Henry RapoportCite this: J. Org. Chem. 1979, 44, 13, 2176–2180Publication Date (Print):June 1, 1979Publication History Published online1 May 2002Published inissue 1 June 1979https://doi.org/10.1021/jo01327a030Request reuse permissionsArticle Views202Altmetric-Citations23LEARN 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 InReddit PDF (732 KB) Get e-Alertsclose Get e-Alerts
Les préjudices résultant de l'exécution provisoire : la Cour de cassation persiste et signe (2011)

International audience
Antibodies against membrane interleukin 1 alpha activate accessory cells to stimulate proliferation of T lymphocytes. (1990)

Some monoclonal antibodies (mAbs) against interleukin (IL) 1 alpha have been found to activate antigen-presenting cells (APC, human peripheral blood monocytes and B lymphocytes), so that unstimulated T lymphocytes cultured with them are induced to proliferate and secrete IL-2. Control mAbs of the same isotypes and mAbs against IL-1 beta do not activate APC. In the absence of APC, mAbs against IL-1 alpha do not induce proliferation of T lymphocytes. Mitomycin C-treated activated APC still induce T-cell proliferation. Proliferation of T lymphocytes cannot be induced by culture supernatants and requires contact with APC activated by mAbs against IL-1 alpha. The observations imply that surface membrane IL-1 alpha can function as a triggering molecule on APC, which could play an important role in the initiation of immune responses by T lymphocytes.
Apolipoprotein J and Alzheimer's amyloid β solubility (1996)

Apolipoprotein J (apoJ) has been found associated with soluble amyloid beta (sA beta) in plasma and cerebrospinal fluid in normal individuals and co-deposited with fibrillar A beta in Alzheimer's cerebrovascular and parenchymal lesions. Although studies in vitro and in vivo indicate that apoJ is a major carrier protein for sA beta, its role in the fibrillogenesis process is not known. We report herein that apoJ in its native high-density lipoprotein lipidic environment is fully active to interact with A beta peptides. Furthermore, apoJ prevents aggregation and polymerization of synthetic A beta in vitro. The interaction was stable for at least 14 days at 37 degrees C in physiologic buffers, and the peptide retrieved after complex dissociation at low pH retained its inherent aggregation properties. In addition, the binding to apoJ protects synthetic A beta from proteolytic degradation; both A beta 1-42 and A beta 1-40 were more resistant to proteolysis by trypsin and chymotrypsin when complexed to apoJ. The data suggest that the interaction may preclude sA beta aggregation in biological fluids and point to a protecting role of apoJ for complexed A beta species.
Comparison of Immunohistochemistry, Acid-Fast Staining, and Cultivation for Detection of Mycobacterium Paratuberculosis in Goats (1994)

Forty-seven paired specimens of ileum and mesenterial lymph nodes from goats originating from 2 herds with paratuberculosis were investigated. Culture of the specimens for Mycobacterium paratuberculosis was compared with Ziehl-Neelsen staining and with immunohistochemical tests on paraffin-embedded tissue sections, using a M. paratuberculosis immune serum and an avidin-biotin-alkaline phosphatase method. Immunohistochemical techniques detected most positive samples and produced more clearly visible reactions than did acid-fast staining. Eighteen of 47 samples were positive by immunohistochemical methods, whereas 15 and 10 were positive for acid-fast staining and culture, respectively. Immunohistochemical techniques may represent a valuable adjunct to standard techniques for diagnosis of paratuberculosis in goats.
The role of indoleamine 2,3-dioxygenase (IDO) in the pathophysiology of interferon-alpha-induced depression. (2004)

The mechanisms by which administration of interferon-alpha induces neuropsychiatric side effects, such as depressive symptoms and changes in cognitive function, are not clear as yet. Direct influence on serotonergic neurotransmission may contribute to these side effects. In addition, the enzyme indoleamine 2,3-dioxygenase (IDO), which converts tryptophan into kynurenine, may play an important role, first, because IDO activation leads to reduced levels of tryptophan, the precursor of serotonin (5-HT), and thus to reduced central 5-HT synthesis. Second, kynurenine metabolites such as 3-hydroxy-kynurenine (3-OH-KYN) and quinolinic acid (QUIN) have toxic effects on brain function. 3-OH-KYN is able to produce oxidative stress by increasing the production of reactive oxygen species (ROS), and QUIN may produce overstimulation of hippocampal N-methyl-D-aspartate (NMDA) receptors, which leads to apoptosis and hippocampal atrophy. Both ROS overproduction and hippocampal atrophy caused by NMDA overstimulation have been associated with depression.
Adult ADHD and comorbid disorders: clinical implications of a dimensional approach (2017)

Attention-deficit/hyperactivity disorder (ADHD) in the adult population is frequently associated with comorbid psychiatric diseases that complicate its recognition, diagnosis and management.The prevalence of ADHD in the general adult population is 2.5% and it is associated with substantial personal and individual burden. The most frequent comorbid psychopathologies include mood and anxiety disorders, substance use disorders, and personality disorders. There are strong familial links and neurobiological similarities between ADHD and the various associated psychiatric comorbidities. The overlapping symptoms between ADHD and comorbid psychopathologies represent challenges for diagnosis and treatment. Guidelines recommend that when ADHD coexists with other psychopathologies in adults, the most impairing condition should generally be treated first.Early recognition and treatment of ADHD and its comorbidities has the potential to change the trajectory of psychiatric morbidity later in life. The use of validated assessment scales and high-yield clinical questions can help identify adults with ADHD who could potentially benefit from evidence-based management strategies.
Risk factors of renal failure progression two years prior to dialysis. (1999)

Diastolic hypertension and low protidemia are the 2 most important factors predicting progression of renal failure. A predictive synergy was furthermore pointed out between low protidemia or diastolic hypertension with proteinuria and cholesterol. On the contrary anemia attenuates progression linked to low protidemia, diastolic hypertension, proteinuria and high cholesterol.
Production of Chimeric Pigs and the Analysis of Chimerism using Mitochondrial Deoxyribonucleic Acid as a Cell Marker (1994)

Two injection methods were examined for making chimeras between Chinese pigs (Meishan) and European pigs (Landrace or Landrace x Large White). Furthermore, mitochondrial DNA (mtDNA) polymorphism was detected as a cell marker for the analysis of chimerism. In the first experiment, blastomeres were transplanted into embryos at the 4-16-cell stage. Of 41 transplanted embryos transferred into 3 females, 12 were single-colored, but no overt chimeras were obtained. Judging from coat color and mtDNA in white blood cells, 2 piglets in 2 litters were derived from injected blastomeres, and 10 piglets in 3 litters were derived from recipient blastomeres. In the second experiment, inner cell mass cells of Day 6 Landrace embryos were injected into blastocoels of Day 6 Meishan embryos. Of 35 injected embryos transferred into 3 females, 2 overt chimeras of each sex were obtained in a single litter. In the overt male chimera, mtDNA clearly showed chimerism in spleen, pancreas, brain, kidney, lung, liver, heart, testis, and small intestine. The overt female chimera showed chimerism not only in blood but also in germ line according to a progeny test. No chimerism was detected in any of the 21 single-colored piglets in the second experiment.
Synthesis of 4-Hydroxy-1H-indole-2-carbonitrile via a Vinylnitrene Cyclization (1991)

Abstract Literature methods to prepare 1 failed and a reaction sequence was developed to prepare 4-hydroxy-1H-indole-2-carbonitrile (1) by means of an azide decomposition to form the indole ring. The 2-cyano functionality could not be introduced directly but was derived by functionalization of an ester.
Database correlation method for GSM location (2002)

Cellular location methods based on angle of arrival (AOA) or time difference (e.g. E-OTD) measurements assume line-of-sight propagation between base stations and the mobile station. This assumption is not valid in urban microcellular environments. We present a database correlation method (DCM) that can utilize any location-dependent signals available in cellular systems. This method works best in densely built urban areas. An application of DCM to GSM, using signal strength measurements, is described and trial results from urban and suburban environments are given. Comparison with AOA and E-OTD trials shows that DCM is a competitive alternative for GSM location in urban and suburban environments.
Model-informed COVID-19 vaccine prioritization strategies by age and serostatus (2021)

Limited initial supply of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine raises the question of how to prioritize available doses. We used a mathematical model to compare five age-stratified prioritization strategies. A highly effective transmission-blocking vaccine prioritized to adults ages 20 to 49 years minimized cumulative incidence, but mortality and years of life lost were minimized in most scenarios when the vaccine was prioritized to adults greater than 60 years old. Use of individual-level serological tests to redirect doses to seronegative individuals improved the marginal impact of each dose while potentially reducing existing inequities in COVID-19 impact. Although maximum impact prioritization strategies were broadly consistent across countries, transmission rates, vaccination rollout speeds, and estimates of naturally acquired immunity, this framework can be used to compare impacts of prioritization strategies across contexts.
HIV Drug Resistance (1993)

Since the spread of tobacco from the Americas hundreds of years ago, tobacco cigarettes and, more recently, alternative tobacco products have become global products of nicotine addiction. Within the evolving alternative tobacco product space, electronic ...Read More
Minisatellite binding protein Msbp-1 is a sequence-specific single-stranded DNA-binding protein (1991)

Msbp-1 is a minisatellite-specific DNA-binding protein. Using synthetic binding substrates, we now show that Msbp-1 binds not to double-stranded DNA, but exclusively to single-stranded DNA. Binding is specific to the guanine-rich strand of the minisatellite duplex, interactions with the cytosine-rich strand being undetectable by southwestern analysis. Furthermore, the binding site required for successful DNA-protein interactions appears to be two or more minisatellite repeat units. We have also isolated, by whole-genome PCR and cloning, one Msbp-1 binding site from the human genome. Again, the binding strand of this molecule contains a repetitive G-rich structure equivalent to that of a small minisatellite. These observations are discussed with respect to other single-stranded DNA-binding proteins known to play a role in recombination processes.
ApoC-III gene polymorphisms and risk of coronary artery disease (2002)

Several polymorphisms in the apolipoprotein C-III (apoC-III) gene have been associated with hypertriglyceridemia, but the link with coronary artery disease risk is still controversial. In particular, apoC-III promoter sequence variants in the insulin responsive element (IRE), constitutively resistant to downregulation by insulin, have never been investigated in this connection. We studied a total of 800 patients, 549 of whom had angiographically documented coronary atherosclerosis, whereas 251 had normal coronary arteriograms. We measured plasma lipids, insulin, apoA-I, apoB, and apoC-III and assessed three polymorphisms in the apoC-III gene, namely, T-455C in the IRE promoter region, C1100T in exon 3, and Sst1 polymorphic site (S1/S2) in the 3' untranslated region. Each variant influenced triglyceride levels, but only the T-455C (in homozygosity) and S2 alleles influenced apoC-III levels. In coronary artery disease (CAD) patients, 18.6% were homozygous for the -455C variant compared with only 9.2% in CAD-free group (P < 0.001). In logistic regression models, homozygosity for -455C variant was associated with a significantly increased risk of CAD (OR = 2.5 and 2.18 for unadjusted and adjusted models, respectively) suggesting that it represents an independent genetic susceptibility factor for CAD.