gebhart/patrepeval huggingface dataset:
Negative regulators of T‐cell activation: potential targets for therapeutic intervention in cancer, autoimmune disease, and persistent infections (2009)

The generation of productive adaptive immune responses depends on the antigen-specific activation of T and B cells. The outcome of T-cell receptor engagement is influenced by signals from both positive and negative regulatory molecules that can either activate or inhibit T-cell function. CD28 and cytotoxic T-lymphocyte antigen-4 are the prototypical members of an immunoglobulin domain-containing protein family that play important roles in the control of T-cell responses against infection, cancer, and in autoimmune disease. Although the precise molecular details of their functions are still under active investigation, tumors and chronic pathogens seem to have exploited these pathways to achieve immune evasion. Furthermore, malfunction of the inhibitory arm of the immune response appears responsible for the development of multiple autoimmune pathologies. As a result, the negative regulators of T-cell activation have become attractive targets for therapeutic intervention in cancer, chronic infection, and autoimmune disease. The application of findings from basic research has provided insight into the manipulation of these pathways in the clinic and offers promising strategies for the treatment of disease.
Human Fibrin Is a Physiologic Delivery System for Bone Morphogenetic Protein (1988)

To investigate a physiologic delivery system, bone morphogenetic protein (BMP) in a carrier of other bone matrix noncollagenous proteins (BMP/NCP) was implanted as a composite of a fibrin clot in the thigh of a mouse. Comparable amounts of BMP/NCP alone and fibrin alone were implanted as controls. New bone yields were measured by random point analysis using a video camera and computer system and by ash weight measurement. Histologic examinations, beginning as early as three to seven days postimplantation, showed more extensive proliferation of mesenchymal cells in response to the composite than to lyophilized BMP alone. Correlated microradiographic and histologic observations showed that the composite also produced larger volumes of new bone than the BMP control group. The composite produced approximately three times more bone than BMP alone, and the difference was consistent and statistically significant. Lyophilized pellets of a composite of fibrin and BMP, prepared as volume control implants, also showed more new bone formation than the BMP alone, but the differences were less than with the wet clot composites. The relatively high yields of new bone from both wet clot and lyophilized composites suggest that the fibrin clot may perform an immunochemical function and act as a distributor of BMP. A human fibrin delivery system for BMP warrants further investigation for reconstructive orthopedic operations.
Covalent stabilization of nanostructures: Robust block copolymer templates from novel thermoreactive systems (2005)

Abstract Structurally robust block copolymer templates with feature sizes of approximately 10 nm were prepared from functionalized poly(methyl methacrylate)‐ b ‐polystyrene block copolymers. By the inclusion of benzocyclobutene crosslinking groups in the polystyrene block, the covalent stabilization of thin films to both thermal treatment and solvent exposure became possible. In addition, the crosslinking of the poly(styrene‐benzocyclobutene) domains at 220 °C, followed by the removal of poly(methyl methacrylate), provided a robust, crosslinked nanostructure with greater processing and fabrication potential. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1028–1037, 2005
Fertilization and early embryology: Isolation and culture of inner cell mass cells from human blastocysts (1994)

Totipotent non-committed inner cell mass (ICM) cells from human blastocyts, if demonstrated to be capable of proliferating in vitro without differentiation, will have several beneficial uses, not only in the treatment of neurodegenerative and genetic disorders, but also as a model in studying the events involved in embryogenesis and genomic manipulation. Nine patients admitted to an in-vitro fertilization programme donated 21 spare embryos for this study. All 21 embryos were grown from the 2-pronuclear until blastocyst stages on a human tubal epithelial monolayer in commercial Earle's medium (Medicult, Denmark) supplemented with 10% human serum. The medium was changed after blastocyst formation to Chang's medium supplemented with 1000 units/ml of human leukaemia inhibitory factor (HLIF) and the embryos left undisturbed for 72 h to allow the hatched ICM and trophoblast to attach to the feeder monolayer. Nineteen of the 21 embryos from nine patients produced healthy ICM lumps which could be separated and grown in vitro. Two of the lumps differentiated into fibroblasts while the remaining 17 (eight patients) produced cells with typical stem cell-like morphology, were alkaline phosphatase positive and could be maintained for two passages. It was possible to retain the stem cell-like morphology, alkaline phosphatase positiveness and normal karyotype through the two passages in all of them using repeated doses of HLIF every 48 to 72 h. This is the first report on the successful isolation of human ICM cells and their continued culture for at least two passages in vitro.
Substituenteneffekte auf die CC‐Bindungsstärke, 3. Die thermische Stabilität 2,2‐disubstituierter Malononitrile (1983)

Abstract Die Produkte, die Geschwindigkeitskonstanten und die Aktivierungsparameter des homolytischen thermischen Zerfalls der substituierten Malononitrile 8a – e wurden bestimmt. Es wurde eine lineare Beziehung zwischen den freien Aktivierungsenthalpien Δ G ≠ (300°C) der Thermolyse und den durch Kraftfeldrechnungen (MM2‐Kraftfeld) errechneten Spannungsenthalpien H sp von 8 festgestellt. Aus dem Vergleich dieser Beziehung mit der entsprechenden Korrelation von C q C q ‐Alkanen 8) ergibt sich für 1,1‐Dicyanalkylradikale 10 eine Resonanzenergie von 9.2 kcal mol −1 . Die Beziehungen zwischen den Spannungsenthalpien von 8 und den Strukturen sowie den Rotationsbarrieren werden diskutiert.
SYSTEMIC LUPUS ERYTHEMATOSUS AND ABDOMINAL PAIN (1983)

Abdominal pain is a common symptom in systemic lupus erythematosus. We report two patients with recurrent severe attacks of abdominal pain, often necessitating hospital admission, which were not diagnosed until laparotomy. In one an active arteritis of the mesenteric arteries was seen, with infarction of the jejunum and ileum, and in the second infarction of the ileum with haemorrhage and conglutination of red cells, but no true arteritis.
Stimulation of collagen secretion by relaxin and effect of oestrogen on relaxin binding in uterine cervical cells of pigs (1993)

The role of relaxin and oestrogen in the remodelling of connective tissue was investigated by testing collagenase-dispersed cells (3 x 10(5) cells per well) from the uterine cervix of gilts for relaxin binding and collagen secretion. Relaxin-binding sites on these cells were quantified by specific binding of a saturating dose of 125I-labelled monotyrosyl relaxin at optimal conditions. Oestrogen at doses from 0.4 to 50 ng ml-1 increased relaxin binding in a time- and dose-dependent manner. Scatchard plot analysis exhibited curvilinearity, which suggested two classes of relaxin-binding sites. The addition of relaxin (0, 100, 500 ng ml-1) alone (P < 0.05) or in combination with oestrogen (oestradiol benzoate: 0, 50, 250 ng ml-1) increased protein secretion into the culture medium. Hydroxyproline concentration (as an index of collagen) in the medium was increased (P < 0.05) only in the presence of both relaxin and oestrogen. Actinomycin D (500 ng ml-1) and cycloheximide (500 ng ml-1) inhibited hydroxyproline secretion induced by combined relaxin and oestrogen treatment. Dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cAMP: 0, 0.1, 1.0, 5.0 mmol l-1) was a potent stimulator of hydroxyproline secretion. These results indicate that relaxin, probably via a cAMP pathway, stimulates hydroxyproline secretion in the presence of oestrogen through a protein- and RNA-synthesis dependent process. Oestrogen plays a role in augmenting the sensitivity of uterine cervical cells to relaxin in the pig.
Adenosine instead of supranormal potassium in cardioplegic solution improves cardioprotection (2007)

Adenosine instead of supranormal potassium in cold crystalloid cardioplegia gives satisfactory cardiac arrest, improves post cardioplegic left ventricular systolic function and efficiency, and attenuates myocardial cell damage.
The tertiary amide as an effective director of ortho lithiation (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe tertiary amide as an effective director of ortho lithiationPeter Beak and Roger A. BrownCite this: J. Org. Chem. 1982, 47, 1, 34–46Publication Date (Print):January 1, 1982Publication History Published online1 May 2002Published inissue 1 January 1982https://pubs.acs.org/doi/10.1021/jo00340a008https://doi.org/10.1021/jo00340a008research-articleACS PublicationsRequest reuse permissionsArticle Views2804Altmetric-Citations183LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
A Method to Reduce Errors of String Recognition Based on Combination of Several Recognition Results with Per-Character Alternatives (2019)

We consider the problem on recognition of a string object presented in several video stream frames. In order to maximize the output accuracy, we combine several results of the recognition. To this end, we consider a model of result of a string object recognition. The model takes into account the estimations of alternative results of per-character classification. Also, we propose an algorithm to combine results of a string recognition according to this model. The algorithm was evaluated on a MIDV-500 dataset of document images. The experimental results show that the proposed algorithm allows to achieve the high accuracy of recognition result due to an analysis of several images, and the use of the estimations of alternative results of per-character classification gives the higher results then a combination of strings that contain only the final alternatives of each character.
Quantum dynamics of bond breaking in a dissipative environment: Indirect and direct photodesorption of neutrals from metals (1996)

The dynamics of uv/visible laser-induced nonthermal desorption of neutral molecules from metal surfaces are studied by Liouville–von Neumann equations for quantum open systems. A one-dimensional, two-state Gadzuk–Antoniewicz model is adopted, representative for NO/Pt(111). Electronic quenching due to coupling of the adsorbate negative ion resonance to the metal electrons is treated within the Lindblad dynamical semigroup approach. Both indirect (hot-electron mediated) and hypothetical direct (dipole) excitation processes are considered. For the indirect pathways, DIET (single-excitation) and DIMET (multiple-excitation) limits are studied using one- and double-dissipative channel models, respectively. To reproduce experimental desorption yields and desorbate translational energies, we estimate the quenching lifetime for NO/Pt(111) to be less than 5 fs. We also extend previous quantum treatments of photodesorption processes to the case of coordinate-dependent quenching rates. Further, the characteristic scaling laws of desorption yields versus laser fluence are derived for each of the individual excitation pathways. Finally, the possibility to control photoreactivity at surfaces by different, vibration-promoted schemes (surface heating, ir+uv two-photon strategies, use of pulsed uv lasers) is examined.
METAL: fast and efficient meta-analysis of genomewide association scans (2010)

METAL, including source code, documentation, examples, and executables, is available at http://www.sph.umich.edu/csg/abecasis/metal/.
Restricted expression of Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genes in Kaposi sarcoma. (1996)

Kaposi sarcoma (KS) is the leading neoplasm of HIV-infected patients and is also found in several HIV-negative populations. Recently, DNA sequences from a novel herpesvirus, termed KS-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV-8) have been identified within KS tissue from both HIV-positive and HIV-negative cases; infection with this agent has been proposed as a possible factor in the etiology or pathogenesis of the tumor. Here we have examined the pattern of KSHV/HHV-8 gene expression in KS and find it to be highly restricted. We identify and characterize two small transcripts that represent the bulk of the virus-specific RNA transcribed from over 120 kb of the KSHV genome in infected cells. One transcript is predicted to encode a small membrane protein; the other is an unusual polyadenylylated RNA that accumulates in the nucleus to high copy number. This pattern of viral gene expression suggests that most infected cells in KS are latently infected, with lytic viral replication likely restricted to a much smaller subpopulation of cells. These findings have implications for the therapeutic utility of currently available antiviral drugs targeted against the lytic replication cycle.
Prevalence of Acid-Reducing Agents (ARA) in Cancer Populations and ARA Drug–Drug Interaction Potential for Molecular Targeted Agents in Clinical Development (2013)

Acid-reducing agents (ARAs) are the most commonly prescribed medications in North America and Western Europe. There are currently no data describing the prevalence of their use among cancer patients. However, this is a paramount question due to the potential for significant drug-drug interactions (DDIs) between ARAs, most commonly proton pump inhibitors (PPIs), and orally administered cancer therapeutics that display pH-dependent solubility, which may lead to decreased drug absorption and decreased therapeutic benefit. Of recently approved orally administered cancer therapeutics, >50% are characterized as having pH-dependent solubility, but there are currently no data describing the potential for this ARA-DDI liability among targeted agents currently in clinical development. The objectives of this study were to (1) determine the prevalence of ARA use among different cancer populations and (2) investigate the prevalence of orally administered cancer therapeutics currently in development that may be liable for an ARA-DDI. To address the question of ARA use among cancer patients, a retrospective cross-sectional analysis was performed using two large healthcare databases: Thomson Reuters MarketScan (N = 1,776,443) and the U.S. Department of Veterans Affairs (VA, N = 1,171,833). Among all cancer patients, the total prevalence proportion of ARA use (no. of cancer patients receiving an ARA/total no. of cancer patients) was 20% and 33% for the MarketScan and VA databases, respectively. PPIs were the most commonly prescribed agent, comprising 79% and 65% of all cancer patients receiving a prescription for an ARA (no. of cancer patients receiving a PPI /no. of cancer patients receiving an ARA) for the MarketScan and VA databases, respectively. To estimate the ARA-DDI liability of orally administered molecular targeted cancer therapeutics currently in development, two publicly available databases, (1) Kinase SARfari and (2) canSAR, were examined. For those orally administered clinical candidates that had available structures, the pKa's and corresponding relative solubilities were calculated for a normal fasting pH of 1.2 and an "ARA-hypochlorhydric" pH of 4. Taking calculated pKa's and relative solubilities into consideration, clinical candidates were classified based on their risk for an ARA-DDI. More than one-quarter (28%) of the molecules investigated are at high risk for an ARA-DDI, and of those high risk molecules, nearly three-quarters (73%) are being clinically evaluated for at least one of five cancer types with the highest prevalence of ARA use (gastrointestinal, pancreatic, lung, glioblastoma multiforme, gastrointestinal stromal tumor (GIST)). These data strongly suggest that with the clinical development of ARA-DDI-susceptible cancer therapeutics will come continued challenges for drug-development scientists, oncologists, and regulatory agencies in ensuring that patients achieve safe and efficacious exposures of their cancer therapeutics and thus optimal patient outcomes.
Low-Dose Angiotensin II Increases Glucose Disposal Rate During Euglycemic Hyperinsulinemia (1993)

To study the metabolic effects of angiotensin II we examined the glucose disposal rate and calf blood flow in healthy men (n = 39) during euglycemic hyperinsulinemia followed by a period with simultaneous angiotensin II infusion at a low dose (0.1 ng/kg/min). Angiotensin II infusion abruptly increased the glucose disposal rate significantly as compared with glucose disposal rate during euglycemic hyperinsulinemia only. There were no differences in blood glucose or plasma insulin between the euglycemic hyperinsulinemic and the angiotensin II infusion period. During hyperinsulinemia alone, blood pressure was unchanged while calf muscle blood flow increased significantly as compared with the baseline period, while during the angiotensin infusion the systolic blood pressure increased and calf blood flow decreased significantly as compared with the hyperinsulinemic period. We conclude that angiotensin II within physiological range stimulates insulin-mediated glucose uptake in healthy men. The mechanisms are, however, unclear, but changes in blood flow are probably not responsible for the observed effects.
Massive Electrostatic Effects on Heteropolar C–C Disconnections: Transforming a Phenyl Anion into a Potent Leaving Group (2005)

Abstract The SASAPOS protocol – a general reaction sequence which allows the complete exchange of various neutral ligands X in organic, elementorganic, and inorganic systems by cationic ligands L + – has been applied to a small variety of pentafluoro benzene derivatives C 6 F 5 –E (E = –C(O)H, –C(N–Ph)H, –PCl 2 /–P(L + ) 2 , –H) yielding the ion clusters C 6 (L + ) 5 –E (F 3 CSO 3 – ) 5 . The reaction conditions required to observe a heteropolar C–C or C–P disconnection, with a highly stabilized pentakisonio‐substituted phenyl anion as the key intermediate, are specified. When E = H, the latter compound also figures as the key intermediate during H/D exchange under basic conditions. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)
Recent progress in Li-rich layered oxides as cathode materials for Li-ion batteries (2014)

This review systematically summarized Li-rich layered oxides and states the strategies to enhance such materials when used in Li-ion batteries.
Human Cytosolic 3α-Hydroxysteroid Dehydrogenases of the Aldo-keto Reductase Superfamily Display Significant 3β-Hydroxysteroid Dehydrogenase Activity (2004)

The source of NADPH-dependent cytosolic 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity is unknown to date. This important reaction leads e.g. to the reduction of the potent androgen 5alpha-dihydrotestosterone (DHT) into inactive 3beta-androstanediol (3beta-Diol). Four human cytosolic aldo-keto reductases (AKR1C1-AKR1C4) are known to act as non-positional-specific 3alpha-/17beta-/20alpha-HSDs. We now demonstrate that AKR1Cs catalyze the reduction of DHT into both 3alpha- and 3beta-Diol (established by (1)H NMR spectroscopy). The rates of 3alpha- versus 3beta-Diol formation varied significantly among the isoforms, but with each enzyme both activities were equally inhibited by the nonsteroidal anti-inflammatory drug flufenamic acid. In vitro, AKR1Cs also expressed substantial 3alpha[17beta]-hydroxysteroid oxidase activity with 3alpha-Diol as the substrate. However, in contrast to the 3-ketosteroid reductase activity of the enzymes, their hydroxysteroid oxidase activity was potently inhibited by low micromolar concentrations of the opposing cofactor (NADPH). This indicates that in vivo all AKR1Cs will preferentially work as reductases. Human hepatoma (HepG2) cells (which lack 3beta-HSD/Delta(5-4) ketosteroid isomerase mRNA expression, but express AKR1C1-AKR1C3) were able to convert DHT into 3alpha- and 3beta-Diol. This conversion was inhibited by flufenamic acid establishing the in vivo significance of the 3alpha/3beta-HSD activities of the AKR1C enzymes. Molecular docking simulations using available crystal structures of AKR1C1 and AKR1C2 demonstrated how 3alpha/3beta-HSD activities are achieved. The observation that AKR1Cs are a source of 3beta-tetrahydrosteroids is of physiological significance because: (i) the formation of 3beta-Diol (in contrast to 3alpha-Diol) is virtually irreversible, (ii) 3beta-Diol is a pro-apoptotic ligand for estrogen receptor beta, and (iii) 3beta-tetrahydrosteroids act as gamma-aminobutyric acid type A receptor antagonists.
Bilirubin and glutathione have complementary antioxidant and cytoprotective roles (2009)

Glutathione (GSH) and bilirubin are prominent endogenous antioxidant cytoprotectants. Despite tissue levels that are thousands of times lower than GSH, bilirubin is effective because of the biosynthetic cycle wherein it is generated from biliverdin by biliverdin reductase (BVR). When bilirubin acts as an antioxidant, it is oxidized to biliverdin, which is immediately reduced by BVR to bilirubin. Why does the body employ both of these 2 distinct antioxidant systems? We show that the water-soluble GSH primarily protects water soluble proteins, whereas the lipophilic bilirubin protects lipids from oxidation. Mice with deletion of heme oxygenase-2, which generates biliverdin, display greater lipid than protein oxidation, while the reverse holds for GSH depletion. RNA interference depletion of BVR increases oxidation of lipids more than protein. Depletion of BVR or GSH augments cell death in an oxidant-specific fashion.