gebhart/patrepeval huggingface dataset:
A Defect in Tryptophan Catabolism Impairs Tolerance in Nonobese Diabetic Mice (2003)

The predisposition of nonobese diabetic (NOD) mice to develop autoimmunity reflects deficiencies in both peripheral and central tolerance. Several defects have been described in these mice, among which aberrant antigen-presenting cell function and peroxynitrite formation. Prediabetes and diabetes in NOD mice have been targeted with different outcomes by a variety of immunotherapies, including interferon (IFN)-gamma. This cytokine may be instrumental in specific forms of tolerance by virtue of its ability to activate immunosuppressive tryptophan catabolism. Here, we provide evidence that IFN-gamma fails to induce tolerizing properties in dendritic cells from highly susceptible female mice early in prediabetes. This effect is associated with impaired tryptophan catabolism, is related to transient blockade of the Stat1 pathway of intracellular signaling by IFN-gamma, and is caused by peroxynitrite production. However, the use of a peroxynitrite inhibitor can rescue tryptophan catabolism and tolerance in those mice. This is the first report of an experimental autoimmune disease in which defective tolerance is causally linked to impaired tryptophan catabolism.
ATOMIC LAYER DEPOSITION OF SiO2 USING CATALYZED AND UNCATALYZED SELF-LIMITING SURFACE REACTIONS (1999)

SiO 2 thin films were deposited with atomic layer control using self-limiting surface reactions. The SiO 2 growth was achieved by separating the binary reaction SiCl 4 + 2H 2 O → SiO 2 + 4HCl into two half-reactions. Successive application of the half-reactions in an ABAB… sequence produced atomic-layer-controlled SiO 2 deposition. SiO 2 films were grown at temperatures of 600–800 K, with SiCl 4 and H 2 O reactant exposures of ~10 9 L ( 1 L = 10 -6 Torr s). Employing pyridine ( C 5 H 5 N ) as a catalyst, the SiO 2 films could be deposited at much lower temperatures and reactant exposures. The pyridine catalyst lowered the required SiO 2 deposition temperature from 600 K to 300 K and reduced the reactant exposure required for complete reactions from ~10 9 L to ~ 10 4 L. In addition, the SiO 2 growth rates increased from 0.75 Å per AB cycle at 800 K to 2.1 Aring; per AB cycle at 300 K. The deposited films were stoichiometric SiO 2 and were extremely flat, with a roughness nearly identical to the initial substrate surface. The films also displayed dielectric breakdown strengths similar to thermally deposited SiO 2 films. The ability to deposit conformal SiO 2 thin films with atomic layer control over a wide range of temperatures should find numerous applications in thin film device fabrication.
Programmable logic using giant-magnetoresistance and spin-dependent tunneling devices (invited) (2000)

Programmable logic functions may be realized with giant-magnetoresistance or spin-dependent tunneling devices in conjunction with relatively simple circuitry. These functions may be implemented as conventional programmed logic arrays using the magnetic devices as nonvolatile programming elements or as arrays of universal logic gates whereby the core logic functions are magnetically programmed. Both methodologies are described in this article along with rapidly reconfigurable variations that have applications in high performance and adaptive computing. Various design considerations of these schemes are presented along with simulation results of proposed circuits. Among the potential advantages of these magnetic logic devices are nonvolatility of both programming information and data and the ability to reconfigure an entire logic array into any one of a number of configurations in a single clock cycle.
Synthesis of Novel Folic Acid-Functionalized Biocompatible Block Copolymers by Atom Transfer Radical Polymerization for Gene Delivery and Encapsulation of Hydrophobic Drugs (2005)

Two synthetic routes to folic acid (FA)-functionalized diblock copolymers based on 2-(methacryloyloxy)ethyl phosphorylcholine [MPC] and either 2-(dimethylamino)ethyl methacrylate [DMA] or 2-(diisopropylamino)ethyl methacrylate [DPA] were explored. The most successful route involved atom transfer radical polymerization (ATRP) of MPC followed by the tertiary amine methacrylate using a 9-fluorenylmethyl chloroformate (Fmoc)-protected ATRP initiator. Deprotection of the Fmoc groups produced terminal primary amine groups, which were conjugated with FA to produce two series of novel FA-functionalized biocompatible block copolymers. Nonfunctionalized MPC-DMA diblock copolymers have been previously shown to be effective synthetic vectors for DNA condensation; thus, these FA-functionalized MPC-DMA diblock copolymers appear to be well suited to gene therapy applications based on cell targeting strategies. In contrast, the FA-MPC-DPA copolymers are currently being evaluated as pH-responsive micellar vehicles for the delivery of highly hydrophobic anticancer drugs.
The Matter Simulation (R)evolution (2018)

To date, the program for the development of methods and models for atomistic and continuum simulation directed toward chemicals and materials has reached an incredible degree of sophistication and maturity. Currently, one can witness an increasingly rapid emergence of advances in computing, artificial intelligence, and robotics. This drives us to consider the future of computer simulation of matter from the molecular to the human length and time scales in a radical way that deliberately dares to go beyond the foreseeable next steps in any given discipline. This perspective article presents a view on this future development that we believe is likely to become a reality during our lifetime.
Analysis of Mutations in Fibroblast Growth Factor (FGF) and a Pathogenic Mutation in FGF Receptor (FGFR) Provides Direct Evidence for the Symmetric Two-End Model for FGFR Dimerization (2005)

Two competing models for fibroblast growth factor (FGF) receptor (FGFR) dimerization have recently emerged based on ternary FGF-FGFR-heparin crystal structures. In the symmetric two-end model, heparin promotes dimerization of two FGF-FGFR complexes by stabilizing bivalent interactions of the ligand and receptor through primary and secondary sites and by stabilizing direct receptor-receptor contacts. In the asymmetric model, there are no protein-protein contacts between the two FGF-FGFR complexes, which are bridged solely by heparin. To identify the correct mode of FGFR dimerization, we abolished interactions at the secondary ligand-receptor interaction site, which are observed only in the symmetric two-end model, using site-directed mutagenesis. Cellular studies and real-time binding assays, as well as matrix-assisted laser desorption ionization-time of flight analysis, demonstrate that loss of secondary ligand-receptor interactions results in diminished FGFR activation due to decreased dimerization without affecting FGF-FGFR binding. Additionally, structural and biochemical analysis of an activating FGFR2 mutation resulting in Pfeiffer syndrome confirms the physiological significance of receptor-receptor contacts in the symmetric two-end model and provides a novel mechanism for FGFR gain of function in human skeletal disorders. Taken together, the data validate the symmetric two-end model of FGFR dimerization and argue against the asymmetric model of FGFR dimerization.
Controlled Ring-Opening Polymerization of Lactide and Glycolide (2004)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTControlled Ring-Opening Polymerization of Lactide and GlycolideOdile Dechy-Cabaret, Blanca Martin-Vaca, and Didier BourissouView Author Information Laboratoire Hétérochimie Fondamentale et Appliquée du CNRS (UMR 5069), Université Paul Sabatier, 118, route de Narbonne, 31062 Toulouse Cedex 04, France Cite this: Chem. Rev. 2004, 104, 12, 6147–6176Publication Date (Web):October 5, 2004Publication History Received26 April 2004Published online5 October 2004Published inissue 1 December 2004https://pubs.acs.org/doi/10.1021/cr040002shttps://doi.org/10.1021/cr040002sresearch-articleACS PublicationsCopyright © 2004 American Chemical SocietyRequest reuse permissionsArticle Views34594Altmetric-Citations2015LEARN 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 SUBJECTS:Ligands,Monomers,Organic polymers,Plastics,Ring-opening polymerization Get e-Alerts
Linagliptin Improves Insulin Sensitivity and Hepatic Steatosis in Diet-Induced Obesity (2012)

Linagliptin (TRADJENTA™) is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor. DPP-4 inhibition attenuates insulin resistance and improves peripheral glucose utilization in humans. However, the effects of chronic DPP-4 inhibition on insulin sensitivity are not known. The effects of long-term treatment (3-4 weeks) with 3 mg/kg/day or 30 mg/kg/day linagliptin on insulin sensitivity and liver fat content were determined in diet-induced obese C57BL/6 mice. Chow-fed animals served as controls. DPP-4 activity was significantly inhibited (67-89%) by linagliptin (P<0.001). Following an oral glucose tolerance test, blood glucose concentrations (measured as area under the curve) were significantly suppressed after treatment with 3 mg/kg/day (-16.5% to -20.3%; P<0.01) or 30 mg/kg/day (-14.5% to -26.4%; P<0.05) linagliptin (both P<0.01). Liver fat content was significantly reduced by linagliptin in a dose-dependent manner (both doses P<0.001). Diet-induced obese mice treated for 4 weeks with 3 mg/kg/day or 30 mg/kg/day linagliptin had significantly improved glycated hemoglobin compared with vehicle (both P<0.001). Significant dose-dependent improvements in glucose disposal rates were observed during the steady state of the euglycemic-hyperinsulinemic clamp: 27.3 mg/kg/minute and 32.2 mg/kg/minute in the 3 mg/kg/day and 30 mg/kg/day linagliptin groups, respectively; compared with 20.9 mg/kg/minute with vehicle (P<0.001). Hepatic glucose production was significantly suppressed during the clamp: 4.7 mg/kg/minute and 2.1 mg/kg/minute in the 3 mg/kg/day and 30 mg/kg/day linagliptin groups, respectively; compared with 12.5 mg/kg/minute with vehicle (P<0.001). In addition, 30 mg/kg/day linagliptin treatment resulted in a significantly reduced number of macrophages infiltrating adipose tissue (P<0.05). Linagliptin treatment also decreased liver expression of PTP1B, SOCS3, SREBP1c, SCD-1 and FAS (P<0.05). Other tissues like muscle, heart and kidney were not significantly affected by the insulin sensitizing effect of linagliptin. Long-term linagliptin treatment reduced liver fat content in animals with diet-induced hepatic steatosis and insulin resistance, and may account for improved insulin sensitivity.
Substituted 3-phenyl-7H-thiazolo(3,2-b)(1,2,4)triazin-7-ones as antiinflammatory agents with immunomodulating properties. (1989)

After structure-activity relationship studies (SAR) on a novel class of substituted thiazolo(3,2-b)(1,2,4)triazin-7-ones, HWA-131 (3-(3,5-di-tert.butyl-4-hydroxyphenyl)-7H-thiazolo(3,2-b)(1,2,4)triaz in-7-one) was selected for incremental pharmacological investigations. This compound was effective in not only preventing, but also curing established arthritic disorders of rats such as adjuvant and type II collagen arthritis as well as those of mice such as chronic graft-versus-host (CGVH) disease, a model for systemic lupus erythematosus (SLE). Further, this non-immunosuppressive drug effectively inhibited the carrageenan-induced paw oedema, attenuated the active Arthus reaction, and demonstrated antierythema as well as antipyretic activity. Part of the antiinflammatory effects of this new compound is most probably related to its antioxidative activity, as well as inhibition of lipoxygenase metabolites. HWA-131's good gastric tolerance may have to do with its limited ability to inhibit the production of cyclooxygenase metabolites. Based on our data, we are sure that HWA-131 will be an effective nonsteroidal antiinflammatory agent, with immunomodulating properties, to combat human autoimmune disorders.
Comparison of OPO and Mark-III FEL for tissue ablation at 6.45 μm (2002)

We have investigated the experimental consequences of two picosecond infrared lasers, both tuned to 6.45micrometers and focused on ocular tissue. The exposure conditions were comparable, other than pulse repetition rate, where an optical parametric oscillator/amplifier laser (OPA) system operates at a kilohertz and the Mark-III FEL at 3 gigahertz. In both cases, the peak intensity was near 2x10<SUP>14</SUP> W/m<SUP>2</SUP> and the total delivered energy was approximately 125 mJ. The Mark-III consistently ablates tissue, while the OPA fails to ablate or to damage corneal tissue. In particular, there is no experimental evidence for protein denaturation due to OPA irradiation. WE account for these observations in terms of a theoretical model based on thermal diffusion and threshold conditions for superheating and chemical kinetics. We comment on the relevance of tissue geometry.
Expression and Function of Myostatin in Obesity, Diabetes, and Exercise Adaptation (2011)

Myostatin is a member of the transforming growth factor-β/bone morphogenetic protein (TGF-β/BMP) superfamily of secreted factors that functions as a potent inhibitor of skeletal muscle growth. Moreover, considerable evidence has accumulated that myostatin also regulates metabolism and that its inhibition can significantly attenuate the progression of obesity and diabetes. Although at least part of these effects on metabolism can be attributable to myostatin's influence over skeletal muscle growth and therefore on the total volume of metabolically active lean body mass, there is mounting evidence that myostatin affects the growth and metabolic state of other tissues, including the adipose and the liver. In addition, recent work has explored the role of myostatin in substrate mobilization, uptake, and/or utilization of muscle independent of its effects on body composition. Finally, the effects of both endurance and resistance exercise on myostatin expression, as well as the potential role of myostatin in the beneficial metabolic adaptations occurring in response to exercise, have also begun to be delineated in greater detail. The purpose of this review was to summarize the work to date on the expression and function of myostatin in obesity, diabetes, and exercise adaptation.
Differing effects of right ventricular pacing and left bundle branch block on left ventricular function. (1993)

The left ventricle seems to be activated much more rapidly with right ventricular pacing than with left bundle branch block. This applies even when left bundle branch block is present before pacing. Electromechanical delay, contraction and relaxation times, and extent of incoordinate ventricular wall motion differ strikingly between the two conditions. The use of right ventricular pacing as an experimental model of left bundle branch block in humans must be re-examined.
Hyperbranched fluoropolymer and linear poly(ethylene glycol) based amphiphilic crosslinked networks as efficient antifouling coatings: An insight into the surface compositions, topographies, and morphologies (2004)

Abstract Polymer coatings with features of differing hydrophilicity, mobility, and topography, distributed across a substrate in microscopic and nanoscopic patches were designed as complex materials equipped with sufficient variability in composition, structure, and dynamics to inhibit interactions associated with biomacromolecular fouling. These complex polymer coatings were prepared by the in situ phase separation and crosslinking of mixtures of hyperbranched fluoropolymer (HBFP) and diamino‐terminated poly(ethylene glycol) (PEG), for which the degree of crosslinking, compositions, topographies, and morphologies were varied by alteration of the PEG/HBFP stoichiometries (14, 29, 45, and 55 wt % PEG). This article examines the physicochemical details of HBFP–PEG network coatings prepared on glass substrates, functionalized by 3‐aminopropyltriethoxysilane, as characterized by atomic force microscopy (AFM), contact‐angle measurements, X‐ray photoelectron spectroscopy (XPS), differential scanning calorimetry (DSC), and thermogravimetric analysis. Upon incubation in water or artificial seawater, the surfaces underwent reconstruction, which was believed to be driven by the swelling of the PEG domains and the energetic favorability offered by the segregation of PEG to the solid–water interface. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 6193–6208, 2004
Cytogenetic studies of familial and sporadic Alzheimer disease (1981)

We present cytogenetic findings in 7 familial and 5 sporadic Alzheimer disease (AD) patients and 34 unaffected relatives, spouses, and normal controls. Our study was prompted by reports of increased chromosome abnormalities in patients and family members at risk for AD. Coded peripheral blood chromosome preparations were evaluated for aneuploidy, aberration rates, and banding patterns. Statistical analyses of our results showed no increase in aneuploidy or aberrations in AD patients, their relatives, or normals. Chromosome loss or gain in aneuploid cells was not specific except in two individuals. These two older persons studied, one with AD and one unaffected, were observed to have increased sex chromosome aneuploidy. This finding was attributed to aging and was not considered to be an effect of AD.
Directed regiospecificity of 1,3‐dipolar cycloaddition of 2‐diazopropane to 4‐ and 5‐substituted pyridazin‐3(2H)‐ones (1991)

Abstract 6‐Methoxy‐2‐methylpyridazin‐3(2 H )‐one ( 1 ) gave with 2‐diazopropane ( 8 ) a mixture of 3 H ‐pyrazolo[3,4‐ d ]‐pyridazin‐4(5 H )‐one derivative 12 , as the main product, and ‐7(6 H )‐one derivative 10 , as the minor product. On the other hand, 4‐substituted pyridazin‐3(2 H )‐ones 2, 3 , and 4 gave 3 H ‐pyrazolo[3,4‐ d ]pyridazin‐7(6 H )‐one 10 , exclusively, while 5‐substituted pyridazin‐3(2 H )‐ones 5, 6 , and 7 produced only the isomeric 3 H ‐pyrazolo[3,4‐ H ]pyridazin‐4(5 H )‐one 12 . The 5‐phenylsulfonyl derivative 13 gave with 8 by elimination of a molecule of nitrogen, followed by rearrangement, 1,2‐diazepine derivative 15 and with an excess of 8 3 H ‐pyrazolo[3,4‐ d ][1,2]diazepine derivative 16. 1 ,2‐Dimethylpyridazine‐3,6‐(1 H ,2 H )‐dione and its derivatives 18 and 19 produced 3 H ‐pyrazolo[3,4‐ d ]pyridazine‐4,7(5 H ,6 H )‐dione derivative 23 , while from 17 and 1‐diazoindane ( 24 ) the spiro compound 27 was obtained. The 1,2‐dihydro and 3a,7a‐dihydro intermediates 21 and 25 were isolated.
Impaired negative feedback suppression of bile acid synthesis in mice lacking βKlotho (2005)

We have generated a line of mutant mouse that lacks betaKlotho, a protein that structurally resembles Klotho. The synthesis and excretion of bile acids were found to be dramatically elevated in these mutants, and the expression of 2 key bile acid synthase genes, cholesterol 7alpha-hydroxylase (Cyp7a1) and sterol 12alpha-hydroxylase (Cyp8b1), was strongly upregulated. Nuclear receptor pathways and the enterohepatic circulation, which regulates bile acid synthesis, seemed to be largely intact; however, bile acid-dependent induction of the small heterodimer partner (SHP) NR0B2, a common negative regulator of Cyp7a1 and Cyp8b1, was significantly attenuated. The expression of Cyp7a1 and Cyp8b1 is known to be repressed by dietary bile acids via both SHP-dependent and -independent regulations. Interestingly, the suppression of Cyp7a1 expression by dietary bile acids was impaired, whereas that of Cyp8b1 expression was not substantially altered in betaklotho mice. Therefore, betaKlotho may stand as a novel contributor to Cyp7a1-selective regulation. Additionally, betaKlotho-knockout mice exhibit resistance to gallstone formation, which suggests the potential future clinical relevance of the betaKlotho system.
Collaborative Brushing and Linking for Co‐located Visual Analytics of Document Collections (2009)

Abstract Many real‐world analysis tasks can benefit from the combined efforts of a group of people. Past research has shown that to design visualizations for collaborative visual analytics tasks, we need to support both individual as well as joint analysis activities. We present Cambiera, a tabletop visual analytics tool that supports individual and collaborative information foraging activities in large text document collections. We define collaborative brushing and linking as an awareness mechanism that enables analysts to follow their own hypotheses during collaborative sessions while still remaining aware of the group's activities. With Cambiera, users are able to collaboratively search through documents, maintaining awareness of each others' work and building on each others' findings.
Adaptive dielectric liquid lens (2008)

A tunable-focus liquid lens using dielectrophoretic effect is demonstrated. When a voltage is applied to a dielectric liquid droplet, the generated electric field inside the droplet is inhomogeneous. As a result, the liquid bears a dielectric force and its surface profile can be reshaped which causes the focal length to change. Adaptive lenses with different apertures are fabricated and their performances evaluated. In comparison to the patterned-electrode liquid lenses, our lens uses continuous electrode which is much simpler for fabrication.
Beyond heuristics (2010)

The security demands on modern system administration are enormous and getting worse. Chief among these demands, administrators must monitor the continual ongoing disclosure of software vulnerabilities that have the potential to compromise their systems in some way. Such vulnerabilities include buffer overflow errors, improperly validated inputs, and other unanticipated attack modalities. In 2008, over 7,400 new vulnerabilities were disclosed--well over 100 per week. While no enterprise is affected by all of these disclosures, administrators commonly face many outstanding vulnerabilities across the software systems they manage. Vulnerabilities can be addressed by patches, reconfigurations, and other workarounds; however, these actions may incur down-time or unforeseen side-effects. Thus, a key question for systems administrators is which vulnerabilities to prioritize. From publicly available databases that document past vulnerabilities, we show how to train classifiers that predict whether and how soon a vulnerability is likely to be exploited. As input, our classifiers operate on high dimensional feature vectors that we extract from the text fields, time stamps, cross references, and other entries in existing vulnerability disclosure reports. Compared to current industry-standard heuristics based on expert knowledge and static formulas, our classifiers predict much more accurately whether and how soon individual vulnerabilities are likely to be exploited.