gebhart/patrepeval huggingface dataset:
The 2′-Trifluoromethyl Analogue of Indomethacin Is a Potent and Selective COX-2 Inhibitor (2013)

Indomethacin is a potent, time-dependent, nonselective inhibitor of the cyclooxygenase enzymes (COX-1 and COX-2). Deletion of the 2'-methyl group of indomethacin produces a weak, reversible COX inhibitor, leading us to explore functionality at that position. Here, we report that substitution of the 2'-methyl group of indomethacin with trifluoromethyl produces CF<sub>3</sub>-indomethacin, a tight-binding inhibitor with kinetic properties similar to those of indomethacin and unexpected COX-2 selectivity (IC<sub>50</sub> mCOX-2 = 267 nM; IC<sub>50</sub> oCOX-1 > 100 μM). Studies with site-directed mutants reveal that COX-2 selectivity results from insertion of the CF<sub>3</sub> group into a small hydrophobic pocket formed by Ala-527, Val-349, Ser-530, and Leu-531 and projection of the methoxy group toward a side pocket bordered by Val-523. CF<sub>3</sub>-indomethacin inhibited COX-2 activity in human head and neck squamous cell carcinoma cells and exhibited in vivo anti-inflammatory activity in the carrageenan-induced rat paw edema model with similar potency to that of indomethacin.
The QseC sensor kinase: A bacterial adrenergic receptor (2006)

Quorum sensing is a cell-to-cell signaling mechanism in which bacteria respond to hormone-like molecules called autoinducers (AIs). The AI-3 quorum-sensing system is also involved in interkingdom signaling with the eukaryotic hormones epinephrine/norepinephrine. This signaling activates transcription of virulence genes in enterohemorrhagic Escherichia coli O157:H7. However, this signaling system has never been shown to be involved in virulence in vivo, and the bacterial receptor for these signals had not been identified. Here, we show that the QseC sensor kinase is a bacterial receptor for the host epinephrine/norepinephrine and the AI-3 produced by the gastrointestinal microbial flora. We also found that an alpha-adrenergic antagonist can specifically block the QseC response to these signals. Furthermore, we demonstrated that a qseC mutant is attenuated for virulence in a rabbit animal model, underscoring the importance of this signaling system in virulence in vivo. Finally, an in silico search found that the periplasmic sensing domain of QseC is conserved among several bacterial species. Thus, QseC is a bacterial adrenergic receptor that activates virulence genes in response to interkingdom cross-signaling. We anticipate that these studies will be a starting point in understanding bacterial-host hormone signaling at the biochemical level. Given the role that this system plays in bacterial virulence, further characterization of this unique signaling mechanism may be important for developing novel classes of antimicrobials.
All-trans-retinoic acid: what is it good for? (1992)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1992.10.11.1659 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 1403047 All-trans-retinoic acid: what is it good for? R P Warrell JrxR P Warrell JrSearch for articles by this author https://doi.org/10.1200/JCO.1992.10.11.1659 First Page PDF © 1992 by American Society of Clinical Oncology
Allosteric modulation of the muscarinic M 4 receptor as an approach to treating schizophrenia (2008)

Current antipsychotics provide symptomatic relief for patients suffering from schizophrenia and related psychoses; however, their effectiveness is variable and many patients discontinue treatment due to side effects. Although the etiology of schizophrenia is still unclear, a leading hypothesis implicates an imbalanced dopaminergic system. Muscarinic acetylcholine (ACh) receptors regulate dopamine levels in key areas of the brain involved in psychosis, with the M(4) subtype emerging as a key regulator of dopaminergic hyperactivity. Unfortunately, no selective small molecule tools exist to provide pharmacological validation of this hypothesis. Here, we describe the discovery of a small molecule modulator, LY2033298, that is highly selective for human M(4) receptors by virtue of targeting an allosteric site on this receptor. Pharmacological assays confirmed the selectivity of LY2033298 for the M(4) receptor and revealed the highest degree of positive allosteric enhancement of ACh potency thus far identified. Radioligand binding assays also show this compound to directly potentiate agonist binding while having minimal effects on antagonist binding. Mutational analysis identified a key amino acid (D(432)) in the third extracellular loop of the human M(4) receptor to be critical for selectivity and agonist potentiation by LY2033298. Importantly, LY2033298 was active in animal models predictive of clinical antipsychotic drug efficacy indicating its potential use as a first-in-class, selective, allosteric muscarinic antipsychotic agent.
Computational Color Constancy: Survey and Experiments (2011)

Computational color constancy is a fundamental prerequisite for many computer vision applications. This paper presents a survey of many recent developments and state-of-the-art methods. Several criteria are proposed that are used to assess the approaches. A taxonomy of existing algorithms is proposed and methods are separated in three groups: static methods, gamut-based methods, and learning-based methods. Further, the experimental setup is discussed including an overview of publicly available datasets. Finally, various freely available methods, of which some are considered to be state of the art, are evaluated on two datasets.
FAST EDGE-DIFFRACTION FOR SOUND PROPAGATION IN COMPLEX VIRTUAL ENVIRONMENTS (2009)

We present an algorithm for fast computation of diffraction paths for geometric-acoustics in complex environments based on the UTD formulation. Our method extends ray-frustum tracing to efficiently compute paths in the shadow region caused by long diffracting edges. Our approach can handle general scenes with moving sources, receivers, and dynamic objects. We evaluate the accuracy through comparisons with physically validated geometric simulations. In practice, our edge diffraction algorithm can perform sound propa-gation at nearly interactive rates in dynamic scenarios on a multi-core PC. 1.
Dirhodium(ii) tetraacetate catalysed reactions of diazo thioamides: isolation and cycloaddition of anhydro-4-hydroxy-1,3-thiazolium hydroxides (thioisomünchnones), an approach to analogues of dehydrogliotoxin (2003)

Dirhodium(II) tetraacetate catalysed reaction of the indoline diazo thioamide 8 gives the thioisomünchnone 9, a stable characterisable solid. This masked thiocarbonyl ylide undergoes 1,3-dipolar cycloaddition with N-methylmaleimide and maleic anhydride to give the exo-cycloadducts 10 and 11, characterised by X-ray crystallography. The thioisomünchnone 18, derived from diazo thioamide 17, is an extremely stable crystalline mesoionic system which can be characterised by X-ray crystallography but fails to undergo intramolecular cycloaddition. The related thioisomünchnone 19 can be generated by reaction of indoline-2-thione 7 with bromoacetyl chloride in the presence of triethylamine, and undergoes cycloaddition to give adducts 20 and 21.
Proton-Coupled Electron Transfer in a Model for Tyrosine Oxidation in Photosystem II (2003)

Theoretical calculations of a model for tyrosine oxidation in photosystem II are presented. In this model system, an electron is transferred to ruthenium from tyrosine, which is concurrently deprotonated. This investigation is motivated by experimental measurements of the dependence of the rates on pH and temperature (Sjödin et al. J. Am. Chem. Soc. 2000, 122, 3932). The mechanism is proton-coupled electron transfer (PCET) at pH < 10 when the tyrosine is initially protonated and is single electron transfer (ET) for pH > 10 when the tyrosine is initially deprotonated. The PCET rate increases monotonically with pH, whereas the single ET rate is independent of pH and is 2 orders of magnitude faster than the PCET rate. The calculations reproduce these experimentally observed trends. The pH dependence for the PCET reaction arises from the decrease in the reaction free energies with pH. The calculations indicate that the larger rate for single ET arises from a combination of factors, including the smaller solvent reorganization energy for ET and the averaging of the coupling for PCET over the reactant and product hydrogen vibrational wave functions (i.e., a vibrational overlap factor in the PCET rate expression). The temperature dependence of the rates, the solvent reorganization energies, and the deuterium kinetic isotope effects determined from the calculations are also consistent with the experimental results.
Reactive Co-Evaporation of YBCO as a Low-Cost Process for Fabricating Coated Conductors (2009)

We discuss implementation of reactive co-evaporation (RCE) to deposit high temperature superconducting films on metal tapes. Our method utilizes alternating high-rate deposition and oxygenation and can be extended to coating of moving tape in a continuous fashion. We have demonstrated our method with YBa <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> Cu <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">7</sub> films on 8 cm long ion-beam assisted deposition textured template tapes. Critical current densities of approximately 2.5 MA/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> at 75.5 K were achieved in HTS films with 2 mum in thickness, and a maximum measured self-field critical current of 950 A/cm-width was achieved in a 6 mum thick film. We discuss some practical possibilities for manufacturing superconducting wire and discuss a cost model for this RCE process. We make the case that the cost of HTS deposition using RCE in manufacturing can be less than $5/kAmiddotm.
Silicon-carbide high-voltage (400 V) Schottky barrier diodes (1992)

The authors describe the fabrication and characteristics of the first high-voltage (400-V) silicon-carbide (6H-SiC) Schottky barrier diodes. Measurements of the forward I-V characteristics of these diodes demonstrate a low forward voltage drop of approximately 1.1 V at an on-state current density of 100 A/cm/sup 2/ for a temperature range of 25 to 200 degrees C. The reverse I-V characteristics of these devices exhibit a sharp breakdown, with breakdown voltages exceeding 400 V at 25 degrees C. In addition, these diodes are shown to have superior reverse recovery characteristics when compared with high-speed silicon P-i-N rectifiers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Formulation of bovine respiratory syncytial virus fusion protein with CpG oligodeoxynucleotide, cationic host defence peptide and polyphosphazene enhances humoral and cellular responses and induces a protective type 1 immune response in mice (2009)

Respiratory syncytial virus (RSV) is the leading cause of serious respiratory tract disease in children and calves; however, RSV vaccine development has been slow due to early observations that formalin-inactivated vaccines induced Th2-type immune responses and led to disease enhancement upon subsequent exposure. Hence, there is a need for novel adjuvants that will promote a protective Th1-type or balanced immune response against RSV. CpG oligodeoxynucleotides (ODNs), indolicidin, and polyphosphazene were examined for their ability to enhance antigen-specific immune responses and influence the Th-bias when co-formulated with a recombinant truncated bovine RSV (BRSV) fusion protein (DeltaF). Mice immunized with DeltaF co-formulated with CpG ODN, indolicidin, and polyphosphazene (DeltaF/CpG/indol/PP) developed higher levels of DeltaF-specific serum IgG, IgG1 and IgG2a antibodies when compared with DeltaF alone, and displayed an increase in the frequency of gamma interferon-secreting cells and decreased interleukin (IL)-5 production by in vitro restimulated splenocytes, characteristic of a Th1 immune response. These results were observed in both C57BL/6 and BALB/c strains of mice. When evaluated in a BRSV challenge model, mice immunized with DeltaF/CpG/indol/PP developed significantly higher levels of BRSV-neutralizing serum antibodies than mice immunized with the DeltaF protein alone, and displayed significantly less pulmonary IL-4, IL-5, IL-13 and eotaxin and reduced eosinophilia after challenge. These results suggest that co-formulation of DeltaF with CpG ODN, host defence peptide and polyphosphazene may result in a safe and effective vaccine for the prevention of BRSV and may have implications for the development of novel human RSV vaccines.
Melanoma immunotherapy using mature DCs expressing the constitutive proteasome (2013)

Duke Clinical Research Institute/Duke Translational Medicine Institute, Duke Melanoma Consortium, and Duke University Department of Surgery.
Decreased Expression of Membrane IL-5 Receptor α on Human Eosinophils: I. Loss of Membrane IL-5 Receptor α on Airway Eosinophils and Increased Soluble IL-5 Receptor α in the Airway After Allergen Challenge (2002)

IL-5 is a key cytokine for eosinophil maturation, recruitment, activation, and possibly the development of inflammation in asthma. High concentrations of IL-5 are present in the airway after Ag challenge, but the responsiveness of airway eosinophils to IL-5 is not well characterized. The objectives of this study were to establish, following airway Ag challenge: 1) the expression of membrane (m)IL-5Ralpha on bronchoalveolar lavage (BAL) eosinophils; 2) the responsiveness of these cells to exogenous IL-5; and 3) the presence of soluble (s)IL-5Ralpha in BAL fluid. To accomplish these goals, blood and BAL eosinophils were obtained from atopic subjects 48 h after segmental bronchoprovocation with Ag. There was a striking reduction in mIL-5Ralpha on airway eosinophils compared with circulating cells. Furthermore, sIL-5Ralpha concentrations were elevated in BAL fluid, but steady state levels of sIL-5Ralpha mRNA were not increased in BAL compared with blood eosinophils. Finally, BAL eosinophils were refractory to IL-5 for ex vivo degranulation, suggesting that the reduction in mIL-5Ralpha on BAL eosinophils may regulate IL-5-mediated eosinophil functions. Together, the loss of mIL-5Ralpha, the presence of sIL-5Ralpha, and the blunted functional response (degranulation) of eosinophils to IL-5 suggest that when eosinophils are recruited to the airway, regulation of their functions becomes IL-5 independent. These observations provide a potential explanation for the inability of anti-IL-5 therapy to suppress airway hyperresponsiveness to inhaled Ag, despite a reduction in eosinophil recruitment.
Tianeptine in an experimental medicine model of antidepressant action (2015)

Changes in emotional processing have been shown following acute administration of a range of monoaminergic antidepressants, and may represent an important common neuropsychological mechanism underpinning their therapeutic effects. Tianeptine is an agent that challenges the traditional monoaminergic hypothesis of antidepressant action, though its exact mode of action remains controversial. Healthy volunteers were randomised to receive a single dose of tianeptine (12.5 mg) or placebo, and subsequently completed a battery of tasks measuring emotional processing, including facial expression recognition, emotional memory and attentional vigilance, as well as working and verbal memory. Tianeptine-treated subjects were less accurate at identifying facial expressions, though this was not valence specific. The tianeptine group also showed reduced positive affective memory and reduced attentional vigilance to positive stimuli. There were no effects on emotional categorization or non-emotional cognition. The negative biases in aspects of emotional processing observed following acute tianeptine administration are at variance with the positive biases generally seen after acute administration of conventional antidepressant drugs, despite tianeptine's putative antidepressant efficacy. This is an intriguing finding in the context of the lack of consensus regarding tianeptine's mechanism of action; however, it may be consistent with the reported ability of acute tianeptine to increase the re-uptake of serotonin.
Plenoptic modeling (1995)

Article Free Access Share on Plenoptic modeling: an image-based rendering system Authors: Leonard McMillan Department of Computer Science, University of North Carolina at Chapel Hill, CB 3175 Sitterson Hall, Chapel Hill, NC Department of Computer Science, University of North Carolina at Chapel Hill, CB 3175 Sitterson Hall, Chapel Hill, NCView Profile , Gary Bishop Department of Computer Science, University of North Carolina at Chapel Hill, CB 3175 Sitterson Hall, Chapel Hill, NC Department of Computer Science, University of North Carolina at Chapel Hill, CB 3175 Sitterson Hall, Chapel Hill, NCView Profile Authors Info & Claims SIGGRAPH '95: Proceedings of the 22nd annual conference on Computer graphics and interactive techniquesSeptember 1995 Pages 39–46https://doi.org/10.1145/218380.218398Published:15 September 1995Publication History 651citation5,126DownloadsMetricsTotal Citations651Total Downloads5,126Last 12 Months352Last 6 weeks50 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Bacterial outer membrane vesicles and the host–pathogen interaction (2005)

Extracellular secretion of products is the major mechanism by which Gram-negative pathogens communicate with and intoxicate host cells. Vesicles released from the envelope of growing bacteria serve as secretory vehicles for proteins and lipids of Gram-negative bacteria. Vesicle production occurs in infected tissues and is influenced by environmental factors. Vesicles play roles in establishing a colonization niche, carrying and transmitting virulence factors into host cells, and modulating host defense and response. Vesicle-mediated toxin delivery is a potent virulence mechanism exhibited by diverse Gram-negative pathogens. The biochemical and functional properties of pathogen-derived vesicles reveal their potential to critically impact disease.
Cardiac Troponin I Is Associated With Impaired Hemodynamics, Progressive Left Ventricular Dysfunction, and Increased Mortality Rates in Advanced Heart Failure (2003)

cTnI is associated with impaired hemodynamics, elevated BNP levels, and progressive left ventricular dysfunction in patients with HF. cTnI may be a novel, useful tool in identifying patients with HF who are at increased risk for progressive ventricular dysfunction and death.
Analysis and optimization of packaged inductively degenerated common-source low-noise amplifiers with ESD protection (2005)

The effects of packaging in inductively degenerated common-source low-noise amplifiers (LNAs) with electrostatic discharge (ESD) protection are studied and the performance of the packaged LNA is optimized. Equations describing the input impedance, transconductance, voltage gain, and noise figure (NF) of the packaged amplifier are derived and the effects of the LNA input matching network, package, and ESD parasitics on these amplifier quantities are highlighted. From the equations, several design guidelines for the packaged LNA are obtained and a systematic approach for the ESD-protected LNA optimization is deduced. It is also shown that, in the presence of an equivalent parallel package parasitic capacitance C/sub p/, the NF in a well-optimized LNA is easily dominated by the losses of the input-matching network instead of the active device noise. Based on the theoretical results, a packaged inductively degenerated common-source LNA with ESD protection is designed in a 0.13-/spl mu/m CMOS process. The amplifier provides a forward gain (S/sub 21/) of almost 18 dB at 2 GHz with an NF of 1.6 dB while consuming 8.4 mW from a 1.2-V supply.
Validation Study of the Accuracy of a Postoperative Nomogram for Recurrence After Radical Prostatectomy for Localized Prostate Cancer (2002)

PURPOSE: A postoperative nomogram for prostate cancer was developed at Baylor College of Medicine. This nomogram uses readily available clinical and pathologic variables to predict 7-year freedom from recurrence after radical prostatectomy. We evaluated the predictive accuracy of the nomogram when applied to patients of four international institutions. PATIENTS AND METHODS: Clinical and pathologic data of 2,908 patients were supplied for validation, and 2,465 complete records were used. Nomogram-predicted probabilities of 7-year freedom from recurrence were compared with actual follow-up in two ways. First, the area under the receiver operating characteristic curve (AUC) was calculated for all patients and stratified by the time period of surgery. Second, calibration of the nomogram was achieved by comparing the predicted freedom from recurrence with that of an ideal nomogram. For patients in whom the pathologic report does not distinguish between focal and established extracapsular extension (an input variable of the nomogram), two separate calculations were performed assuming one or the other. RESULTS: The overall AUC was 0.80 when applied to the validation data set, with individual institution AUCs ranging from 0.77 to 0.82. The predictive accuracy of the nomogram was apparently higher in patients who were operated on between 1997 and 2000 (AUC, 0.83) compared with those treated between 1987 and 1996 (AUC, 0.78). Nomogram predictions of 7-year freedom from recurrence were within 10% of an ideal nomogram. CONCLUSION: The postoperative Baylor nomogram was accurate when applied at international treatment institutions. Our results suggest that accurate predictions may be expected when using this nomogram across different patient populations.
Heritability of the Varroa‐specific hygienic behaviour in honey bees (Hymenoptera: Apidae) (2000)

Summary The hygienic behaviour of the honey bees is considered to be a potential characteristic associated with resistance to Varroa destructor n.sp. In this study the heritability of the hygienic behaviour of Apis mellifera L. bees was estimated on the basis of the mother–daughter regression. Data were obtained from measurements of the bees' hygienic behaviour towards V. destructor ‐infested cells and towards pin‐killed sealed brood. The heritability for the hygienic behaviour towards V. destructor ‐infested brood cells was h 2 = 0.18 (± 0.27) and h 2 = 0.36 (± 0.30) for the hygienic behaviour towards dead brood cells. The repeatability was likewise higher for the pin‐killed brood assay ( W = 0.46) compared with the assay using living mites‐infested brood cells ( W = 0.24). The genetic correlation between the behavioural responses to either the mite‐infested or pin‐killed brood cells was calculated to be r g = 0.61 (± 0.51) and the phenotypic correlation to be r p = 0.11 (p = 0.28, n = 100). Since hygienic colonies demonstrate resistance to brood diseases such as American foulbrood and chalkbrood, it may be worthwhile to intensify the expression of the hygienic behaviour through selective breeding and thus strengthen these potential characteristics associated with resistance to V. destructor in honey bee stock.