gebhart/patrepeval huggingface dataset:
Alkamides from Piper longum and Piper nigrum as Inhibitors of IL-6 action (2010)

Blocking of IL-6 has been postulated to be an effective therapy in the pathogenesis of several inflammatory diseases. The current study was performed to examine the potential effects of alkamides isolated from P. longum and P. nigrum on IL-6 induced Stat3 activation and identify the structure-activity relationship of these alkamides in human hepatoma cells. Among 10 alkamides isolated from P. longum and P. nigrum, compounds 6, 7 and 9 were identified as strong inhibitors of IL-6 action, which inhibit IL-6 induced Stat3-dependent luciferase activities. These inhibitory activities were positively influenced by the presence of piperidine moiety.
Influence of misalignment of a scintillator array and a multi-anode PMT for 4-layer DOI PET detector (2012)

We are developing a depth of interaction (DOI) detector having a crystal block composed of four layers of a scintillation crystal array. By removing reflectors between crystal elements for every two lines and shifting reflector patterns depending on layers, responses of all crystal elements in the four layers can be mapped to a 2-dimentional (20) position histogram after applying conventional Anger-type calculation. Because this method projects four times more number of crystal responses onto the position histogram than conventional non-DOI detectors do. Slight difference of light distribution on a multi-anode photomultiplier tube (MA-PMT) discriminates each crystal responses. In particular, location of the crystal responses in the position histogram is sensitive to spatial relationship between the crystal block and the MA-PMT at the edge side of the responses. In this paper, to set up the crystal block appropriate position, we developed an optical camera-based system for positioning of the crystal block. Using this system, we studied the influence of positioning accuracy of the crystal block on the crystal responses in the 20 position histogram. We used a MA-PMT with a 49 × 49 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> effective area in 52 × 52 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> opening window and anode interval of 6 mm. We prepared two types of crystal blocks, a non-DOI crystal block and the four-layer DOI crystal block, and obtained 20 position histograms with shifting each crystal block from a corner of the MA-PMT to the center. The crystal blocks were composed of 2.8 x 2.8 x 7.5 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> GSO crystal elements. We found that all responses of the non-DOI detector can be discriminated, even it was on the corner of the MA-PMT, however, responses of the DOI detector are not able to be discriminated on the edge sides of the 2D position histogram e
Supplementary material from "The N-linking glycosylation system from Actinobacillus pleuropneumoniae is required for adhesion and has potential use in glycoengineering" (2017)

<i>Actinobacillus pleuropneumoniae</i> is a mucosal respiratory pathogen causing contagious porcine pleuropneumonia. Pathogenesis studies have demonstrated a major role for the capsule, exotoxins and outer membrane proteins. <i>A. pleuropneumoniae</i> can also glycosylate proteins, using a cytoplasmic <i>N</i>-linked glycosylating enzyme designated NGT, but its transcriptional arrangement and role in virulence remains unknown. We investigated the NGT locus and demonstrated that the putative transcriptional unit consists of <i>rimO</i>, <i>ngt</i> and a glycosyltransferase termed <i>agt.</i> From this information we used the <i>A. pleuropneumoniae</i> glycosylation locus to decorate an acceptor protein, within <i>Escherichia coli,</i> with a hexose polymer that reacted with an anti-dextran antibody. Mass spectrometry analysis of a truncated protein revealed that this operon could add up to 29 repeat units to the appropriate sequon. We demonstrated the importance of NGT in virulence, by creating deletion mutants and testing them in a novel respiratory cell line adhesion model. This study demonstrates the importance of the NGT glycosylation system for pathogenesis and its potential biotechnological application for glycoengineering.
Heterocyclic Dications as a New Class of Telomeric G-Quadruplex Targeting Agents (2012)

Small molecules that can induce and stabilize G-quadruplex DNA structures represent a novel approach for anti-cancer and anti-parasitic therapy and extensive efforts have been directed towards discovering lead compounds that are capable of stabilizing quadruplexes. The purpose of this study is to explore conformational modifications in a series of heterocyclic dications to discover structural motifs that can selectively bind and stabilize specific G-quadruplexes, such as those present in the human telomere. The G-quadruplex has various potential recognition sites for small molecules; however, the primary interaction site of most of these ligands is the terminal tetrads. Similar to duplex-DNA groove recognition, quadruplex groove recognition by small molecules offers the potential for enhanced selectivity that can be developed into a viable therapeutic strategy. The compounds investigated were selected based on preliminary studies with DB832, a bifuryl-phenyl diamidine with a unique telomere interaction. This compound provides a paradigm that can help in understanding the optimum compound-DNA interactions that lead to quadruplex groove recognition. DNA recognition by the DB832 derivatives was investigated by biophysical experiments such as thermal melting, circular dichroism, mass spectrometry and NMR. Biological studies were also performed to complement the biophysical data. The results suggest a complex binding mechanism which involves the recognition of grooves for some ligands as well as stacking at the terminal tetrads of the human telomeric G-quadruplex for most of the ligands. These molecules represent an excellent starting point for further SAR analysis for diverse modes of quadruplex recognition and subsequent structure optimization for drug development.
Multiplexed Electrochemical Detection of Three Cardiac Biomarkers cTnI, Ctnt and Bnp Using Nanostructured ZnO-sensing Platform (2018)

First demonstration of simultaneous detection of three cardiac biomarkers in clinically relevant range with sensor's analytical performance and linear response of detection showed potential utility in screening clinical samples for early diagnosis of acute myocardial infarction and chronic heart failure.
Evaluation of Strategies for Highly Transient Operation of Diesel-Gas Engines (2018)

The balancing of the electric grid has become more challenging due to the expansion of fluctuating renewable energy sources for electric power generation. The importance of power plants driven by internal combustion engines will increase since they can react flexibly and quickly to changes in the energy demand. With regard to the emission of pollutants and CO2, gas fueled engines are favored for gensets. However, it is more challenging to meet the dynamic load requirements with a gas engine than with a conventional diesel engine because the load acceptance of the gas engine is limited by the occurrence of knocking combustion. Dual fuel engines are a good compromise between these two engine concepts; they can use gaseous fuel during steady state engine operation and increase the diesel share during transient modes to improve the dynamic behavior. The high number of degrees of freedom of dual fuel combustion concepts requires advanced operating strategies. The aim of this paper is to investigate and evaluate strategies to improve the transient behavior of a 20-cylinder large bore diesel-gas engine (displacement 6.24 dm3 per cylinder) for a genset application. In the investigations, the latest turbocharging technology is applied in combination with a turbine waste gate. A wide range diesel injector that covers the whole diesel injection range of approximately 1 % to 100 % diesel fraction1 of the rated power fuel mass provides the basis for the most flexible diesel injection. A 1D simulation tool was used to model and optimize the genset in transient operation. The combustion process was simulated with Vibe heat release rate models. The optimized transient engine operating strategies were validated on a highly dynamic single cylinder research engine test bed. The paper provides a comparison of different strategies that use these technologies to improve the dynamic behavior of the genset in island mode operation during a 50 % load step. Key to meeting the challenging requirements is an optimized diesel injection strategy or even a switch from gas operation mode to diesel operation mode during the load step. Based on the results of simulation and engine testing, potential ways to minimize engine speed drop and recovery time after the load demand increase are evaluated.
Abstract 17619: Deep RNA-Sequencing Uncovers a Broad Species- And Cell-Specific lincRNA Repertoire That Modulates Human Macrophage Activation and Associates With Cardiometabolic Diseases (2017)

Introduction: Sustained and dysfunctional macrophage activation promotes inflammatory cardiometabolic disorders (CMDs), but the role of long non-coding RNAs in human macrophage activation and CMDs ...
Beyond Bile Acids: Targeting Farnesoid X Receptor (FXR) with Natural and Synthetic Ligands (2014)

The modulation of FXR receptor remains an attractive area in drug discovery to develop novel therapeutic opportunities for liver and metabolic disorders. Despite the large variety of FXR ligands reported so far, only a very restricted number of agonists have entered in clinical settings. In this review article we provide the reader with an overview on the different classes of natural and synthetic ligands that have been developed by academic groups and pharmaceutical companies to target FXR. We discuss their structure-activity relationships, analyzing the binding modes that some of these compounds adopt to interact with the receptor.
Multiplexed Fluorescent Microarray for Human Salivary Protein Analysis Using Polymer Microspheres and Fiber-optic Bundles (2013)

Herein, we describe a protocol for simultaneously measuring six proteins in saliva using a fiber-optic microsphere-based antibody array. The immuno-array technology employed combines the advantages of microsphere-based suspension array fabrication with the use of fluorescence microscopy. As described in the video protocol, commercially available 4.5 μm polymer microspheres were encoded into seven different types, differentiated by the concentration of two fluorescent dyes physically trapped inside the microspheres. The encoded microspheres containing surface carboxyl groups were modified with monoclonal capture antibodies through EDC/NHS coupling chemistry. To assemble the protein microarray, the different types of encoded and functionalized microspheres were mixed and randomly deposited in 4.5 μm microwells, which were chemically etched at the proximal end of a fiber-optic bundle. The fiber-optic bundle was used as both a carrier and for imaging the microspheres. Once assembled, the microarray was used to capture proteins in the saliva supernatant collected from the clinic. The detection was based on a sandwich immunoassay using a mixture of biotinylated detection antibodies for different analytes with a streptavidin-conjugated fluorescent probe, R-phycoerythrin. The microarray was imaged by fluorescence microscopy in three different channels, two for microsphere registration and one for the assay signal. The fluorescence micrographs were then decoded and analyzed using a homemade algorithm in MATLAB.
Synthesis and Structure−Activity Relationships of Nonaromatic Taxoids:  Effects of Alkyl and Alkenyl Ester Groups on Cytotoxicity (1997)

Several new nonaromatic taxoids are synthesized by means of the beta-lactam synthon method. These include taxoids modified with 3-methylbut-2-enoate, 3-methylbutanoate, and cyclohexanecarboxylate groups in place of the benzoate at the C-2 position. In addition, taxoids with 2-methylprop-1-enyl, 2-methylpropyl, (E)-prop-1-enyl, and cyclohexyl groups at the C-3' position are also prepared in combination with the modifications at C-2. The alkyl and alkenyl ester groups at C-2 displayed pronounced effects on the in vitro cytotoxicity. Two of the fully aliphatic taxoids possess similar or stronger activity than paclitaxel and docetaxel. It is clear that the 2-benzoate does not play a unique role, and replacement with the appropriate alkyl and alkenyl groups provides taxoids with equivalent or superior activity.
ChemInform Abstract: Synthetic Studies on the 1,6‐Methano(10)annulene Skeleton: A New Route that Provides Derivatives Substituted at the Bridge and on the Annulene Ring. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Superconducting Spin Valve Effect of a V Layer Coupled to an Antiferromagnetic[Fe/V]Superlattice (2005)

We studied superconducting V layers deposited on an antiferromagnetically coupled [Fe(2)V(11)](20) superlattice. The parallel upper critical magnetic field exhibits an anomalous T dependence up to the ferromagnetic saturation field of the superlattice, indicating that the superconducting transition temperature T(S) decreases when rotating the relative sublattice magnetization directions of the superlattice from antiparallel to parallel. This proves that the pair breaking effect of a Fe2 layer is reduced if at a distance of 1.5 nm a second Fe2 layer with antiparallel spin orientation exists.
Incidence and clinicobiologic characteristics of leukemic B-cell chronic lymphoproliferative disorders with more than one B-cell clone (2003)

Leukemic B-chronic lymphoproliferative disorders (B-CLPDs) are generally believed to derive from a monoclonal B cell; biclonality has only occasionally been reported. In this study, we have explored the incidence of B-CLPD cases with 2 or more B-cell clones and established both the phenotypic differences between the coexisting clones and the clinicobiologic features of these patients. In total, 53 B-CLPD cases with 2 or more B-cell clones were studied. Presence of 2 or more B-cell clones was suspected by immunophenotype and confirmed by molecular/genetic techniques in leukemic samples (n = 42) and purified B-cell subpopulations (n = 10). Overall, 4.8% of 477 consecutive B-CLPDs had 2 or more B-cell clones, their incidence being especially higher among hairy cell leukemia (3 of 13), large cell lymphoma (2 of 10), and atypical chronic lymphocytic leukemia (CLL) (4 of 29). In most cases the 2 B-cell subsets displayed either different surface immunoglobulin (sIg) light chain (n = 37 of 53) or different levels of the same sIg (n = 9 of 53), usually associated with other phenotypic differences. Compared with monoclonal cases, B-CLL patients with 2 or more clones had lower white blood cell (WBC) and lymphocyte counts, more frequently displayed splenomegaly, and required early treatment. Among these, the cases in which a CLL clone coexisted with a non-CLL clone were older and more often displayed B symptoms, a monoclonal component, and diffuse infiltration of bone marrow and required early treatment more frequently than cases with monoclonal CLL or 2 CLL clones.
Smooth vs. pieced-interval dynamic modeling of impulsive events in multibody mechanical systems (2007)

Impulsive responses often arise in mechanical systems due to collision, impact, joint clearances, machine tool interaction, and material handling processes. Impulsive events take place during very short-lived intervals, and are normally associated with redistribution of momentum. The redistribution of momentum may take place instantaneously or during a very short interval, thus giving rise to discontinuities in the system's velocities. In this context, two modeling approaches are presented. The first approach adopts a smooth representation over the short-lived interval. In this case, the impulsive event is modeled while taking into consideration the mechanics of the contacting bodies. The second is a discontinuous dynamic model, in which the impulsive event is assumed to take place at an instant of time. The corresponding instantaneous redistribution of momentum results in jump discontinuities in the system's velocities, which are calculated to update the system state vector for starting the next interval. The merits of the two modeling approaches are stated in the light of numerical simulations.
Re: Steroid Receptor Coactivator-3 Regulates Glucose Metabolism in Bladder Cancer Cells through Coactivation of Hypoxia Inducible Factor 1α (2014)

No AccessJournal of UrologyInvestigative Urology1 Dec 2014Re: Steroid Receptor Coactivator-3 Regulates Glucose Metabolism in Bladder Cancer Cells through Coactivation of Hypoxia Inducible Factor 1α Anthony AtalaMD Anthony AtalaAnthony Atala More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.09.027AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Steroid Receptor Coactivator-3 Regulates Glucose Metabolism in Bladder Cancer Cells through Coactivation of Hypoxia Inducible Factor 1α." The Journal of Urology, 192(6), p. 1885 © 2014 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 192Issue 6December 2014Page: 1885Supplementary Materials Advertisement Copyright & Permissions© 2014 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anthony Atala More articles by this author Expand All Advertisement PDF downloadLoading ...
Small Molecule Imaging Agent for Mutant KRAS G12C (2021)

Multiple potent covalent inhibitors for mutant KRAS G12C have been described and some are in clinical trials. These small molecule inhibitors potentially allow for companion imaging probe development, thereby expanding the chemical biology toolkit to investigate mutant KRAS biology. Herein, we synthesized and tested a series of fluorescent companion imaging drugs (CID) for KRAS G12C, using two scaffolds, ARS-1323 and AMG-510. We created four fluorescent derivatives of each by attaching BODIPY dyes. We found that two fluorescent derivatives (BODIPY FL and BODIPY TMR) of ARS-1323 bind mutant KRAS and can be used for biochemical binding screens. Unfortunately, these drugs could not be used as direct imaging agents in cells, likely because of non-specific membrane labeling. To circumvent this challenge, we then used a two step procedure in cancer cells where an ARS-1323 alkyne is used for target binding followed by fluorescence imaging after <i>in situ</i> click chemsitry with picolyl azide Alexa Fluor 647. We show that this approach can be used to image mutant KRAS G12C directly in cells. Given the current lack of mutant KRAS G12C specific antibodies, these reagents could be useful for specific fluorescence imaging.
Development of spatial nearest-neighbor analysis and Clustering/Gibbs statistical methodology for filament percolation in dielectric breakdown and forming process in ReRAM devices (2021)

In this work, we develop a spatial nearest-neighbor analysis methodology to investigate the spatial distribution (pattern) of filaments (or Breakdown (BD) spots) obtained by various physical experimental measurements, such as recently developed Photon Emission Microscopy (PEM) for ReRAM [1], Scanning Tunneling Microscopy (STM) [2], and IR-thermography [3]. For non-uniform spatial distributions of BD spots, a spatial clustering model is successfully used to explain the experimental data. For filament formation, found in ReRAM devices, a Gibbs process model using a Markov-Chain Monte-Carlo (MCMC) approach is developed to successfully account for the inhibitory and attractive interaction among filaments with a generalized Morse potential.
Nanocomposite Alloy Design for High Frequency Power Conversion Applications (2012)

This chapter contains sections titled: Introduction Engineering Approaches Example Material Archetypes Summary and Conclusion Acknowledgement
The Serendipitous Story of Sildenafil: An Unexpected Oral Therapy for Erectile Dysfunction (2018)

The approval of sildenafil initiated a global conversation about ED that had profound implications for patients, methods of clinical practice, and academic sexual medicine. These changes will catalyze continued advances in ED treatment. Goldstein I, Burnett AL, Rosen RC, et al. The serendipitous story of sildenafil: an unexpected oral therapy for erectile dysfunction. Sex Med Rev 2019;7:115-128.
Excited-State Distortions of Cyclometalated Ir(III) Complexes Determined from the Vibronic Structure in Luminescence Spectra (2007)

The luminescence spectra of [(tpy)(2)Ir(CN-t-Bu)2](CF(3)SO(3)) in methylcyclohexane glass and frozen n-nonane at 15 K reveal well-resolved vibronic fine structure. The vibronic peaks are assigned by comparison with the vibrational frequencies obtained from Raman and IR spectra and those obtained using DFT electronic structure calculations. The magnitudes of the distortions along the normal coordinates are calculated by fitting the emission spectra using the time-dependent theory of spectroscopy. Broadening effects and the MIME frequency observed at room temperature are interpreted. The most highly distorted normal modes involve atomic motions on the tpy ligand, consistent with the metal to ligand/ligand centered assignment of the electronic transition.
P hysiological C ontrol of I mmune R esponse and I nflammatory T issue D amage by H ypoxia -I nducible F actors and A denosine A 2A R eceptors (2004)

Immune cell-mediated destruction of pathogens may result in excessive collateral damage to normal tissues, and the failure to control activated immune cells may cause immunopathologies. The search for physiological mechanisms that downregulate activated immune cells has revealed a critical role for extracellular adenosine and for immunosuppressive A2A adenosine receptors in protecting tissue from inflammatory damage. Tissue damage-associated deep hypoxia, hypoxia-inducible factors, and hypoxia-induced accumulation of adenosine may represent one of the most fundamental and immediate tissue-protecting mechanisms, with adenosine A2A receptors triggering "OFF" signals in activated immune cells. In these regulatory mechanisms, oxygen deprivation and extracellular adenosine accumulation serve as "reporters," while A2A adenosine receptors serve as "sensors" of excessive tissue damage. The A2A receptor-triggered generation of intracellular cAMP then inhibits activated immune cells in a delayed negative feedback manner to prevent additional tissue damage. Targeting A2A adenosine receptors may have important clinical applications.
Proceedings of the 17th International Conference on Management of Data (2011)

For close to two decades, the International Conference on Management of Data (COMAD), modeled along the lines of ACM SIGMOD, has been the premier international database conference hosted in India. The first COMAD was held in Hyderabad in 1989, and the most recent version was hosted in Nagpur during December 2010. The 17th edition in the COMAD series will be held at the International Institute of Information Technology, Bangalore (IIITB), during December 19-21, 2011. Bangalore, also called Bengaluru, is nicknamed the Garden City, and was once called a pensioner's paradise. Today, it is better known as the primary hub for India's Information Technology sector.

COMAD seeks to provide the community of researchers, practitioners, developers and users of data management technologies, a forum to present and discuss problems, solutions, innovations, experiences and emerging trends. During the past few years, the scope of COMAD 2011 has expanded to include, in addition to traditional database areas, topics in Web, Information Retrieval and Data Mining.