gebhart/patrepeval huggingface dataset:
Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor (2016)

The ongoing Zika virus (ZIKV) outbreak is linked to severe neurological disorders. ZIKV relies on its NS2B/NS3 protease for polyprotein processing; hence, this enzyme is an attractive drug target. The 2.7 angstrom; crystal structure of ZIKV protease in complex with a peptidomimetic boronic acid inhibitor reveals a cyclic diester between the boronic acid and glycerol. The P2 4-aminomethylphenylalanine moiety of the inhibitor forms a salt-bridge with the nonconserved Asp(83) of NS2B; ion-pairing between Asp(83) and the P2 residue of the substrate likely accounts for the enzyme's high catalytic efficiency. The unusual dimer of the ZIKV protease:inhibitor complex seen in the crystal may provide a model for assemblies formed at high local concentrations of protease at the endoplasmatic reticulum membrane, the site of polyprotein processing.
Interleukin‐1β promotes oligodendrocyte death through glutamate excitotoxicity (2003)

Glutamate excitotoxicity is implicated in the progressive loss of oligodendrocytes in multiple sclerosis, but how glutamate metabolism is dysregulated in the disease remains unclear. Because there is microglia activation in all stages of multiple sclerosis, we determined whether a microglia product, interleukin-1beta, could provide the mechanism for glutamate excitotoxicity. We found that whereas interleukin-1beta did not kill oligodendrocytes in pure culture, it produced apoptosis of oligodendrocytes in coculture with astrocytes and microglia. This requirement for a mixed glia environment suggests that interleukin-1beta impairs the well-described glutamate-buffering capacity of astrocytes. In support, antagonists at AMPA/kainate glutamate receptors, NBQX and CNQX, blocked the interleukin-1beta toxicity to oligodendrocytes. Another microglia/macrophage cytokine, tumor necrosis factor-alpha, also evoked apoptosis of oligodendrocytes in a mixed glia environment in an NBQX-blockable manner. These results provide a mechanistic link between the persistent and insidious microglia activation that is evident in all stages of multiple sclerosis, with the recent appreciation that glutamate excitotoxicity leads to the destruction of oligodendrocytes in the disease.
ChemInform Abstract: METALATION AND METAL‐HALOGEN EXCHANGE REACTIONS OF IMIDAZOLES (1983)

Abstract Über das entsprechende 5‐Lithiat werden aus dem Imidazolderivat (I) die Verbindungen (II), (IIIa) (mit CO 2 ) und (IIIb) (mit p‐Methyl‐benzaldehyd) und über (IIa), das Bromid (IV) und das entsprechende 4‐Lithiat die Verbindungen (V) dargestellt.
Distribution State Estimation Based on Improved Particle Swarm Optimization (2012)

Based on non-linear characteristics of distributed generation(DG) and measurement configuration features in distribution network,this paper introduced natural selection mechanism into theparticle swarm optimization(PSO) algorithm to enhance the global search ability,and overcome the shortcoming of PSO that it is easy to fall into local optimal solution.This paper applied the improved PSO algorithm to the distributed state estimation.A numerical example simulation shows that its convergence speed and estimation accuracy will greatly improve,and it can prove the superiority of the algorithm.
Structures of ζ and ζ′ Phases in the Ag—Ga System. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
<i>PHR1</i> , a pH-Regulated Gene of <i>Candida albicans</i> , is Required for Morphogenesis (1995)

Candida albicans, like many fungi, exhibits morphological plasticity, a property which may be related to its biological capacity as an opportunistic pathogen of humans. Morphogenesis and alterations in cell shape require integration of many cellular functions and occur in response to environmental signals, most notably pH and temperature in the case of C. albicans. In the course of our studies of differential gene expression associated with dimorphism of C. albicans, we have isolated a gene, designated PHR1, which is regulated in response to the pH of the culture medium. PHR1 expression was repressed at pH values below 5.5 and induced at more alkaline pH. The predicted amino acid sequence of the PHR1 protein was 56% identical to that of the Saccharomyces cerevisiae Ggp1/Gas1 protein, a highly glycosylated cell surface protein attached to the membrane via glycosylphosphatidylinositol. A homozygous null mutant of PHR1 was constructed and found to exhibit a pH-conditional morphological defect. At alkaline pH, the mutant, unlike the parental type, was unable to conduct apical growth of either yeast or hyphal growth forms. This morphological aberration was not associated with defective cytoskeletal polarization or secretion. The results suggest that PHR1 defines a novel function required for apical cell growth and morphogenesis.
Inhibition of Integrin-Mediated Platelet Aggregation, Fibrinogen-Binding, and Interactions with Extracellular Matrix by Nonpeptidic Mimetics of Arg-Gly-Asp (1993)

The interaction of the activated platelet integrin, glycoprotein IIb-IIIa (GPIIb-IIIa) with fibrinogen and von-Willebrand factor (vWF) is essential for platelet aggregation. The minimal structure required for this integrin's binding to fibrinogen is the Arg-Gly-Asp (RGD) sequence. Inasmuch as normal level of GPIIb-IIIa-RGD interactions are required for maintaining hemostasis, elevated platelet aggregation can cause adverse pathological effects. We have previously reported that nonpeptidic mimetics of RGD, consisting of carboxylate and guanidinium groups of Asp and Arg divided by a linear 11-atom spacer, acquired a significant affinity for the GPIIb-IIIa integrin and inhibited platelet aggregation. The structural requirements for the interactions of the RGD sequence with GPIIb-IIIa and the inhibitory potential of a newly designed series of mimetics on platelet aggregation and interactions with extracellular matrix (ECM) were assayed herein. Adenosine-diphosphate (ADP)-induced platelet aggregation was inhibited in a dose-dependent manner by various RGD mimetics, with a maximal inhibition of 80-100% with an IC50 of 3 microM for the most potent inhibitor, NS-11, in which a six-membered ring was introduced into the spacer chain, which exceeded the IC50 attained with the original RGDS peptide. The inhibitory effect of the RGD mimetics was attributed to their specific interaction with the GPIIb-IIIa integrin, since these mimetics inhibited the binding of the PAC-1 mAb to GPIIb-IIIA. Furthermore, the binding of 125I-labeled fibrinogen to platelets was inhibited by the RGD surrogates in a dose-dependent and saturable manner. The RGD-mimetics also inhibited up to 70% the adhesion, aggregation, and deposition of platelets onto ECM.(ABSTRACT TRUNCATED AT 250 WORDS)
Low-Temperature Signal Transduction: Induction of Cold Acclimation-Specific Genes of Alfalfa by Calcium at 25 degrees C (1995)

Antonio F. Monroy, Rajinder S. Dhindsa, Low-Temperature Signal Transduction: Induction of Cold Acclimation-Specific Genes of Alfalfa by Calcium at 25°C, The Plant Cell, Vol. 7, No. 3 (Mar., 1995), pp. 321-331
Characterization of Bovine Viral Diarrhoea-Mucosal Disease Virus-specific Proteins in Bovine Cells (1987)

The presence of virus-specific polypeptides in bovine viral diarrhoea-mucosal disease (BVD) virus-infected bovine cells was studied by radiolabelling in the presence of a hypertonic initiation block (HIB) and by analysis by SDS-PAGE. These experiments were complemented by radioimmunoprecipitations with anti-BVD hyperimmune serum of infected cells labelled under isotonic conditions. A total of 12 polypeptides (Mr 165, 135, 118, 80, 75, 62, 56 to 58, 48, 37, 32, 35 and 19, all X 10(-3)) were identified in infected cells. Time course analysis of the induction of the viral polypeptides indicated that they could be detected as early as 4 h post-infection and their synthesis reached a plateau between 12 and 20 h post-infection. The most abundant polypeptides were the ones that could be detected earliest. HIB was found to be an excellent adjunct to existing techniques in the identification of viral polypeptides. Seven of these polypeptides had not been reported previously. This is the first report of the direct detection of BVD virus-induced polypeptides in infected cells without the aid of immunoprecipitation. The sum of the molecular masses of these polypeptides is greater than the coding capacity of the genome; therefore precursor-product relationships must exist between these polypeptides.
On the equilibrium of heterogeneous substances (1878)

Review of the article ''On the Equilibrium of Heterogeneous Substances'', which was published in ''Transactions of the Connecticut Academy of Arts and Sciences'', vol. 3 (1874-78), pp. 108-248 and 343-524.
Structural Dynamics of the <i>Streptomyces lividans</i> K<sup>+</sup> Channel (SKC1):  Oligomeric Stoichiometry and Stability<sup>,</sup> (1997)

SKC1, a 160-residue potassium channel with two putative transmembrane (TM) segments was recently identified from Streptomyces lividans. Its high levels of expression, small size, and ease of purification make SKC1 an ideal candidate for high-resolution structural studies. We have initiated the structural characterization of this channel by assessing its oligomeric behavior, stability in detergent, general hydrodynamic properties, and preliminary secondary structure content. SKC1 was readily expressed and purified to homogeneity by sequential metal-chelate and gel filtration chromatography. Standard SDS-PAGE, together with chemical cross-linking analysis indicated that SKC1 behaves as a tightly associated tetramer even in the presence of SDS. Using a gel shift assay to assess its oligomeric state, we determined that SKC1 is stable as a tetramer in most detergents and can be maintained in nonionic detergent solutions for extended periods of time. The tetramer is also stable at relatively high temperatures, with an oligomer-to-monomer transition occurring at approximately 65 degrees C. The Stokes radius of the micellar complex is 5 nm as determined from gel filtration chromatography of SKC1 in dodecyl maltoside. Preliminary estimations of secondary structure from CD spectroscopy showed that the channel exists mostly in alpha-helical conformation, with more than 50% alpha-helical, close to 20% beta-sheet, 10% beta-turn, and about 15% unassigned or random coil. These results are consistent with the idea that a bundle of alpha-helices forming a tetramer around the ion-conductive pathway is the common structural motif for members of the voltage-dependent channel superfamily.
Coupled electrical and thermal 3D IC centric microfluidic heat sink design and technology (2011)

Through-silicon via (TSV) technology, an enabler for 3D ICs, has evolved, enabling thinner and shorter TSVs within substantially thinned wafers to achieve faster interconnects, large bandwidth density, and low power consumption. Yet, heat dissipation in 3D ICs becomes more and more challenging, especially in applications that require stacking of multiple processor and memory chips. Microfluidic cooling has been proposed as a solution to reject heat from 3D stacks that contain processor chips. However, current liquid cooling technology inevitably increases the wafer thickness, which is contrary to TSV technology trend. To date, little work has been done to optimize heat sink design to benefit TSV performance, and no attempt has been made to analyze the corresponding impact of a particular heat sink design on the performance of the electrical TSVs. A heat sink design without consideration of TSV performance can greatly diminish the advantages of 3D ICs. This paper presents a holistic cooling solution for 3D ICs, which not only meets thermal requirements, but also minimizes TSV parasitics that impact latency, bandwidth density, and power consumption. This paper will report: a) the design of a 3D-centric heat sink, b) the fabrication of the heat sink and associated high aspect ratio integrated TSVs, c) the thermal testing of the liquid-cooled heat sink and comparison to air-cooled heat sink, and d) the impact of the heat sink geometry on TSV capacitance.
SOX9 Protein Induces a Chondrogenic Phenotype of Mesangial Cells and Contributes to Advanced Diabetic Nephropathy (2011)

Diabetic nephropathy (DN) is the most important chronic kidney disease. We previously reported that Smad1 transcriptionally regulates the expression of extracellular matrix in DN. Phenotypic change in mesangial cells (MCs) is a key pathologic event in the progression of DN. The aim of this study is to investigate a novel mechanism underlying chondrogenic phenotypic change in MCs that results in the development of DN. MCs showed chondrogenic potential in a micromass culture, and BMP4 induced the expression of chondrocyte markers (SRY-related HMG Box 9 (SOX9) and type II collagen (COL2)). Advanced glycation end products induced the expression of chondrocyte marker proteins downstream from the BMP4-Smad1 signaling pathway in MCs. In addition, hypoxia also induced the expression of BMP4, hypoxia-inducible factor-1α (HIF-1α), and chondrocyte markers. Overexpression of SOX9 caused ectopic expression of proteoglycans and COL2 in MCs. Furthermore, forced expression of Smad1 induced chondrocyte markers as well. Dorsomorphin inhibited these inductions. Glomerular expressions of HIF-1α, BMP4, and chondrocyte markers were observed in diabetic nephropathy mice. These positive stainings were observed in mesangial sclerotic lesions. SOX9 was partially colocalized with HIF-1α and BMP4 in diabetic glomeruli. BMP4 knock-in transgenic mice showed not only similar pathological lesions to DN, but also the induction of chondrocyte markers in the sclerotic lesions. Here we demonstrate that HIF-1α and BMP4 induce SOX9 expression and subsequent chondrogenic phenotype change in DN. The results suggested that the transdifferentiation of MCs into chondrocyte-like cells in chronic hypoxic stress may result in irreversible structural change in DN.
Network Address Translation (NAT) Behavioral Requirements for Unicast UDP (2007)

This document defines basic terminology for describing different types of Network Address Translation (NAT) behavior when handling Unicast UDP and also defines a set of requirements that would allow many applications, such as multimedia communications or online gaming, to work consistently.Developing NATs that meet this set of requirements will greatly increase the likelihood that these applications will function properly.
An improved blood substitute. In vivo evaluation of its hemodynamic effects. (1997)

The purpose of the present study was to assess the ability of an improved free hemoglobin based blood substitute to serve as a resuscitative fluid in the treatment of hemorrhagic shock. Comparison studies were performed by using blood autotransfusion as a positive control. The hemodynamic parameters studied included cardiac index, mean arterial pressure, pulse pressure, heart rate, stroke volume index, and total peripheral resistance. Tissue oxygenation was measured in the biceps femori muscle by polarography. Hemorrhagic shock (at 40% of the total blood volume) in anesthetized rats caused severe disturbances in hemodynamic parameters and tissue oxygenation. Shock was characterized by a 66% drop in cardiac index, a 67% drop in mean arterial pressure with a significant increase in total peripheral resistance, and a 78% reduction in tissue oxygenation, all lasting 30 min. Resuscitation from shock with the blood substitute was effective in restoring hemodynamic parameters, producing vasodilation, and improving tissue oxygenation. Autotransfusion with blood also restored hemodynamics. However, lower tissue oxygenation and lack of vasodilation were noted. Therefore, the modified hemoglobin solution yielded better results than blood in the resuscitation of rats after hemorrhagic shock. The vasodilatory activity and the reduction of vasoconstriction that followed hemorrhage can be primarily linked with adenosine, which possesses vasodilatory and anti-inflammatory properties, and is used in our technology as an intermolecular cross linking reagent and hemoglobin surface modifier.
Calculations on location and dimensions of holes in a clarinet (1964)

For a cylindrical woodwind and in particular for a clarinet, methods are derived to calculate location and diameier of the holes. In a simple way the calculations are carried out for each hole separately, and independently of the other holes. Corrections are introduced for the influence on the resonance frequency of the overblowing hole and of the row of closed holes in the main tube. The usefulness of the formulae is proved by calculating all holes of a B-flat-Boehm-clarinet. It appears that if the clarinet is assumed to be cylindrical from the top downwards, the pressure antinode is located at 7 mm below the top. Some phenomena accompanying tuning of the clarinet are clarified.
Surfactant Limited Aggregation of Hydrophobic Molecules in Water (1997)

The precipitation in water of hydrophobic molecules has been studied in presence of addded surfactants. Amorphous particles grow trough aggregation of clusters of hydrophobic molecules; the growth is terminated by adsorption of surfactant. The particle sizes vary according to the concentrations of hydrophobic molecules and of surfactant molecules. Two regimes have been found for the use of surfactant molecules: at low surfactant concentrations, an efficient regime where all surfactant molecules are adsorbed on the surfaces of the growing particles; at high surfactant concentrations, a wasteful regime, where excess surfactant molecules are left in water. Attempts to reduce the particle sizes by adding increasing amounts of surfactant become inefficient at some point where most of the added surfactant remains in water. These results are explained by a kinetic aggregation of hydrophobic molecules and adsorption of surfactant. The results of experiments are well reproduced by simulations where aggregation is allowed to proceed unimpeded for a time τ, and then adsorption of the surfactant starts. In these conditions, particle sizes are determined by the rate of aggregation and by the value of this time delay.
Staphylococcus aureus intestinal colonization is associated with increased frequency of S. aureuson skin of hospitalized patients (2007)

We found that hospitalized patients with S. aureus nares and/or stool carriage frequently had S. aureus on their skin and on nearby environmental surfaces. S. aureus intestinal colonization was associated with increased frequency of positive skin cultures, which could potentially facilitate staphylococcal infections and nosocomial transmission.
Clinical pharmacology of clemastine in healthy dogs (2004)

Abstract The pharmacokinetic properties of clemastine were investigated in six healthy dogs and compared with the effect of the drug recorded as inhibition of wheal formation induced by intradermal injections of histamine. Clemastine clearance was high (median: 2.1 L h −1 kg −1 ) and the volume of distribution large (13.4 L kg −1 ). The half‐life after intravenous administration was 3.8 h and the plasma protein binding level in vitro was 98%. After oral administration, the bioavailability was only 3%. Given intravenously, clemastine (0.1 mg kg −1 ) inhibited wheal formation completely for 7 h, whereas the effect after oral administration (0.5 mg kg −1 ) was minor. The data show that most dosage regimens suggested in the literature for the oral administration of clemastine to dogs are likely to give too low a systemic exposure of the drug to allow effective therapy.
Synthesis and enhanced ethanol sensing characteristics of α-Fe<sub>2</sub>O<sub>3</sub><i>/</i>SnO<sub>2</sub>core–shell nanorods (2008)

Alpha-Fe(2)O(3)/SnO(2) core-shell nanorods are synthesized via a three-step process. X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses reveal that their diameters and lengths are respectively in the ranges 35-120 nm and 0.35-1.2 microm, and the thickness of the shell composed of 3.5 nm SnO(2) nanoparticles is about 10 nm. The core-shell nanostructures exhibit a dramatic improvement in ethanol sensing characteristics compared to pure alpha-Fe(2)O(3) nanorods. The sensor response is up to 19.6 under 10 ppm ethanol exposure at 220 degrees C. Both the response time and the recovery time of the core-shell structures are less than 30 s. Based on the space-charge layer model and semiconductor heterojunction theory, the small thickness of the SnO(2) shell and the formation of heterojunctions contribute to the enhanced ethanol sensing characteristics. Our results demonstrate that one-dimensional metal oxide core-shell nanostructures whose shell thickness is smaller than the Debye length are very promising materials for fabricating gas sensors with good performances.
Non-steroidal anti-inflammatory drugs and amyotrophic lateral sclerosis: Results from five prospective cohort studies (2012)

Animal and pathological studies suggest that inflammation may contribute to amyotrophic lateral sclerosis (ALS) pathology and that non-steroidal anti-inflammatory drugs (NSAIDs) might be protective. However, there are no prospective data on the relation between NSAID use and ALS risk in humans. The relation between NSAID use and ALS risk was explored in five large prospective cohort studies (the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health - AARP Diet and Health Study). Detailed NSAID information was sought from 780,000 participants, 708 of whom developed ALS during follow-up. Cox proportional hazards models were used within each cohort and cohort-specific estimates were pooled with random effects models. Results showed that neither non-aspirin NSAID use, nor aspirin use was associated with ALS risk overall. The multivariable, pooled relative risk was 0.96 (95% CI 0.76-1.22) among non-aspirin NSAID users compared with non-users. Duration of NSAID use in years and frequency of NSAID use were not associated with ALS risk overall. In conclusion, the results do not support an overall effect of NSAIDs on ALS risk, but because NSAIDs have heterogeneous effects, a role of individual compounds cannot be excluded.
Reduced Encoding Diffusion Spectrum Imaging Implemented With a Bi-Gaussian Model (2008)

Diffusion spectrum imaging (DSI) can map complex fiber microstructures in tissues by characterizing their 3-D water diffusion spectra. However, a long acquisition time is required for adequate q-space sampling to completely reconstruct the 3-D diffusion probability density function. Furthermore, to achieve a high q-value encoding for sufficient spatial resolution, the diffusion gradient duration and the diffusion time are usually lengthened on a clinical scanner, resulting in a long echo time and low signal-to-noise ratio of diffusion-weighted images. To bypass long acquisition times and strict gradient requirements, the reduced-encoding DSI (RE-DSI) with a bi-Gaussian diffusion model is presented in this study. The bi-Gaussian extrapolation kernel, based on the assumption of the bi-Gaussian diffusion signal curve across biological tissue, is applied to the reduced q-space sampling data in order to fulfill the high q-value requirement. The crossing phantom model and the manganese-enhanced rat model served as standards for accuracy assessment in RE-DSI. The errors of RE-DSI in estimating fiber orientations were close to the noise limit. Meanwhile, evidence from a human study demonstrated that RE-DSI significantly decreased the acquisition time required to resolve complex fiber orientations. The presented method facilitates the application of DSI analysis on a clinical magnetic resonance imaging system.