gebhart/patrepeval huggingface dataset:
Rate-determining step in the action of adenosine deaminase (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRate-determining step in the action of adenosine deaminaseRichard V. WolfendenCite this: Biochemistry 1969, 8, 6, 2409–2412Publication Date (Print):June 1, 1969Publication History Published online1 May 2002Published inissue 1 June 1969https://pubs.acs.org/doi/10.1021/bi00834a023https://doi.org/10.1021/bi00834a023research-articleACS PublicationsRequest reuse permissionsArticle Views182Altmetric-Citations31LEARN 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 Get e-Alerts
The Antimicrobial Peptide NK-2, the Core Region of Mammalian NK-Lysin, Kills Intraerythrocytic <i>Plasmodium falciparum</i> (2008)

In a time of dramatically increasing resistance of microbes to all kinds of antibiotics, natural antimicrobial peptides and synthetic analogs thereof have emerged as compounds with potentially significant therapeutical applications against human pathogens. Only very few of these peptide antibiotics have been tested against protozoan pathogens that are a major cause of morbidity and mortality in large parts of the world. Here, we studied the effect of NK-2, a peptide representing the cationic core region of the lymphocytic effector protein NK-lysin, on the malaria parasite Plasmodium falciparum. Whereas noninfected red blood cells were hardly affected, human erythrocytes infected with the parasite were rapidly permeabilized by NK-2 in the micromolar range. Loss of plasma membrane asymmetry and concomitant exposure of phosphatidylserine upon infection appears to be the molecular basis for the observed target preference of NK-2, as can be demonstrated by annexin V binding. The peptide also affects the viability of the intracellular parasite, as evidenced by the drop in DNA content of cultured parasites. Accumulated evidence derived from permeabilization assays using parasites and liposomes as targets and from fluorescence microscopy of infected erythrocytes treated with fluorescently labeled NK-2 indicates that the positively charged peptide electrostatically interacts with the altered and negatively charged plasma membrane of the infected host cell and traverses this membrane as well as the parasitophorous vacuole membrane to reach its final target, the intracellular parasite. The apparent affinity for foreign membranes that resulted in the death of a eukaryotic parasite residing in human host cells makes NK-2 a promising template for novel anti-infectives.
Regulation of collagen synthesis by inhibitory Smad7 in cardiac myofibroblasts (2007)

Transforming growth factor-beta(1) (TGF-beta(1)) signal and downstream Smads play an important role in tissue fibrosis and matrix remodeling in various etiologies of heart failure. Inhibitory Smad7 (I-Smad7) is an inducible regulatory Smad protein that antagonizes TGF-beta(1) signal mediated via direct abrogation of R-Smad phosphorylation. The effect of ectopic I-Smad7 on net collagen production was investigated using hydroxyproline assay. Adenovirus-mediated I-Smad7 gene (at 100 multiplicity of infection) transfer was associated with significant decrease of collagen synthesis in the presence and absence of TGF-beta(1) in primary rat cardiac myofibroblasts. In I-Smad7-infected cells, we also observed the ablation of TGF-beta(1)-induced R-Smad2 phosphorylation vs. LacZ controls. Overdriven I-Smad7 was associated with significantly increased expression of immunoreactive 65-kDa matrix metalloproteinase-2 (MMP-2) protein in culture medium of myofibroblast compared with LacZ-infected cells. Expression of the 72-kDa MMP-2 variant, e.g., the inactive form, was not altered by exogenous I-Smad7 transfection/overexpression. Furthermore, I-Smad7 overexpression was associated with a significant increase and decrease in expression of p27 and phospho-Rb protein, respectively, as well as reduced [(3)H]thymidine incorporation vs. Ad-LacZ-infected controls. We suggest that negative modulation of R-Smad phosphorylation by ectopic I-Smad7 may contribute to the downregulation of collagen in cardiac myofibroblasts and may suppress the proliferation of these cells. Thus treatments targeting the collagen deposition by overexpression of I-Smad7 may provide a new therapeutic strategy for cardiac fibrosis.
Diversified Structural Basis of a Conserved Molecular Mechanism for pH‐Dependent Dimerization in Spider Silk N‐Terminal Domains (2015)

Conversion of spider silk proteins from soluble dope to insoluble fibers involves pH-dependent dimerization of the N-terminal domain (NT). This conversion is tightly regulated to prevent premature precipitation and enable rapid silk formation at the end of the duct. Three glutamic acid residues that mediate this process in the NT from Euprosthenops australis major ampullate spidroin 1 are well conserved among spidroins. However, NTs of minor ampullate spidroins from several species, including Araneus ventricosus ((Av)MiSp NT), lack one of the glutamic acids. Here we investigate the pH-dependent structural changes of (Av)MiSp NT, revealing that it uses the same mechanism but involves a non-conserved glutamic acid residue instead. Homology modeling of the structures of other MiSp NTs suggests that these harbor different compensatory residues. This indicates that, despite sequence variations, the molecular mechanism underlying pH-dependent dimerization of NT is conserved among different silk types.
Carbamates with Differential Mechanism of Inhibition Toward Acetylcholinesterase and Butyrylcholinesterase (2008)

Most carbamates are pseudoirreversible inhibitors of cholinesterases. Phenothiazine carbamates exhibit this inhibition of acetylcholinesterase but produce reversible inhibition of butyrylcholinesterase, suggesting that they do not form a covalent bond with the catalytic serine. This atypical inhibition is attributable to pi-pi interaction of the phenothiazine moiety with F329 and Y332 in butyrylcholinesterase. These residues are in a helical segment, referred to here as the E-helix because it contains E325 of the catalytic triad. The involvement of the E-helix in phenothiazine carbamate reversible inhibition of butyrylcholinesterase is confirmed using mutants of this enzyme at A328, F329, or Y332 that show typical pseudoirreversible inhibition. Thus, in addition to various domains of the butyrylcholinesterase active site gorge, such as the peripheral anionic site and the pi-cationic site of the Omega-loop, the E-helix represents a domain that could be exploited for development of specific inhibitors to treat dementias.
A New Approach to Casing Design for Salt Formations (1985)

ABSTRACT Data from over forty incidences of casing collapse in the Midcontinent area is used to develop a new design method for casing to be set across salt formations. The new method reduces overdesign of casing 37% over hydrostatic collapse designs while predicting all failures. This design method involves modification of the standard Von Mises equations to account for the nonuniform collapse loads generally presented by salt formations. The modification involves use of curved beam theory and correlation to field data. It is valid across the midcontinent region and may be adapted to other areas. Additionally, tight casing due to excessive elastic deformation may be considered as well as failure due to plastic collapse. Discussion includes current industry design methods and the mechanics of formation flow.
Enhancement of the human antibody response by C8-substituted guanine ribonucleosides in synergy with interleukin 2. (1985)

The antigen-specific primary antibody response of human lymphocytes in vitro was studied with respect to dependency upon the lymphokine interleukin 2 (IL 2) and its subsequent modulation by C8-substituted guanine ribonucleosides. The specific response to sheep erythrocytes was shown to be dependent on the presence of IL 2 in culture. However, addition of optimal concentrations of the nucleoside, 7-methyl-8-oxoguanosine (7m8oGuo), to cultures containing antigen and IL 2 resulted in marked amplification of the underlying antibody response. This synergistic effect between 7m8oGuo and IL 2 was antigen dependent and could not be accounted for by summation of the independent antigen-specific and nonspecific (polyclonal) components. That IL 2 itself was in fact responsible for both the specific response to antigen and the synergistic interaction with 7m8oGuo was confirmed in experiments with purified IL 2 produced by recombinant DNA technology. The response to antigen was enhanced by 7m8oGuo in a dose-dependent fashion. The results of kinetic studies demonstrated that this nucleoside is fully effective within the context of an ongoing immune response, because addition of 7m8oGuo could be delayed up to 3 days of the 6-day culture period without loss of subsequent immunoenhancement. Lymphocyte populations largely depleted of T cells were capable of mounting vigorous responses to antigen in the presence of 7m8oGuo so long as IL 2, either partially purified or purified recombinant material, was added to culture.
Development of a Gene Knockout System Using Mobile Group II Introns (Targetron) and Genetic Disruption of Acid Production Pathways in Clostridium beijerinckii (2013)

Clostridium beijerinckii is a well-known solvent-producing microorganism with great potential for biofuel and biochemical production. To better understand and improve the biochemical pathway to solvents, the development of genetic tools for engineering C. beijerinckii is highly desired. Based on mobile group II intron technology, a targetron gene knockout system was developed for C. beijerinckii in this study. This system was successfully employed to disrupt acid production pathways in C. beijerinckii, leading to pta (encoding phosphotransacetylase)- and buk (encoding butyrate kinase)-negative mutants. In addition to experimental characterization, the mutant phenotypes were analyzed in the context of our C. beijerinckii genome-scale model. Compared to those of the parental strain (C. beijerinckii 8052), acetate production in the pta mutant was substantially reduced and butyrate production was remarkably increased, while solvent production was dependent on the growth medium. The pta mutant also produced much higher levels of lactate, suggesting that disrupting pta influenced the energy generation and electron flow pathways. In contrast, acetate and butyrate production in the buk mutant was generally similar to that of the wild type, but solvent production was consistently 20 to 30% higher and glucose consumption was more rapid and complete. Our results suggest that the acid and solvent production of C. beijerinckii can be effectively altered by disrupting the acid production pathways. As the gene disruption method developed in this study does not leave any antibiotic marker in a disrupted allele, multiple and high-throughput gene disruption is feasible for elucidating genotype and phenotype relationships in C. beijerinckii.
Migrating from 8- to 16-bit processors (2002)

During the mid 1990's, there has been a major upswing in the growth of applications requiring 16-bit microcontrollers. Dataquest have estimated that the growth of 16-bit devices will be more than double that of the combined growth of all categories of microcontrollers, at 43.9%. The main reasons for the growth in 16-bit applications is that pricing is becoming very competitive and traditional 8-bit applications typically require more processing power examples of these applications range from disk drive controllers, to airbags, to cellular communications. The trend for MCU users in embedded control systems is to migrate from assembly language to higher level languages such as C. The enhancement of instruction sets and addressing modes does not only make life easier for the assembly language programmer. When C code is compiled, the availability of lower-level resources such as efficient register use and data manipulation capabilities greatly increase the efficiency of the compiled C code. This is true for both code size generated and execution speed. Many of the enhancements of the M68HC12 have been a direct result of the recognition that M68HCll users need more performance and the option to migrate to a high level language without the penalties in code efficiency normally associated with such a step.
Experimental study of a high-efficiency low-emission surface combustor-heater (1991)

The surface combustor-heater is a combined combustion/heat-transfer device in which the heat-exchange surfaces are embedded in a stationary bed of refractory material where gaseous fuel is burned. Because of intensive heat radiation from the hot solid particles and enhanced heat convection from the gas flow to the heat-exchange tubes, heat transfer is significantly intensified. Removing heat simultaneously with the combustion process has the benefit of reducing the combustion temperature, which suppresses NO{sub x} formation. A basic experimental study was conducted on a 60-kW bench-scale surface combustor-heater with two rows of water-cooled tube coils to evaluate its performance and explore the mechanism of combined convective-radiative heat transfer and its interaction with combustion in the porous matrix. Combustion stability in the porous matrix, heat-transfer rates, emissions, and pressure drop through the unit have been investigated for the variable parameters of operation and unit configurations. Experimental results have demonstrated that high combustion intensity (up to 2.5 MW/m{sup 2}), high heat-transfer rates (up to 310 kW/m{sup 2}), high density of energy conversion (up to 8 MW/m{sup 3}), as well as ultra-low emissions (NO{sub x} and CO as low as 15 vppm*) have been achieved. The excellent performance of the test unit and the extensive data obtained from the present experimental study provide the basis for further development of high-efficiency and ultra low-emission water heaters, boilers, and process heaters based on the surface combustor-heater concept. 4 refs., 16 figs.
Self-Emulsifying Drug Delivery System for Enhancing Bioavailability and Lymphatic Delivery of Tacrolimus (2014)

A self-emulsifying drug delivery system (SEDDS) containing tacrolimus has been developed to enhance the bioavailability and lymphatic delivery of tacrolimus. Solubility tests, combination tests, and phase diagrams were constructed for different sorts and ratios of oils, surfactants, and cosurfactants to identify optimal formulation. Optimized SEDDS was assessed for droplet size, zeta potential, stability in various media, and in vitro release. The tacrolimus-loaded SEDDS and commercial capsule (Prograf®) were orally administered (5 mg/kg) to rats. Whole blood, and mesenteric and axillary lymph node samples were taken and the concentrations of tacrolimus were measured to evaluate pharmacokinetic characteristics and the lymphatic delivery effects. The optimized SEDDS droplets were approximately 40 nm in size and stable enough to endure gastric pH environments. The release rate of tacrolimus from SEDDS was significantly higher than that from the commercial capsule. The bioavailability of tacrolimus in SEDDS after oral administration was significantly improved versus that of Prograf®. The lymphatic targeting efficiency of the prepared SEDDS formulation showed significantly greater than that of Prograf®. Our research indicates that prepared SEDDS can be an alternative to the conventional oral formulation of tacrolimus. Furthermore, SEDDS should be explored as a potential drug carrier for other lipophilic drugs.
Hydroacoustic Calibration With Imploding Glass Spheres (2000)

Abstract : Calibration and validation of acoustic source and propagation models plays an important role in the hydroacoustic component of Comprehensive Nuclear-Test-Ban Treaty (CTBT) monitoring. This validation requires that we have a loud acoustic source with sufficient low-frequency energy that could be easily deployed in the Sound Fixing and Ranging (SOFAR) channel. SUS charges (Signal Underwater Source, 0.82 kg of explosive) have been used for this purpose for years, but safety and environmental concerns make these sources impractical. Light bulbs with sinkers have long been used as shallow acoustic sources, but are too small for the purposes stated. Here we describe investigations into the use of thin-walled glass spheres as calibration sources. Since glass becomes stronger under pressure, a method is needed to reliably initiate the failure of the sphere at a specified depth. A prototype-smashing device, called a spherecracker, was designed for this purpose. It consists of a 4-inch-diameter piston with a 1/4-inch diameter ram. The end cap on the device's cylinder tapers to a 1-inch diameter opening with a rupture disk calibrated to fail within 5% of the failure pressure. The ram initiates failure by punching a hole into the glass sphere. In March 1999 we conducted an experiment with a 10-inch-diameter glass sphere at Dabob Bay, Washington. The sphere was tethered and lowered to a depth of 600 ft. A metal pipe was then slid down the tether line as a smashing device. This implosion produced a pressure pulse with peak amplitude of 9x10(11) microPa at 1 meter and duration of 1 msec. The signal was recorded at a sampling rate of 100 kHz, and the spectrum shows energy from 50-50000 Hz. The low-frequency source level is approximately 200 dB re 1-microPa. In February 2000 a test was conducted with a 22-liter glass sphere off the coast of San Diego at a depth of 685 meters in water that was 1200 meters deep.
A Review of Flexible and Weaveable Fiber-Like Supercapacitors (2013)

The rapid development of small, thin, lightweight, and even flexible wearable electronic devices has led to a growing need for matchable textile energy storage devices with high performance. Among different sources, supercapacitors are capable of providing higher power density than their counterparts and are drawing tremendous interest from both research and engineering communities. Just in the past two years, flexible and weaveable fiber-like supercapacitors have emerged and attracted increasing research attention. In this up-to-date review, after a brief introduction of supercapacitor principle, performance, and electrode/electrolyte materials, we summarize the current development of two types of fiber-like supercapacitors, as well as various advanced fiber electrode materials that have been utilized. Finally, we discuss integrated fiber-like power systems incorporated with fiber-like supercapacitors and fiberlike energy harvesting and conversion devices, and identify new research trends in materials, fabrication, and future applications.
Electromagnetically levitated flywheel energy storage system with very low internal impedance (2002)

This paper describes an original concept of electromagnetically levitated flywheel energy storage capable of very fast discharges and, consequently, unusually high pulsed power in rapid pulses, with short rise time. The anisotropy and nonuniformity of the compensation winding allows not only for the very low internal impedance, but also for the reduction of losses during the electrical discharge by a partial decoupling from excitation. A discussion of force management, excitation management and related effects recommends the use of ferromagnetic structures, for both drum and disk topologies, in order to achieve the desired performance.
Large-scale reprogramming of cranial neural crest gene expression by retinoic acid exposure (2004)

Although retinoic acid (RA), the active form of vitamin A, is required for normal embryonic growth and development, it is also a powerful teratogen. Infants born to mothers exposed to retinoids during pregnancy have a 25-fold increased risk for malformations, nearly exclusively of cranial neural crest-derived tissues. To characterize neural crest cell responses to RA, we exposed murine crest cultures to teratogenic levels of RA and subjected their RNA to microarray-based gene expression profile analysis using Affymetrix MG-U74Av2 GeneChips. RNAs were isolated from independent cultures treated with 10(-6) M RA for 6, 12, 24, or 48 h. Statistical analyses of gene expression profile data facilitated identification of the 205 top-ranked differentially regulated genes whose expression was reproducibly changed by RA over time. Cluster analyses of these genes across the independently treated sample series revealed distinctive kinetic patterns of altered gene expression. The largest group was transiently affected within the first 6 h of exposure, representing early responding genes. Group 2 showed sustained induction by RA over all times, whereas group 3 was characterized by the suppression of a time-dependent expression increase normally seen in untreated cells. Additional patterns demonstrated time-dependent increased or decreased expression among genes not normally regulated to a significant extent. Gene function analysis revealed that more than one-third of all RA-regulated genes were associated with developmental regulation, including both canonical and noncanonical Wnt signaling pathways. Multiple genes associated with cell adhesion and cell cycle regulation, recognized targets for the biological effects of RA, were also affected. Taken together, these results support the hypothesis that the teratogenic effects of RA derive from reprogramming gene expression of a host of genes, which play critical roles during embryonic development regulating pathways that determine subsequent differentiation of cranial neural crest cells.
Antifibrotic Activity of Diarylheptanoids from<i>Betula platyphylla</i>toward HSC-T6 Cells (2012)

A chemical investigation of the n-butanol fraction of the inner bark of Betula platyphylla led to the isolation of seven diarylhepanoids, (-)-centrolobol (1), aceroside VII (2), aceroside VIII (3), (3R)-1,7-bis-(4-hydroxyphenyl)-3-heptanol-3-O-[2,6-bis-O-(β-D-apiofuranosyl)-β-D-glucopyranoside (4), 1,7-bis-(4-hydroxyphenyl)-5-hepten-3-one (5), platyphyllone (6) and platyphylloside (7). The antifibrotic effects of these isolates were evaluated with HSC-T6 cells by assessing cell proliferation. Among them, compounds 1, 2, 5 and 6 significantly inhibited the proliferation of HSCs in a dose-dependent manner at concentrations from 10 µM to 100 µM. Compound 5 in particular dramatically decreased the collagen content and increased the Caspase-3/7 activity. Taken together, the antifibrotic activity of B. platyphylla and its constituents might suggest therapeutic potential against liver fibrosis.
Viscosity and Elasticity of Oil Surfaces and Oil-Water Interfaces (1955)

A study of the rheological properties of lubricating oils was made by means of semiquantitative measurements of the viscosity and elasticity of surface and interfacial films. A torsion-pendulum type, surface viscometer was used. A refined, uncompounded mineral oil was shown to possess neither surface nor interfacial viscosity or elasticity. One additive in mineral oil showed surface viscosity and elasticity, and two additives developed these properties at an oil-water interface. The aged, viscous surface and interfacial films studied were found to be non-Newtonian.