gebhart/patrepeval huggingface dataset:
Learning from Directed Evolution: <i>Thermus aquaticus</i> DNA Polymerase Mutants with Translesion Synthesis Activity (2011)

DNA is being constantly damaged by endo- and exogenous agents such as reactive oxygen species, chemicals, radioactivity, and ultraviolet radiation. Additionally, DNA is inherently labile, and this can result in, for example, the spontaneous hydrolysis of the glycosidic bond that connects the sugar and the nucleobase moieties in DNA; this results in abasic sites. It has long been obscure how cells achieve DNA synthesis past these lesions, and only recently has it been discovered that several specialized DNA polymerases are involved in translesion synthesis. The underlying mechanisms that render one DNA polymerase competent in translesion synthesis while another DNA polymerase fails are still indistinct. Recently two variants of Taq DNA polymerase that exhibited higher lesion bypass ability than the wild-type enzyme were identified by directed-evolution approaches. Strikingly, in both approaches it was independently found that substitution of a single nonpolar amino acid side chain by a cationic side chain increases the capability of translesion synthesis. Here, we combined both mutations in a single enzyme. We found that the KlenTaq DNA polymerase that bore both mutations superseded the wild-type as well as the respective single mutants in translesion-bypass proficiency. Further insights in the molecular basis of the detected gain of translesion-synthesis function were obtained by structural studies of DNA polymerase variants caught in processing canonical and damaged substrates. We found that increased positive charge of the surface potential in the area proximal to the negatively charged substrates promotes translesion synthesis by KlenTaq DNA polymerase, an enzyme that has very limited naturally evolved capability to perform translesion synthesis. Since expanded positively charged surface potential areas are also found in naturally evolved translesion DNA polymerases, our results underscore the impact of charge on the proficiency of naturally evolved translesion DNA polymerases.
Nucleoside Diphosphate-sugar 4-Epimerases I. Uridine Diphosphate Glucose 4-Epimerase of Wheat Germ (1969)

Uridine diphosphate (UDP)-glucose 4-epimerase (EC 5.1.3.2) has been purified over 1000-fold from extracts of wheat germ by MnCl(2) treatment, (NH(4))(2)SO(4) fractionation, Sephadex column chromatography, and adsorption onto and elution from calcium phosphate gel. The enzyme has a pH optimum of 9.0. Km values are 0.1 mm for UDP-d-galactose and 0.2 mm for UDP-d-glucose. NAD is required for activity; K(a) = 0.04 mm. NADH is an inhibitor strictly competitive with NAD; K(i) = 2 mum. Wheat germ also contains UDP-l-arabinose 4-epimerase (EC 5.1.3.5) and thymidine diphosphate (TDP)-glucose 4-epimerase which are distinct from UDP-glucose 4-epimerase.
Tumor necrosis factor-α–dependent expression of phosphodiesterase 2: role in endothelial hyperpermeability (2005)

The pleiotropic cytokine tumor necrosis factor-alpha (TNF-alpha) and thrombin lead to increased endothelial permeability in sepsis. Numerous studies demonstrated the significance of intracellular cyclic nucleotides for the maintenance of endothelial barrier function. Actions of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are terminated by distinct cyclic nucleotide phosphodiesterases (PDEs). We hypothesized that TNF-alpha could regulate PDE activity in endothelial cells, thereby impairing endothelial barrier function. In cultured human umbilical vein endothelial cells (HUVECs), we found a dramatic increase of PDE2 activity following TNF-alpha stimulation, while PDE3 and PDE4 activities remained unchanged. Significant PDE activities other than PDE2, PDE3, and PDE4 were not detected. TNF-alpha increased PDE2 expression in a p38 mitogen-activated protein kinase (MAPK)-dependent manner. Endothelial barrier function was investigated in HUVECs and in isolated mice lungs. Selective PDE2 up-regulation sensitized HUVECs toward the permeability-increasing agent thrombin. In isolated mice lungs, we demonstrated that PDE2 inhibition was effective in preventing thrombin-induced lung edema, as shown with a reduction in both lung wet-to-dry ratio and albumin flux from the vascular to bronchoalveolar compartment. Our findings suggest that TNF-alpha-mediated up-regulation of PDE2 may destabilize endothelial barrier function in sepsis. Inhibition of PDE2 is therefore of potential therapeutic interest in sepsis and acute respiratory distress syndrome (ARDS).
Integrated Microchannel Cooling for Power Electronic Modules (2016)

Abstract The power electronic module plays a key role in the power system by providing the needed physical support, electrical contact and insulation, and thermal pathway for power devices. Using wide bandgap power semiconductors in the power modules enables high-frequency and low-loss switching at relatively high temperatures for efficient power conversion. These advantages could lead to an increase in power-density for the power module as well as a reduction of cost, weight, and volume at the system level. However, the highly integrated power module requires advanced thermal management solutions for effective heat removal from the active chips to achieve high reliability. The evaluation of thermal performance for the power module is critical for its packaging design, because most of the heat generated by the semiconductors is dissipated through the module package. It is even more critical for the gallium nitride (GaN)-based power modules due to the lower thermal conductivity of the GaN material compared with that of silicon and silicon carbide. This paper provides a brief introduction of power modules in conventional packaging design and a review of several new packaging structures with advanced thermal management solutions. The direct-bonded-copper (DBC) substrate with integrated microchannel cooling designed for a new packaging structure is proposed for highly integrated power modules. In this design, the cooling microchannels are embedded inside the aluminum nitride (AlN) layer of the DBC substrate. In finite element analysis (FEA) simulation model of the new package, six high-voltage GaN transistors are arranged on the top surface of the DBC substrate to realize a three-phase inverter circuit. Three straight embedded microchannels with a cross-sectional area of 0.3 mm × 5 mm are located underneath the GaN devices. The average maximum temperature of the GaN devices in the new package is around 72 °C (50 W power loss applied on each die), which is about 16 °C lower than that in the traditional power module package. A thermal transfer coefficient of 2000 W/m2 K, which is equivalent to the liquid cooling condition, is applied on the bottom surface of the baseplate in the traditional package. Enhanced heat dissipation capability is demonstrated using this integrated microchannel cooling method. Further study will focus on the fabrication of a prototype and experimental testing.
Pulsed Laser Deposition of Transparent Conducting Indium Tin Oxide Films in Magnetic Field Perpendicular to Plume (2001)

In 2 O 3 doped with 5 wt% SnO 2 (indium-tin oxide(ITO)(5 wt%)) films have been deposited on glass and quartz substrates in a magnetic field generated from three pieces of rare–earth permanent magnets (1.25 T flux density) placed at every 120° angle to surround the plume produced by pulsed laser deposition using an ArF laser (λ=193 nm). In all experiments, a repetition rate of 10 Hz, an energy density of 1.5 J/cm 2 , and an irradiation time of 20–30 min (12000–18000 shots) were used. The lowest resistivity of 7.2×10 -5 Ω·cm and an optical transmittance of more than 90% in the visible region of the spectrum were obtained for approximately 30-nm-thick ITO (5 wt%) films deposited at a substrate temperature of 300°C in oxygen with a flow rate of 2 sccm. Very smooth surfaces with an average surface roughness of 0.61 nm were observed by scanning electron microscope (SEM) and atomic force microscope (AFM).
A DS-CDMA tracking mode receiver with joint channel/delay estimation and MMSE detection (2001)

A tracking mode receiver for asynchronous direct-sequence CDMA is presented based on the extended Kalman filter (EKF). The EKF jointly estimates the delays and multipath coefficients of the received CDMA waveform, and provides a modified minimum mean-square error (MMSE) estimate of the user data (MMSE-EKF). In order to obtain a practical algorithm, each user signal is tracked individually, with the remaining users modeled as colored Gaussian noise. However, the EKFs are coupled through the multiple access interference (MAI) covariance estimates. In order to obtain meaningful performance measures, approximate worst-case undesired user delays that minimize the desired user SNR and delay estimation Cramer-Rao bound are obtained. It is shown that such worst-case delays can be efficiently computed using the alternating maximization (A-M) algorithm. The resulting bit error rate (BER) performance of the MMSE-EKF tracking receiver is evaluated through a combination of simulation and analysis. The mean-time to lose lock (MTTLL) for a genie-aided EKF delay estimator is also obtained using the A-M computed delays.
Influence of Dietary Quercetin on Glutathione Redox Status in Mice (2008)

Flavonoids such as quercetin have been shown to serve as a protective defense against oxidative damage in vivo. However, the bioavailability of quercetin depends on the food source and type of glycosidic moiety linked to the molecule. In this study, mice were fed 1 mg/day quercetin in the form of quercetin aglycone, rutin, apple, or onion, and reduced glutathione (GSH), oxidized glutathione (GSSG), and protein-GSH mixed disulfides were determined to investigate the influence of dietary quercetin on the GSH redox status in metabolically active tissues, mitochondria, and plasma of mice. All quercetin treatment groups produced increases in the GSH:GSSG ratio and decreases in mixed disulfide levels in hepatic tissue. Cardiac tissue did not change in response to dietary quercetin; however, cardiac mitochondria demonstrated a reduction in the GSH:GSSG ratio and an increase in protein mixed disulfide levels. No significant changes were observed in the plasma GSH:GSSG ratio, but mixed disulfide levels were decreased for all of the diets. The changes in plasma redox status did not parallel the changes in the tissues. Onion fed mice demonstrated the greatest increases in GSH:GSSG ratios and the greatest decreases in protein mixed disulfide levels of all diets compared. For all treatment groups, increases in the GSH:GSSG ratios corresponded with decreases in protein mixed disulfide levels. The results of this study indicate that quercetin influences GSH:GSSG ratios and protein thiolation in a tissue-specific manner and that these effects are dependent on food source and bioavailability.
Irinotecan Pharmacogenetics: Influence of Pharmacodynamic Genes (2008)

This is the first comprehensive pharmacogenetic investigation of irinotecan pharmacodynamic factors, and our findings suggest that genetic variation in the pharmacodynamic genes may influence the efficacy of irinotecan-containing therapies in advanced colorectal cancer patients.
THE CRYSTAL STRUCTURE OF MERCURY-SUBSTITUTED POPLAR PLASTOCYANIN AT 1.9-ANGSTROMS RESOLUTION (1985)

The crystal structure of Hg(II)-plastocyanin has been determined and refined at a resolution of 1.9 A. The crystals were prepared by soaking crystals of Cu(II)-plastocyanin from poplar leaves (Populus nigra var. italica) in a solution of a mercuric salt. Replacement of the Cu(II) atom in plastocyanin by Hg(II) causes only minor changes in the geometry of the metal site, and there are few significant changes elsewhere in the molecule. It is concluded that, as in the case of the native protein, the geometry of the metal site is determined by the polypeptide. The weak metal-S(methionine) bond found in Cu(II)-plastocyanin remains weak in Hg(II)-plastocyanin. The "flip" of a proline side chain close to the metal site from a C gamma-exo conformation in Cu(II)-plastocyanin to a C gamma-endo conformation in Hg(II)-plastocyanin suggests that this region of the molecule is particularly flexible. Crystallographic evidence for the close similarity of the Hg(II)- and Cu(II)-plastocyanin structures was originally obtained from electron density difference maps at 2.5-A resolution. The refinement of the structure was begun with a set of atomic coordinates taken from the structure of Cu(II)-plastocyanin. A Hg(II) atom was substituted for the Cu(II) atom, and the side chains of 6 residues in the vicinity of the metal site were omitted. Three series of stereochemically restrained least-squares refinement calculations were interspersed with two stages of model adjustment followed by phase extension. Fifty-nine water molecules were located. The final structure has a crystallographic residual R = 0.16.
A Highly Sensitive and Subspecies-Specific Surface Antigen Enzyme- Linked Immunosorbent Assay for Diagnosis of Johne's Disease (2006)

Johne's disease (JD), or paratuberculosis, caused by Mycobacterium avium subsp. paratuberculosis, is one of the most widespread and economically important diseases of livestock and wild ruminants worldwide. Control of JD could be accomplished by diagnosis and good animal husbandry, but this is currently not feasible because commercially available diagnostic tests have low sensitivity levels and are incapable of diagnosing prepatent infections. In this study, a highly sensitive and subspecies-specific enzyme-linked immunosorbent assay was developed for the diagnosis of JD by using antigens extracted from the surface of M. avium subsp. paratuberculosis. Nine different chemicals and various intervals of agitation by vortex were evaluated for their ability to extract the surface antigens. Various quantities of surface antigens per well in a 96-well microtiter plate were also tested. The greatest differences in distinguishing between JD-positive and JD-negative serum samples by ethanol vortex enzyme-linked immunosorbent assay (EVELISA) were obtained with surface antigens dislodged from 50 microg/well of bacilli treated with 80% ethanol followed by a 30-second interval of agitation by vortex. The diagnostic specificity and sensitivity of the EVELISA were 97.4% and 100%, respectively. EVELISA plates that had been vacuum-sealed and then tested 7 weeks later (the longest interval tested) had diagnostic specificity and sensitivity rates of 96.9 and 100%, respectively. In a comparative study involving serum samples from 64 fecal culture-positive cattle, the EVELISA identified 96.6% of the low-level fecal shedders and 100% of the midlevel and high-level shedders, whereas the Biocor ELISA detected 13.7% of the low-level shedders, 25% of the mid-level shedders, and 96.2% of the high-level shedders. Thus, the EVELISA was substantially superior to the Biocor ELISA, especially in detecting low-level and midlevel shedders. The EVELISA may form the basis for a highly sensitive and subspecies-specific test for the diagnosis of JD.
Inducible Heat Shock Protein 70 Promotes Myelin Autoantigen Presentation by the HLA Class II (2004)

In this study, we investigated the role of the inducible form of heat shock protein 70 (hsp70) in the presentation of the major putative autoantigen in multiple sclerosis, myelin basic protein (MBP), in the context of appropriate MHC class II. By coimmunoprecipitation, we found that MBP is associated with hsp70 in APC in an ATP/ADP-dependent manner. Additionally, using confocal microscopy, hsp70 was detected in the endocytic pathway of APC, where it colocalized with MBP and HLA-DR. The immunodominant epitopes of MBP 85-99 and 80-99 were shown to bind selectively and specifically to hsp70 by surface plasmon resonance. The functional significance of MBP interaction with hsp70 was demonstrated by the detection of enhanced responses of an MBP-specific T cell hybridoma to MBP and MBP 80-99 with increasing levels of hsp70 and reduced responses when hsp70 expression was diminished within APC-expressing DRA*0101, DRB1*1501 (DR1501). However, when MBP 85-99 was used as the stimulus, T cell hybridoma responses were not enhanced by hsp70 overexpression within APC, suggesting that hsp70 contributes to Ag processing rather than Ag presentation. The importance of a direct association between MBP and hsp70 in the presentation pathways was demonstrated by enhanced efficacy of MBP presentation by APC transfected with a plasmid vector encoding a fusion hsp70-MBP protein. This is the first report on the involvement of self-inducible hsp70 in MHC class II-dependent autoantigen processing by APC. It implicates that aberrant self hsp expression may lead to the enhancement/modulation of autoimmune responses.
Atomic layer deposition of RuO2 thin films on SiO2 using Ru(EtCp)<inf>2</inf> and O2 plasma (2015)

Ruthenium dioxide (RuO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) thin films can be used as the electrode material for future technology nodes. In this work, atomic layer deposition (ALD) was used to deposit thin films of RuO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> on SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> using bis-(ethylcyclopentadienyl)-ruthenium [Ru(EtCp) <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ] as the precursor and oxygen (O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) plasma as the reducing agent. The thermal stability of the deposited films were investigated in the N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ambient and in the forming-gas environments using rapid thermal processing (RTP). High-resolution transmission electron microscope (HR-TEM) and atomic force microscopy (AFM) were also employed to explore the growth mechanism of the RuO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> thin films on SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> .
Calcium activity versus "calcium threshold" as the key factor in the induction of yeast flocculation in simulated industrial fermentations (1991)

Yeast flocculation is regulated by two parameters: the free-calcium activity and the "calcium threshold" or the quantity of calcium at which cells flocculate in a turbidimetric test. The study of the influence of different factors such as calcium concentration, pH, and chelating agents on flocculation has led us to put forward the following hypothesis. Flocculation occurs when the calcium threshold becomes equal to free-calcium activity, i.e., when the medium contains the exact quantity of calcium necessary for flocculation to occur. This hypothesis has been confirmed under standard laboratory culture conditions and in simulated industrial fermentations. Key words: flocculation, yeast, Saccharomyces cerevisiae, calcium induction.
Diagnostic support in the Oxford System of Medicine (1988)

The Oxford System of Medicine (OSM) project was started in 1985 with the aim of producing a working specification for a decision support system for general practitioners. The feasibility of such a project seems to depend upon designing a system that is acceptable to general practitioners and acquiring, verifying and maintaining the knowledge base. The authors consider that a knowledge-based theory of decision making, coupled to strategic and policy defining knowledge about diagnosis or any other task, and separated from the simple facts of medicine could be the cornerstone for a decision support system that is flexible enough to provide a suitable environment for author, editor and general practitioner. They present an example of diagnostic consultation starting with the problem of a swelling joint.
Mechanistic modeling of epoxy-amine kinetics. 1. Model compound study (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanistic modeling of epoxy-amine kinetics. 1. Model compound studyJovan Mijovic, Arnon Fishbain, and Jony WijayaCite this: Macromolecules 1992, 25, 2, 979–985Publication Date (Print):January 1, 1992Publication History Published online1 May 2002Published inissue 1 January 1992https://pubs.acs.org/doi/10.1021/ma00028a072https://doi.org/10.1021/ma00028a072research-articleACS PublicationsRequest reuse permissionsArticle Views1335Altmetric-Citations130LEARN 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
Re: syndromic management of genital ulcer disease: the operational and social aspects -letter- (1997)

The main argument for promoting the syndromic management of STDs has been the lack of facilities and paucity of trained personnel. The authors question this not very scientific and ethical approach to achieve this goal. (non-author abstract)
Synthesis of 1-(hydroxyalkoxy)pyrimidines, a novel series of acyclic nucleoside analogues (1990)

Syntheses of 1-(3-hydroxypropoxy), 1-[3-hydroxy-2-(hydroxymethyl)propoxy], 1-(2,3-dihydroxypropoxy), and 1-(3,4-dihydroxybutoxy) derivatives of thymine (1a–d) and uracil (2a–d) are described. These acyclonucleosides were obtained by cyclisation of appropriately functionalised ureas with either ethyl 3,3-diethoxy-2-methylpropionate (4) or methyl 3,3-dimethoxypropionate (5). The uracils (2a–d) were converted into cytosine analogues (3a–d)via intermediate 4-(1,2,4-triazol-1-yl) derivatives. (E)-5-(2-Bromovinyl)(36) and 5-vinyl (37) analogues of (2a) were prepared by palladium(II)-catalysed cross-coupling reactions on the 5-iodo derivative (32). The 5-fluoro-1-(hydroxyalkoxy)uracils (41) and (42) were obtained by alkylation of 5-fluoro-1-hydroxyuracil with a suitably functionalised halide. None of this series of acyclonucleosides showed activity in antiviral tests in cell cultures.