gebhart/patrepeval huggingface dataset:
Evernimicin (SCH27899) Inhibits both Translation and 50S Ribosomal Subunit Formation in Staphylococcus aureus Cells (2000)

The effects of the everninomicin antibiotic evernimicin (SCH27899) on growing Staphylococcus aureus cells were investigated. Cellular growth rates and viable cell numbers decreased with increasing antibiotic concentrations. The rate of protein synthesis, measured as (35)S-amino acid incorporation, declined in parallel with the growth rate. Significantly, the formation of the 50S ribosomal subunit was inhibited in a dose-dependent fashion as well. 30S ribosomal subunit synthesis was not affected over the same concentration range. Evernimicin did not stimulate the breakdown of mature ribosomal subunits. Pulse-chase labeling experiments revealed a reduced rate of 50S subunit formation in drug-treated cells. Two erythromycin-resistant strains of S. aureus that carried the ermC gene were as sensitive as wild-type cells to antibiotic inhibition. In addition, two methicillin-resistant S. aureus organisms, one sensitive to erythromycin and one resistant to the macrolide, showed similar sensitivities to evernimicin. These results suggest a use for this novel antimicrobial agent against antibiotic-resistant bacterial infections.
T cell receptor diversity in severe combined immunodeficiency following HLA-haploidentical bone marrow transplantation. (1991)

We have studied T cell receptor (TCR) diversity in a group of six patients with severe combined immunodeficiency (SCID) previously treated by HLA-haploidentical bone marrow transplantation (BMT). At the time of study, all patients had developed stable T cell chimerism and full reconstitution of T cell functions in the absence of acute or chronic graft-versus-host disease. Peripheral blood lymphocytes (PBL) were analysed by immunofluorescence using a panel of monoclonal antibodies (MoAb) against TCR variable (V) region epitopes including V beta 5, V beta 6, V beta 8, V beta 12, and V alpha 2. Our results showed that in each patient studied a low but significant portion of PBL reacted with each anti-TCR V region epitope MoAb used, in a manner that was, on statistical grounds, indistinguishable from results obtained with PBL from healthy controls. We conclude that within the experimental resolution of a limited number of anti-TCR V region epitope MoAb, T cell reconstitution following BMT for SCID, even when performed across a full HLA-haplotype barrier, leads to an apparently normal TCR diversity. These novel findings may be relevant in the evaluation of functional capacities of T cells that have differentiated from transplanted precursor cells in an HLA-haplodifferent environment.
Dihydropteridine reductase deficiency in man: From biology to treatment (2003)

In 1975, dihydropteridine reductase (DHPR) deficiency was first recognized as a cause of tetrahydrobiopterin (BH(4)) deficiency, leading to hyperphenylalaninemia (HPA) and impaired biogenic amine deficiency. So far, more than 150 patients scattered worldwide have been reported and major progresses have been made in the understanding of physiopathology, screening, diagnosis, treatment, and molecular genetics of this inherited disease. Present knowledge on different aspects of DHPR deficiency, largely derived from authors' personal experience, is traced in this article.
Network support for personal information services to PCS users (2002)

Future personal communications services (PCS) networks will provide mobile users with integrated personal information services and applications (PISA), such as personalized news and financial information, banking and file access. The authors propose a system architecture for delivery of PISA based on distributed servers, and discuss the connection-oriented support services it may require from the PCS network. In this architecture real mobility on the part of the user may result in virtual mobility of the server, which the authors propose be handled by a service handoff procedure broadly analogous to a PCS call handoff. They describe components of the service handoff procedure and the PCS network support they entail. They also discuss how users' service profiles can be maintained in this architecture.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The 1A protein of respiratory syncytial virus is an integral membrane protein present as multiple, structurally distinct species (1989)

The respiratory syncytial virus (RSV) 1A protein was previously identified as a 7.5-kilodalton (kDa) nonglycosylated species that, on the basis of its predicted sequence determined from the sequence of its mRNA, contains a hydrophobic central domain that was suggestive of membrane interaction. Here, four major, structurally distinct intracellular species of the 1A protein were identified in cells infected by RSV or by a recombinant vaccinia virus expressing the 1A gene. The four species of 1A were: (i) the previously described, nonglycosylated 7.5-kDa species that appeared to be the full-length, unmodified 1A protein; (ii) a nonglycosylated 4.8-kDa species that was carboxy-coterminal with the 7.5-kDa species and might be generated by translational initiation at the second AUG in the sequence; (iii) a 13- to 15-kDa species that contained one or two N-linked carbohydrate side chains of the high-mannose type; and (iv) a 21- to 30-kDa glycosylated species that appeared to be generated from the 13- to 15-kDa species by further modification of the N-linked carbohydrate. All four forms of the 1A protein were synthesized and processed on intracellular membranes, and several lines of biochemical evidence showed that all four species were integral membrane proteins. Thus, the 1A protein is a third RSV integral membrane protein and is present as such in both glycosylated and nonglycosylated forms. With the use of antiserum raised against a synthetic peptide representing the C terminus of the 1A protein, indirect immunofluorescence showed that the 1A protein was expressed at the cell surface. Antibody-antigen complexes formed at the surface of intact infected cells were immunoprecipitated, showing that the 7.5-kDa, 13- to 15-kDa, and 21- to 30-kDa, but not the 4.8-kDa, species, were accessible to extracellular antibodies. Thus, the 1A protein is a candidate to be a viral surface antigen. The small size, gene map location integral membrane association, and cell surface expression of the 1A protein strongly suggested that it is a counterpart to the SH protein that has been described for simian virus type 5. We suggest that, in the future, the RSV 1A protein be given the same designation, namely, SH.
Distinct roles for Fgf, Wnt and retinoic acid in posteriorizing the neural ectoderm (2002)

Early neural patterning in vertebrates involves signals that inhibit anterior (A) and promote posterior (P) positional values within the nascent neural plate. In this study, we have investigated the contributions of, and interactions between, retinoic acid (RA), Fgf and Wnt signals in the promotion of posterior fates in the ectoderm. We analyze expression and function of cyp26/P450RAI, a gene that encodes retinoic acid 4-hydroxylase, as a tool for investigating these events. Cyp26 is first expressed in the presumptive anterior neural ectoderm and the blastoderm margin at the late blastula. When the posterior neural gene hoxb1b is expressed during gastrulation, it shows a strikingly complementary pattern to cyp26. Using these two genes, as well as otx2 and meis3 as anterior and posterior markers, we show that Fgf and Wnt signals suppress expression of anterior genes, including cyp26. Overexpression of cyp26 suppresses posterior genes, suggesting that the anterior expression of cyp26 is important for restricting the expression of posterior genes. Consistent with this, knock-down of cyp26 by morpholino oligonucleotides leads to the anterior expansion of posterior genes. We further show that Fgf- and Wnt-dependent activation of posterior genes is mediated by RA, whereas suppression of anterior genes does not depend on RA signaling. Fgf and Wnt signals suppress cyp26 expression, while Cyp26 suppresses the RA signal. Thus, cyp26 has an important role in linking the Fgf, Wnt and RA signals to regulate AP patterning of the neural ectoderm in the late blastula to gastrula embryo in zebrafish.
Cells Expressing Indoleamine 2,3-Dioxygenase Inhibit T Cell Responses (2002)

Pharmacological inhibition of indoleamine 2,3-dioxygenase (IDO) activity during murine gestation results in fetal allograft rejection and blocks the ability of murine CD8(+) dendritic cells to suppress delayed-type hypersensitivity responses to tumor-associated peptide Ags. These observations suggest that cells expressing IDO inhibit T cell responses in vivo. To directly evaluate the hypothesis that cells expressing IDO inhibit T cell responses, we prepared IDO-transfected cell lines and transgenic mice overexpressing IDO and assessed allogeneic T cell responses in vitro and in vivo. T cells cocultured with IDO-transfected cells did not proliferate but expressed activation markers. The potency of allogeneic T cell responses was reduced significantly when mice were preimmunized with IDO-transfected cells. In addition, adoptive transfer of alloreactive donor T cells yielded reduced numbers of donor T cells when injected into IDO-transgenic recipient mice. These outcomes suggest that genetically enhanced IDO activity inhibited T cell proliferation in vitro and in vivo. Genetic manipulation of IDO activity may be of therapeutic utility in suppressing undesirable T cell responses.
High-performance polygon rendering (1988)

This paper describes a system architecture for realtime display of shaded polygons. Performance of 100,000 lighted, 4-sided polygons per second is achieved. Vectors and points draw at the rate of 400,000 per second. High-speed pan and zoom, alpha blending, realtime video input, and antialiased lines are supported. The architecture heavily leverages parallelism in several forms: pipeline, vector, and array processing. It is unique in providing efficient and balanced graphics that support interactive design and manipulation of solid models. After an overview of algorithms and computational requirements, we describe the details of the implementation. Finally, the unique features enabled by the architecture are highlighted.
Syntheses of various 5‐(bromoaryl)‐substituted uracils (1995)

Abstract The Suzuki Pd(0)‐catalyzed coupling between arylboronic acids and aryl bromides or iodides in weakly alkaline medium, previously further developed by us, has been used for regioselective preparation of 5‐(2′‐bromo‐5′‐furyl)‐, 5‐(2′‐bromo‐4′‐furyl)‐, 5‐(2′‐bromo‐5′‐thienyl)‐, 5‐(2′‐bromo‐4′‐thienyl)‐, 5‐(4′‐bromo‐2′‐thiazolyl)‐, 5‐(3′‐bromophenyl)‐, 5‐(6′‐bromo‐2′‐pyridyl)‐ and 5‐(4′‐bromo‐2′‐pyrimidyl)‐substituted 2,4‐di‐ t ‐butoxypyrimidines. In the coupling between 2,4‐di‐ t ‐butoxy‐5‐pyrimidineboronic acid and the nine different aryl dibromides that were tried as coupling partners, only the 2,4‐ and 2,5‐dibromothiazoles did not give satisfactory yields, 15% and 0%, respectively. The other seven aryl dibromides gave the desired 5‐(bromoaryl)‐2,4‐di‐ t ‐butoxypyrimidines in 58‐89% yield. Attempts to synthesise 2,4‐di‐ t ‐butoxy‐5‐(2′‐bromo‐4′‐thienyl)pyrimidine from 2‐bromo‐4‐iodothiophene failed. Dealkylation of the 5‐(bromoaryl)‐2,4‐di‐ t ‐butoxypyrimidines in 2.5 M hydrochloric acid gave the corresponding 5‐(bromoaryl)uracils in almost quantitative yields.
Ligation of VLA-4 on T cells stimulates tyrosine phosphorylation of a 105-kD protein. (1992)

The VLA/integrins are a family of heterodimeric adhesion receptors shown to be involved in cell-to-cell and cell-to-extracellular matrix (ECM) interactions. Given recent evidence that VLA molecules can synergize with the CD3/T cell receptor (TCR) pathway to activate T cells, it is important to identify biochemical event(s) generated by these molecules. Here, we report that the engagement of VLA-4 on T cells with specific antibodies or its ligand activates protein-tyrosine kinase (PTK) activity as detected by antiphosphotyrosine immunoblotting. The crosslinking of VLA-beta 1 (CD29) with a specific monoclonal antibody (mAb) (anti-4B4) plus anti-mouse immunoglobulin resulted in the rapid tyrosine phosphorylation of a 105-kD protein (pp105) in the human T cell line H9, as well as in peripheral resting T cells. The increase in tyrosine phosphorylation of pp105 was specifically mediated by VLA-4, since mAbs against alpha 4, but not against other VLA alpha chains, could induce this phosphorylation. In addition, the binding of T cells with the CS1 alternatively spliced segment of fibronectin (the binding site recognized by VLA-4) induced pp105 tyrosine phosphorylation. Crosslinking the CD3 complex or VLA-4 molecules with mAbs demonstrated that each of these molecules stimulated the tyrosine phosphorylation of unique sets of proteins with different kinetics, suggesting that these two receptor systems are coupled to distinct PTKs. Since tyrosine phosphorylation of cellular proteins has been shown to be a crucial biochemical event in cell growth, our findings suggest that the induction of pp105 tyrosine phosphorylation via VLA-4 may play a role in the transduction of activation signals through this molecule.
C-11 Choline PET/CT Imaging for Differentiating Malignant From Benign Prostate Lesions (2008)

C-11 choline PET/CT is a valuable noninvasive imaging technology in the diagnosis of PCa. The parameter P/M could differentiate PCa from benign lesions better than SUV.
Genotyping of Hepatitis C Virus Types 1, 2, 3, and 4 by a One-Step LightCycler Method Using Three Different Pairs of Hybridization Probes (2002)

Determination of hepatitis C virus (HCV) genotypes has become increasingly important during the last years for prediction of the clinical course and the outcome of antiviral therapy. Therefore, numerous different methods have been developed to enable HCV genotyping. However, many of them are very laborious and expensive, leading to limited usage in daily routine diagnostics. We have established a method which combines the speed of the new LightCycler technology with the use of amplification products generated for diagnostic quantitative HCV RNA determination. Differentiation of HCV genotypes is performed with these amplicons in a single step by using fluorophore-labeled hybridization probes. Although currently only two different acceptor fluorophores are available for the LightCycler, types 1, 2, 3, and 4, which are by far the prevailing HCV genotypes in Europe and the United States, can be distinguished. Genotypes of specimens from 190 chronically HCV-infected patients were determined by the LightCycler method and compared with the results of nucleotide sequencing. Concordant results were obtained for all samples. This new method offers a fast and convenient possibility to determine the quantitative HCV RNA load and the genotype in large-scale settings within about 4 h.
Prefetching using Markov predictors (1997)

Prefetching is one approach to reducing the latency of memory operations in modern computer systems. In this paper, we describe the Markov prefetcher. This prefetcher acts as an interface between the on-chip and off-chip cache, and can be added to existing computer designs. The Markov prefetcher is distinguished by prefetching multiple reference predictions from the memory subsystem, and then prioritizing the delivery of those references to the processor.This design results in a prefetching system that provides good coverage, is accurate and produces timely results that can be effectively used by the processor. In our cycle-level simulations, the Markov Prefetcher reduces the overall execution stalls due to instruction and data memory operations by an average of 54% for various commercial benchmarks while only using two thirds the memory of a demand-fetch cache organization.
Field‐free, sheathless cell focusing in exponentially expanding hydrophoretic channels for microflow cytometry (2013)

Cell focusing into a narrow stream is an essential step prior to counting and sorting cells in microfluidic devices for flow cytometry and cell sorting applications. Hydrodynamic focusing techniques, however, rely on the need for large volumes of sheath liquid and complex mechanical setup for flow control, preventing miniaturization of the systems. Although microfluidic methods based on active or passive particle control offer sheathless and efficient focusing, they often accompany fabrication complexities or bulky external setups, and operate in a certain range of flow rates. We present here a microfluidic device to focus cells into a narrow stream. The device employs hydrophoresis to guide cells by locally patterned slanted grooves, and channel expansion to improve focusing efficiency and produce a narrow stream of cells. This device principle allows easy improvement of focusing efficiency by adding more expansion steps. Adjusting channel expansion also ensures successful cell focusing without defocusing by inertial effects even at high Reynolds numbers. Using this device, we successfully produced a narrow stream of cells having size variation of >11% in a coefficient of variation (CV), achieving a narrow cell stream with a focusing variation below CV of 3.0%.
Mutagenicity and toxicity studies of several α,β‐unsaturated aldehydes in the Salmonella typhimurium mutagenicity assay (1987)

Abstract α,β‐Unsaturated aldehydes are reactive compounds which are ubiquitous in the environment. This class of compounds has been tested for mutagenicity in Salmonella typhimurium by a number of groups who have obtained differing results. The present studies were undertaken to test the mutagenicity and toxicity of two novel α,β‐unsaturated aldehydes, specifically trans,trans‐muconaldehyde and trans‐4‐hydroxynonenal, and to re‐examine the mutagenicity of crotonaldehyde. Trans,trans‐muconaldehyde is a newly found microsomal metabolite of benzene, and trans‐4‐hydroxynonenal is a toxic aldehyde formed endogenously during lipid peroxidation. Compounds were tested in S. typhimurium strain TA 100 using a 30‐min liquid preincubation procedure. The present mutagenicity studies indicate that these α,β‐unsaturated aldehydes at first appear to be mutagenic, although only at concentrations which decrease survival counts, and result in a disappearance of the bacterial lawn. The colonies observed on mutagenicity test plates are not mutants but rather pin point survivors.
Pyocyanin Alters Redox Homeostasis and Carbon Flux through Central Metabolic Pathways in Pseudomonas aeruginosa PA14 (2007)

The opportunistic pathogen Pseudomonas aeruginosa produces colorful, redox-active antibiotics called phenazines. Excretion of pyocyanin, the best-studied natural phenazine, is responsible for the bluish tint of sputum and pus associated with P. aeruginosa infections in humans. Although the toxicity of pyocyanin for other bacteria, as well as its role in eukaryotic infection, has been studied extensively, the physiological relevance of pyocyanin metabolism for the producing organism is not well understood. Pyocyanin reduction by P. aeruginosa PA14 is readily observed in standing liquid cultures that have consumed all of the oxygen in the medium. We investigated the physiological consequences of pyocyanin reduction by assaying intracellular concentrations of NADH and NAD+ in the wild-type strain and a mutant defective in phenazine production. We found that the mutant accumulated more NADH in stationary phase than the wild type. This increased accumulation correlated with a decrease in oxygen availability and was relieved by the addition of nitrate. Pyocyanin addition to a phenazine-null mutant also decreased intracellular NADH levels, suggesting that pyocyanin reduction facilitates redox balancing in the absence of other electron acceptors. Analysis of extracellular organic acids revealed that pyocyanin stimulated stationary-phase pyruvate excretion in P. aeruginosa PA14, indicating that pyocyanin may also influence the intracellular redox state by decreasing carbon flux through central metabolic pathways.
Tyrosine Phosphorylation of Transmembrane Ligands for Eph Receptors (1997)

Axonal pathfinding in the nervous system is mediated in part by cell-to-cell signaling events involving members of the Eph receptor tyrosine kinase (RTK) family and their membrane-bound ligands. Genetic evidence suggests that transmembrane ligands may transduce signals in the developing embryo. The cytoplasmic domain of the transmembrane ligand Lerk2 became phosphorylated on tyrosine residues after contact with the Nuk/Cek5 receptor ectodomain, which suggests that Lerk2 has receptorlike intrinsic signaling potential. Moreover, Lerk2 is an in vivo substrate for the platelet-derived growth factor receptor, which suggests crosstalk between Lerk2 signaling and signaling cascades activated by tyrosine kinases. It is proposed that transmembrane ligands of Eph receptors act not only as conventional RTK ligands but also as receptorlike signaling molecules.
Mechanism of Cu/Pd-Catalyzed Decarboxylative Cross-Couplings: A DFT Investigation (2014)

The reaction mechanism of decarboxylative cross-couplings of benzoates with aryl halides to give biaryls, which is cooperatively catalyzed by copper/palladium systems, was investigated with DFT methods. The geometries and energies of all starting materials, products, intermediates, and transition states of the catalytic cycle were calculated for the two model reactions of potassium 2- and 4-fluorobenzoate with bromobenzene in the presence of a catalyst system consisting of copper(I)/1,10-phenanthroline and the anionic monophosphine palladium complex [Pd(PMe3)Br](-). Several neutral and anionic pathways were compared, and a reasonable catalytic cycle was identified. The key finding is that the transmetalation has a comparably high barrier as the decarboxylation, which was previously believed to be solely rate-determining. The electronic activation energy of the transmetalation is rather reasonable, but the free energy loss in the initial Cu/Pd adduct formation is high. These results suggested that research aimed at further improving the catalyst should target potentially bridging bidentate ligands likely to assist in the formation of bimetallic intermediates. Experimental studies confirm this somewhat counterintuitive prediction. With a bidentate, potentially bridging ligand, designed to support the formation of bimetallic adducts, the reaction temperature for decarboxylative couplings was reduced by 70 °C to only 100 °C.
Radio frequency induced ionized collisional flow model for application at atmospheric pressures (2004)

We present the development and application of a versatile finite-element method to discretize direct current and radio frequency (rf) induced plasma-sheath dynamics, using multifluid equations. For the former, argon gas is assumed, and the solution is verified by comparison with a theoretical model obtained from the literature. For rf discharges, partially ionized helium gas is considered between two electrodes coated in a dielectric material. The computed solutions for charge densities, the ion velocity and the neutral gas density and crossflow distributions show expected trends. Specifically, ion and electron number densities at the peak discharge current are compared with published numerical results. The derived electric field is utilized with a simple phenomenological model applicable to the transverse velocity in a one-dimensional situation to predict the anticipated hump in the near wall profile. The next step of extending the model, through future work, to two dimensions and for polyphase supply as implemented in realistic configurations is greatly facilitated by the generality of the chosen finite-element method.