gebhart/patrepeval huggingface dataset:
Vancomycin Resistance in Gram-Positive Cocci (2005)

The first vancomycin-resistant clinical isolates of Enterococcus species were reported in Europe in 1988. Similar strains were later detected in hospitals on the East Coast of the United States. Since then, vancomycin-resistant enterococci have spread with unexpected rapidity and are now encountered in hospitals in most countries. This article reviews the mode of action and the mechanism of bacterial resistance to glycopeptides, as exemplified by the VanA type, which is mediated by transposon Tn1546 and is widely spread in enterococci. The diversity, regulation, evolution, and recent dissemination of methicillin-resistant Staphylococcus aureus are then discussed.
Tunable-focus microlens arrays on curved surfaces (2010)

We present a microlens array consisting of multiple liquid-based tunable-focus microlenses omnidirectionally fabricated on a hemisphere, resulting in large field of view. Polymer bridge structure is formed between microlenses to reduce the stress and deformation in each lens structure. Each microlens in the array is formed via a water-oil interface at its lens aperture. Photopatterned thermo-responsive hydrogel actuators are used to regulate the curvature of the water-oil interface, thus tuning the focal length, ranging from millimeters to infinity.
Differentiation between alpha promoter and regulator regions of herpes simplex virus 1: the functional domains and sequence of a movable alpha regulator. (1982)

The herpes simplex virus genome consists of at least three groups of genes--alpha, beta, and gamma--whose expression is coordinately regulated and sequentially ordered in a cascade fashion. We have established that the elements involved in regulation of alpha genes are a sequence that promotes gene expression and a sequence that confers alpha regulation on the gene by responding to trans-acting regulatory signals. The domains of these sequences were mapped by determining the regulation of thymidine kinase (TK) in L cells converted to TK+ phenotype by chimeric TK indicator genes. The chimeric genes were constructed from appropriate portions of the TK gene fused to donor sequences derived from the 5' nontranscribed and nontranslated leader portions of the viral alpha gene 4. The results were as follows. (i) The natural beta TK indicator extending 5' up to -80 and the chimeric alpha TK extending 5' up to -110 both converted cells to TK+ phenotype but were not regulated. (ii) A segment of the regulator region of the alpha gene 4, extending 5' from position -110, confers inducible alpha-type regulation when fused to the nonregulated but expressible beta TK indicator described above. (iii) The extent of gene induction appears to hinge on the size of the regulatory region inserted into the chimeric gene and correlates with the presence of repeated consensus sequences and G+C-rich inverted repeats in the regulatory region of the alpha gene 4 and other alpha genes.
Identification of Cell Surface Molecules Involved in Dystroglycan-Independent Lassa Virus Cell Entry (2011)

Although O-mannosylated dystroglycan is a receptor for Lassa virus, a causative agent of Lassa fever, recent findings suggest the existence of an alternative receptor(s). Here we identified four molecules as receptors for Lassa virus: Axl and Tyro3, from the TAM family, and dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and liver and lymph node sinusoidal endothelial calcium-dependent lectin (LSECtin), from the C-type lectin family. These molecules enhanced the binding of Lassa virus to cells and mediated infection independently of dystroglycan. Axl- or Tyro3-mediated infection required intracellular signaling via the tyrosine kinase activity of Axl or Tyro3, whereas DC-SIGN- or LSECtin-mediated infection and binding were dependent on a specific carbohydrate and on ions. The identification of these four molecules as Lassa virus receptors advances our understanding of Lassa virus cell entry.
Sarcolemmal nNOS anchoring reveals a qualitative difference between dystrophin and utrophin (2010)

Duchenne muscular dystrophy (DMD) is a lethal muscle disease caused by dystrophin deficiency. In normal muscle, dystrophin helps maintain sarcolemmal stability. Dystrophin also recruits neuronal nitric oxide synthase (nNOS) to the sarcolemma. Failure to anchor nNOS to the membrane leads to functional ischemia and aggravates muscle disease in DMD. Over the past two decades, a great variety of therapeutic modalities have been explored to treat DMD. A particularly attractive approach is to increase utrophin expression. Utrophin shares considerable sequence, structural and functional similarity with dystrophin. Here, we test the hypothesis that utrophin also brings nNOS to the sarcolemma. Full-length utrophin cDNA was expressed in dystrophin-deficient mdx mice by gutted adenovirus or via transgenic overexpression. Subcellular nNOS localization was determined by immunofluorescence staining, in situ nNOS activity staining and microsomal preparation western blot. Despite supra-physiological utrophin expression, we did not detect nNOS at the sarcolemma. Furthermore, transgenic utrophin overexpression failed to protect mdx muscle from exercise-associated injury. Our results suggest that full-length utrophin cannot anchor nNOS to the sarcolemma. This finding might have important implications for the development of utrophin-based DMD therapies.
Identification of the Major Steps in Botulinum Toxin Action (2004)

Botulinum toxin is a uniquely potent substance synthesized by the organisms Clostridium botulinum, Clostridium baratii, and Clostridium butyricum. This toxin, which acts preferentially on peripheral cholinergic nerve endings to block acetylcholine release, is both an agent that causes disease (i.e., botulism) as well as an agent that can be used to treat disease (e.g., dystonia). The ability of botulinum toxin to produce its effects is largely dependent on its ability to penetrate cellular and intracellular membranes. Thus, toxin that is ingested or inhaled can bind to epithelial cells and be transported to the general circulation. Toxin that reaches peripheral nerve endings binds to the cell surface then penetrates the plasma membrane by receptor-mediated endocytosis and the endosome membrane by pH-induced translocation. Internalized toxin acts in the cytosol as a metalloendoprotease to cleave polypeptides that are essential for exocytosis. This review seeks to identify and characterize all major steps in toxin action, from initial absorption to eventual paralysis of cholinergic transmission.
Expansion of immunostimulatory dendritic cells among the myeloid progeny of human CD34+ bone marrow precursors cultured with c- kit ligand, granulocyte-macrophage colony-stimulating factor, and TNF- alpha . (1995)

Human CD34+ bone marrow progenitors cultured in the presence of granulocyte-macrophage CSF (GM-CSF) develop along a myeloid pathway, and the addition of exogenous TNF-alpha leads to the differentiation of dendritic cells among the myeloid progeny. These bone marrow CD34+ -derived dendritic cell that develop during 2-wk culture have the same morphologic, phenotypic, and functional properties that distinguish mature dendritic cells in blood. c-kit ligand does not directly influence dendritic cell differentiation per se, but rather increases the total cell number in synergistic combination with GM-CSF and TNF-alpha. This degree of expansion translates into an effective yield of approximately 1.7 x 10(6) mature dendritic cells per single ml of normal adult human bone marrow, compared with approximately 10(6) dendritic cells usually obtained from 450 to 500 ml of peripheral blood. In addition to dendritic cells that constitute approximately 10 to 15% of the total myeloid progeny, the cultures contain monocytes/macrophages and intermediate granulocytic precursors. Monocytes/macrophages and dendritic cells together comprise all of the class II MHC-positive progeny. Sorted cells bearing the CD14+ HLA-DR+ phenotype of mature monocytes are at least 1.5 to 2 logs less active than CD14- HLA-DR+ dendritic cells as stimulators in the allogeneic MLR, even though both CD14+ and CD14- subpopulations share expression of several costimulatory ligands. The synergistic combination of c-kit ligand, GM-CSF, and TNF-alpha therefore expands substantial numbers of immunostimulatory CD14- HLA-DR+ dendritic cells from defined CD34+ progenitors in human bone marrow. This should facilitate the use of dendritic cells in the manipulation of T cell-mediated immune responses.
HER-2 Testing in Breast Cancer Using Parallel Tissue-Based Methods (2004)

A testing algorithm for HER-2 determination is most efficient by using immunohistochemistry as the method of choice, with FISH performed for cancers with indeterminate results (2+ score). Successful quality control and quality assurance programs are a prerequisite for such approaches.
A rapid nested polymerase chain reaction method to detect circulating cancer cells in breast cancer patients using multiple marker genes (2014)

The aim of the present study was to develop a simple and rapid method for the detection of circulating cancer cells using multiple tumor markers and to investigate the clinical significance of circulating cancer cells in breast cancer patients. A novel rapid nested polymerase chain reaction (PCR) assay, with high sensitivity and specificity, was evaluated, which was considered to be suitable for clinical application. The rapid nested PCR method was used to detect the circulating cancer cells of 142 breast cancer patients, using a panel of marker genes (FAM83A, NPY1R and KRT19), which were identified by the Digital Gene Expression Displayer Tool of the National Cancer Institute-Cancer Genome Anatomy Project. In total, 79.6% of the 142 breast cancer patient blood samples were found to express at least one tumor marker. In addition, the number of positive markers was found to significantly correlate with the disease stage and presence of distant metastasis. Furthermore, positivity for more than one tumor marker appeared to predict a reduced survival time in breast cancer patients.
Active motion artifact cancellation for wearable health monitoring sensors using collocated MEMS accelerometers (2005)

This paper presents an active noise cancellation technique for recovering wearable biosensor signals corrupted by bodily motion. A finger mounted photoplethysmograph (PPG) ring sensor with a collocated MEMS accelerometer is considered. The system by which finger acceleration disturbs PPG output is identified and a means of modeling this relationship is prescribed using either FIR or Laguerre models. This means of modeling motivates the use of a recursive least squares active noise cancellation technique using the MEMS accelerometer reading as an input for a FIR or Laguerre model. The model parameters are identified and tuned in real time to minimize the power of the recovered PPG signal. Experiments show that the active noise cancellation method can recover pulse information from PPG signals corrupted with up to 2G of acceleration with 85% improvement in mean squared error.
Nitric Oxide in Experimental Joint Inflammation (2003)

The host response to infection or injury initiates a cascade of events involving recruitment of leukocytes and the release of multiple inflammatory mediators. One of these mediators, nitric oxide (NO), not only represents an important microbicidal agent in host defense, but also functions as a biological signaling and effector molecule in inflammation and immunity. However, overproduction of NO can be autotoxic and contribute to tissue damage and has been implicated in pathogenesis of tumors, and infectious, autoimmune and chronic degenerative diseases. NO is generated via constitutive and inducible nitric oxide synthases (iNOS) which catalyze the oxidation of a guanidino nitrogen associated with L-arginine. Whereas endothelial NOS (eNOS) and neuronal NOS (nNOS) are constitutively expressed, iNOS is transcriptionally induced by bacterial constituents and inflammatory mediators, including TNF alpha and IL-1. In an experimental model of bacterial component-induced joint inflammation and tissue degradation, functionally distinct roles of the constitutive NOS and iNOS were demonstrated. Following systemic delivery of an arthritogenic dose of streptococcal cell walls (SCW), these bacterial peptidoglycan-polysaccharide complexes disseminate and target the peripheral joints, liver and spleen of the treated animals. Following deposition of the SCW in the peripheral joints, an initial innate inflammatory response to the bacterial components progresses into an adaptive immune response with the recruitment and activation of mononuclear phagocytes and T lymphocytes. With the release of cytokines and inflammatory mediators, there is an upregulation of gene expression for iNOS, but not the constitutive nNOS or eNOS. Nonetheless, the constitutive NOS isoforms, regulated by calcium fluxes and interaction with calmodulin, may also enhance NO production. Increased release of NO was detected not only in the synovium, but also in the circulation, and plasma levels of nitrate plus nitrite, the stable products of NO reactions, correlated with disease progression. Following inhibition of NO production with nonspecific NOS inhibitors, such as N(G)-monomethyl-L-arginine, which target all three isoforms, there is a striking therapeutic benefit with reduced signs and symptoms of erosive arthritis. In contrast, selective targeting of iNOS with N-iminoethyl-L-lysine resulted in exacerbation of the synovial inflammation and degradation of joint structures. Based on these data, it appears that the constitutive isoforms of NOS contribute to the pathophysiology of the arthropathy, and that induced NOS and NO may function, in part, in a protective pathway. Moreover, the suppression of NO following treatment with TNF alpha antagonists results in reduced inflammation and the associated synovial pathology. Collectively, these data implicate discrete roles for the NOS isoforms in the emergence of local tissue pathology and underscore the need to define the specific pathways that are being targeted for interventional strategies.
Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers (2015)

There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo-electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 "locks" two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.
Force interaction of high pressure glow discharge with fluid flow for active separation control (2006)

Radio frequency based discharges at atmospheric pressures are the focus of increased interest in aerodynamics because of the wide range of potential applications including, specifically, actuation in flows at moderate speeds. Recent literature describing promising experimental observations, especially on separation control, has spurred efforts in the development of parallel theoretical modeling to lift limitations in the current understanding of the actuation mechanism. The present effort demonstrates higher fidelity first-principle models in a multidimensional finite-element framework to predict surface discharge-induced momentum exchange. The complete problem of a dielectric barrier discharge at high pressure with axially displaced electrodes is simulated in a self-consistent manner. Model predictions for charge densities, the electric field, and gas velocity distributions are shown to mimic trends reported in the experimental literature. Results show that a residual of electrons remains deposited on the dielectric surface downstream of the exposed powered electrode for the entire duration of the cycle and causes a net electric force in the direction from the electrode to the downstream surface. For the first time, results document the mitigation process of a separation bubble formed due to flow past a flat plate inclined at 12° angle of attack. This effort sets the basis for extending the formulation further to include polyphase power input in multidimensional settings, and to apply the simulation method to flows past common aerodynamic configurations.
N-Fluorobenzenesulfonimide: A Practical Reagent For Electrophilic Fluorinations (1991)

N-Fluorobenzenesulfonimide [1; (PhSO2)2NF] is a stable, crystalline electrophilic fluorinating agent prepared in one step from commercially available benzenesulfonimide. It allows the fluorination of neutral and carbanionic nucleophiles ranging from slightly activated aromatic compounds to highly reactive aryl- and vinyllithium derivatives in good yield.
Compressive Sampling and Lossy Compression (2008)

Recent results in compressive sampling have shown that sparse signals can be recovered from a small number of random measurements. This property raises the question of whether random measurements can provide an efficient representation of sparse signals in an information-theoretic sense. Through both theoretical and experimental results, we show that encoding a sparse signal through simple scalar quantization of random measurements incurs a significant penalty relative to direct or adaptive encoding of the sparse signal. Information theory provides alternative quantization strategies, but they come at the cost of much greater estimation complexity.
Dust Mite Proteolytic Allergens Induce Cytokine Release from Cultured Airway Epithelium (1998)

Endogenous proteolytic enzymes have been shown to be potential sources of airway inflammation inducing proinflammatory cytokine release from respiratory epithelial cells; however, whether any of the exogenous proteases from important allergen sources such as the house dust mite present in our environment behave in a similar fashion is unclear. To this end, we have investigated whether the mite cysteine and serine proteolytic allergens, Der p 1 and Der p 9, respectively, induced cytokine production from primary human bronchial epithelial cells and from the epithelial cell line BEAS-2B. Cells were exposed to mite proteases, and cells or supernatants were assayed for cytokine release, cytokine mRNA expression, and modulation of intracellular calcium ion concentration. Both proteases induced concentration- and time-dependent increases in the release of granulocyte-macrophage (GM)-CSF, IL-6, and IL-8 as well as an increase in the expression of IL-6 mRNA. Cytokine release and mRNA expression were first observed at 8 h and 2 h after protease exposure, respectively. The minimum concentration of each protease that was required to stimulate GM-CSF, IL-6, and IL-8 release was approximately 10 ng/ml. Cytokine release was initiated by 1 to 2 h of protease exposure, although maximum concentrations were detected only after a 24-h incubation. IL-6, but not IL-8 and GM-CSF, was shown to be degraded by both proteases at concentrations of > 2 microg/ml. The proteases also stimulated changes in the intracellular calcium ion concentration. All mite protease-induced phenomena were inhibited using appropriate protease inhibitors. These results suggest that the proteolytic activity of an allergen may stimulate the release of proinflammatory cytokines from human bronchial epithelium.
Enzymatic synthesis of high‐purity structured lipids with caprylic acid at 1,3‐positions and polyunsaturated fatty acid at 2‐position (2001)

Abstract We attempted to synthesize high‐purity structured triacylglycerols (TAG) with caprylic acid (CA) at the 1,3‐positions and a polyunsaturated fatty acid (PUFA) at the 2‐position by a two‐step enzymatic method. The first step was synthesis of TAG of PUFA (TriP), and the second step was acidolysis of TriP with CA. Candida antarctica lipase was effective for the first reaction. When a reaction medium of PUFA/glycerol (3∶1, mol/mol) and 5% immobilized Candida lipase was mixed for 24 h at 40°C and 15 mm Hg, syntheses of TAG of γ‐linolenic, arachidonic, eicosapentaenoic, and docosahexaenoic acids reached 89, 89, 88, and 83%, respectively. In these reactions, the lipase could be used for at least 10 cycles without significant loss of activity. In the second step, the resulting trieicosapentaenoin was acidolyzed at 30°C for 48h with 15 mol parts CA using 7% of immobilized Rhizopus delemar lipase. The CA content in the acylglycerol fraction reached 40 mol%. To increase the content further, the acylglycerols were extracted from the reaction mixture with n ‐hexane and were allowed to react again with CA under conditions similar to those of the first acidolysis. After three successive acidolysis reactions, the CA content reached 66 mol%. The content of dicapryloyl‐eicosapentaenoyl‐glycerol reached 86 wt% of acylglycerols, and the ratio of 1,3‐dicapryloyl‐2‐eicosapentaenoyl‐glycerol to 1(3),2‐dicapryloyl‐3(1)‐eicosapentaenoyl‐glycerol was 98∶2 (w/w). In this reaction, the lipase could be used for at least 20 cycles without significant loss of activity. Repeated acidolysis of the other TriP with CA under similar conditions synthesized 1,3‐dicapryloyl‐2‐γ‐linolenoyl‐glycerol, 1,3‐dicapryloyl‐2‐arachidonoyl‐glycerol, and 1,3‐dicapryloyl‐2‐docosahexaenoyl‐glycerol in yields of 58, 87, and 19 wt%, respectively.
Source Packet Routing in Networking (SPRING) Problem Statement and Requirements (2016)

The ability for a node to specify a forwarding path, other than the normal shortest path, that a particular packet will traverse, benefits a number of network functions. Source-based routing mechanisms have previously been specified for network protocols but have not seen widespread adoption. In this context, the term "source" means "the point at which the explicit route is imposed"; therefore, it is not limited to the originator of the packet (i.e., the node imposing the explicit route may be the ingress node of an operator's network). This document outlines various use cases, with their requirements, that need to be taken into account by the Source Packet Routing in Networking (SPRING) architecture for unicast traffic. Multicast use cases and requirements are out of scope for this document.
Dynamic characterization of a lightweight, highly maneuverable spacecraft using modal and finite element analyses (1992)

The Lawrence Livermore National Laboratory is engaged in a technology development project which includes designing a lightweight, autonomous, highly maneuverable space vehicle, commonly referred to as a probe. The current probe design includes a guidance and control system that requires complete information on the dynamic response of the probe during operation. A finite element model of the probe was constructed to provide analytical information on the dynamic response to specific operational inputs. In order to verify the assumptions made in the model, a mass mock-up of the probe was constructed at LLNL and an experimental modal survey was performed to determine the frequencies, damping values and deflection shapes for each natural mode of the mock-up. The experimental modal parameters were compared with the parameters obtained through modal analysis of the finite element model to provide a measure of the correlation between the model and the actual structure. This report describes the experimental modal testing and analysis of the mass mock-up and compares the experimental results with the finite element results.