gebhart/patrepeval huggingface dataset:
Turning off the signal: desensitization of β‐adrenergic receptor function (1990)

Cellular responses to many hormones and neurotransmitters wane rapidly despite continuous exposure of cells to these stimuli. This phenomenon, termed desensitization, has been particularly well studied for the stimulation of cAMP levels by plasma membrane beta-adrenergic receptors (beta AR). The molecular mechanisms underlying rapid beta AR desensitization do not appear to require internalization of the receptors, but rather an alteration in the functioning of beta AR themselves that uncouples the receptors from the stimulatory G protein Gs. This uncoupling phenomenon involves phosphorylation of beta AR by at least two kinases, PKA and the beta AR kinase (beta ARK), which are activated under different desensitizing conditions. Receptor phosphorylation by the two kinases leads to desensitization of the receptor response via distinct biochemical mechanisms, and additional cytosolic factors appear to be involved in the case of beta ARK. Numerous experimental approaches have been used recently to elucidate the molecular details of this ubiquitous biological process.
Optimization as a Model for Few-Shot Learning (2017)

Though deep neural networks have shown great success in the large data domain, they generally perform poorly on few-shot learning tasks, where a model has to quickly generalize after seeing very few examples from each class. The general belief is that gradient-based optimization in high capacity models requires many iterative steps over many examples to perform well. Here, we propose an LSTM-based meta-learner model to learn the exact optimization algorithm used to train another learner neural network in the few-shot regime. The parametrization of our model allows it to learn appropriate parameter updates specifically for the scenario where a set amount of updates will be made, while also learning a general initialization of the learner network that allows for quick convergence of training. We demonstrate that this meta-learning model is competitive with deep metric-learning techniques for few-shot learning.
Limits of diffusion in the hydrolysis of substrates by the phosphotriesterase from Pseudomonas diminuta (1991)

The catalytic mechanism for the enzymatic hydrolysis of a series of paraoxon analogues by the phosphotriesterase from Pseudomonas diminuta has been determined. The Brønsted plots relating the pKa of the leaving group to the observed kinetic parameters, Vmax and V/Km, are both nonlinear. This observation is consistent with a change in the rate-limiting step from chemical to physical events as the pKa of the leaving group is decreased. This conclusion is confirmed by the effects of solvent viscosity on Vmax and V/Km for the same series of analogues. The data were fitted to the scheme E k1A in equilibrium k2 EA k3----EP k7----E'P k9----E + products where EA is the enzyme-substrate complex, EP is the enzyme-product complex, E'P is the enzyme-product complex after a viscosity-independent unimolecular reaction, and the values for k1, k2, k7, and k9 are 4.1 X 10(7) M-1 s-1, 2550 s-1, 3370 s-1, and 5940 s-1, respectively. The magnitude of the chemical step, represented by k3, is dependent on the pKa of the leaving group phenol as predicted by the Brønsted equation (log k3 = beta pKa + C) where beta = -1.8 and the constant (C) = 17.7. The magnitude of beta indicates that the transition state for substrate hydrolysis is very product-like.
Signaling MSD (Maximum SID Depth) using IS-IS (2016)

This document proposes a way to expose Maximum SID Depth (MSD)
supported by a node at node and/or link level by an ISIS Router. In a
Segment Routing (SR) enabled network a centralized controller that
programs SR tunnels at the head-end node needs to know the MSD
information at node level and/or link level to push the label stack of
an appropriate depth.
The MPM-2 antibody inhibits mitogen-activated protein kinase activity by binding to an epitope containing phosphothreonine-183. (1994)

Mitogen-activated protein (MAP) kinases are a family of serine/threonine kinases implicated in the control of cell proliferation and differentiation. We have found that activated p42mapk is a target for the phosphoepitope antibody MPM-2, a monoclonal antibody that recognizes a cell cycle-regulated phosphoepitope. We have determined that the MPM-2 antibody recognizes the regulatory region of p42mapk. Binding of the MPM-2 antibody to active p42mapk in vitro results in a decrease in p42mapk enzymatic activity. The MPM-2 phosphoepitope can be generated in vitro on bacterially expressed p42mapk by phosphorylation with either isoform of MAP kinase kinase (MKK), MKK1, or MKK2. Analysis of p42mapk proteins mutated in their regulatory sites shows that phosphorylated Thr-183 is essential for the binding of the MPM-2 antibody. MPM-2 binding to Thr-183 is affected by the amino acid present in the other regulatory site, Tyr-185. Substitution of Tyr-185 with phenylalanine results in strong binding of the MPM-2 antibody, whereas substitution with glutamic acid substantially diminishes MPM-2 antibody binding. The MPM-2 phosphoepitope antibody recognizes an amino acid domain incorporating the regulatory phosphothreonine on activated p42mapk in eggs during meiosis and in mammalian cultured cells during the G0 to G1 transition.
Cloning and characterization of HTK, a novel transmembrane tyrosine kinase of the EPH subfamily. (1994)

Using a polymerase chain reaction based strategy, we identified a novel transmembrane tyrosine kinase in CD34+ human bone marrow cells and a human hepatocellular carcinoma cell line, Hep3B. This protein, hepatoma transmembrane kinase or Htk, shares amino acid similarity with the EPH subfamily of tyrosine kinases. The HTK gene is located on human chromosome 7. The predicted 987-amino acid sequence of Htk includes a transmembrane region and signal sequence. In the predicted extracellular domain, a cysteine-rich region and tandem fibronectin type III repeats are present while a single uninterrupted catalytic domain is present in the intracellular domain. These features are consistent with other members of the Eph subfamily. Antibodies raised against Htk extracellular domain immunoprecipitated a 120-kDa protein from either in vitro translated HTK or Hep3B cells which localized primarily to the Hep3B membrane subcellular fraction. Purified in vitro translated Htk was enzymatically active and autophosphorylated on tyrosine in kinase assays. Furthermore, antibodies against Htk ECD were agonistic, inducing Htk tyrosine phosphorylation in transfected NIH3T3 cells. Northern blot analysis demonstrated a single HTK transcript abundantly present in placenta and in a range of primary tissues and malignant cell lines. HTK appears to be expressed in fetal but not adult brain and in primitive and myeloid but not lymphoid hematopoietic cells. The novel transmembrane protein, Htk, may function as a receptor with an expression pattern suggesting a role in events mediating differentiation and development.
Standards in commercial security (1992)

With the spread of the adoption of standards in commercial systems, where the operation of the computing environment may be essential to the success of a companies business, the need for inclusion of security in open system environments is becoming recognised. Across the areas of open system standardisation extensions to the base standards are being defined to facilitate secure interworking. These include: security extensions the EDIFACT EDI message standards; security for the IEE 1003 POSIX, UNIX based operating system interface standards; security facilities for OSI application standards such as the CCITT X.400 message handling system and X.500 directory system; the OSI network and transport layer communications security protocols as well as the IEEE 802 secure LAN standard; and the OSI physical layer encryption device interface. The paper outlines the approach taken in each of these areas and suggests the relative role of the different placements and forms of security.
Nitric Oxide Protects Cultured Rat Hepatocytes from Tumor Necrosis Factor-α-induced Apoptosis by Inducing Heat Shock Protein 70 Expression (1997)

Nitric oxide (NO) and tumor necrosis factor-alpha (TNFalpha) play important roles in the pathogenesis of liver disease during acute inflammation. The present study was designed to elucidate the effect of NO pre-exposure on TNFalpha-induced hepatotoxicity. Pretreatment of primary cultures of rat hepatocytes with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) induced the expression of heat shock protein 70 (HSP70) mRNA and protein, which was associated with thermotolerance and cytoprotection from TNFalpha+actinomycin D-induced hepatotoxicity and apoptosis. SNAP transiently changed the intracellular redox state by inducing glutathione (GSH) oxidation associated with the formation of S-nitrosoglutathione (GSNO). HSP70 mRNA was also induced by the GSH-oxidizing agent diamide and the GSH-conjugating agent N-ethylmaleimide, suggesting that NO induces HSP70 expression through GSH oxidation. The protective effect of SNAP pretreatment on TNFalpha-induced apoptosis correlated with the level of HSP70 expression. SNAP pretreatment inhibited reactive oxygen intermediate generation and lipid peroxidation effects that were reversed by blocking HSP70 expression using an antisense oligonucleotide to HSP70. Finally, endogenous NO formation, induced in hepatocytes stimulated with interferon-gamma and interleukin-1beta, led to the formation of GSNO and GSSG, induced HSP70, and attenuated TNFalpha-mediated cytotoxicity. These findings demonstrated that NO can induce resistance to TNFalpha-induced hepatotoxicity, possibly through the stimulation of HSP70 expression.
The Effects of Irreversible Electroporation (IRE) on Nerves (2011)

This finding is indicative of the preservation of nerve involving malignant tumors with respect to the application of IRE pulses to ablate tumors completely. In summary, IRE may be a promising treatment tool for any tumor involving nerves.
Reduction of metastatic properties of BL6 melanoma cells expressing terminal fucose(alpha)1-2-galactose after alpha1,2-fucosyltransferase cDNA transfection. (1997)

We reported previously that transfection of BL6 melanoma cells that do not express the alpha1,3-galactosyltransferase (alpha1,3GT) gene with the alpha1,3GT cDNA resulted in synthesis and expression of alpha-galactosyl epitopes (Gal(alpha)1-3Gal(beta)1-4GlcNAc-R) and an impairment of their metastatic potentials. It was of interest to test whether inhibition of metastatic properties of BL6 melanoma cells is specifically associated with the appearance of the terminal alpha-Gal or whether capping N-acetyllactosamine with another oligosaccharide would also affect the metastatic properties of BL6 melanoma cells. For this purpose, BL6-2 clone isolated from B16BL6 melanoma was transfected with the alpha1,2-fucosyltransferase (alpha1,2FT) cDNA. The alpha1,2FT catalyzes a transglycosylation reaction, resulting in syntheses of the Fuc(alpha)1-2Gal(beta)1-4GlcNAc-R structure, which is known as the H antigen of O blood group in humans and is also synthesized in some cells of mice. Transfection of BL6 melanoma cells with the alpha1,2FT cDNA resulted in the appearance of the terminal Fuc(alpha)1-2Gal(beta)1-4GlcNAc-R epitopes reacting with the Ulex europaeus agglutinin lectin. In parallel, the transfected cells showed a decrease in N-acetyllactosamine sialylation. Decline in sialylation of the transfected cells is likely to be the result of competition between alphal,2FT and alpha2,3- or alpha2,6-sialyltransferases for the common substrate N-acetyllactosamine (Gal(beta)1-4GlcNAc-R) on N-linked carbohydrate chains of glycoproteins and glycolipids. The alpha1,2FT-transfected BL6-2 cells showed an increase in homotypic aggregation. In parallel, metastatic ability of the alpha1,2FT-transfected BL6-2 cells was reduced significantly in the immunocompetent as well as immunosuppressed (X-irradiated) mice. Thus, these data imply that capping N-acetyllactosamine with alphaGal or alphaFuc and the corresponding reduction in sialylation of BL6-2 melanoma cells were associated with reduction of their metastatic potential.
Is the Complement Activation Product C3a a Proinflammatory Molecule? Re-evaluating the Evidence and the Myth (2015)

The complement activation product C3a is often described as a proinflammatory mediator, alongside its downstream cousin, C5a. However, emerging studies show that C3a has several anti-inflammatory facets in vivo. For example, in the acute inflammatory response, C3a acts in direct opposition to C5a, through preventing the accumulation of neutrophils in inflamed tissues by independently regulating their mobilization. This acute, protective, and opposing activity of C3a to C5a is also illustrated in models of septicemia. In this article, we reinvestigate the discovery and original classification of C3a as a proinflammatory mediator and highlight the emerging studies demonstrating anti-inflammatory effects for C3a in the immune response. It is our hope that this review illuminates these apparently contradictory roles for C3a and challenges the general dogma surrounding C3a, which, historically, has ubiquitously been described as a proinflammatory mediator. In light of this, we urge investigators to use "inflammatory modulator" as the descriptor for C3a.
Towards new mycobacterial vaccines. (1994)

BCG, the Bacillus of Calmette and Guérin, has been used as a vector for the presentation of foreign antigens. The nef gene of HIV was cloned and expressed in BCG. A specific cellular immune response against Nef was observed following inoculation of mice. As a model system beta-galactosidase has also been expressed in BCG. Antibody responses against beta-galactosidase in addition to cellular responses were observed. Mucosal immunity was demonstrated after oral immunization of mice. With the aim of isolating new vaccines against tuberculosis, transposon mutagenesis was investigated. By using Tn610, representative libraries of Mycobacterium smegmatis insertion mutants were constructed.
There Is a Pathologic Relationship Between ApoE- 4 and Alzheimer's Disease (1995)

The recently published letter by Riggs and Keefover 1 suggests that the ever-present bane of epidemiologic studies, selection bias, may account for the observed association between ApoE-e 4 [apolipoprotein E e 4 allele] and late-onset AD [Alzheimer's disease]. This association has now been replicated in many clinic-based epidemiologic and autopsy groups throughout the world. We suspect that the delay in publication of the letter caused its authors to miss significant publications concerning the protective role of ApoE-e 2 2-5 and the rationale for ApoE genotype—specific trajectories of risk for AD with increasing age ( Figure ). That risk related to the e 4 allele and benefit related to the e 2 allele diminish with age in surviving individuals is consistent with published work 3,6 and work by others presented at scientific meetings. The competing risks of heart disease and death also related to ApoE-e 4 are unlikely to account for the ApoE-e
Securing M2M With Post-Quantum Public-Key Cryptography (2013)

In this paper, we present an ASIC implementation of two post-quantum public-key cryptosystems (PKCs): NTRUEncrypt and TTS. It represents a first step toward securing machine-to-machine (M2M) systems using strong, hardware-assisted PKC. In contrast to the conventional wisdom that PKC is too “expensive” for M2M sensors, it actually can lower the total cost of ownership because of cost savings in provision, deployment, operation, maintenance, and general management. Furthermore, PKC can be more energy-efficient because PKC-based security protocols usually involve less communication than their symmetric-key-based counterparts, and communication is getting relatively more and more expensive compared with computation. More importantly, recent algorithmic advances have brought several new PKCs, NTRUEncrypt and TTS included, that are orders of magnitude more efficient than traditional PKCs such as RSA. It is therefore our primary goal in this paper to demonstrate the feasibility of using hardware-based PKC to provide general data security in M2M applications.
Engineering anti‐GD2 monoclonal antibodies for cancer immunotherapy (2013)

Ganglioside GD2 is highly expressed on neuroectoderm-derived tumors and sarcomas, including neuroblastoma, retinoblastoma, melanoma, small cell lung cancer, brain tumors, osteosarcoma, rhabdomyosarcoma, Ewing's sarcoma in children and adolescents, as well as liposarcoma, fibrosarcoma, leiomyosarcoma and other soft tissue sarcomas in adults. Since GD2 expression in normal tissues is restricted to the brain, which is inaccessible to circulating antibodies, and in selected peripheral nerves and melanocytes, it was deemed a suitable target for systemic tumor immunotherapy. Anti-GD2 antibodies have been actively tested in clinical trials for neuroblastoma for over the past two decades, with proven safety and efficacy. The main limitations have been acute pain toxicity associated with GD2 expression on peripheral nerve fibers and the inability of antibodies to treat bulky tumor. Several strategies have been developed to reduce pain toxicity, including bypassing complement activation, using blocking antibodies, or targeting of O-acetyl-GD2 derivative that is not expressed on peripheral nerves. To enhance anti-tumor efficacy, anti-GD2 monoclonal antibodies and fragments have been engineered into immunocytokines, immunotoxins, antibody drug conjugates, radiolabeled antibodies, targeted nanoparticles, T-cell engaging bispecific antibodies, and chimeric antigen receptors. The challenges of these approaches will be reviewed to build a perspective for next generation anti-GD2 therapeutics in cancer therapy.
Quantifying repetitive hand activity for epidemiological research on musculoskeletal disorders – Part II: comparison of different methods of measuring force level and repetitiveness (2006)

This paper focuses on comparisons between the different methods of assessing repetitive hand activities. Various methods were used to measure hand force and repetitiveness of hand activities on 733 subjects in the study described by Bao et al. (2006). Two definitions of repetitiveness were used in analysis of detailed time studies of repetitive hand activities and four parameters of the American Conference of Governmental Industrial Hygienists (ACGIH) hand activity level (HAL) and the Strain Index methods were estimated by ergonomists and used to quantify repetitiveness. Hand forces were measured or estimated using three different methods: 1) measured with a force gauge or mimicked on a force gauge (force matching); 2) estimated by ergonomists using rating scales; 3) self-reports by subjects. The jobs were also evaluated using the ACGIH HAL and Strain Index methods when different repetitiveness quantification methods were used. Results showed that different definitions of repetitive exertion might lead to measuring different physical exposure phenomena and produce very different results. There were poor correlations between the measures of repetitiveness estimated by the different methods. Correlations between force quantifications using different methods were also poor. This suggests that parameters measured by different methods might not be interchangeable. Both the ACGIH HAL and Strain Index methods identified more 'hazardous' jobs when repetitiveness was estimated by ergonomists than when it was calculated by detailed time studies of forceful hand exertions. The Strain Index method identified more 'hazardous' jobs than the ACGIH HAL method. Overall, the between-methods agreements were found to be moderate to substantial.
Kinetic Analysis of an Efficient DNA-Dependent TNA Polymerase (2005)

alpha-l-Threofuranosyl nucleoside triphosphates (tNTPs) are tetrafuranose nucleoside derivatives and potential progenitors of present-day beta-d-2'-deoxyribofuranosyl nucleoside triphosphates (dNTPs). Therminator DNA polymerase, a variant of the 9 degrees N DNA polymerase, is an efficient DNA-directed threosyl nucleic acid (TNA) polymerase. Here we report a detailed kinetic comparison of Therminator-catalyzed TNA and DNA syntheses. We examined the rate of single-nucleotide incorporation for all four tNTPs and dNTPs from a DNA primer-template complex and carried out parallel experiments with a chimeric DNA-TNA primer-DNA template containing five TNA residues at the primer 3'-terminus. Remarkably, no drop in the rate of TNA incorporation was observed in comparing the DNA-TNA primer to the all-DNA primer, suggesting that few primer-enzyme contacts are lost with a TNA primer. Moreover, comparison of the catalytic efficiency of TNA synthesis relative to DNA synthesis at the downstream positions reveals a difference of no greater than 5-fold in favor of the natural DNA substrate. This disparity becomes negligible when the TNA synthesis reaction mixture is supplemented with 1.25 mM MnCl(2). These results indicate that Therminator DNA polymerase can recognize both a TNA primer and tNTP substrates and is an effective catalyst of TNA polymerization despite changes in the geometry of the reactants.
The interaction between salinity and boron toxicity affects the subcellular distribution of ions and proteins in wheat leaves (2003)

ABSTRACT Salinity aggravates B toxicity symptoms in several plant species. In the present study the interactive effects of B toxicity and salinity stresses on the subcellular distribution of boron, cations and proteins in basal and apical leaf sections of wheat were investigated. High B supply increased total B concentrations in all leaf parts, but values remained below 25 mg B kg −1 dry weight (DW) in basal sections, whereas they reached more than 600 mg B kg −1 DW in leaf tips. In basal leaf sections intercellular soluble B concentrations closely reflected the external supply, whereas intracellular soluble B concentrations remained lower by a factor of two, indicating some retention of excess B in the apoplast. Combined salinity and B toxicity stresses significantly increased soluble B concentrations in inter‐ and intracellular compartments of basal leaf sections in comparison with either stress alone, probably related to salinity‐induced changes in water status. The combined stresses also induced quantitative and qualitative changes in inter‐, but not intracellular protein composition. Most obvious was the induction of a 25 kDa protein and an increase in amount of a 33 kDa protein. It is suggested that these changes might be due to structural modifications of the cell wall. The concentration of soluble boron in cells is proposed to be an indicator of boron toxicity.
Gas Fermentation for Commercial Biofuels Production (2013)

With diminishing global reserves of crude oil and increasing demand, especially from developing countries, the pressure on oil supply will grow. Although the 2007-2010 fi‐ nancial crisis brought down the price of crude oil (per barrel) from a record peak of US $145 in July 2008, factors such as recovering global economies and political instability in the Middle East have restored the price of crude oil to the US$100 mark. At current rate of consumption, the global reserves of petroleum are predicted to be exhausted within 50 years [1, 2]. This, coupled with the deleterious environmental impacts that result from accumulating atmospheric CO2 from the burning of fossil fuels, the development of af‐ fordable, and environmentally sustainable fuels is urgently required. Many countries have responded to this challenge by legislating mandates and introducing policies to stimulate research and development (R&D) and commercialization of technologies that allow the production of low cost, low fossil carbon emitting fuels. For instance, the Euro‐ pean Union (EU) has mandated member countries to a target of deriving 10% of all transportation fuel from renewable sources by 2020 [3]. Between 2005 and 2010, renewa‐ ble energies such as solar, wind, and biofuels have been increasing at an average annual rate of 15-50% [4]. Renewable energy accounted for an estimated 16% of global final en‐ ergy consumption in 2009 [4].