gebhart/patrepeval huggingface dataset:
A Na+ Channel Mutation Linked to Hypokalemic Periodic Paralysis Exposes a Proton-selective Gating Pore (2007)

The heritable muscle disorder hypokalemic periodic paralysis (HypoPP) is characterized by attacks of flaccid weakness, brought on by sustained sarcolemmal depolarization. HypoPP is genetically linked to missense mutations at charged residues in the S4 voltage-sensing segments of either CaV1.1 (the skeletal muscle L-type Ca(2+) channel) or NaV1.4 (the skeletal muscle voltage-gated Na(+) channel). Although these mutations alter the gating of both channels, these functional defects have proven insufficient to explain the sarcolemmal depolarization in affected muscle. Recent insight into the topology of the S4 voltage-sensing domain has aroused interest in an alternative pathomechanism, wherein HypoPP mutations might generate an aberrant ionic leak conductance by unblocking the putative aqueous crevice ("gating-pore") in which the S4 segment resides. We tested the rat isoform of NaV1.4 harboring the HypoPP mutation R663H (human R669H ortholog) at the outermost arginine of S4 in domain II for a gating-pore conductance. We found that the mutation R663H permits transmembrane permeation of protons, but not larger cations, similar to the conductance displayed by histidine substitution at Shaker K(+) channel S4 sites. These results are consistent with the notion that the outermost charged residue in the DIIS4 segment is simultaneously accessible to the cytoplasmic and extracellular spaces when the voltage sensor is positioned inwardly. The predicted magnitude of this proton leak in mature skeletal muscle is small relative to the resting K(+) and Cl(-) conductances, and is thus not likely to fully account for the aberrant sarcolemmal depolarization underlying the paralytic attacks. Rather, it is possible that a sustained proton leak may contribute to instability of V(REST) indirectly, for instance, by interfering with intracellular pH homeostasis.
<i>Ex vivo</i> monitoring of human cytomegalovirus‐specific CD8+ T‐cell responses using QuantiFERON<sup>®</sup>‐CMV (2007)

We have developed a novel diagnostic technology to monitor the human cytomegalovirus (HCMV)-specific CD8+ T-cell responses that is based on the detection of secreted interferon-gamma (IFN-gamma) in the whole blood (referred to as QuantiFERON -CMV). Evaluation of QuantiFERON -CMV in healthy individuals revealed that this technology was at least as sensitive and with some HCMV epitopes more sensitive than the ELISPOT for detecting ex vivo IFN-gamma. Results from QuantiFERON -CMV assays showed 97% (36/37 individuals) agreement with the anti-HCMV serology test in healthy individuals. Furthermore, we also show that this technology can be used to assess HCMV-specific T-cell responses in transplant patients. This study shows that QuantiFERON -CMV is a simple, reproducible, and reliable test for the detection of IFN-gamma in response to HCMV CD8+ T-cell epitopes, and may be a valuable diagnostic test for the detection of HCMV infection and a useful clinical tool for monitoring the immune response in immunosuppressed patients during therapy.
Recombinant Treponema pallidum rare outer membrane protein 1 (Tromp1) expressed in Escherichia coli has porin activity and surface antigenic exposure (1996)

We recently reported the cloning and sequencing of the gene encoding a 31-kDa Treponema pallidum subsp. pallidum rare outer membrane porin protein, designated Tromp1 (D. R. Blanco, C. I. Champion, M. M. Exner, H. Erdjument-Bromage, R. E. W. Hancock, P. Tempst, J. N. Miller, and M. A. Lovett, J. Bacteriol. 177:3556-3562, 1995). Here, we report the stable expression of recombinant Tromp1 (rTromp1) in Escherichia coli. rTromp1 expressed without its signal peptide and containing a 22-residue N-terminal fusion resulted in high-level accumulation of a nonexported soluble protein that was purified to homogeneity by fast protein liquid chromatography (FPLC). Specific antiserum generated to the FPLC-purified rTromp1 fusion identified on immunoblots of T. pallidum the native 31-kDa Tromp1 protein and two higher-molecular-mass oligomeric forms of Tromp1 at 55 and 80 kDa. rTromp1 was also expressed with its native signal peptide by using an inducible T7 promoter. Under these conditions, rTromp1 fractionated predominantly with the E. coli soluble and outer membrane fractions, but not with the inner membrane fraction. rTromp1 isolated from the E. coli outer membrane and reconstituted into planar lipid bilayers showed porin activity based on average single-channel conductances of 0.4 and 0.8 nS in 1 M KCl. Whole-mount immunoelectron microscopy using infection-derived immune serum against T. pallidum indicated that rTromp1 was surface exposed when expressed in E. coli. These findings demonstrate that rTromp1 can be targeted to the E. coli outer membrane, where it has both porin activity and surface antigenic exposure.
Conversion from Arithmetic to Boolean Masking with Logarithmic Complexity. (2014)

A general technique to protect a cryptographic algorithm against side-channel attacks consists in masking all intermediate variables with a random value. For cryptographic algorithms combining Boolean operations with arithmetic operations, one must then perform conversions between Boolean masking and arithmetic masking. At CHES 2001, Goubin described a very elegant algorithm for converting from Boolean masking to arithmetic masking, with only a constant number of operations. Goubin also described an algorithm for converting from arithmetic to Boolean masking, but withO(k) operations where k is the addition bit size. In this paper we describe an improved algorithm with time complexity O(logk) only. Our new algorithm is based on the Kogge-Stone carry look-ahead adder, which computes the carry signal inO(logk) instead ofO(k) for the classical ripple carry adder. We also describe an algorithm for performing arithmetic addition modulo 2 k directly on Boolean shares, with the same complexityO(logk) instead ofO(k). We prove the security of our new algorithm against rst-order attacks. Our algorithm performs well in practice, as for k = 64 we obtain a 23% improvement compared to Goubin's algorithm. Our solution naturally extends to higher-order countermeasures with complexityO(n 2 logk) instead ofO(n 2 k) for n shares.
Structures of mannose-6-phosphate isomerase from<i>Salmonella typhimurium</i>bound to metal atoms and substrate: implications for catalytic mechanism (2009)

Mannose-6-phosphate isomerase (MPI) catalyzes the interconversion of mannose 6-phosphate and fructose 6-phosphate. X-ray crystal structures of MPI from Salmonella typhimurium in the apo form (with no metal bound) and in the holo form (with bound Zn2+) and two other structures with yttrium bound at an inhibitory site and complexed with Zn2+ and fructose 6-phosphate (F6P) were determined in order to gain insights into the structure and the isomerization mechanism. Isomerization involves acid/base catalysis with proton transfer between the C1 and C2 atoms of the substrate. His99, Lys132, His131 and Asp270 are close to the substrate and are likely to be the residues involved in proton transfer. The interactions observed at the active site suggest that the ring-opening step is probably catalyzed by His99 and Asp270. An active-site loop consisting of residues 130-133 undergoes conformational changes upon substrate binding. Zn2+ binding induces structural order in the loop consisting of residues 50-54. The metal atom appears to play a role in substrate binding and is probably also important for maintaining the architecture of the active site. Isomerization probably follows the previously suggested cis-enediol mechanism.
A half-molecule GK plasmacytoma. (1969)

A 76-year-old man had a 2-year history and evidence of extensive plasmacytoma throughout his lymph nodes, liver and spleen but no certain bone involvement. This was associated with the production of a half-molecule of γGK-globulin, molecular weight 75,000 which in the urine gave unusual results to testing. Half-molecules are considered in relation to current theories of immunoglobulin synthesis.
Performance management in component-oriented systems using a Model Driven Architecture/spl trade/ approach (2003)

Developers often lack the time or knowledge to profoundly understand the performance issues in largescale component-oriented enterprise applications. This situation is further complicated by the fact that such applications are often built using a mix of in-house and commercial-off-the-shelf (COTS) components. This paper presents a methodology for understanding and predicting the performance of component-oriented distributed systems both during development and after they have been built. The methodology is based on three conceptually separate parts: monitoring, modelling and performance prediction. Performance predictions are based on UML models created dynamically by monitoring-and-analysing a live or under-development system. The system is monitored using non-intrusive methods and run-time data is collected. In addition, static data is obtained by analysing the deployment configuration of the target application. UML models enhanced with performance indicators are created based on both static and dynamic data, showing performance hot spots. To facilitate the understanding of the system, the generated models are traversable both horizontally at the same abstraction level between transactions, and vertically between different layers of abstraction using the concepts defined by the Model Driven Architecture. The system performance is predicted and performance-related issues are identified in different scenarios by generating workloads and simulating the performance models. Work is under way to implement a framework for the presented methodology with the current focus on the Enterprise Java Beans technology.
Process groups and group communications: classifications and requirements (1990)

Different distributed applications are examined and their requirements for group communication support are outlined. The concept of a process group is defined. On the basis of internal structures and external behavior, groups are classified into different categories and their properties are discussed. Group communication is an OS-level abstraction that offers convenience and clarity to the programmer.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Shark - a System for Management, Synchronization and Exchange of Knowledge in Mobile User Groups (2002)

Abstract: New wireless protocols like W-LAN and Bluetooth allow establishing spontaneous networks and peer-to-peer exchange of information. At the same time standards like Semantic Web and Topic Maps gain acceptance that add semantics to information. This paper introduces Shark. Shark is an acronym and stands for “Mobile Shared Knowledge”. Shark organizes knowledge with help of Topic Maps, synchronizes knowledge inside closed user groups but also enables a peer-to-peer exchange of knowledge by means of Bluetooth. This paper gives an overview of the system and its communication protocols.
Abstract 1633: Novel specific- and dual- tryptophan-2,3-dioxygenase (TDO) and indoleamine-2,3-dioxygenase (IDO) inhibitors for tumor immunotherapy (2014)

Abstract Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase is an central immune checkpoint mechanism that controls peripheral immune tolerance and tumor resistance to immune attack. The IDO pathway mediates immunosuppressive effects by expression of the IDO1 gene by tumor cells and/or host antigen presenting cells. Tryptophan depletion and generation of kynurenine generate downstream signals through GCN2, WARS, mTOR and AHR that ultimately lead to anergy of tumor-specific effector CD8+ T cells and activation of Tregs. High expression of IDO correlates negatively with clinical prognosis in patients with a variety of malignancies. Recently, it has been described that tumors can also achieve immunosuppressive effects mediated by tryptophan degradation through expression of TDO, an enzyme functionally and structurally related to IDO1. Therefore, development of small molecules that can prevent tryptophan degradation mediated by IDO1, TDO or both is a prime goal for immunotherapy of cancer. Here we report the discovery of a novel class of imidazoisoindole-based compounds that show potent and selective inhibition of TDO and IDO1, as well as compounds that show potent dual inhibition of both TDO and IDO1. We present structure-activity relationship studies that explore the molecular determinants of potency and specificity for TDO and IDO1. Compounds of these classes were tested for activity in in vitro assays using purified recombinant human and murine TDO and IDO1 as well as in cells expressing IDO1 or TDO. Many of these compounds are 10-200 fold more potent (IC50 &lt; 50 nM) than previously published TDO-specific inhibitors. The pharmacokinetic properties of these compounds are being investigated and lead optimization efforts are in progress. Citation Format: Mario R. Mautino, Richard A. Metz, Firoz Jaipuri, Jesse Waldo, Sanjeev Kumar, Agnieszka Marcinowicz-Flick, Hima Potturi, James T. Adams, Clarissa Van Allen, Nicholas N. Vahanian, Charles J. Link. Novel specific- and dual- tryptophan-2,3-dioxygenase (TDO) and indoleamine-2,3-dioxygenase (IDO) inhibitors for tumor immunotherapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1633. doi:10.1158/1538-7445.AM2014-1633
Multi-Tiered Approach to Improving the Reliability of Multi-Level Cell PRAM (2012)

Phase change RAM (PRAM) is a promising memory technology because of its fast read access time, high storage density and very low standby power. Multi-level Cell (MLC) PRAM which has been introduced to further improve the storage density, comes at a price of lower reliability. This paper focuses on a cost-effective solution for improving the reliability of MLC-PRAM. As the first step, we study in detail the causes of hard and soft errors and develop error models to capture these effects. Next we propose a multi-tiered approach that spans architecture, circuit and system levels to increase the reliability. At the architecture level, we use a combination of Gray code encoding and 2-bit interleaving to partition the errors so that a lower strength error correction coding (ECC) can be used for half of the bits that are in the odd block. We use sub block flipping and threshold resistance tuning to reduce the number of errors in the even block. For even higher reliability, we use a simple BCH based ECC on top of these techniques. We show that the propose multi-tiered approach enables us to use a low cost ECC with 2-error correction capability (t=2) instead of one with t=8 to achieve a block failure rate of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-8</sup> .
Improved Assessment of Isolated Islet Tissue Volume Using Digital Image Analysis (1998)

Accurate and consistent measurement of tissue volume is critical to performing many types of islet research; however, conventional visual determination of isolated islet yields through a microscope is heavily operator dependent. An improved method of islet volume determination using digital image analysis (DIA) was developed to remove operator bias and automate the islet counting process. A series of 140 porcine islet isolations were used to evaluate the DIA method in three separate stages. In Stage 1 ( n = 29 isolations), the conventional and DIA methods were correlated with two other independent islet quantitation methods: insulin extraction, and DNA extraction. It was found that volumes determined by DIA correlated more closely with insulin content and DNA content than did conventionally determined volumes. In Stages 2 and 3 ( n = 54 and 57 isolations, respectively), it was shown that an increase in the number of fields analyzed by DIA did not significantly improve the quality of the correlations. Inclusion of very small tissue (<50 fun in diameter), which is ignored in the conventional protocol affected yields by less than 10% and did not significantly improve the correlation with insulin or DNA content. Quantitation of isolated islet tissue volume using DIA has been shown to be rapid, consistent, and objective. In the laboratory, use of this method as the standard for islet volume measurement will allow more meaningful comparison of experimental results between centers. In the clinic, its use will allow more accurate dosing of transplanted tissue. © 1998 Elsevier Science Inc.
New opportunities for US banks in Cuba. (2015)

The article reports that U.S. President Barack Obama has ordered an amendment of the country's trade and travel policies on Cuba. Topics noted include the positive impact of the removal of trade, travel, and financial institution restrictions on U.S. banks in Cuba, U.S. banks' focus on improving debit card usage and relationships with Cuban banks, annual bank remittance for Cuba, and expansion of the amount of trade financing.
Stereospecific Binding of the Potent Narcotic Analgesic [ <sup>3</sup> H]Etorphine to Rat-Brain Homogenate (1973)

Etorphine, the most potent narcotic analgesic known, was labeled with tritium by catalytic exchange. This drug exhibits stereospecific, saturable binding to rat-brain homogenate. At saturation, the stereospecific binding is 0.1-0.15 pmol/mg of protein. Specific binding is inhibited high salt concentrations, sulfhydryl reagents, and proteolytic enzymes, but is unaffected by phospholipases A and C, sodium azide, sodium fluoride, and prostaglandins E(1) and E(2). Competition for binding of [(3)H]etorphine correlates with agonist and antagonist potencies. The stable, stereospecific binding of an active narcotic analgesic supports the existence of opiate receptors.
Elevated subcortical choline metabolites in cognitively and clinically asymptomatic HIV patients (1999)

1H MRS imaging detects higher Cho in subcortical brain early in HIV disease, when individuals are clinically and neuropsychologically asymptomatic, whereas lower NAA is only found in subcortical brain in individuals with severe neuropsychological impairments. Quantitative 1H MRS imaging may play a role in the objective assessment of the presence, magnitude, and progression of brain involvement in HIV infection.
Pressure Phase Diagram of the Organic Superconductor β-(BEDT-TTF)<sub>2</sub>I<sub>3</sub> (1985)

Low temperature phase diagram of β-(BEDT-TTF) 2 I 3 as a function of pressure ( P ) is determined by resistivity measurement. The superconducting transition temperature ( T c ) rises from 1.1–1.5 K ( P =0 kbar) to around 7.4 K ( P =1.3 kbar) and decreases to 1.2 K ( P =7 kbar). We propose that two kinds of superconducting states exist in this salt and that ambient pressure gives two stable states which have T c 's of around 8 K as well as around 1.3 K. The upper critical field, H c2 , along the c * -axis is also presented.
Analysis of Authorizations in SAP R/3 (2009)

Abstract. Today many companies use an ERP (Enterprise Resource Planning) system such as SAP R/3 to run their daily business ranging from financial issues down to the actual control of a production line. Already due to their sheer size, these systems are very complex. In particular, developing and maintaining the authorization setup is a challenge. The goal of our effort is to automatically analyze the authorization setup of an SAP R/3 system against business policies. To this end we formalize the processes, authorization setup as well as the business policies in firstorder logic. Then, properties can be (dis)proven fully automatically with our theorem prover Spass. We exemplify our approach on the purchase process, a typical constituent of any SAP R/3 installation. 1
Digital Architecture for Driving Large LED Arrays with Dynamic Bus Voltage Regulation and Phase Shifted PWM (2007)

This paper introduces a digital architecture suitable for driving a large number of High Brightness Light Emitting Diodes (HB-LEDs) with improved system efficiency and reduced EMI. Key advantages are achieved by combining and coordinating control of the power converter and LED strings, resulting in a system with deterministic load behavior. Uniform phase shifting of LED strings is performed to minimize load current variations, resulting in reduced output capacitance, improved converter efficiency and reduced system EMI. LED string voltages are detected online and used in a feedforward path for dynamic bus voltage scaling, resulting in improved system efficiency at low dimming levels. Experimental results are presented for a 15 W boost converter with FPGA based digital control driving a 64 LED array with 8 LED strings.
Protective effect of a novel, potent inhibitor of poly(adenosine 5′-diphosphate-ribose) synthetase in a porcine model of severe bacterial sepsis* (2002)

Treatment with a potent PARS inhibitor improved survival and cardiovascular status and attenuated an important mediator component of the inflammatory response in a lethal porcine model of sepsis.
Inter-domain routing in multiprovider optical networks: game theory and simulations (2005)

Multiprovider inter-domain routing can be modeled using game theory, since the domains (or the domain operators) act as players trying to maximize their revenues. Each domain decides what intra-domain connection alternatives it advertises for inter-domain traffic and what the key attributes are of these intra-domain connections (allocation cost, latency, bandwidth or confidence level of availability). The advertised parameters affect the routing algorithm, the selected inter-domain path as well as the payoff of all the operators. As the broadband communication networks become optical, our model assumes a two layer network consisting of autonomous domains, where the optical cross-connects have limited wavelength conversion capability. In this paper we study the dependency of the domain income and the advertised cost of connection alternatives, assuming "cheapest-path" routing. We examined basic scenarios of inter-domain routing and determined Nash and Pareto equilibrium for different network load levels, where provider tariffs and end-user satisfaction were taken into account simultaneously. Beside analytical results, we ran simulations which met our expectations.
Recent Developments in Variable Compression Ratio Engines (1966)

<div class="htmlview paragraph">In an effort to produce military tank engines with more power per cubic foot of bulk and more power per pound of weight, Continental Aviation and Engineering Corp. has applied the Variable Compression Ratio (VCR) piston to an already developed, aircooled diesel engine.</div> <div class="htmlview paragraph">In this engine design, compression ratio is automatically varied within the piston by the use of hydraulic circuitry employing a control valve operating in response to changes in peak combustion pressure.</div> <div class="htmlview paragraph">To accomplish the dual objectives of smaller volume and lighter weight, Continental is developing, under U.S. Army sponsorship, an engine that is currently capable of producing 1.3 gross horsepower per cubic inch of piston displacement. Weight, including all engine and transmission cooling equipment, is 2.3 lb/gross horsepower.</div> <div class="htmlview paragraph">This paper presents the developmental background and some interesting technical details of this project.</div>