gebhart/patrepeval huggingface dataset:
Molecular modeling of cardiac glycoside binding by the human sequence monoclonal antibody 1B3 (2005)

Abstract The amino acid sequences of the heavy‐ and light‐chain variable regions of the high‐affinity human sequence antidigoxin monoclonal antibody 1B3 (mAb 1B3) were determined, and a structural model for the mAb's variable region was developed by homology modeling techniques. The structural model provided the basis for computationally docking digoxin and eight related cardiac glycosides into the putative binding site of mAb 1B3. Analysis of the consensus binding mode obtained for digoxin showed that the cardenolide moiety of digoxin is deeply embedded in a predominantly hydrophobic, narrow cavity, whereas the terminal, γ‐carbohydrate group is solvent‐exposed. The docking results indicated that the primary driving forces for digoxin binding by mAb 1B3 are hydrophobic interactions with the digoxin steroid ring system and hydrogen bonds with the digitoxose groups. The binding model accounts for the experimentally observed variations in mAb 1B3 binding affinity for various structural analogs of digoxin used previously to develop a 3D structure–activity relationship model of drug binding (Farr CD, Tabet MR, Ball WJ Jr, Fishwild DM, Wang X, Nair AC, Welsh WJ. Three‐dimensional quantitative structure–activity relationship analysis of ligand binding to human sequence antidigoxin monoclonal antibodies using comparative molecular field analysis. J Med Chem 2002;45:3257–3270). In particular, the hydrogen bond pattern is consistent with the unique sensitivity of mAb 1B3's binding affinity to the number of sugar residues present in a cardiac glycoside. The hydrophobic environment about the steroid moiety of digoxin is compatible with the mAb's reduced affinity for ligands that possess hydrophilic hydroxyl and acetyl group modifications in this region. The model also indicated that most of the amino acid residues in contact with the ligand reside in or about the three complementarity determining regions (CDRs) of the heavy chain and the third CDR of the light chain. A comparison of the 1B3 binding model with the crystal structures of two murine antidigoxin mAbs revealed similar binding patterns used by the three mAbs, such as a high frequency of occurrence of aromatic, hydrophobic residues in the CDRs and a dominant role of the heavy chain CDR3 in antigen binding. Proteins 2005. © 2005 Wiley‐Liss, Inc.
ASSURED: Architecture for Secure Software Update of Realistic Embedded Devices (2018)

Secure firmware update is an important stage in the Internet of Things (IoT) device life-cycle. Prior techniques, designed for other computational settings, are not readily suitable for IoT devices, since they do not consider idiosyncrasies of a realistic large-scale IoT deployment. This motivates our design of architecture for secure software update of realistic embedded devices (ASSURED), a secure and scalable update framework for IoT. ASSURED includes all stakeholders in a typical IoT update ecosystem, while providing end-to-end security between manufacturers and devices. To demonstrate its feasibility and practicality, ASSURED is instantiated and experimentally evaluated on two commodity hardware platforms. Results show that ASSURED is considerably faster than current update mechanisms in realistic settings.
Current collection at the shuttle orbiter during the tethered satellite system tether break (1999)

We present measurements of currents, orbiter potentials, and plasma spectra during high‐voltage arcing coincident with the tether break event on the Tethered Satellite System reflight. In addition to the unexpectedly high tether currents observed, plasma spectra indicate the presence of ion and electron populations with broad energy ranges. These data were used in combination with satellite and orbiter current collection models to investigate the circuit behavior of the system's components. We find that arcing at the lower end of the tether supported the current flow in the tether during each phase of the break event, but with different mechanisms dominant depending on the location of the break point. With the break point inside deployer control structures, current arced to the orbiter ground, charging it to high negative potentials and allowing secondary ionization of neutral molecules near orbiter conducting surfaces. The most likely source of these neutrals is air trapped inside the tether at 1 atm of pressure that escaped through the hole in the tether insulation. When the break point was exposed to the exterior environment the tether current arced directly to the plasma. As long as the break point remained near the orbiter, the collection of electrons by conducting surfaces caused it to float at a low level of negative charging. The source of the energetic electrons detected in the payload bay remains uncertain. However, they can only have come from a region within the sheath that was more negatively charged than the orbiter's conducting surfaces.
New thermally enhanced packages for power MOSFETs in battery pack applications (2003)

Recent advances in silicon technology have enabled smaller, higher-efficiency devices by increasing the transistor cell density on the silicon level to 178 million cells per square inch. These silicon capabilities represent a major advance over the devices available just a few years ago, and it is important that advances in packaging technology keep pace. Because of the demanding power and size requirements of next-generation portable devices, new compact packages with superior current-handling capabilities will be increasingly important. In this article, a new thermally enhanced package technology from Vishay Siliconix will be introduced for use in cellular phone 1-2 cell Li+ battery-protection circuits. With the die attach copper pad soldered directly to the printed circuit board, this new packaging technique provides a direct, low-resistance thermal path to the substrate on which the device is mounted. Characteristics of thermally enhanced 1212-8 package will be compared to that of the industry standard TSSOP-8 package through review of the MOSFET packaging trends used in today's battery pack protection circuits.
Triarylaminium Salt Free Radicals<sup>1</sup> (1955)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTriarylaminium Salt Free Radicals1Robert I. WalterCite this: J. Am. Chem. Soc. 1955, 77, 22, 5999–6002Publication Date (Print):November 1, 1955Publication History Published online1 May 2002Published inissue 1 November 1955https://pubs.acs.org/doi/10.1021/ja01627a061https://doi.org/10.1021/ja01627a061research-articleACS PublicationsRequest reuse permissionsArticle Views886Altmetric-Citations80LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Penalizing Closest Point Sharing for Automatic Free Form Shape Registration (2010)

For accurate registration of overlapping free form shapes, different points in one shape must select different points in another as their most sensible correspondents. To reach this ideal state, in this paper we develop a novel algorithm to penalize those points in one shape that select the same closest point in another as their tentative correspondents. The novel algorithm then models the relative weight change over time of a tentative correspondence as the difference between the negative functions of the numbers of points in one shape that actually and ideally select the same closest point in another. Such modeling results in an optimal estimation of the weights of different tentative correspondences, in the sense of deterministic annealing, that lead the camera motion parameters to be estimated in the weighted least squares sense. The proposed algorithm is initialized using the pure translational motion derived from the centroids difference of the overlapping free form shapes being registered. Experimental results show that it outperforms three selected state-of-the-art algorithms on the whole for the accurate and robust registration of real overlapping free form shapes captured using two different laser scanners under typical imaging conditions.
Establishing a Gender Bias Task Force (1986)

Symposium: Seventh Annual Conference of the National Association of Women Judges: Conference Presentations
Anticancer Effects of Thymoquinone, Caffeic Acid Phenethyl Ester and Resveratrol on A549 Non-small Cell Lung Cancer Cells Exposed to Benzo(a)pyrene (2013)

Our results revealed up-regulation of the key upstream signaling factors, which ultimately cause increase in their regulatory p53 levels affecting the induction of G2/M cell cycle arrest and apoptosis. Overall these results provide mechanistic insights for understanding the molecular basis and utility of the anti-tumor activity of TQ, RES and CAPE.
Importance Sampling for Estimating Exact Probabilities in Permutational Inference (1988)

Abstract This article discusses importance sampling as an alternative to conventional Monte Carlo sampling for estimating exact significance levels in a broad class of two-sample tests, including all of the linear rank tests (with or without censoring), homogeneity tests based on the chi-squared, hypergeometric, and likelihood ratio statistics, the Mantel—Haenszel trend test, and Zelen's test for a common odds ratio in several 2 × 2 contingency tables. Inference is based on randomly selecting 2 × k contingency tables from a reference set of all such tables with fixed marginals. Through a network algorithm, the tables are selected in proportion to their importance for reducing the variance of the estimated Monte Carlo p-value. Spectacular gains, up to four orders of magnitude, are achieved relative to conventional Monte Carlo sampling. The technique is illustrated on four real data sets.
Bacterial selenocysteine synthase (1998)

Selenocysteine synthase from Escherichia coli is a pyridoxal-5'-phosphate-containing enzyme which catalyses the conversion of seryl-tRNA(Sec) into selenocysteyl-tRNA(Sec). Analysis of amino acid sequences indicated that selenocysteine synthase belongs to the alpha/gamma superfamily of pyridoxal-5'-phosphate-dependent enzymes. To identify the lysine residue carrying the prosthetic group, the genes coding for the selenocysteine synthases from Moorella thermoacetica and Desulfomicrobium baculatum were cloned and sequenced and their derived amino acid sequences were aligned with those from E. coli and Haemophilus influenzae. Three lysine residues were found to be conserved; they were mutated into asparagine and one of them, Lys295, was found to be essential for activity. Proteolytic fragmentation of the E. coli enzyme reduced with borohydride, and mass-spectrometric and sequence analysis of the chromophoric peptide proved that Lys295 was modified. Kinetic analysis of the enzyme showed that thiophosphate served as a substrate leading to cysteyl-tRNA(Sec) synthesis, albeit with a 330-fold lower catalytic efficiency. Selenide and, to a much lesser degree, sulfide could also be used by the enzyme but only at much higher concentrations. These data together with the finding that selenophosphate synthetase is highly specific for selenide indicate that the phosphate moiety of selenophosphate provides selenocysteine synthase with the discrimination specificity against sulfur.
Increased AST and GGT activity as marker of RT-PCR inhibition in RNA extracts from peripheral blood. (2001)

The presence of HCV RNA in PMBC, with simultaneous absence of the virus in the plasma (7.8%), suggests that blood is better material for HCV RNA detection than plasma or serum in the diagnostic procedures of patients with chronic hepatitis C as well as in monitoring the antiviral therapy. We studied 111 patients with chronic hepatitis C (anti-HCV+) and elevated level of at least one biochemical marker: AST, ALAT, GGT, AP and bilirubin. Inhibition of amplification was 2% in plasma and 34% in whole blood samples. We applied modification of extraction to reduce the inhibitory effect on PCR, by introducing additional purification of the RNA extract in the Chomczyński method. After our modification of extraction was applied, inhibition was reduced to 1%. In attempt to identify such inhibitory markers that would label the samples, in which additional RNA extract purification should be applied, we analysed the activity of AST and ALAT enzymes, the key markers for parenchymal liver damage; GGT and AP, the markers for cholestatic hepatitis as well as bilirubin. We observed that the increased GGT and AST activities were correlated with the inhibition of RT-PCR. This correlation was statistically significant; for AST (Mann-Whitney test p = 0.09654 and Kolmogorow-Smirnow test p = 0.01543) and for GGT (Mann-Whitney test p = 0.02419 and Kolmogorow-Smirnow test p = 0.01921).
Nitrogen-15 nuclear magnetic resonance spectroscopy. Furazans and related systems (1978)

In the past few years, nitrogen-15 nuclear magnetic resonance spectroscopy, ^(15)N NMR, has shown considerable utility in solving organic structural problems. A particular advantage of ^(15)N NMR is the large range of chemical shifts and the general sensitivity of these shifts to structural changes. In this paper, we report on the insight that high-resolution ^(15)N NMR offers as to the electronic effects operating in compounds 1-8.
Pretraining Deep Actor-Critic Reinforcement Learning Algorithms With Expert Demonstrations (2018)

Pretraining with expert demonstrations have been found useful in speeding up the training process of deep reinforcement learning algorithms since less online simulation data is required. Some people use supervised learning to speed up the process of feature learning, others pretrain the policies by imitating expert demonstrations. However, these methods are unstable and not suitable for actor-critic reinforcement learning algorithms. Also, some existing methods rely on the global optimum assumption, which is not true in most scenarios. In this paper, we employ expert demonstrations in a actor-critic reinforcement learning framework, and meanwhile ensure that the performance is not affected by the fact that expert demonstrations are not global optimal. We theoretically derive a method for computing policy gradients and value estimators with only expert demonstrations. Our method is theoretically plausible for actor-critic reinforcement learning algorithms that pretrains both policy and value functions. We apply our method to two of the typical actor-critic reinforcement learning algorithms, DDPG and ACER, and demonstrate with experiments that our method not only outperforms the RL algorithms without pretraining process, but also is more simulation efficient.
Analysis of reduced monoclonal antibodies using size exclusion chromatography coupled with mass spectrometry (2009)

Size-exclusion chromatography (SEC) has been widely used to detect antibody aggregates, monomer, and fragments. SEC coupled to mass spectrometry has been reported to measure the molecular weights of antibody; antibody conjugates, and antibody light chain and heavy chain. In this study, separation of antibody light chain and heavy chain by SEC and direct coupling to a mass spectrometer was further studied. It was determined that employing mobile phases containing acetonitrile, trifluoroacetic acid, and formic acid allowed the separation of antibody light chain and heavy chain after reduction by SEC. In addition, this mobile phase allowed the coupling of SEC to a mass spectrometer to obtain a direct molecular weight measurement. The application of the SEC-MS method was demonstrated by the separation of the light chain and the heavy chain of multiple recombinant monoclonal antibodies. In addition, separation of a thioether linked light chain and heavy chain from the free light chain and the free heavy chain of a recombinant monoclonal antibody after reduction was also achieved. This optimized method provided a separation of antibody light chain and heavy chain based on size and allowed a direct measurement of molecular weights by mass spectrometry. In addition, this method may help to identify peaks eluting from SEC column directly.
Phosphoinositide 3-kinase is involved in the induction of the human sperm acrosome reaction downstream of tyrosine phosphorylation (1998)

In somatic cells phosphoinositide 3-kinase (PI 3-kinase) is activated upon interaction with both receptor tyrosine kinases (RTK) and G-proteins resulting in the production of moieties involved in the inositol phospholipid signalling pathway. As G proteins, RTK and the inositol phospholipids have all been implicated in the human sperm acrosome reaction, experiments were carried out to determine whether PI 3-kinase was also involved in this phenomenon. Wortmannin is a selective inhibitor of PI 3-kinase and was shown to significantly inhibit the acrosome reaction induced by both mannose-bovine serum albumin (mannose-BSA) (10, 50 and 100 nM) and a polyclonal antibody raised against an extracellular region of the sperm zona receptor kinase (ZRK, at 100 nM only). Wortmannin did not inhibit the A23187- or progesterone-induced acrosome reaction. These results suggest that PI 3-kinase is involved in the human sperm acrosome reaction. The levels of tyrosine phosphorylation of sperm proteins as detected by Western blotting using antiphosphotyrosine antibodies was not affected by wortmannin in agonist (A23187 and mannose-BSA)-stimulated spermatozoa. This indicated that PI 3-kinase operates downstream of tyrosine phosphorylation in the signal transduction cascade which leads to the human sperm acrosome reaction.
Beta-Cell Dedifferentiation and Type 2 Diabetes (2013)

Type 2 diabetes is caused by enhanced insulin resistance and reduced insulin secretion. New data provide support for beta-cell dedifferentiation as a cause of reduced insulin secretion.
Plasma nanoscience: setting directions, tackling grand challenges (2011)

This review paper presents historical perspectives, recent advances and future directions in the multidisciplinary research field of plasma nanoscience. The current status and future challenges are presented using a three-dimensional framework. The first and the largest dimension covers the most important classes of nanoscale objects (nanostructures, nanofeatures and nanoassemblies/nanoarchitectures) and materials systems, namely carbon nanotubes, nanofibres, graphene, graphene nanoribbons, graphene nanoflakes, nanodiamond and related carbon-based nanostructures; metal, silicon and other inorganic nanoparticles and nanostructures; soft organic nanomaterials; nano-biomaterials; biological objects and nanoscale plasma etching. In the second dimension, we discuss the most common types of plasmas and plasma reactors used in nanoscale plasma synthesis and processing. These include low-temperature non-equilibrium plasmas at low and high pressures, thermal plasmas, high-pressure microplasmas, plasmas in liquids and plasma–liquid interactions, high-energy-density plasmas, and ionized physical vapour deposition as well as some other plasma-enhanced nanofabrication techniques. In the third dimension, we outline some of the 'Grand Science Challenges' and 'Grand Socio-economic Challenges' to which significant contributions from plasma nanoscience-related research can be expected in the near future. The urgent need for a stronger focus on practical, outcome-oriented research to tackle the grand challenges is emphasized and concisely formulated as from controlled complexity to practical simplicity in solving grand challenges.
Phytochrome-regulated expression of the genes encoding the small GTP-binding proteins in peas. (1993)

We examined the effect of light on the mRNA levels of 11 genes (pra1-pra9A, pra9B, and pra9C) encoding the small GTP-binding proteins that belong to the ras superfamily in Pisum sativum. When the dark-grown seedlings were exposed to continuous white light for 24 hr, the levels of several pra mRNAs in the pea buds decreased: pra2 and pra3 mRNAs decreased markedly; pra4, pra6, and pra9A mRNAs decreased slightly; the other 6 pra mRNAs did not decrease. We studied the kinetics of mRNA accumulation for pra2, pra3, and pra9B in detail during white light illumination and compared them with those of the phytochrome gene and the small subunit gene of ribulose bisphosphate carboxylase: mRNA levels of pra2 and pra3 decreased in a manner similar to that of phytochrome while that of the small subunit increased as was expected. The decreases were triggered by a 2-min monochromatic red light (660 nm) irradiation. The effect of red light was reversed by subsequent exposure to far-red light, indicating an involvement of phytochrome as a photoreceptor in this light-regulated event. This work reports negative regulation of mRNA levels of small GTP-binding proteins by light, mediated by phytochrome.
In vitro activity of CGP 31608, a new penem (1987)

The in vitro activity of CGP 31608, a semisynthetic penem derivative, was compared with that of Sch 34343, imipenem, cefoxitin, cefuroxime, and ceftazidime and other beta-lactams, when appropriate, against 628 recent isolates and other beta-lactam-resistant strains. The MICs of CGP 31608 against 90% of the members of the family Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae, Neisseria spp., Bacteroides spp., Clostridium spp., staphylococci, and Streptococcus pneumoniae were between 0.25 and 8 micrograms/ml. The susceptibility of beta-lactamase-producing strains and known porin mutants of the Enterobacteriaceae suggests that CGP 31608 is resistant to many important beta-lactamases (including the mutationally derepressed chromosomal enzymes) and is not excluded from the bacterial cell in strains expressing these known porin mutations. Generally, CGP 31608 was less active than imipenem, Sch 34343, and the cephalosporins, except against Pseudomonas aeruginosa. The activity of CGP 31608 against Staphylococcus aureus (including methicillin-resistant strains) was greater than that of the cephalosporins. The major target site in Escherichia coli K-12 for CGP 31608 was penicillin-binding protein 2. The serum protein binding of 5 micrograms of CGP 31608 per ml was 14%, and serum had little effect on activity.
Increased serum levels of matrix metalloproteinase‐9 predict clinical outcome of patients with early B‐cell chronic lymphocytic leukaemia (2003)

MMP-9 serum levels predict disease behaviour and help to refine the prognosis of stage A CLL patients.