gebhart/patrepeval huggingface dataset:
The T790M “gatekeeper” mutation in <i>EGFR</i> mediates resistance to low concentrations of an irreversible EGFR inhibitor (2008)

Patients with non-small cell lung cancer (NSCLC) harboring activating mutations in the epidermal growth factor receptor (EGFR) kinase domain tend to respond well to the tyrosine kinase inhibitors, gefitinib and erlotinib. However, following clinical response, these patients typically relapse within a year of treatment. In many cases, resistance is caused by an acquired secondary EGFR kinase domain mutation, T790M. In vitro studies have shown that a new class of EGFR-irreversible inhibitors could overcome the resistance conferred by T790M. Clinical trials are under way to examine the efficacy of one of these inhibitors, HKI-272, in patients with NSCLC who initially responded to gefitinib/erlotinib and subsequently relapsed. To anticipate the possibility that patients who respond to irreversible inhibitors will develop secondary resistance to such inhibitors, as has been seen in other similar settings, we modeled acquired resistance to the dual EGFR/HER2-irreversible tyrosine kinase inhibitor HKI-272 in a NSCLC cell culture model. We found that HKI-272-resistant clones fall into two biochemical groups based on the retention of EGFR phosphorylation in the presence of the drug. Cells that retain phosphorylated EGFR have acquired the secondary mutation T790M. Moreover, HKI-272 can overcome T790M resistance only at suprapharmacologic concentrations. We further model mutations at EGFR C797 as a mechanism of resistance to irreversible EGFR inhibitors and show that although these mutants are resistant to the irreversible inhibitor, they retain erlotinib sensitivity. Our findings suggest that HKI-272 treatment at maximally tolerated dosing may lead to the emergence of T790M-mediated resistance, whereas treatment with a more potent irreversible inhibitor could yield a resistance mutation at EGFR C797.
Sleep and its homeostatic regulation in mice lacking the adenosine A<sub>1</sub>receptor (2003)

Sleep deprivation (SD) increases extracellular adenosine levels in the basal forebrain, and pharmacological manipulations that increase extracellular adenosine in the same area promote sleep. As pharmacological evidence indicates that the effect is mediated through adenosine A1 receptors (A1R), we expected A1R knockout (KO) mice to have reduced rebound sleep after SD. Male homozygous A1R KO mice, wild-type (WT) mice, and heterozygotes (HET) from a mixed 129/C57BL background were implanted during anesthesia with electrodes for electroencephalography (EEG) and electromyography (EMG). After 1 week of recovery, they were allowed to adapt to recording leads for 2 weeks. EEG and EMG were recorded continuously. All genotypes had a pronounced diurnal sleep/wake rhythm after 2 weeks of adaptation. We then analyzed 24 h of baseline recording, 6 h of SD starting at light onset, and 42 h of recovery recording. Neither rapid eye movement sleep (REM sleep) nor non-REM sleep (NREMS) amounts differed significantly between the groups. SD for 6 h induced a strong NREMS rebound in all three groups. NREMS time and accumulated EEG delta power were equal in WT, HET and KO. Systemic administration of the selective A1R antagonist 8-cyclopentyltheophylline (8-CPT) inhibited sleep for 30 min in WT, whereas saline and 8-CPT both inhibited sleep in KO. We conclude that constitutional lack of adenosine A1R does not prevent the homeostatic regulation of sleep.
Wall-Effect/Gel-Droplet Model of Disproportionate Permeability Reduction (2000)

Abstract Many polymers and gels can reduce the permeability to water more than that to oil or gas. However, the mechanism of this disproportionate permeability reduction is not clear. This paper considers a promising potential explanation that is based on a combined "wall-effect" and "gel-droplet" model. Disproportionate permeability reduction can be explained by a wall-effect model if the gelant is prepared from or matches the wetting phase, and by a gel-droplet model if the gelant is prepared from or matches the non-wetting phase. The combined model predicts that disproportionate permeability reduction should increase with increasing residual nonwetting-phase saturation. New experimental results support this prediction. Maintaining high residual oil saturations in the treated region of an oil zone could significantly reduce damage to oil productivity after a gel treatment. The disproportionate permeability reduction increased with increased pressure drawdown between 45 psi/ft to 180 psi/ft. Therefore, to a certain extent, an increase in pressure drawdown after a gel treatment might reduce damage to oil productivity without increasing water production.
High-Gain Optical Amplification of Europium–Aluminum (Eu<sup>3+</sup>–Al)-Nanocluster-Doped Planar Polymer Waveguides (2007)

We have fabricated a planar poly(methyl methacrylate) (PMMA) optical waveguide doped with 10 wt % Eu–Al nanoclusters, and have successfully demonstrated optical amplification at 610 nm excited by a N2 laser (λ=337 nm). The gain of the optical amplification was found to be as high as 5.57 dB/mm, which, to the best of our knowledge, is the highest observed for various rare-earth (RE)-doped planar optical waveguides. An Er–Al-nanocluster-doped PMMA optical waveguide has also been successfully fabricated, and guided emission at around 1.55 µm has been observed in spite of the large absorption loss induced by PMMA. The RE-metal nanoclusters can therefore be regarded as promising candidates as the active materials for polymer-based waveguide-type optical amplification devices.
Biosynthesis of Heparin/Heparan Sulfate (1995)

O-Sulfation at C-3 of N-sulfated GlcN units concludes polymer modification and the formation of antithrombin binding regions in the biosynthesis of heparinlheparan sulfate. The resulting GlcNSO s(3.0S0s) units are largely restricted to heparin chains with high affinity for antithrombin (H A heparin). Low affinity (LA) heparin fails to serve as a substrate in the 3-0-sulfotransferase reaction yet contains potentiaI3-0-sulfate acceptor sites (Kusche, M., Torri, G., Casu, B., and Lindahl, U. (1990) J. Bioi. Chern. 265,[7292][7293][7294][7295][7296][7297][7298][7299][7300], as verified in the present study using a novel sequencing procedure. O-Desulfated, re-N-sulfated LA heparin, as well as an octasaccharide fraction isolated after heparinase I digestion of LA heparin, both yielded labeled H A components following incubation with solubilized mouse mastocytoma microsomal enzymes and [s5Sladenosine 3'-phosphate 5'phosphosulfate (PAPS), suggesting that the 3-0-sulfotransferase may be inhibited by sulfated saccharide sequences outside the 3-0-sulfate acceptor region. Indeed, the addition of LA heparin precluded enzymatic 3-0sulfation of a synthetic pentasaccharide substrate. The K,.. for the pentasaccharide was determined to ~be 6 f.A.M. Incubations of mixed pentasaccharide substrate and saccharide inhibitors revealed K, values for intact LA heparin and for a heparin octasaccharide fraction of ~1.3 and ~0.7 f.A.M, respectively. Inhibition experiments with selectively desulfated heparin indicated that both IdoA 2-0-sulfate and GlcN 6-0-sulfate groups contributed to the inhibition of the 3-0-sulfotransferase. By contrast, chondroitin sulfate or dermatan sulfate showed no significant inhibitory activity. It is proposed that the regulation of GlcN 3-0-sulfation during biosynthesis of heparinlheparan sulfate depends on the topological organization of the membrane-bound enzyme machinery in the intact cell.
Approaching the Lower Bounds on Q for Electrically Small Electric-Dipole Antennas Using High Permeability Shells (2010)

We study the effect of surrounding electrically small, top-loaded, electric-dipole antennas with a thin shell of high-permeability magnetic material. The magnetic polarization currents induced in the thin shell of magnetic material reduce the internal stored energy, resulting in a lower as compared to conventional designs. The simulated 's of thin-magnetic-shell cylindrical and spherical antennas are compared to recently derived lower bounds on . The high permeability shells reduce the of these antennas to values below the lower bounds for purely global electric current sources. In the case of the spherical electric-dipole antenna, a sufficiently large value of permeability enables the to be reduced to a value that is only 1.11 times the Chu lower bound.
Stabilization of a high-power diode-side-pumped intracavity-frequency-doubled CW Nd:YAG laser by compensating for thermal lensing of a KTP crystal and Nd:YAG rods (1999)

We have analyzed the stability of a high-power diode-side-pumped intracavity-frequency-doubled CW Nd:YAG laser. It is found that large green power fluctuations observed experimentally are suppressed by compensating thermal lensing of the nonlinear crystal KTP and that of the Nd:YAG rods with an advanced resonator design. Stable CW green powers of 27 W with a beam quality of M/sup 2/=8 and 16 W with M/sup 2/=1.2 (TEM/sub 00/-mode) were generated.
A reduced complexity implementation of the Log-Map algorithm for turbo-codes decoding (2002)

In this paper, we propose a reduced complexity implementation scheme of the Log-Map algorithm for turbo-codes decoding. By re-arranging the structure of the computation and using adaptive approximation, the computation in the Log-Map algorithm such as the state metric and the log-likelihood ratio calculation could be simplified or reduced adaptively. Simulation results show that more than 45% of the computation can be reduced with almost no performance degradation.
Speech scrambling with Hadamard transform in frequency domain (2003)

A speech scrambling algorithm is proposed in this paper based on Hadamard transform in frequency domain. It has a larger key space than the permutation algorithms. Simulations of this algorithm used in telephone communication were carried out. The results showed that this algorithm has low residual intelligibility and the recovered speech quality is fairly good. Fast algorithm is provided to reduce the computational cost.
Posttranslational processing and targeting of transgenic human defensin in murine granulocyte, macrophage, fibroblast, and pituitary adenoma cell lines (1993)

Human defensins are 29 to 30 amino acid (aa) antimicrobial peptides that are among the principal constituents of the neutrophil's azurophil granules. To determine the tissue specificity of posttranslational processing and subcellular targeting of defensins, the cDNA for a 94 aa human preprodefensin was transduced into murine cell lines (NIH 3T3 embryonic fibroblasts, AtT-20 pituitary adenoma, J774.1 and RAW 264.7 macrophages, and 32D and 32D cl3 granulocytes) using retroviral vectors. All transduced cell types expressed and to a variable extent constitutively secreted a 75 aa prodefensin formed by the removal of the amino terminal signal sequence. In AtT-20 cells, the 75 aa form accumulated intracellularly in granules and was releasable by secretagogues. Proteolytic processing to mature defensins was seen only in myeloid cells (J774.1, RAW 264.7, 32D, and 32D cl3). Newly formed mature defensin was rapidly degraded in J774.1 and RAW 264.7 macrophages, but accumulated stably in multivesicular bodies in 32D cells and in cytoplasmic granules of 32D cl3 cells. Our data suggest that the enzymatic and transport machinery required to process preprodefensin to mature defensin and to store it in cytoplasmic granules is a specialized feature of cells of granulocytic lineage.
The Specificities of Four Yeast Dihydrouridine Synthases for Cytoplasmic tRNAs (2004)

Dihydrouridine is a highly abundant modified nucleoside found widely in tRNAs of eubacteria, eukaryotes, and some archaea. In cytoplasmic tRNA of Saccharomyces cerevisiae, dihydrouridine occurs exclusively at positions 16, 17, 20, 20A, 20B, and 47. Here we show that the known dihydrouridine synthases Dus1p and Dus2p and two previously uncharacterized homologs, Dus3p (encoded by YLR401c) and Dus4p (YLR405w), are required for all of the dihydrouridine modification of cytoplasmic tRNAs in S. cerevisiae. We have mapped the in vivo position specificity of the four Dus proteins, by three complementary approaches: determination of the molar ratio of dihydrouridine in purified tRNAs from different dus mutants; microarray analysis of a large number of tRNAs based on differential hybridization of uridine and dihydrouridine-containing tRNAs to the complementary oligonucleotides; and the development and use of a novel dihydrouridine mapping technique, employing primer extension. We show that each of the four Dus proteins has a distinct position specificity: Dus1p for U(16) and U(17), Dus2p for U(20), Dus3p for U(47), and Dus4p for U(20a) and U(20b).
Role of exotoxin A in inducing severe Pseudomonas aeruginosa infections in mice (1995)

The effects of exotoxin A (EXA) from Pseudomonas aeruginosa on polymorphonuclear leucocytes (PMNLs) were studied in a mouse model and in vitro. P. aeruginosa PA103, which produced EXA, was 20 times more virulent for normal mice than was its EXA-deficient mutant, PA103-29. EXA was detected in the plasma of mice infected with P. aeruginosa PA103, and its presence correlated with increasing numbers of bacteria in the blood and internal organs. A monoclonal antibody (MAb) against EXA prevented the death of the mice if it was given simultaneously with, or 2 h before, infection with strain PA103. The number of PMNLs in murine blood decreased by 50% within 30 min of intravenous injection of EXA, but this decrease was prevented by simultaneous or prior injection of MAb to the toxin. EXA inhibited in-vitro phagocytosis and killing of P. aeruginosa by human and murine PMNLs and decreased the number of the PMNLs by between 60 and 68%. Collectively, these results not only confirm that EXA is toxic in vivo, but also suggest that this toxin accelerates the growth of virulent P. aeruginosa in mice.
FET Q switch for pulsed NMR (1977)

A Q switch which shortens the ringing time in pulsed NMR equipment is described. It uses a field-effect transistor as the Q-switching element. A convenient method of generating the control signal is shown. The device performs well and is simple to construct and adjust.
The Relationship of Skill Level to Anterior Cruciate Ligament Injury (1998)

There are many different variables that contribute to a player's skill level. Although these variables may relate to ACL injury and may be responsible for the differential in injury rate between men and women, skill level as represented by collegiate division does not relate to ACL injury. When considering possible etiologies of the differential in ACL injury rates between men and women, the use of the term "skill" should be avoided, and more specific terms used.
SHORT NOTICES (1987)

Journal Article SHORT NOTICES Get access Studia Patristica XVIII. Papers of the Ninth International Conference on Patristic Studies, Oxford 1983. Volume One. Historica: Theologica—Gnostica—Biblica. Edited by ELIZABETH A. LIVINGSTONE. Pp. xiii + 358. Kalamazoo, Michigan: Cistercian Publications, 1985. Paperback $40. STUART G. HALL STUART G. HALL Search for other works by this author on: Oxford Academic Google Scholar The Journal of Theological Studies, Volume 38, Issue 2, October 1987, Pages 621-b–622, https://doi.org/10.1093/jts/38.2.621-b Published: 01 October 1987
Modified Newton's method applied to potential field-based navigation for mobile robots (2006)

This paper investigates the inherent oscillation problem of potential field methods (PFMs) in the presence of obstacles and in narrow passages. These problems can cause slow progress and system instability in implementation. To overcome these two problems, in this paper, we propose a modification of Newton's method. The use of the modified Newton's method, which applies anywhere C/sub 2/ continuous navigation functions are defined, greatly improves system performance when compared to the standard gradient descent approach. To the best of our knowledge, ours is the first systematic approach to the oscillation problems in PFMs. We have validated this technique by comparing its performance with the gradient descent method in obstacle-avoidance tasks with different potential models and parameter changes.
Ultrastructural observations on Ehrlichia equi organisms in equine granulocytes (1976)

The ultrastructure of the etiological agent of equine ehrlichiosis, Ehrlichia equi, was studied in equine peripheral leukocytes. The organisms occurred within membrane-lined cytoplasmic vacuoles of neutrophils and eosinophils. Ovoid, round, and rod-shaped profiles were observed. From 1 to 33 organisms were present in a thin-section profile of a cytoplasmic vacuole. Many cells contained multiple organism-containing vacuoles. The organisms had a cell wall and plasma membrane, and internally they consisted of electron-dense and lucid areas. A great variation in size was observed. The morphological features were most consistent with agents of the genus Ehrlichia.
Model reaction for the synthesis of polyhydroxyurethanes from cyclic carbonates with amines: Substituent effect on the reactivity and selectivity of ring‐opening direction in the reaction of five‐membered cyclic carbonates with amine (2001)

Abstract This article focuses on the substituent effect on the reactivity and selectivity of the ring‐opening direction in the reaction of five‐membered cyclic carbonates with n ‐hexylamine. The reactivity of the cyclic carbonate and the formation selectivity of the adduct with a secondary hydroxyl group increased as a stronger electron‐withdrawing group was introduced at the α‐methylene of the cyclic carbonate. These results are discussed on the basis of the stability of intermediates, primary and secondary alcoholate anions, Mulliken charges on carbonyl carbon, and the bond lengths and orders of the OCO single bond. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3678–3685, 2001
Fabrication of comb-shaped microactuator for multi-degrees-of-freedom system (2003)

The authors describe a fabrication method for a comb-shaped microactuator as an element of a multi-degree-of-freedom system. This microactuator is combined with an elastic sheet. The construction of a series of these microactuators corresponds to that of a muscular model. An anisotropic etching technique of [110]-oriented silicon is a very useful method to obtain the comb-shaped actuator with a high aspect ratio. By means of photolithography and this technique, a series of microactuators can be obtained easily. The structure of a multi-degree-of-freedom system is introduced. The strategy to control a series of several actuators is explained. The fabrication process of the comb-shaped microactuator is outlined.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Three-dimensional structural aspects of the design of new protein molecules (1986)

Abstract A knowledge of the three-dimensional structure of proteins is an essential prerequisite for the design of new molecules. When the tertiary structure is not available from high-resolution X-ray or n.m.r. analysis, the success of prediction is improved by using a relational database of known protein structures. This can be searched to provide information on secondary structure motifs and domains which are recognized by characteristic sequence patterns and which are assembled as ‘spare parts’ by using computer graphics. Similar techniques can be used to give approximate structures for amino-acid replacements, deletions and insertions introduced by mutagenesis. The resulting structures are optimized by using interactive graphics, energy minimization and molecular dynamics.
Knockdown of occludin expression leads to diverse phenotypic alterations in epithelial cells (2005)

The function of occludin (Occ) in the tight junction is undefined. To gain insight into its role in epithelial cell biology, occludin levels in Madin-Darby canine kidney II cells were suppressed by stably expressing short interfering RNA. Suppression of occludin was associated with a decrease in claudins-1 and -7 and an increase in claudins-3 and -4. Claudin-2 levels were unaffected. The tight junction "fence" function was not impaired in suppressed Occ (Occ-) clones, as determined by BODIPY-sphingomyelin diffusion in the membrane. The most striking changes were those related to control of the cytoskeleton and the "gate" function of tight junctions. A reduced ability of Occ- clones to extrude apoptotic cells from the monolayers suggested that neighbors of apoptotic cells either failed to sense their presence or were unable to coordinate cytoskeletal activity necessary for their extrusion. To further test the extent to which actin cytoskeletal activity depends on the presence of occludin, Occ- and Occ+ monolayers were depleted of cholesterol. Previous studies showed that cholesterol depletion is associated with reorganization of the actin cytoskeleton and a fall in transepithelial electrical resistance. In contrast to control Occ (Occ+) cells, transepithelial electrical resistance did not fall significantly in cholesterol-depleted Occ- monolayers and they failed to generate Rho-GTP, one of the signaling molecules involved in regulating the actin cytoskeleton. While steady-state transepithelial electrical resistance was similar in all clones, tight junction permeability to mono- and divalent inorganic cations was increased in Occ- monolayers. In addition, there was a disproportionately large increase in permeability to monovalent organic cations, up to 6.96 A in diameter. Chloride permeability was unaffected and there was little change in mannitol flux. The data suggest that occludin transduces external (apoptotic cells) and intramembrane (rapid cholesterol depletion) signals via a Rho signaling pathway that, in turn, elicits reorganization of the actin cytoskeleton. Impaired signaling in the absence of occludin may also alter the dynamic behavior of tight junction strands, as reflected by an increase in permeability to large organic cations; the permeability of ion pores formed of claudins, however, is less affected.
Abrogation of Head and Neck Squamous Cell Carcinoma Growth by Epidermal Growth Factor Receptor Ligand Fused to <b> <i>Pseudomonas</i> </b> Exotoxin Transforming Growth Factor α-PE38 (2004)

These results indicate that topical or intratumoral administration of low doses of TGF-alpha-PE38 may demonstrate antitumor effects in HNSCC without associated systemic toxicity.
Web applications design and maintenance using symbolic model checking (2003)

We present an approach to automatic checking of the correctness of Web applications structure during their lifecycle. The approach adopts the well-established symbolic model checking technique and the associated tool SMV. A formalism allows the designer to describe the model of a Web-based system. Computation Tree Logic (CTL) is adopted as language to define the properties to be verified. The approach has been implemented in a tool to provide automatic support in the design of Web applications. The system embeds the NuSMV model checker to perform verification. Verification is carried out after building the finite state model of a site in the model checker input language. To this purpose the system parses the HTML source code of Web pages, including code for dynamic pages. Properties are expressed using a user friendly interface for Web application developers that automatically translates properties in CTL formulas.