gebhart/patrepeval huggingface dataset:
IsK and KvLQT1: Mutation in Either of the Two Subunits of the Slow Component of the Delayed Rectifier Potassium Channel Can Cause Jervell and Lange-Nielsen Syndrome (1997)

The Jervell and Lange-Nielsen syndrome (JLNS) comprises profound congenital sensorineural deafness associated with syncopal episodes. These are caused by ventricular arrhythmias secondary to abnormal repolarisation, manifested by a prolonged QT interval on the electrocardiogram. Recently, in families with JLNS, Neyroud et al. reported homozygosity for a single mutation in KVLQT1 , a gene which has previously been shown to be mutated in families with dominantly inherited isolated long QT syndrome [Neyroud et al . (1997) Nature Genet ., 15, 186-189]. We have analysed a group of families with JLNS and shown that the majority are consistent with mutation at this locus: five families of differing ethnic backgrounds were homozygous by descent for markers close to the KVLQT1 gene and a further three families from the same geographical region were shown to be homozygous for a common haplotype and to have the same homozygous mutation of the KVLQT1 gene. However, analysis of a single small consanguineous family excluded linkage to the KVLQT1 gene, establishing genetic heterogeneity in JLNS. The affected children in this family were homozygous by descent for markers on chromosome 21, in a region containing the gene IsK . This codes for a transmembrane protein known to associate with KVLQT1 to form the slow component of the delayed rectifier potassium channel. Sequencing of the affected boys showed a homozygous mutation, demonstrating that mutation in the IsK gene may be a rare cause of JLNS and that an indistinguishable phenotype can arise from mutations in either of the two interacting molecules.
A mode-locked fibre laser system for multi-point intra-cavity gas spectroscopy (2003)

We have described a new way of realising a multi-point, multi-gas sensor system based on a mode-locked fibre laser with potential application for trace gas detection in environmental and safety monitoring. Although based specifically on erbium-fibre lasers, the principles could be extended to other laser types, for example, Tm/sup 3+/ fiber lasers in silica glass or the use of semiconductor optical amplifiers which are commercially available for the 1300-1600 nm region, extending the range of gas sensors possible. Preliminary experiments have been conducted to test the principles and research is currently in progress to demonstrate a fully multiplexed system.
Crystal structure of tetraaqua-(4,4′-diamino-1,1′-biphenyl-2,2′-disulfonato-κN)(4,4′-bipyridyl-κN)zinc(II) trihydrate, C22H32N4O13S2Zn (2015)

Abstract C 22 H 32 N 4 O 13 S 2 Zn, triclinic, P 1̅ (no. 2), a = 9.496(1) Å, b = 10.016(1) Å, c = 16.334(2) Å, α = 102.297(10)°, β = 93.625(10)°, γ = 111.313(10)°, V = 1397.1 Å 3 , Z = 2, R gt (F) = 0.0383, wR ref (F 2 ) = 0.1020, T = 296 K.
Conformationally Constrained Butyrophenones with Mixed Dopaminergic (D2) and Serotoninergic (5-HT2A, 5-HT2C) Affinities:  Synthesis, Pharmacology, 3D-QSAR, and Molecular Modeling of (Aminoalkyl)benzo- and -thienocycloalkanones as Putative Atypical Antipsychotics (1999)

A series of novel conformationally restricted butyrophenones (2-(aminoethyl)- and 3-(aminomethyl)thieno- or benzocycloalkanones bearing (6-fluorobenzisoxazolyl)piperidine, (p-fluorobenzoyl)piperidine, (o-methoxyphenyl)piperazine, or linear butyrophenone fragments) were prepared and evaluated as atypical antipsychotic agents by in vitro assays of affinity for dopamine receptors (D(1), D(2)) and serotonin receptors (5-HT(2A), 5-HT(2C)) and by in vivo assays of antipsychotic potential and the risk of inducing extrapyramidal side effects. Potency and selectivity depended mainly on the amine fragment connected to the cycloalkanone structure. As a group, compounds with a benzisoxazolyl fragment had the highest 5-HT(2A) activities, followed by the benzoylpiperidine derivatives; in general, alpha-substituted cycloalkanone derivatives were more active than the corresponding beta-substituted congeners. CoMFA (comparative molecular field analysis) and docking studies showed electrostatic, steric, and lipophilic determinants of 5-HT(2A) and D(2) affinities and 5-HT(2A)/D(2) selectivity. The in vitro and in vivo pharmacological profiles of N-[(4-oxo-4H-5, 6-dihydrocyclopenta[b]thiophene-5-yl)ethyl]-4-(6-fluorobenzisox azol-3 -yl)piperidine (23b, QF 0510B), N-[(4-oxo-4,5,6, 7-tetrahydrobenzo[b]thiophene-5-yl)ethyl]-4-(6-fluorobenzisoxazol- 3-y l)piperidine (24b, QF 0610B), and N-[(7-oxo-4,5,6, 7-tetrahydrobenzo[b]thiophene-6-yl)ethyl]-4-(6-fluorobenzisoxazol- 3-y l)piperidine (29b, QF 0902B) suggest that they may be effective antipsychotic drugs with low propensity to induce extrapyramidal side effects.
Murine susceptibility to two-stage skin carcinogenesis is influenced by the agent used for promotion (1984)

Several approaches were employed to investigate whether murine stock and strain differences in susceptibility to two-stage skin carcinogenesis are due to differences in the metabolism of the initiating aromatic hydrocarbons, or the consequences of the agents used for promotion. A cell-mediated mutagenesis assay was used to quantitatively compare the abilities of cultured newborn SENCAR, DBA/2, C57BL/6 and BALB/c keratinocytes to metabolize dimethylbenz[a]anthracene (DMBA) to mutagenic and cytotoxic metabolites. At equivalent concentrations of DMBA, throughout a 25-fold range in promutagen concentration, C57BL/6, BALB/c and SENCAR keratinocyte-dependent mutant frequencies were very similar and approximately twice DBA/2 keratinocyte-dependent mutant frequencies. In in vivo tumor studies, C57BL/6 mice were more sensitive than SENCAR mice to complete skin carcinogenesis protocols employing repetitive weekly treatments with DMBA and benzo[a]pyrene (BP). At equivalent concentrations of either DMBA or BP, C57BL/6 mice developed carcinomas sooner, and had a greater number of carcinomas per animal. SENCAR mice were very sensitive to two-stage skin carcinogenesis protocols employing BP and DMBA as initiators and benzoyl peroxide and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoters. C57BL/6 mice were relatively refractory to TPA promotion but sensitive to promotion with benzoyl peroxide. These findings suggest that murine stock and strain-dependent differences in sensitivity to two-stage skin carcinogenesis may not be due to major differences in the metabolism of the initiating hydrocarbons, but are partially the consequences of the agents used for promotion.
Angiopoietin-2 is related to tumor angiogenesis in gastric carcinoma: possible in vivo regulation via induction of proteases. (2001)

Tumor angiogenesis progresses by a dynamic balance between tumor vascular regression and growth. Angiopoietin (Ang)-2 (the natural antagonist for the angiogenic Tie-2 receptor) and vascular endothelial growth factor (VEGF) are thought to be critical regulators in this process; therefore, these may play a critical role in cancer aggressiveness. The aim of this study was to clarify the clinical and biological significance of the expression of Ang-2 in human gastric cancers and to investigate the relationship between Ang-2 together with VEGF and the induction of proteases such as matrix metalloproteinases (MMPs) in the process of tumor development. Eighty-five individuals with gastric cancer, who had undergone surgery without preoperative treatment, were studied. A stable transfectant of the human MKN-7 gastric cancer cell lines with an Ang-2 expression vector was used for the experimental study. First, we examined the relationship between the mRNA expression of Angs by Northern blot analysis and clinicopathological features. High Ang-2-expression cases showed more frequent vascular involvement and more advanced stages of disease compared with low Ang-2-expression cases (P < 0.05). With regard to prognosis, the survival time for patients in the high-Ang-2 mRNA group was significantly shorter (P < 0.05). When we examined the localization of Ang-2 in human gastric cancers, immunohistochemical analysis revealed that this protein was expressed predominantly in cancer tissues when compared with normal tissues. Interestingly it was expressed not only in endothelia cells (ECs) but also in cancer cells. Second, Ang-2-transfected cells were implanted in vivo into the gastric walls of nude mice. Ang-2-transfectant mice developed highly metastatic tumors with hypervascularity as compared with MKN-7 or control vector-transfectant tumors. There was a significant correlation between Ang-2 mRNA expression and lower grade of vessel maturation. Third, on the basis of the in vivo data, we focused on production of proteases such as MMPs to investigate possible mechanisms in these processes. MMP-1, MMP-9, and urokinase-type plasminogen activator in ECs were strongly up-regulated by Ang-2 in the presence of VEGF in vitro. These data suggest that production of Ang-2 is implicated in tumor development in human gastric cancers. Its production may contribute to tumor angiogenesis by induction of proteases in ECs, which may be enhanced in the presence of VEGF.
Electrochemical polymerization and deposition on carbon fibers (1980)

Ab8tract -
Hybrids: then and now (1995)

Very different from their turn-of-the-century forebears, modern hybrid electric vehicles (HEV) are almost as clean as pure EVs and have the range of conventional cars. The author discusses the advantages of HEV and describes the two basic types of HEV, parallel and serial. The serial type has a downsized engine on board that drives a generator that supplements the batteries and can charge them when they run low. In the parallel type the ICE and the electric motor can both deliver propulsion power to the wheels. The advantages of these two types of HEV are discussed. The parallel HEV is then discussed in more detail.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Anaplastic lymphoma kinase activity is essential for the proliferation and survival of anaplastic large-cell lymphoma cells (2005)

The roles of aberrant expression of constitutively active ALK chimeric proteins in the pathogenesis of anaplastic large-cell lymphoma (ALCL) have been well defined; nevertheless, the notion that ALK is a molecular target for the therapeutic modulation of ALK+ ALCL has not been validated thus far. Select fused pyrrolocarbazole (FP)-derived small molecules with ALK inhibitory activity were used as pharmacologic tools to evaluate whether functional ALK is essential for the proliferation and survival of ALK+ ALCL cells in culture. These compounds inhibited interleukin 3 (IL-3)-independent proliferation of BaF3/NPM-ALK cells in an ALK inhibition-dependent manner and significantly blocked colony formation in agar of mouse embryonic fibroblast (MEF) cells harboring NPM-ALK. Inhibition of NPM-ALK phosphorylation in the ALK+ ALCL-derived cell lines resulted in significant inhibition of cell proliferation and induction of apoptotic-cell death, while having marginal effects on the proliferation and survival of K562, an ALK- leukemia cell line. ALK inhibition resulted in cell-cycle G1 arrest and inactivation of ERK1/2, STAT3, and AKT signaling pathways. Potent and selective ALK inhibitors may have therapeutic application for ALK+ ALCL and possibly other solid and hematologic tumors in which ALK activation is implicated in their pathogenesis.
In vitro synthesis and assembly of picornaviral capsid intermediate structures (1982)

Cell-free translation of encephalomyocarditis RNA in extracts of rabbit reticulocytes results in the synthesis of viral proteins indistinguishable from those produced during virus infection of cells. The viral capsid proteins are produced in an active form capable of assembly into viral capsid intermediate structures. Protomers (5S), pentamers (14S), and shell-like structures (75 to 85S) can be detected after prolonged incubation in the extracts. Proteolytic cleavage of capsid precursor proteins appears to be a prerequisite for assembly, in apparent contrast to cell-associated assembly. Assembly of pentamers is also preceded by conversion of protein epsilon 1 to epsilon in a step which may reflect an amino-terminal blocking reaction.
Histochemical analysis of newly synthesized and accumulated sulfated glycosaminoglycans during musculogenesis in the embryonic chick leg (1989)

The leg musculature from 11, 14, and 17 day chick embryos was analyzed histochemically to investigate the temporal and spatial distribution of various types of sulfated glycosaminoglycans present during skeletal muscle development. Types of glycans were identified by selective degradation with specific glycosidases and nitrous acid coupled with Alcian blue staining procedures for sulfated polyanions and with [35S]sulfate autoradiography. On day 11, radiolabeled chondroitin sulfate glycosaminoglycans are localized extracellularly in both the myogenic and connective tissue cell populations. By day 17, incorporation of [35S]sulfate into chondroitin sulfate is substantially reduced, although Alcian blue-stained chondroitin sulfate molecules are still detectable. With increasing age and developmental state of the tissues, radiolabeled and stained dermatan sulfate and heparan sulfate progressively increase in relative quantity compared to chondroitin sulfate both in muscle and in associated connective tissue elements. These changes in glycosaminoglycans correlate well with similar changes previously determined biochemically and further document the alterations in extracellular matrix components during embryonic skeletal myogenesis.
Microsomal retinoic acid metabolism. Effects of cellular retinoic acid-binding protein (type I) and C18-hydroxylation as an initial step. (1994)

This report extends our observation that cellular retinoic acid-binding protein type I (CRABP) serves as substrate for retinoic acid metabolism by testis microsomes. Retinoic acid bound to excess CRABP was metabolized at 70% of the unbound retinoic acid rate with testis microsomes and at the same rates as unbound retinoic acid with kidney and lung microsomes. Chromatography of testis, lung, kidney, and liver microsomal incubations provided two sets of metabolites each, P1 and P2. The composition of P2 was characteristic of the individual tissue. CRABP had modest quantitative affects on P2 composition, but did not affect P2 qualitatively. Retinoids bound to CRABP, isolated from a testis microsomal incubation, consisted of 50% retinoic acid, 32% P1 and 17% P2, suggesting that CRABP may bind retinoic acid metabolites in vivo. The effect of CRABP on the rate of metabolism was retinoid specific. Two major components of P2, 4-hydroxy-retinoic acid and 4-oxo-retinoic acid, when bound to CRABP were metabolized slowly, if at all, by testis microsomes, in contrast to CRABP-bound retinoic acid which had an elimination t1/2 of 40 min. Unbound retinoic acid, 4-hydroxy-retinoic acid, and 4-oxo-retinoic acid had elimination t1/2 values of 35, 40, and 9 min, respectively. Reduced metabolism of CRABP-bound C4-derivatized retinoids suggests pathways of retinoic acid metabolism besides the one initiated by C4-hydroxylation. This was corroborated by identification of 18-hydroxy-retinoic acid as a testis, lung, and liver microsomal retinoic acid metabolite. Ketoconazole inhibited the metabolism by testis microsomes of free and CRABP-bound retinoic acid with IC50 values of 2 and 0.7 microM, respectively, denoting catalysis by cytochrome P-450. These results indicate that cloistering retinoic acid in CRABP, while permitting metabolism, may operate throughout CRABP-expressing tissues as a mechanism of controlling the concentrations of free retinoic acid.
A Phase 2 Exploratory Study of a Novel Interleukin-1 Receptor Inhibitor (EBI-005) in the Treatment of Moderate-to-Severe Allergic Conjunctivitis (2015)

These results support use of an adapted, multiple-challenge, direct conjunctival allergen model to assess efficacy of EBI-005 in late phase AC. In the CAPT, EBI-005 showed statistically significant improvements in clinically meaningful symptoms (ocular itching, tearing, and nasal symptoms) at multiple time points for moderate-to-severe AC subjects.
Hemodynamic and Angiographic Guidelines in Selection of Patients for Femorofemoral Bypass (1978)

Although crossover femorofemoral grafts have had good long-term patency, all patients have not been symptomatically improved. Seventy-one patients underwent 80 femorofemoral bypasses from 1968 to 1978. Hemodynamic assessment included preoperative and postoperative segmental Doppler pressures and femoral artery waveform recordings. Preoperative and selective postoperative arteriography was routinely performed. Twenty-nine failures occurred predominantely in two groups, those with greater than 50% stenosis of the donor iliac artery and those with severe recipient limb outflow occlusive disease. Ten patients with normal outflow beds bilaterally associated with 10% to 50% stenosis of the donor iliac artery underwent successful femorofemoral reconstruction. Progression of donor iliac artery disease was seen in only two patients. Cumulative five-year patency was 74%. Operative mortality totaled three (3.8%). This study supports the use of femorofemoral bypass as a primary procedure when proper guidelines are used.
Recent Developments in the Research and Practice of Earthquake Engineering in Australia (2008)

This paper presents multidisciplinary facets of earthquake engineering research and developments in Australia over the past decade. Past and current research into seismic activity modelling and the associated challenges is first described. The Component Attenuation model (CAM) that provides estimates for the seismic displacement demand in regions lacking strong motion data is then introduced, along with other models developed by conventional methods. Research into the seismic performances of typical Australian construction, which incorporates the use of unreinforced masonry, steel and concrete, has been summarised together with a brief report on current activities with risk modelling and the earthquake loading standard. A new two-tier displacement based approach for assessing the seismic performance of structures is presented along with future trends in earthquake engineering.
Combinatorial problems motivated by comma-free codes (2003)

Abstract In the paper some combinatorial problems motivated by comma-free codes are considered. We describe these problems, give the most significant known results and methods used, present some new results and formulate open problems.
Crawling Ajax-Based Web Applications through Dynamic Analysis of User Interface State Changes (2012)

Using JavaScript and dynamic DOM manipulation on the client side of Web applications is becoming a widespread approach for achieving rich interactivity and responsiveness in modern Web applications. At the same time, such techniques---collectively known as Ajax ---shatter the concept of webpages with unique URLs, on which traditional Web crawlers are based. This article describes a novel technique for crawling Ajax -based applications through automatic dynamic analysis of user-interface-state changes in Web browsers. Our algorithm scans the DOM tree, spots candidate elements that are capable of changing the state, fires events on those candidate elements, and incrementally infers a state machine that models the various navigational paths and states within an Ajax application. This inferred model can be used in program comprehension and in analysis and testing of dynamic Web states, for instance, or for generating a static version of the application. In this article, we discuss our sequential and concurrent Ajax crawling algorithms. We present our open source tool called Crawljax , which implements the concepts and algorithms discussed in this article. Additionally, we report a number of empirical studies in which we apply our approach to a number of open-source and industrial Web applications and elaborate on the obtained results.
Protein phosphatase 2A is reversibly modified by methyl esterification at its C-terminal leucine residue in bovine brain. (1994)

We have recently described a novel protein carboxyl methylation system that results in the reversible modification of a 36-kDa polypeptide component of a 178-kDa protein in the cytosol of a variety of eucaryotic cells. This reaction, catalyzed by a cytosolic 40-kDa methyl-transferase, results in the methyl esterification of the alpha-carboxyl group of the C-terminal leucine residue. We have now purified the major methylated 36-kDa polypeptide from bovine brain. N-terminal sequence analysis of a tryptic fragment of this polypeptide revealed identity to the catalytic subunit of protein phosphatase 2A. This enzyme exists in the cell predominantly as a trimeric 151-kDa native species containing the 36-kDa catalytic polypeptide that terminates in a leucine residue. We then fractionated bovine brain cytosolic extracts to separate the major phosphatase isoforms 2A1 and 2A2 and found that both could be methylated by a partially purified preparation of the methyltransferase. A synthetic C-terminal octapeptide based on the sequence of the 36-kDa catalytic subunit is neither a substrate nor an inhibitor of this methyltransferase, suggesting that this enzyme recognizes aspects of the tertiary and/or quaternary structure of the native phosphatase. Because this modification reaction is readily reversible in extracts, it may represent a novel strategy of the cell to modulate the function of this protein phosphatase.
SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model (2008)

Neurodegeneration in familial amyotrophic lateral sclerosis (ALS) is associated with enhanced redox stress caused by dominant mutations in superoxide dismutase-1 (SOD1). SOD1 is a cytosolic enzyme that facilitates the conversion of superoxide (O(2)(*-)) to H(2)O(2). Here we demonstrate that SOD1 is not just a catabolic enzyme, but can also directly regulate NADPH oxidase-dependent (Nox-dependent) O(2)(*-) production by binding Rac1 and inhibiting its GTPase activity. Oxidation of Rac1 by H(2)O(2) uncoupled SOD1 binding in a reversible fashion, producing a self-regulating redox sensor for Nox-derived O(2)(*-) production. This process of redox-sensitive uncoupling of SOD1 from Rac1 was defective in SOD1 ALS mutants, leading to enhanced Rac1/Nox activation in transgenic mouse tissues and cell lines expressing ALS SOD1 mutants. Glial cell toxicity associated with expression of SOD1 mutants in culture was significantly attenuated by treatment with the Nox inhibitor apocynin. Treatment of ALS mice with apocynin also significantly increased their average life span. This redox sensor mechanism may explain the gain-of-function seen with certain SOD1 mutations associated with ALS and defines new therapeutic targets.
Novel sub‐ceiling temperature rapid depolymerization‐repolymerization reactions of cyanoacrylate polymers (1996)

Abstract Dilute solutions of unimodal high‐molecular‐weight poly(butyl cyanoacrylate) (“parent” polymer) in tetrahydrofuran (THF) at 21°C underwent rapid depolymerization accompanied by simultaneous repolymerization of the unzipped monomer to yield lower‐molecular‐weight “daughter” polymer following addition of tetrabutylammonium hydroxide (TBAOH), a slow initiator of butyl cyanoacrylate (BCA) monomer. The rate‐determining step for the reaction was tentatively identified as abstraction of the terminal chain proton. Similarly, addition of TBAOH to a THF solution of BCA monomer resulted in initial formation of high‐molecular‐weight (MW) polymer that subsequently rapidly depolymerized with simultaneous formation of TBAOH initiated, low‐MW daughter polymer. The depolymerization‐repolymerization reaction is the relaxation process that occurs following perturbation of the monomer/high‐MW parent polymer equilibrium by low‐MW daughter polymer and proceeds at least 100°C below the ceiling temperature of the parent polymer.