gebhart/patrepeval huggingface dataset:
Crystal structure of the C67A mutant of isopentenyl diphosphate isomerase complexed with a mechanism‐based irreversible inhibitor (2003)

Isopentenyl diphosphate:dimethylallyl diphosphate (IPP:DMAPP) isomerase is a key enzyme in the biosynthesis of isoprenoids. The mechanism of the isomerization reaction involves protonation of the unactivated carbon-carbon double bond in the substrate. Analysis of the 1.97 A crystal structure of the inactive C67A mutant of E. coli isopentenyl diphosphate:dimethylallyl diphosphate isomerase complexed with the mechanism-based inactivator 3,4-epoxy-3-methyl-1-butyl diphosphate is in agreement with an isomerization mechanism involving Glu 116, Tyr 104, and Cys 67. In particular, the results are consistent with a mechanism where Glu116 is involved in the protonation step and Cys67 in the elimination step.
AlGaN/GaN MOS-HEMTs with ZnO gate insulator and chlorine surface treatment (2010)

AlGaN/GaN metal-oxide-semiconductor high-electron-mobility transistors (MOS-HEMTs) were fabricated with ZnO gate insulator and chlorine surface treatment. It is revealed that the chlorine treatment reduced the gate lag phenomenon and enhanced the device performance. The gate leakage current was also reduced about one order of magnitude in comparison to the conventional one. The chlorine-treated MOS-HEMTs exhibited a saturation drain-source current of 0.85 A/mm, a peak extrinsic transconductance of 207 mS/mm, and an off-state breakdown voltage larger than 100V. This significant improvement was owing to the reduction in surface state density, which was resulted from the decrease of Ga dangling bonds and the passivation of N vacancies on the AlGaN surface.
Male reproduction in the polluted environment - review. (2014)

Endocrine Disrupting Chemicals (EDC-s) present in t he environment can cause disturbance in the reproductive biology of animals and humans. While most of the studies focus on the adverse effects on the hormona l system, recent findings indicate a direct effect on germ cells. The present review int roduces laboratory assays used to study several structural and physiological aspects of spermatozoa exposed to EDC-s.
Coarse-grained molecular models of water: a review (2012)

Coarse-grained (CG) models have proven to be very effective tools in the study of phenomena or systems that involve large time- and length-scales. By decreasing the degrees of freedom in the system and using softer interactions than seen in atomistic models, larger timesteps can be used and much longer simulation times can be studied. CG simulations are widely used to study systems of biological importance that are beyond the reach of atomistic simulation, necessitating a computationally efficient and accurate CG model for water. In this review, we discuss the methods used for developing CG water models and the relative advantages and disadvantages of the resulting models. In general, CG water models differ with regards to how many waters each CG group or bead represents, whether analytical or tabular potentials have been used to describe the interactions, and how the model incorporates electrostatic interactions. Finally, how the models are parameterized depends on their application, so, while some are fitted to experimental properties such as surface tension and density, others are fitted to radial distribution functions extracted from atomistic simulations.
Pharmacotherapy of social anxiety disorder: what does the evidence tell us? (2006)

The treatment goals for social anxiety disorder (SAD) are to reduce fear, avoidance, physical distress, disability, and comorbidity. This review illustrates some of the primary studies used to evaluate efficacy of treatments for SAD. The selective serotonin reuptake inhibitors (SSRIs) paroxetine, sertraline, fluoxetine, fluvoxamine, and escitalopram and the serotonin-norepinephrine reuptake inhibitor venlafaxine are effective treatments. They have the additional benefit of being able to treat comorbid conditions. For people who do not respond to serotonin reuptake inhibitors, treatment options include benzodiazepines (clonazepam, alprazolam, and bromazepam), alpha2delta calcium-channel blockers (gabapentin and pregabalin), reversible inhibitors of monoamine oxidase A (moclobemide, although agents in this class are not available in the United States), antiepileptics (levetiracetam), and atypical antipsychotics (olanzapine). The irreversible monoamine oxidase inhibitor phenelzine can be considered an effective third-line therapy. Combination treatments may be beneficial, but more research is needed. Benefits of beta-blockers (propranolol and atenolol) are limited to performance anxiety. Botulinum toxin A may be an effective augmentation treatment option for severe axillary hyperhidrosis in patients with SAD. Studies show that patients with SAD who are maintained on paroxetine, sertraline, or clonazepam have a low relapse rate.
Paraneoplastic cerebellar degeneration (1992)

We reviewed clinical findings and serologic data on 18 men and three women with paraneoplastic cerebellar degeneration (PCD) associated with Hodgkin's disease (HD). The patients were 20 to 77 years old (median, 44). The lymphoma preceded neurologic symptoms by 1 to 54 months in 17/21 patients, but stage or activity did not correlate with severity of neurologic disease; six developed PCD while in HD remission. PCD evolved subacutely (over weeks to months) and was pancerebellar in most. Ten had downbeat nystagmus. Thirteen stabilized in a disabled state (wheelchair- or bed-bound), five stabilized ambulatory, and three, who had progressed to a nonambulatory state, recovered. The clinical findings were usually only cerebellar but one patient had an encephalopathy, three long-tract signs, and two sensory neuropathy. Plasmapheresis (seven patients) and corticosteroids or other immunosuppressant medication (eight patients) did not help; one improved dramatically after treatment with clonazepam. Two patients improved spontaneously. Six patients had serum antibodies that reacted specifically with Purkinje cells. The pattern was distinct from that of PCD with gynecologic cancer (anti-Yo) or small-cell lung cancer (anti-Hu). Western blotting failed to identify a discrete Purkinje cell antigen. Seropositive patients did not differ clinically from their seronegative counterparts. HD-associated PCD is more common in men and in a younger age group than in PCD with other malignancies.
Answering the Earthquake (2004)

During the past several years, the American Catholic Church has suffered an enormous earthquake due to the child sexual abuse crisis that was initially reported on January 6, 2002 by the Boston Globe Spotlight Team. Although the sexual abuse of children by priests had been in the news many times before, the recent case in Boston 14 Conversations resulted in perhaps the largest earthquake ever in the American Catholic Church. While the epicenter of the quake was centered in Boston, there were many significant aftershocks felt across the land. Sadly, Jesuits and Jesuit universities were not immune from the recent horrible news of clergy sexual misconduct. A number of .Jesuits experienced credible accusations of child sexual abuse. One of the Jesuit university presidents resigned after allegations of sexual misconduct surfaced. Sadly, we have been reminded that some priests and bishops (and even some Jesuits) can behave badly in ways that significantly harm others.
Plasma volume estimation using indocyanine green with biexponential regression analysis of the decay curves (1997)

We studied seven analytical methods of estimating the plasma volume from the decay curves of indocyanine green. Fifteen volunteers received 1.0 mg.kg-1 of the dye by intravenous injection and the plasma concentration was measured continuously using spectrophotometry. Plasma volumes were calculated using three single-regression methods (1-a, 1-b, 1-c) and four biexponential regression methods (2-a, 2-b, 2-c, 2-d). The means (SD) of 1-a, 1-b and 1-c were 39 (5.0), 44 (5.7) and 54 (11.5) ml.kg-1, respectively, and these were significantly different from each other (p < 0.05). The values for methods 2-b, 2-c and 2-d were similar to each other: 39 (4.6), 40 (4.1) and 40 (4.0) ml.kg-1, respectively. These required more than 3 min circulation or mixing time. When the time allowed for mixing was less than 3 min (method 2-a) the plasma volume was underestimated. We conclude that plasma volume estimation using indocyanine green and spectrophotometry is most accurate when the mixing time is adequate (3-5 min) and the decay curves are analysed using biexponential regression.
CD34+ hematopoietic progenitor cells are not a major reservoir of the human immunodeficiency virus (1990)

Hematologic abnormalities occur in the majority of patients with acquired immunodeficiency syndrome (AIDS). Infection of the hematopoietic progenitor cells has been proposed as a potential explanation. In this study, different bone marrow cell populations, including the CD34+ hematopoietic progenitor cells, were purified by a fluorescence-activated cell sorter (FACS) and analyzed for the presence of human immunodeficiency virus-1 (HIV-1) proviral DNA using the polymerase chain reaction. A group of 14 patients with AIDS or AIDS-related complex (ARC) was studied (11 with peripheral blood cytopenias). The CD4+ helper cells in the bone marrow were found positive for HIV-1 DNA in all patients. In contrast, CD34+ progenitor cells were positive in only one patient. Two monocyte samples and two samples of CD4-/CD34- lymphocytes/blasts (mainly B and CD8 lymphocytes) were positive. Proviral DNA could not be detected in granulocytes. FACS analysis showed that the percentage of CD34+ hematopoietic progenitor cells was not altered in the bone marrow of AIDS patients in comparison with the HIV-1 seronegative controls. In contrast, the number of CD4+ lymphocytes was markedly reduced in the bone marrow of AIDS patients. These results show that the hematologic abnormalities in AIDS patients are neither explained by direct infection of the hematopoietic progenitor cells with HIV-1 nor by a depletion of progenitor cells.
A variant of DNA polymerase β acts as a dominant negative mutant (1997)

In eukaryotic cells, DNA polymerase beta (polbeta) carries out base-excision repair (BER) required for DNA maintenance, replication, recombination, and drug resistance. A specific deletion in one allele in the coding sequence of the polbeta gene occurs in colorectal and breast carcinomas. The 87-bp deleted region encodes amino acid residues 208-236 in the catalytic domain of the enzyme. Here, we report evidence for expression of the wild-type (WT) and the truncated polbeta proteins in colorectal tumors. To elucidate the potential functional consequences of polbeta truncation, stable HeLa cell lines were established from cloned WT and variant polbetaDelta208-236. Cells expressing the variant protein exhibited substantially decreased BER activity. To test our hypothesis that truncated polbeta may disrupt the function of the WT enzyme, we stably transfected mouse embryonic fibroblast 16.3 cells with polbetaDelta208-236 cDNA. Reverse transcription-PCR and Western blot analyses showed that the new cell line, 16.3DeltaP, expresses the WT and the truncated polbeta mRNA and proteins. BER and binding activities were undetectable in these cells. Furthermore, in vivo the 16.3DeltaP cells were more sensitive to N-methyl-N'-nitro-N-nitrosoguanidine than the 16.3 cells. On adding increasing amounts of 16.3DeltaP protein extracts, the BER and DNA binding activities of extracts of the parent 16.3 cell line progressively declined. These results strongly suggest that truncated polbeta acts as a dominant negative mutant. The defective polbeta may facilitate accumulation of mutations, leading to the expression of a mutator phenotype in tumor cells.
A new model of cancer cachexia: contribution of the ubiquitin-proteasome pathway (1999)

A new model of cachexia is described in which muscle protein metabolism related to the ubiquitin-proteasome pathway was investigated. Cloning of the colon-26 tumor produced a cell line, termed R-1, which induced cytokine (noninterleukin-1beta, interleukin-6 and tumor necrosis factor-alpha)-independent cachexia. Implantation of R-1 cells in mice elicited significant (20-30%) weight loss and decreased blood glucose by 70%, and adipose tissue levels declined by 95% and muscle weights decreased by 20-25%. Food intake was unaffected. The decrease in muscle weight reflected a decline in insoluble, but not soluble, muscle protein that was associated with a significant increase in net protein degradation. The rate of ubiquitin conjugation of proteins was significantly elevated in muscles of cachectic mice. Furthermore, the proteasome inhibitor lactacystin blocked the increase in protein breakdown but had no significant effect on proteolysis. Several markers of the ubiquitin-proteasome pathway, E2(14k) mRNA and E2(14k) protein and ubiquitin-protein conjugates, were not elevated. Future investigations with this new model should gain further insights into the mechanisms of cachexia and provide a background to evaluate novel and more efficacious therapies.
The β<sub>2</sub>-Adrenergic Receptor Delivers an Antiapoptotic Signal to Cardiac Myocytes Through G<sub>i</sub>-Dependent Coupling to Phosphatidylinositol 3′-Kinase (2000)

Recent studies have shown that chronic beta-adrenergic receptor (beta-AR) stimulation alters cardiac myocyte survival in a receptor subtype-specific manner. We examined the effect of selective beta(1)- and beta(2)-AR subtype stimulation on apoptosis induced by hypoxia or H(2)O(2) in rat neonatal cardiac myocytes. Although neither beta(1)- nor beta(2)-AR stimulation had any significant effect on the basal level of apoptosis, selective beta(2)-AR stimulation protected myocytes from apoptosis. beta(2)-AR stimulation markedly increased mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) activation as well as phosphatidylinositol-3'-kinase (PI-3K) activity and Akt/protein kinase B phosphorylation. beta(1)-AR stimulation also markedly increased MAPK/ERK activation but only minimally activated PI-3K and Akt. Pretreatment with pertussis toxin blocked beta(2)-AR-mediated protection from apoptosis as well as the beta(2)-AR-stimulated changes in MAPK/ERK, PI-3K, and Akt/protein kinase B. The selective PI-3K inhibitor, LY 294002, also blocked beta(2)-AR-mediated protection, whereas inhibition of MAPK/ERK activation at an inhibitor concentration that blocked agonist-induced activation but not the basal level of activation had no effect on beta(2)-AR-mediated protection. These findings demonstrate that beta(2)-ARs activate a PI-3K-dependent, pertussis toxin-sensitive signaling pathway in cardiac myocytes that is required for protection from apoptosis-inducing stimuli often associated with ischemic stress.
The Induction and Abolition of Specific Immunosuppression of Heart Allografts in Rats by Use of Donor Blood and Cyclophosphamide (1975)

Intravenous pretreatment of WAG/Rij rats with BN blood 14 days before transplantation leads to permanent survival of BN heart allografts. Pretreatment with donor blood in the reverse donor-host combination gives rise to accelerated rejection of WAG/Rij hearts. Addition of 100 mg/kg Cy to the pretreatment with donor blood in the WAG/Rij to BN model resulted in permanent graft acceptance, presumably due to the phenomenon of immunologic enhancement. This effect could be observed only if the interval between drug administration and antigen pretreatment was short. The use of Cy had a more profound and long-lasting effect on humoral than on cellular immunity. Addition of 100 mg/kg Cy to the active enhancement protocol in the "easy" BN to WAG/Rij combination produced permanent graft survival in an immunologic setting reminiscent of immunologic tolerance. The combined pretreatment with donor blood and 50 mg/kg Cy in this donor-host combination abolished the operation of immunologic enhancement, which could be induced if donor blood was given alone.
An Improved Process for the <i>N</i>-Alkylation of Indoles Using Chiral <i>N</i>-Protected 2-Methylaziridines (2002)

An improved process for the N-alkylation of indoles using N-protected homochiral aziridines has been developed. This procedure allows reduced quantities of homochiral starting material to be used and leads to improved overall yields and operability.
CLB5: a novel B cyclin from budding yeast with a role in S phase. (1992)

Budding yeast strains have three CLN genes, which have limited cyclin homology. At least one of the three is required for cell cycle START. Four B cyclins are known in yeast; two have been shown to function in mitosis. We have discovered a fifth B-cyclin gene, called CLB5, which when cloned on a CEN plasmid can rescue strains deleted for all three CLN genes. CLB5 transcript abundance peaks in G1, coincident with the CLN2 transcript but earlier than the CLB2 transcript. CLB5 deletion does not cause lethality, either alone or in combination with other CLN or CLB deletions. However, strains deleted for CLB5 require more time to complete S phase, suggesting that CLB5 promotes some step in DNA synthesis. CLB5 is the only yeast cyclin whose deletion lengthens S phase. CLB5 may also have some role in promoting the G1/S transition, because cln1 cln2 strains require both CLN3 and CLB5 for viability on glycerol media and cln1,2,3- strains require CLB5 for rescue by the Drosophila melanogaster cdc2 gene. In conjunction with cln1,2,3- rescue by CLB5 overexpression and the coincident transcriptional regulation of CLB5 and CLN2, these observations are suggestive of partial functional redundancy between CLB5 and CLN genes.
Fluorescence in situ hybridization (FISH): an increasingly demanded tool for biomarker research and personalized medicine (2014)

Extensive studies of the genetic aberrations related to human diseases conducted over the last two decades have identified recurrent genomic abnormalities as potential driving factors underlying a variety of cancers. Over the time, a series of cutting-edge high-throughput genetic tests, such as microarrays and next-generation sequencing, have been developed and incorporated into routine clinical practice. Although it is a classical low-throughput cytogenetic test, fluorescence in situ hybridization (FISH) does not show signs of fading; on the contrary, it plays an increasingly important role in detecting specific biomarkers in solid and hematologic neoplasms and has therefore become an indispensable part of the rapidly developing field of personalized medicine. In this article, we have summarized the recent advances in FISH application for both de novo discovery and routine detection of chromosomal rearrangements, amplifications, and deletions that are associated with the pathogenesis of various hematopoietic and non-hematopoietic malignancies. In addition, we have reviewed the recent developments in FISH methodology as well.
Loss of glucocerebrosidase 1 activity causes lysosomal dysfunction and α-synuclein aggregation (2015)

Lysosomal dysfunction is a common pathological feature of neurodegenerative diseases. GTP-binding protein type A1 (GBA1) encodes β-glucocerebrosidase 1 (GCase 1), a lysosomal hydrolase. Homozygous mutations in GBA1 cause Gaucher disease, the most common lysosomal storage disease, while heterozygous mutations are strong risk factors for Parkinson's disease. However, whether loss of GCase 1 activity is sufficient for lysosomal dysfunction has not been clearly determined. Here, we generated human neuroblastoma cell lines with nonsense mutations in the GBA1 gene using zinc-finger nucleases. Depending on the site of mutation, GCase 1 activity was lost or maintained. The cell line with GCase 1 deficiency showed indications of lysosomal dysfunction, such as accumulation of lysosomal substrates, reduced dextran degradation and accumulation of enlarged vacuolar structures. In contrast, the cell line with C-terminal truncation of GCase 1 but with intact GCase 1 activity showed normal lysosomal function. When α-synuclein was overexpressed, accumulation and secretion of insoluble aggregates increased in cells with GCase 1 deficiency but did not change in mutant cells with normal GCase 1 activity. These results demonstrate that loss of GCase 1 activity is sufficient to cause lysosomal dysfunction and accumulation of α-synuclein aggregates.
Magnetic Materials, Bulk (2000)

Abstract Magnetism is classified according to the nature of the bulk magnetic response in a magnetic field. Types of magnetism are defined as are the terms of magnetic behavior. Bulk magnetic materials may be classified as either soft or hard. The important soft magnetic materials, characterized by high permeability and low coercivity, include iron and low carbon steel, iron–silicon alloys, iron–aluminum and iron–aluminum–silicon alloys, cobalt–iron (Permendurs) and nickel–iron alloys (Permalloys), ferrites, and amorphous magnetic alloys. The iron‐based alloys are used for power distribution transformers and magnetic shielding. The ferrites are used at high frequencies for inductors and communication transformers as well as for microwave devices. Moreover, the use of MnZn ferrite cores in power transformers is increasing rapidly. The hard of permanent magnet materials are characterized by high coercivity and high energy product. Materials in use include the hexagonal barium and strontium ferrites, alnicos, the modified binary cobalt‐base intermetallics containing rare earths, and the ternary neodynium iron‐base intermetallics. Motors, loudspeakers, and disk drives are the largest consumers of hard magnetic materials. The exceptionally large values of maximum energy products and coercivities of the Nd–Fe–B magnets permit use in devices where small size and superior performance are desired. Many of the semihard permanent magnet materials are sufficiently ductile for forming into requisite shapes. Information is presented for several important materials which can be cold formed, rolled to thin foil, and can be stamped into precision parts at high speeds.
A Comparative Study between Stock Price Prediction Models Using Sentiment Analysis and Machine Learning Based on SNS and News Articles (2014)

Because people's interest of the stock market has been increased with the development of economy, a lot of studies have been going to predict fluctuation of stock prices. Latterly many studies have been made using scientific and technological method among the various forecasting method, and also data using for study are becoming diverse. So, in this paper we propose stock prices prediction models using sentiment analysis and machine learning based on news articles and SNS data to improve the accuracy of prediction of stock prices. Stock prices prediction models that we propose are generated through the four-step process that contain data collection, sentiment dictionary construction, sentiment analysis, and machine learning. The data have been collected to target newspapers related to economy in the case of news article and to target twitter in the case of SNS data. Sentiment dictionary was built using news articles among the collected data, and we utilize it to process sentiment analysis. In machine learning phase, we generate prediction models using various techniques of classification and the data that was made through sentiment analysis. After generating prediction models, we conducted 10-fold cross-validation to measure the performance of they. The experimental result showed that accuracy is over 80% in a number of ways and F1 score is closer to 0.8. The result can be seen as significantly enhanced result compared with conventional researches utilizing opinion mining or data mining techniques.