gebhart/patrepeval huggingface dataset:
Genetics of <scp>FTLD</scp>: overview and what else we can expect from genetic studies (2016)

Frontotemporal lobar degeneration (FTLD) comprises a highly heterogeneous group of disorders clinically associated with behavioral and personality changes, language impairment, and deficits in executive functioning, and pathologically associated with degeneration of frontal and temporal lobes. Some patients present with motor symptoms including amyotrophic lateral sclerosis. Genetic research over the past two decades in FTLD families led to the identification of three common FTLD genes (microtubule-associated protein tau, progranulin, and chromosome 9 open reading frame 72) and a small number of rare FTLD genes, explaining the disease in almost all autosomal dominant FTLD families but only a minority of apparently sporadic patients or patients in whom the family history is less clear. Identification of additional FTLD (risk) genes is therefore highly anticipated, especially with the emerging use of next-generation sequencing. Common variants in the transmembrane protein 106 B were identified as a genetic risk factor of FTLD and disease modifier in patients with known mutations. This review summarizes for each FTLD gene what we know about the type and frequency of mutations, their associated clinical and pathological features, and potential disease mechanisms. We also provide an overview of emerging disease pathways encompassing multiple FTLD genes. We further discuss how FTLD specific issues, such as disease heterogeneity, the presence of an unclear family history and the possible role of an oligogenic basis of FTLD, can pose challenges for future FTLD gene identification and risk assessment of specific variants. Finally, we highlight emerging clinical, genetic, and translational research opportunities that lie ahead. Genetic research led to the identification of three common FTLD genes with rare variants (MAPT, GRN, and C9orf72) and a small number of rare genes. Efforts are now ongoing, which aimed at the identification of rare variants with high risk and/or low frequency variants with intermediate effect. Common risk variants have also been identified, such as TMEM106B. This review discusses the current knowledge on FTLD genes and the emerging disease pathways encompassing multiple FTLD genes.
Effects of oral contraceptive steroids on acetaminophen metabolism and elimination (1983)

Plasma acetaminophen elimination was examined in women taking low-dose estrogen oral contraceptive (OC) steroids and in age-matched control women. Fractional rates of elimination and fractional clearances were calculated for each of the metabolic pathways, including oxidation, sulfation, and glucuronidation. The cysteine adduct and mercapturic acid derivative of acetaminophen were used as an index of oxidative biotransformation, a potentially toxic route of metabolism for acetaminophen. Plasma acetaminophen clearance rose from 287 +/- 13 ml/min to 470 +/- 51 ml/min in women taking OC steroids, whereas elimination t1/2 decreased from 2.40 +/- 0.14 hr to 1.67 +/- 0.16 hr. The fractional clearance and rate of elimination of acetaminophen by glucuronidation increased in women taking OC steroids, whereas the clearance and elimination by sulfation did not differ significantly from values in control subjects. Fractional clearance of the cysteine adduct also increased significantly, but clearance of acetaminophen mercapturic acid did not change. These data suggest that the increased clearance of acetaminophen from plasma in women taking OC steroids results from increased glucuronidation of the drug, although the mechanism is not known.
Offspring of Schizophrenics III (1979)

Twenty-nine male offspring of "continuous schizophrenics" (chronic, borderline, and chronic schizoaffective schizophrenics), plus controls, were given neurological and psychological examinations at age 7. Eight of the 29 were found to have high ratings on a factor score that was termed "hyperactive" (increased activity, impulsivity, distractibility, and emotional lability), and three of these boys had high ratings for neurological signs as well. These frequencies were significantly greater than the control values. Mild incoordination, such as awkwardness in performing rapidly alternating movements, was the neurological soft sign most elevated in the index group. Fifteen female offspring of schizophrenics were not found to differ from their controls on these measures. Previous studies of the childhood of male schizophrenics have found behavior patterns similar to the behavior of the boys who scored high on our hyperactive factors. It is thus likely that the "hyperactive cases" in this sample are even more at risk for developing schizophrenia in later life than the other offspring of schizophrenic parents.
Psychological Research Online: Report of Board of Scientific Affairs' Advisory Group on the Conduct of Research on the Internet. (2004)

As the Internet has changed communication, commerce, and the distribution of information, so too it is changing psychological research. Psychologists can observe new or rare phenomena online and can do research on traditional psychological topics more efficiently, enabling them to expand the scale and scope of their research. Yet these opportunities entail risk both to research quality and to human subjects. Internet research is inherently no more risky than traditional observational, survey, or experimental methods. Yet the risks and safeguards against them will differ from those characterizing traditional research and will themselves change over time. This article describes some benefits and challenges of conducting psychological research via the Internet and offers recommendations to both researchers and institutional review boards for dealing with them. ((c) 2004 APA, all rights reserved)
Pressure Effect on the Temperature-Induced Unfolding and Tendency To Aggregate of Myoglobin (1999)

This work demonstrates that pressure-induced partially unfolded states play a very important role in the aggregation of proteins. The high-pressure unfolding of horse heart metmyoglobin results in an intermediate form that shows a strong tendency to aggregate after pressure release. These aggregates are similar to those that are usually observed upon temperature denaturation. Infrared spectra in the amide I region indicate the formation of an intermolecular antiparallel beta-sheet stabilized by hydrogen bonding. The formation of the aggregates is temperature-dependent. Below 30 degrees C, no aggregation is taking place as seen from the infrared spectra. At 45 and 60 degrees C, two types of aggregates are formed: one that can be dissociated by moderate pressures and one that is pressure-insensitive. When precompressed at 5 degrees C, temperature-induced aggregation takes place at lower temperature (38 degrees C) than without pressure pretreatment (74 degrees C).
8-Substituted theophyllines. In vitro inhibition of 3',5'-cyclic adenosine monophosphate phosphodiesterase and pharmacological spectrum in mice (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT8-Substituted theophyllines. In vitro inhibition of 3',5'-cyclic adenosine monophosphate phosphodiesterase and pharmacological spectrum in miceElizabeth B. Goodsell, Herman H. Stein, and Kathleen J. WenzkeCite this: J. Med. Chem. 1971, 14, 12, 1202–1205Publication Date (Print):December 1, 1971Publication History Published online1 May 2002Published inissue 1 December 1971https://pubs.acs.org/doi/10.1021/jm00294a016https://doi.org/10.1021/jm00294a016research-articleACS PublicationsRequest reuse permissionsArticle Views75Altmetric-Citations38LEARN 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
A quadrisection-based combined place and route scheme for standard cells (1989)

A description is given of a placement technique based on hypergraph quadrisection. The authors have developed a standard cell placement procedure based on recursively dividing the netlist into four parts, while minimizing the division cost. They have combined two ideas for placement. One is the extension of the min-cut bisection algorithm to handle quadrisection. The second idea is the simultaneous calculation of min-cut quadrisection and hierarchical global routing. The implementation details are discussed. The results show the implementation to be competitive with simulated annealing.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
GLP-1-mediated gene therapy approaches for diabetes treatment (2014)

Glucagon-like peptide (GLP)-1 is an incretin hormone with several antidiabetic functions including stimulation of glucose-dependent insulin secretion, increase in insulin gene expression and beta-cell survival. Despite the initial technical difficulties and profound inefficiency of direct gene transfer into the pancreas that seriously restricted in vivo gene transfer experiments with GLP-1, recent exploitation of various routes of gene delivery and alternative means of gene transfer has permitted the detailed assessment of the therapeutic efficacy of GLP-1 in animal models of type 2 diabetes (T2DM). As a result, many clinical benefits of GLP-1 peptide/analogues observed in clinical trials involving induction of glucose tolerance, reduction of hyperglycaemia, suppression of appetite and food intake linked to weight loss have been replicated in animal models using gene therapy. Furthermore, GLP-1-centered gene therapy not only improved insulin sensitivity, but also reduced abdominal and/or hepatic fat associated with obesity-induced T2DM with drastic alterations in adipokine profiles in treated subjects. Thus, a comprehensive assessment of recent GLP-1-mediated gene therapy approaches with detailed analysis of current hurdles and resolutions, is discussed.
Prevention of non‐contact anterior cruciate ligament injuries in soccer players. Part 2: A review of prevention programs aimed to modify risk factors and to reduce injury rates (2009)

Soccer is the most commonly played sport in the world, with an estimated 265 million active soccer players participating in the game as on 2006. Inherent to this sport is the higher risk of injury to the anterior cruciate ligament (ACL) relative to other sports. ACL injury causes a significant loss of time from competition in soccer, which has served as the strong impetus to conduct research that focuses to determine the risk factors for injury, and more importantly, to identify and teach techniques to reduce this injury in the sport. This research emphasis has afforded a rapid influx of literature aimed to report the effects of neuromuscular training on the risk factors and the incidence of non-contact ACL injury in high-risk soccer populations. The purpose of the current review is to sequence the most recent literature relating the effects of prevention programs that were developed to alter risk factors associated with non-contact ACL injuries and to reduce the rate of non-contact ACL injuries in soccer players. To date there is no standardized intervention program established for soccer to prevent non-contact ACL injuries. Multi-component programs show better results than single-component preventive programs to reduce the risk and incidence of non-contact ACL injuries in soccer players. Lower extremity plyometrics, dynamic balance and strength, stretching, body awareness and decision-making, and targeted core and trunk control appear to be successful training components to reduce non-contact ACL injury risk factors (decrease landing forces, decrease varus/valgus moments, and increase effective muscle activation) and prevent non-contact ACL injuries in soccer players, especially in female athletes. Pre-season injury prevention combined with an in-season maintenance program may be advocated to prevent injury. Compliance may in fact be the limiting factor to the overall success of ACL injury interventions targeted to soccer players regardless of gender. Thus, interventional research must also consider techniques to improve compliance especially at the elite levels which will likely influence trickle down effects to sub-elite levels. Future research is also needed for male soccer athletes to help determine the most effective intervention to reduce the non-contact ACL injury risk factors and to prevent non-contact ACL injuries.
Molecular determinants of human prorenin processing. (1992)

In humans, active renin is generated by the removal of a 43-amino acid prosegment from the zymogen prorenin. This cleavage event is highly specific, occurring at only one of the seven pairs of basic amino acids in the body of preprorenin. This cleavage site selectivity is also displayed by a number of other proteases in vitro and in mouse pituitary AtT-20 cells transfected with a human preprorenin expression vector, suggesting that specificity of cleavage is directed in part by the primary sequence, the higher order structure, or both of prorenin itself. To test this hypothesis, single amino acid mutations were introduced in the region of human preprorenin surrounding the natural cleavage site, and the resultant recombinant proteins were expressed in cultured Chinese hamster ovary and AtT-20 cells. The results suggest that amino acids in addition to the pair of basic amino acids surrounding the cleavage site affect the ability of both trypsin and the endogenous AtT-20 processing enzyme to cleave prorenin. Notably, although a proline at position -4 is essential for processing of prorenin in AtT-20 cells and is correlated with predicted formation of a beta-turn at this position, site-directed mutations suggest that this structural feature in addition to a pair of basic amino acids is not sufficient to lead to proteolytic activation of prorenin. Displacement of sequences surrounding the cleavage site to a position 10 amino acids toward the amino terminus led to partial processing of a mutated prorenin.(ABSTRACT TRUNCATED AT 250 WORDS)
Silencing Ku80 using small interfering RNA enhanced radiation sensitivity in vitro and in vivo (2007)

Ku80 is an important component of DNA double-strand break repair, and Ku80 deficiency leads to extreme sensitivity to ionizing radiation. We studied whether radiation therapy combined with Ku80 silencing by small interfering RNA enhances radiation sensitivity in vitro and in vivo. Seven human cancer cell lines were transfected with Ku80 siRNA included in hemagglutinating virus of Japan envelope vector. H1299 cells were implanted into male BALB/C nu/nu nude mice treated with Ku80 siRNA and irradiation. The survival rate of cell lines transfected with Ku80 siRNA decreased by 10% to 26% with 2-Gy irradiation compared with untransfected cell lines. The gamma-H2AX phosphorylation-positive rates of Ku80 siRNA combined treatment 0.5 h after irradiation in A549 cells and 6 h in H1299 cells were significantly higher (77.6%, p=0.033 and 76.7%, p=0.026, respectively), compared with the groups not treated with siRNA. H1299 xenograft tumors treated with combined therapy decreased in volume and re-grew slowly compared with radiation alone. Our results indicate that combined therapy consisting of Ku80 siRNA and irradiation contributes to inhibition of tumor growth and may be a novel strategy for cancer treatment.
Transmission of Ultrasound Through Living Human Thorax (1959)

Experiments are described demonstrating the passage of one-mc/sec continuous wave ultrasound through the heart and lungs at power levels of 100 mw/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> at the transducer terminals (a total of 1.25 watts). When the sound was directed through the region of the heart, the ultrasound was modulated by the moving intra-thoracic structures in synchronism with the heart beat. The records obtained were modified both by exercise and by amyl nitrite administered to the subject, but remained synchronous with the heart rate. Modulation of the ultrasound did not occur in two warm corpses. Sonic energy at the levels used to traverse the thorax did not affect a simultaneously recorded electrocardiogram. No deleterious effects have been observed on a subject whose heart was irradiated at 1 watt/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and 3 watts/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> (totals of 12.5 and 37.5 watts, respectively) applied to transducer terminals at intervals over a period of one year (Appendix I). When continuous wave ultrasound was directed through a lung field clear of the heart, it was found that the attenuation varied 50 db between full inspiration and a lung emptying of 3400 cubic cm (0 db = full inspiration). In addition to direct transmission, sound is scattered throughout the thorax. The mechanics of the ultrasonic phenomena are described.
Sams teach yourself sql® in 24 hours, fourth edition (2008)

In just 24 lessons of one hour or less, you will learn professional techniques to design and build efficient databases and query them to extract useful information. Using a straightforward, step-by-step approach, each lesson builds on the previous one, allowing you to learn the essentials of ANSI SQL from the ground up.Example code demonstrates the authors' professional techniques, while exercises written for MySQL offer the reader hands-on learning with an open-source database. Included are advanced techniques for using views, managing transactions, database administration, and extending SQL.Step-by-step instructions carefully walk you through the most common SQL tasks.Q&As, Quizzes, and Exercises at the end of each chapter help you test your knowledge.Notes and Tips point out shortcuts and solutions.New terms are clearly defined and explained.Learn how to... Use SQL-2003, the latest standard for the Structured Query Language Design and deploy efficient, secure databases Build advanced queries for information retrieval Sort, group, and summarize information for best presentation Tune databases and queries for maximum performance Understand database administration and security techniques For more than ten years the authors have studied, applied, and documented the SQL standard and its application to critical database systems.Ryan Stephens and Ron Plew are entrepreneurs, speakers, and cofounders of Perpetual Technologies, Inc. (PTI), a fast-growing IT management and consulting firm which specializes in database technologies. They taught database courses for Indiana University-Purdue University in Indianapolis for five years and have authored more than a dozen books on Oracle, SQL, database design, and the high availability of critical systems.Arie D. Jones is Senior SQL Server database administrator and analyst for PTI. He is a regular speaker at technical events and has authored several books and articles.Category:i¾ DatabaseCovers:i¾ ANSI SQLUser Level:i¾ Beginning-IntermediateRegister your book at informit.com/title/9780672330186 for convenient access to updates and correctionsas they become available.$34.99 USA / $ 37.99 CAN / £ 24.99 Net UK
Applications in the Nuclear Industry for Thermal Spray Amorphous Metal and Ceramic Coatings (2009)

Amorphous metal and ceramic thermal spray coatings have been developed with excellent corrosion resistance and neutron absorption. These coatings, with further development, could be cost-effective options to enhance the corrosion resistance of drip shields and waste packages, and limit nuclear criticality in canisters for the transportation, aging, and disposal of spent nuclear fuel. Iron-based amorphous metal formulations with chromium, molybdenum, and tungsten have shown the corrosion resistance believed to be necessary for such applications. Rare earth additions enable very low critical cooling rates to be achieved. The boron content of these materials and their stability at high neutron doses enable them to serve as high efficiency neutron absorbers for criticality control. Ceramic coatings may provide even greater corrosion resistance for waste package and drip shield applications, although the boron-containing amorphous metals are still favored for criticality control applications. These amorphous metal and ceramic materials have been produced as gas-atomized powders and applied as near full density, nonporous coatings with the high-velocity oxy-fuel process. This article summarizes the performance of these coatings as corrosion-resistant barriers and as neutron absorbers. This article also presents a simple cost model to quantify the economic benefits possible with these new materials.
Compile-time instruction scheduling for superscalar processors (2002)

Superscalar processors might be considered the next step in the evolution of uniprocessors beyond reduced-instruction-set computers (RISCs). The scheduling technology that is described could analogously be considered a major step in the evolution of optimizing compilers for uniprocessor architecture. A superscalar processor is a machine that can issue several instructions per cycle. To fully exploit a superscalar processor of degree n, there must be n instructions concurrently executing at all times. Should such parallelism not be available, stalls and dead time occur where instructions are forced to wait for the results of previous instructions. Thus, superscalar processor code must be carefully ordered to best utilize the inherent performance potential. Software schedulers are basically code reorganizers that increase performance by increasing available instruction parallelism. Given that a good scheduler can significantly improve the performance of compiled code, the superscalar approach becomes viable. The principles of scheduler technology based on the SF 960 scheduler developed by Quantitative Technology Corporation for the Intel i960CA superscalar processor are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Predictive value of pulse oximetry for the development of fetal acidosis (2009)

A low pulse oximetry oxygen saturation <30% for at least 10 min correlates highly with fetal acidosis in cases of non-reassuring FHR. FPO reliably excludes moderate to advanced acidosis and can reduce the frequency of fetal blood analysis (FBA) in cases of non-reassuring cardiotocography (CTG).