gebhart/patrepeval huggingface dataset:
Apolipoprotein A-I as a Marker of Angiographically Assessed Coronary-Artery Disease (1983)

This study was designed to determine whether the plasma level of apolipoprotein A-I is a better discriminator of angiographically documented coronary-artery disease than the level of high-density-lipoprotein (HDL) cholesterol in male subjects. The level of plasma apolipoprotein A-I in 83 patients with coronary-artery disease was 96.7 +/- 4.2 mg per deciliter (mean +/- S.E.M.), which was significantly lower (P less than 0.0001) than the level in 25 patients without coronary-artery disease (146.9 +/- 2.1 mg per deciliter). The levels of HDL cholesterol were also lower (P less than 0.0001) in patients with coronary-artery disease (31.9 +/- 1.5 mg per deciliter) than in those without it (45.9 +/- 2.3 mg per deciliter). A stepwise discriminant analysis, however, indicated the superiority of apolipoprotein A-I over HDL cholesterol in detecting coronary-artery disease. Furthermore, a linear discriminant analysis suggested that although HDL cholesterol by itself was a discriminator of coronary-artery disease, it did not provide a substantial increase in discriminatory value over that provided by apolipoprotein A-I; in contrast, apolipoprotein A-I levels added discriminatory value to the information obtained by measuring HDL cholesterol alone. We conclude that apolipoprotein A-I by itself is more useful than HDL cholesterol for identifying patients with coronary-artery disease.
Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor alpha locus. (1991)

Acute promyelocytic leukemias (APLs) are characterized by a reciprocal balanced translocation that involves chromosomes 15 and 17 [t(15;17)]. We report the isolation and characterization of one of the two reciprocal break sites and demonstrate that the chromosome 17 breakpoint lies within the retinoic acid receptor alpha locus. Nucleotide sequencing of the 15;17 cross-over junction on 15q+ showed that the retinoic acid receptor alpha gene is truncated within its first intron, 370 base pairs upstream from the splicing donor site of exon II. Such a recombination would be expected to generate abnormal RAR alpha mRNA and protein. Southern blot analysis of a number of APLs with chromosome 15- and 17-derived DNA probes revealed similar 15;17 recombinations in the majority of other APLs. Our data are strong evidence that the retinoic acid receptor alpha gene plays a crucial role in the leukemogenesis of APL.
The use of pharmacokinetic models in the development and evaluation of site‐specific drug delivery systems (1990)

Abstract The influence of the pharmacokinetics of drug‐carrier conjugates and free drug and of the pharmacodynamics of therapeutic and toxic responses on the potential for successful targeting is discussed. A simple physiologically based compartmental model is used to explore the potential of drug‐targeted systems versus conventional administration. The major kinetic factors affecting the therapeutic advantage of targeted systems are the blood flow to the target site, the systemic clearance of free drug and the selectivity of release of drug from its carrier. A model independent analysis based on linear systems theory using a recirculating model of drug disposition is also described.
Keten dithioacetals. Part 11. Reaction of 3-cyano-4-methylthio-2(1H)-pyridones with hydrazine and guanidine: synthesis of novel substituted and fused pyrazolo[4,3-c]pyridone and pyrido[4,3-d]pyrimidine derivatives (1978)

The N-methylpyridones (2a–f) were prepared by alkylation of the pyridones (1a–f) with dimethyl sulphate, followed by heating the mixture of N-methyl (2) and O-methyl (3) products with methyl iodide. The pyridone (4c), the quinolone (4d) and the benzoquinolone (5b) derivatives were prepared in the same manner. Treatment of the pyridones (2a–f) and (1a–i) with hydrazine in refluxing propan-2-ol yielded the respective pyrazolo-[4,3-c]pyridone derivatives (7a–o) in excellent yields, and the fused pyridones (4a–e) and (5a–d) afforded the respective fused pyrazolopyridone derivatives (8a–e) and (9a–d) in excellent yields under identical conditions. The reactions of the N-methylpyridones (2a–f), (4c–d), and (5b) with guanidine in the presence of 2 mol of sodium ethoxide similarly gave substituted and fused pyrido [4,3-d]pyrimidine derivatives (11a–f), (12a–b), and (13), respectively.
Computational design of a leucine-rich repeat protein with a predefined geometry (2014)

Structure-based protein design offers a possibility of optimizing the overall shape of engineered binding scaffolds to match their targets better. We developed a computational approach for the structure-based design of repeat proteins that allows for adjustment of geometrical features like length, curvature, and helical twist. By combining sequence optimization of existing repeats and de novo design of capping structures, we designed leucine-rich repeats (LRRs) from the ribonuclease inhibitor (RI) family that assemble into structures with a predefined geometry. The repeat proteins were built from self-compatible LRRs that are designed to interact to form highly curved and planar assemblies. We validated the geometrical design approach by engineering a ring structure constructed from 10 self-compatible repeats. Protein design can also be used to increase our structural understanding of repeat proteins. We use our design constructs to demonstrate that buried Cys play a central role for stability and folding cooperativity in RI-type LRR proteins. The computational procedure presented here may be used to develop repeat proteins with various geometrical shapes for applications where greater control of the interface geometry is desired.
Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process (2003)

Prognosis of multiple sclerosis is highly variable. Clinical variables have been identified that are assessable early in the disease and are predictors of the time from the disease onset to the onset of irreversible disability. Our objective was to determine if these clinical variables still have an effect after the first stages of disability have been reached. We determined the dates of disease onset and assignment of scores of irreversible disability in 1844 patients with multiple sclerosis. We used three scores on the Kurtzke Disability Status Scale as benchmarks of disability accumulation: 4 (limited walking but without aid); 6 (walking with unilateral aid); and 7 (wheelchair bound). We used Kaplan-Meier analyses and Cox regression models to determine the influence of the clinical variables on the time to disability onset. Median times from onset of multiple sclerosis to assignment of a score of 4, 6 and 7 were significantly influenced by gender, age, symptoms and course (relapsing-remitting or progressive) at onset of the disease, degree of recovery from the first relapse, time to a second neurological episode, and the number of relapses in the first 5 years of the disease. Similarly, times from onset of multiple sclerosis to a score of 6 and 7 were influenced by time to a score of 4. In contrast, none of the variables substantially affected the time from a score of 4 to a score of 6 or 7, or from a score of 6 to a score of 7. Early assessable clinical variables significantly influence the time from the onset of multiple sclerosis to the assignment of a disability score of 4, but not the subsequent progression of irreversible disability.
유압식 서킷 복합운동이 비만여성의 신체조성, 혈압, 혈중지질에 미치는 영향 (2011)

이 연구는 12주간의 유압식 서킷 저항성운동훈련이 비만여성의 신체조성, 혈압, 그리고 혈중지질에 어떠한 영향을 미치는가를 규명하고자 하는데 그 목적이 있었다. 이 연구에 참여된 피험자는 총 29명의 30대 비만 여성으로서 체지방률 30% 이상을 기준으로 선정하도록 하였다. 집단의 구분은 무작위의 방법으로 운동훈련집단과 통제집단으로 각각 14명과 15명으로 하였다. 운동훈련집단의 경우 12주 동안 유압식 서킷 복합운동을 일주일에 3회씩 30분간 실시하도록 하였고, 통제집단의 경우 일상생활 이외의 특별한 운동을 실시하지 않도록 관리 하였다. 이 연구에서 실시된 운동프로그램은 유압식 기구를 이용한 12종목의 저항성운동과 각 종목 사이에 1분씩 걷기운동을 최대심박수의 60~80%의 강도로 실시하였다. 이 연구의 결과 시간과 집단에 따른 상호작용효과가 체중, BMI, 체지방률, 엉덩이둘레에 대한 허리둘레의 비(waist-to-hip ratio, 이하WHR), 수축기혈압, 이완기혈압, 중성지방, 총콜레스테롤, 고밀도리포단백콜레스테롤, 그리고 저밀도리포단백콜레스테롤에서 통계적으로 유의하게 나타났다(P < 0.01). 결론적으로 이 연구에서는 유압식 서킷 복합운동방법이 기존의 저항성운동의 제한점을 극복할 수 있는 비만해소의 유익한 운동방법으로 그 가능성을 제시할 수 있었다.
A GaAs power chip set for 3 V cellular communications (1994)

This paper presents a chip set operating at 3 V supply voltage for cellular communications at L-band. A high efficiency power amplifier with a high packing density is reported. It makes use of high power-added-efficiency of MESFET devices in saturated class AB, and harmonic enhancement for the matching circuits. This three stage MMIC amplifier delivers 27 dBm output power with 35 % of power added efficiency with 0 dBm input power. A power switch is also described which achieves a typical insertion loss in the (0.8 dB, 1.0 dB) range and performs 20 dB isolation between the Rx (Receive) and Tx (Transmit) chains. PML also proposes a power MESFET that achieves 33 dBm output power with 55 % drain efficiency and 6 dB associated gain at 1800 MHz.
SNP allele frequency estimation in DNA pools and variance components analysis (2004)

The estimation of single nucleotide polymorphism (SNP) allele frequency in pooled DNA samples has been proposed as a cost-effective approach to whole genome association studies. However, the key issue is the allele frequency window in which a genotyping method operates and provides a statistically reliable answer. We assessed the homogeneous mass extend assay and estimated the variance associated with each experimental stage. We report that a relationship between estimated allele frequency and variance might exist, suggesting that high statistical power can be retained at low, as well as high, allele frequencies. Assuming this relationship, the formation of subpools consisting of 100 samples retains an effective sample size greater than 70% of the true sample size, with a savings of 11-fold the cost of an individual genotyping study, regardless of allele frequency.
Translocase of Outer Mitochondrial Membrane 40 Homolog (TOMM40) Poly-T Length Modulates Lorazepam-Related Cognitive Toxicity in Healthy APOE ε4-Negative Elderly (2011)

Pomara, Nunzio MD; Bruno, Davide PhD; Sidtis, John J. PhD; Lutz, Michael W. PhD; Greenblatt, David J. MD; Saunders, Ann M. PhD; Roses, Allen D. MD Author Information
Clinical and pharmacological properties of ivermectin in rabbits and guinea pigs (1992)

When 400 micrograms ivermectin/kg was administered subcutaneously to rabbits infected with the ear mite Psoroptes cuniculi it significantly reduced the clinical score, and when 500 micrograms ivermectin/kg was administered subcutaneously to guinea pigs with mange due to Trixacaurus caviae it resulted in a clinical cure. In rabbits a subcutaneous dose of 400 micrograms/kg produced high and sustained concentrations of ivermectin in the tissues and body fluids for at least 13 days and its rate of depletion from tissues was similar to that observed in sheep and rats. The mean (+/- sem) maximum concentration in plasma was 42.0 +/- 9.7 ng/ml 37.2 +/- 5.0 hours after administration and the area under the concentration-time curve was 3543 +/- 580 ng/ml hours. After the administration of 500 micrograms ivermectin/kg to guinea pigs orally, subcutaneously or topically the drug could be detected in the plasma only after subcutaneous administration. The mean concentration 72 hours after its administration to four guinea pigs was 0.7 +/- 0.3 ng/ml.
Multi-Agent Remote Predictive Diagnosis of Dangerous Good Transports (2006)

A real-time remote monitoring system for motor-vehicle fleets of dangerous good transport is proposed for the dynamic fleet management, the predictive diagnosis and the failure prognosis of vehicle wear, operating danger, and fraud on goods. Predictive fault diagnosis and failure prognosis are performed by a hierarchical multi-agent architecture based on 2 levels: (i) fault detection and isolation, by wavelet transforms (signal segmentation), Bayesian logic (feature extraction), and cultural algorithms (fault isolation); and (ii) diagnosis-prognosis, by hybrid structures fuzzy/neuro-fuzzy
GENE DISCOVERY INDROSOPHILA: New Insights for Learning and Memory (1998)

Genetic approaches have been used to investigate increasingly complex biological systems. Here we review the current state of genetic analysis of learning and memory in the fruitfly, Drosophila melanogaster. Emerging findings support two main themes. First, discovery and manipulation of genes involved with behavioral plasticity in genetically accessible systems such as D. melanogaster enables dissection of the biochemical, cellular, anatomical, and behavioral pathways of learning and memory. Second, because core cellular mechanisms of simple forms of learning are evolutionarily conserved, biological pathways discovered in invertebrates are likely to be conserved in vertebrate systems as well.
Human metabolism and excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous vegetables. (1998)

Isothiocyanates and their naturally occurring glucosinolate precursors are widely consumed as part of a diet rich in cruciferous vegetables. When plant cells are damaged, glucosinolates are released and converted to isothiocyanates by the enzyme myrosinase. Many isothiocyanates inhibit the neoplastic effects of various carcinogens at a number of organ sites. Consequently, these agents are attracting attention as potential chemoprotectors against cancer. As a prerequisite to understanding the mechanism of the protective effects of these compounds, which is thought to involve the modulation of carcinogen metabolism by the induction of phase 2 detoxication enzymes and the inhibition of phase 1 carcinogen-activating enzymes, we examined the fate of ingested isothiocyanates and glucosinolates in humans. Recently developed novel methods for quantifying isothiocyanates (and glucosinolates after their quantitative conversion to isothiocyanates by purified myrosinase) and their urinary metabolites (largely dithiocarbamates) have made possible a detailed examination of the fates of isothiocyanates and glucosinolates of dietary crucifers. In a series of studies in normal volunteers, we made these findings. First, in nonsmokers, urinary dithiocarbamates were detected only after the consumption of cruciferous vegetables and condiments rich in isothiocyanates and/or glucosinolates. In sharp contrast, the consumption of noncrucifers (corn, tomatoes, green beans, and carrots) did not lead to the excretion of dithiocarbamates. Moreover, the quantities of dithiocarbamates excreted were related to the glucosinolate/isothiocyanate profiles of the cruciferous vegetables administered (kale, broccoli, green cabbage, and turnip roots). Second, eating prepared horseradish containing graded doses of isothiocyanates (12.3-74 micromol; mostly allyl isothiocyanate) led to a rapid excretion of proportionate amounts (42-44%) of urinary dithiocarbamates with first-order kinetics. The ingestion of broccoli in which myrosinase had been heat-inactivated also led to proportionate but low (10-20%) recoveries of urinary dithiocarbamates. Broccoli samples subsequently treated with myrosinase to produce the cognate isothiocyanates were much more completely (47%) converted to dithiocarbamates. Finally, when bowel microflora were reduced by mechanical cleansing and antibiotics, the conversion of glucosinolates became negligible. These results establish that humans convert substantial amounts of isothiocyanates and glucosinolates to urinary dithiocarbamates that can be easily quantified, thus paving the way for meaningful studies of phase 2 enzyme induction in humans.
Fully polynomial Byzantine agreement in t + 1 rounds (1993)

This paper presents a polynomial protocol for reaching Byzantine agreement in t + 1 rounds whenever n > 3t, where n is the number of processors and t is an a priori upper bound on the number of failures.
Phosphorothioate Backbone Modification Modulates Macrophage Activation by CpG DNA (2000)

Macrophages respond to unmethylated CpG motifs present in nonmammalian DNA. Stabilized phosphorothioate-modified oligodeoxynucleotides (PS-ODN) containing CpG motifs form the basis of immunotherapeutic agents. In this study, we show that PS-ODN do not perfectly mimic native DNA in activation of macrophages. CpG-containing PS-ODN were active at 10- to 100-fold lower concentrations than corresponding phosphodiester ODN in maintenance of cell viability in the absence of CSF-1, in induction of NO production, and in activation of the IL-12 promoter. These enhancing effects are attributable to both increased stability and rate of uptake of the PS-ODN. By contrast, PS-ODN were almost inactive in down-modulation of the CSF-1R from primary macrophages and activation of the HIV-1 LTR. Delayed or poor activation of signaling components may contribute to this, as PS-ODN were slower and less effective at inducing phosphorylation of the extracellular signal-related kinases 1 and 2. In addition, at high concentrations, non-CpG PS-ODN specifically inhibited responses to CpG DNA, whereas nonstimulatory phosphodiester ODN had no such effect. Although nonstimulatory PS-ODN caused some inhibition of ODN uptake, this did not adequately explain the levels of inhibition of activity. The results demonstrate that the phosphorothioate backbone has both enhancing and inhibitory effects on macrophage responses to CpG DNA.
Parkin mediates beclin-dependent autophagic clearance of defective mitochondria and ubiquitinated A in AD models (2011)

Intraneuronal amyloid-β (Aβ) may contribute to extracellular plaque deposition, the characteristic pathology of Alzheimer's disease (AD). The E3-ubiquitin ligase parkin ubiquitinates intracellular proteins and induces mitophagy. We previously demonstrated that parkin reduces Aβ levels in lentiviral models of intracellular Aβ. Here we used a triple transgenic AD (3xTg-AD) mouse, which over-expresses APP(Swe), Tau(P301L) and harbor the PS1(M146V) knock-in mutation and found that lentiviral parkin ubiquitinated intracellular Aβ in vivo, stimulated beclin-dependent molecular cascade of autophagy and facilitated clearance of vesicles containing debris and defective mitochondria. Parkin expression decreased intracellular Aβ levels and extracellular plaque deposition. Parkin expression also attenuated caspase activity, prevented mitochondrial dysfunction and oxidative stress and restored neurotransmitter synthesis. Restoration of glutamate synthesis, which was independent of glial-neuronal recycling, depended on mitochondrial activity and led to an increase in γ-amino butyric acid levels. These data indicate that parkin may be used as an alternative strategy to reduce Aβ levels and enhance autophagic clearance of Aβ-induced defects in AD. Parkin-mediated clearance of ubiquitinated Aβ may act in parallel with autophagy to clear molecular debris and defective mitochondria and restore neurotransmitter balance.
Pten Loss Causes Hypertrophy and Increased Proliferation of Astrocytes In vivo (2004)

Somatic mutations of PTEN are found in many types of cancers including glioblastoma, the most malignant astrocytic tumor. PTEN mutation occurs in 25 to 40% of glioblastomas but is rarely observed in low-grade glial neoplasms. To determine the role of Pten in astrocytes and glial tumor formation, we inactivated Pten by a Cre-loxP approach with a GFAP-cre transgenic mouse that induced Cre-mediated recombination in astrocytes. Pten conditional knockout mice showed a striking progressive enlargement of the entire brain. Increased nuclear and soma size was observed in both astrocytes and neurons, which contributed in part to the increase in brain size. Pten-deficient astrocytes showed accelerated proliferation in vitro and aberrant ongoing proliferation in adult brains in vivo. In contrast, neurons lacking Pten did not show alterations in proliferation. This study shows cell-type dependent effects of Pten loss in the adult brain, including increased astrocyte proliferation that may render astroglial cells susceptible to neoplastic transformation or malignant progression.
Improvement of the spatial beam quality of laser sources with an intracavity Bragg grating (2003)

We demonstrate a novel method for improvement of spatial beam quality by use of the angular selectivity of a thick phase grating inserted into various laser cavities. Preliminary experiments with an intentionally degraded beam from a Nd:YVO4 laser have enhanced beam propagation factor M2 by a factor of 4.5. Operation with a broad-area laser diode in an external cavity with a thick grating was achieved. We obtained 100 mW of cw power in a beam with an M2 of 1.3. Moreover, a reduction of the output spectrum by as much as a factor of 3.8 was obtained.
Femoral Head Size and Wear of Highly Cross-linked Polyethylene at 5 to 8 Years (2009)

Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
Fluorination of 3-(3-(Piperidin-1-yl)propyl)indoles and 3-(3-(Piperazin-1-yl)propyl)indoles Gives Selective Human 5-HT1D Receptor Ligands with Improved Pharmacokinetic Profiles (1999)

It has previously been reported that a 3-(3-(piperazin-1-yl)propyl)indole series of 5-HT1D receptor ligands have pharmacokinetic advantages over the corresponding 3-(3-(piperidin-1-yl)propyl)indole series and that the reduced pKa of the piperazines compared to the piperidines may be one possible explanation for these differences. To investigate this proposal we have developed versatile synthetic strategies for the incorporation of fluorine into these ligands, producing novel series of 4-fluoropiperidines, 3-fluoro-4-aminopiperidines, and both piperazine and piperidine derivatives with one or two fluorines in the propyl linker. Ligands were identified which maintained high affinity and selectivity for the 5-HT1D receptor and showed agonist efficacy in vitro. The incorporation of fluorine was found to significantly reduce the pKa of the compounds, and this reduction of basicity was shown to have a dramatic, beneficial influence on oral absorption, although the effect on oral bioavailability could not always be accurately predicted.