gebhart/patrepeval huggingface dataset:
The Effect of Age and Gender on Pharmacokinetics, Pharmacodynamics, and Safety of Febuxostat, a Novel Nonpurine Selective Inhibitor of Xanthine Oxidase (2008)

Febuxostat is a novel nonpurine selective inhibitor of xanthine oxidase, which is currently being developed for the management of hyperuricemia in patients with gout. The effect of age and gender on the pharmacokinetics, pharmacodynamics, and safety of once-daily oral febuxostat 80 mg was assessed in healthy male and female subjects after 7 days. Following multiple dosing with febuxostat, there were no statistically significant differences in the plasma or urinary pharmacokinetic or pharmacodynamic parameters between subjects aged 18 to 40 years and >or=65 years. Although unbound peak concentration (C(max,u)) and area under the concentration-time curve (AUC(24,u)) for febuxostat were higher in women as compared with men (31.5 vs 23.6 ng/mL, P <or= .01, and 62.8 vs 53.9 ng x h/mL, P <or= .05, for C(max,u) and AUC(24,u), respectively), the differences were not considered clinically significant and could be largely accounted for by weight differences between male and female subjects. For pharmacodynamic parameters, even though the percentage decrease in serum uric acid 24-hour mean concentration was slightly greater in women than in men (59% vs 52%, P <or= .01), this difference was not considered clinically meaningful. Febuxostat was well tolerated in male and female subjects in both age groups. Age or gender had no clinically significant effect on the pharmacokinetics, pharmacodynamics, or safety of febuxostat. Therefore, febuxostat does not require any dose adjustments based on age or gender.
Regional tourism, the labour market and education (2023)

La industria turística difiere de otras del sector servicios en que no puede delimitarse en términos de oferta, sino que debe definirse tomando como referencia la demanda. Esto se debe a que los turistas demandan muy distintos bienes y servicios, como alojamiento, transporte, alimentación, servicios culturales, etc. El turismo influye también en el mercado laboral; sin embargo, los análisis del impacto económico no revelan quiénes trabajan en el sector turístico. ¿Son personas jóvenes o mayores, hombres o mujeres, con mayor o menor nivel educativo? A escala regional, el mercado laboral turístico puede también variar debido a las diferencias en cuanto a la estructura turística. En este documento se muestran los métodos para analizar el mercado laboral turístico regional, así como los datos y algunos resultados preliminares utilizando las variaciones regionales de la variable nivel de estudios en Dinamarca en 1996.
The application of pre-reforming technology in the production of hydrogen (1993)

Because of the legislated changes in different hydrocarbon fuels, the hydrogen balance and product mix in refineries is changing. Many oil companies are exploring ways to increase the hydrogen supply in their refineries. Some companies have chosen to build new steam-reforming hydrogen plants; others are looking to debottleneck existing hydrogen plants or to send alternative feeds to their steam reformer. Pre-reforming technology provides refiners with another option to consider in their quest to balance hydrogen production and product mix. Pre-reforming technology may allow refineries to increase hydrogen production under certain circumstances. It may also be used to increase the refiner's flexibility in the feedstocks sent to the hydrogen plant, such as butanes and higher hydrocarbons. This paper addresses the suitability of a pre-reformer both in existing plants and in new hydrogen plant designs. Some other approaches, which may be used either as alternatives to, or in conjunction with, pre-reforming, are also described.
Cache performance for selected SPEC CPU2000 benchmarks (2001)

The SPEC CPU2000 benchmark suite (http://www.spec.org/osg/cpu2000) is a collection of 26 compute-intensive, non-trivial programs used to evaluate the performance of a computer's CPU, memory system, and compilers. The benchmarks in this suite were chosen to represent real-world applications, and thus exhibit a wide range of runtime behaviors. On this webpage, we present functional cache miss ratios and related statistics for selected benchmarks in the SPEC CPU2000 suite. In particular, split L1 cache sizes ranging from 4KB to 1MB with 64B blocks and associativities of 1, 2, 4, 8 and full. Most of this data was collected at the University of Wisconsin-Madison with the aid of the Simplescalar toolset (http://www.simplescalar.org).
Optimal sampling strategies for bayesian estimation of docetaxel (Taxotere) clearance. (1997)

Docetaxel activity has been documented in many solid tumors, including metastatic breast cancer and non-small cell lung cancer. However, as clinical studies in other tumor types are now being conducted, the validation of an optimal sampling strategy would allow the performance of pharmacokinetics/pharmacodynamics studies with minimum inconvenience for the patient. Six optimal sampling strategies with one to six sampling times were computed, based on the D-optimality theory, using population pharmacokinetic parameters estimated from a large pharmacokinetic database of 547 patients treated in previous Phase II studies. Validation of these sampling strategies was performed on a set of 35 patients, from two Phase I studies, who received docetaxel as a 1-h infusion at doses ranging from 50 to 100 mg/m2. Validation consisted of comparing clearance assessed by maximum likelihood estimation obtained using complete plasma concentration-time data (considered as the reference) and clearance determined by Bayesian estimation with an optimal design. For all of the optimal sampling strategies tested, clearance was found to be well estimated when at least two samples were taken. Bayesian estimation with two measured levels (at the end of infusion and at 6 h after the start of infusion) can be selected, because it allows adequate estimation of clearance with a nonsignificant bias of +1.37% and a precision of 12.3%.
Electrokinetic control of sample splitting at a channel bifurcation using isotachophoresis (2009)

We present a novel method for accurately splitting ionic samples at microchannel bifurcations. We leverage isotachophoresis (ITP) to focus and transport sample through a one-inlet, two-outlet microchannel bifurcation. We actively control the proportion of splitting by controlling potentials at end-channel reservoirs (and thereby controlling the current ratio). We explore the effect of buffer chemistry and local electric field on splitting dynamics and propose and validate a simple Kirchoff-type rule controlling the split ratio. We explore the effects of large applied electric fields on sample splitting and attribute a loss of splitting accuracy to electrohydrodynamic instabilities. We propose a scaling analysis to characterize the onset of this instability. This scaling is potentially useful for other electrokinetic flow problems with self-sharpening interfaces
Intrusion detection via static analysis (2002)

One of the primary challenges in intrusion detection is modelling typical application behavior so that we can recognize attacks by their atypical effects without raising too many false alarms. We show how static analysis may be used to automatically derive a model of application behavior. The result is a host-based intrusion detection system with three advantages: a high degree of automation, protection against a broad class of attacks based on corrupted code, and the elimination of false alarms. We report on our experience with a prototype implementation of this technique.
Locally Injective Mappings (2013)

Abstract Mappings and deformations are ubiquitous in geometry processing, shape modeling, and animation. Numerous deformation energies have been proposed to tackle problems like mesh parameterization and volumetric deformations. We present an algorithm that modifies any deformation energy to guarantee a locally injective mapping, i.e., without inverted elements. Our formulation can be used to compute continuous planar or volumetric piecewise‐linear maps and it uses a barrier term to prevent inverted elements. Differently from previous methods, we carefully design both the barrier term and the associated numerical techniques to be able to provide immediate feedback to the user, enabling interactive manipulation of inversion‐free mappings. Stress tests show that our method robustly handles extreme deformations where previous techniques converge very slowly or even fail. We demonstrate that enforcing local injectivity increases fidelity of the results in applications such as shape deformation and parameterization.
Dense Captioning with Joint Inference and Visual Context (2017)

Dense captioning is a newly emerging computer vision topic for understanding images with dense language descriptions. The goal is to densely detect visual concepts (e.g., objects, object parts, and interactions between them) from images, labeling each with a short descriptive phrase. We identify two key challenges of dense captioning that need to be properly addressed when tackling the problem. First, dense visual concept annotations in each image are associated with highly overlapping target regions, making accurate localization of each visual concept challenging. Second, the large amount of visual concepts makes it hard to recognize each of them by appearance alone. We propose a new model pipeline based on two novel ideas, joint inference and context fusion, to alleviate these two challenges. We design our model architecture in a methodical manner and thoroughly evaluate the variations in architecture. Our final model, compact and efficient, achieves state-of-the-art accuracy on Visual Genome [23] for dense captioning with a relative gain of 73% compared to the previous best algorithm. Qualitative experiments also reveal the semantic capabilities of our model in dense captioning.
Major Chromosomal Breakpoint Intervals in Breast Cancer Co-Localize with Differentially Methylated Regions (2012)

Solid tumors exhibit chromosomal rearrangements resulting in gain or loss of multiple chromosomal loci (copy number variation, or CNV), and translocations that occasionally result in the creation of novel chimeric genes. In the case of breast cancer, although most individual tumors each have unique CNV landscape, the breakpoints, as measured over large datasets, appear to be non-randomly distributed in the genome. Breakpoints show a significant regional concentration at genomic loci spanning perhaps several megabases. The proximal cause of these breakpoint concentrations is a subject of speculation, but is, as yet, largely unknown. To shed light on this issue, we have performed a bio-statistical analysis on our previously published data for a set of 119 breast tumors and normal controls (Wiedswang et al., 2003), where each sample has both high-resolution CNV and methylation data. The method examined the distribution of closeness of breakpoint regions with differentially methylated regions (DMR), coupled with additional genomic parameters, such as repeat elements and designated "fragile sites" in the reference genome. Through this analysis, we have identified a set of 93 regional loci called breakpoint enriched DMR (BEDMRs) characterized by altered DNA methylation in cancer compared to normal cells that are associated with frequent breakpoint concentrations within a distance of 1 Mb. BEDMR loci are further associated with local hypomethylation (66%), concentrations of the Alu SINE repeats within 3 Mb (35% of the cases), and tend to occur near a number of cancer related genes such as the protocadherins, AKT1, DUB3, GAB2. Furthermore, BEDMRs seem to deregulate members of the histone gene family and chromatin remodeling factors, e.g., JMJD1B, which might affect the chromatin structure and disrupt coordinate signaling and repair. From this analysis we propose that preference for chromosomal breakpoints is related to genome structure coupled with alterations in DNA methylation and hence, chromatin structure, associated with tumorigenesis.
Reversible Inactivation of HIF-1 Prolyl Hydroxylases Allows Cell Metabolism to Control Basal HIF-1 (2005)

Continuous hydroxylation of the HIF-1 transcription factor alpha subunit by oxygen and 2-oxoglutarate-dependent dioxygenases promotes decay of this protein and thus prevents the transcriptional activation of many genes involved in energy metabolism, angiogenesis, cell survival, and matrix modification. Hypoxia blocks HIF-1alpha hydroxylation and thus activates HIF-1alpha-mediated gene expression. Several nonhypoxic stimuli can also activate HIF-1, although the mechanisms involved are not well known. Here we show that the glucose metabolites pyruvate and oxaloacetate inactivate HIF-1alpha decay in a manner selectively reversible by ascorbate, cysteine, histidine, and ferrous iron but not by 2-oxoglutarate or oxygen. Pyruvate and oxaloacetate bind to the 2-oxoglutarate site of HIF-1alpha prolyl hydroxylases, but their effects on HIF-1 are not mimicked by other Krebs cycle intermediates, including succinate and fumarate. We show that inactivation of HIF-1 hydroxylation by glucose-derived 2-oxoacids underlies the prominent basal HIF-1 activity commonly seen in many highly glycolytic cancer cells. Since HIF-1 itself promotes glycolytic metabolism, enhancement of HIF-1 by glucose metabolites may constitute a novel feed-forward signaling mechanism involved in malignant progression.
Fully recombinant IgG2a Fc multimers (stradomers) effectively treat collagen-induced arthritis and prevent idiopathic thrombocytopenic purpura in mice (2012)

These data suggest that fully human stradomers might serve as valuable tools for the treatment of selected autoimmune disorders and as reagents to study the function of Fc:FcR interactions in vivo.
Stabilization of nerve growth factor in controlled release polymers and in tissue (1997)

We have studied the release of nerve growth factor (NGF), a protein under consideration for treatment of Alzheimer's Disease, from polymer matrices and microspheres to characterize the stability of NGF, the dynamics of NGF release, and the distribution of NGF within the brain interstitium. Poly(ethylene-co-vinyl acetate) (EVAc) disks and poly(L-lactic acid) (PLA) microspheres were formed by codispersing NGF with one of a variety of molecules. The mass of mouse NGF (mNGF) detected following release from EVAc disks into buffered saline varied five-fold over the range of codispersants studied, with carboxymethyldextran providing optimal release, while the mass of recombinant human NGF (rhNGF) released varied four-fold from both EVAc disks and PLA microspheres, with albumin and carboxymethyldextran providing optimal release. Variation of the codispersant species significantly affected NGF release into buffered saline; it also had a noticeable, but small, effect of the amount of NGF found in the brain tissue following implantation of a polymer device. To improve NGF retention in tissue, NGF was conjugated to 70,000 molecular weight dextran and incorporated into a polymeric device. The distribution of NGF was enhanced by conjugation; comparison of NGF concentrations in the brain to a mathematical model of diffusion and elimination suggested that the elimination rate of NGF-dextran conjugate in the tissue was over seven times slower than the elimination rate of NGF. These results indicate that variation of the properties of the controlled release system may be useful in regulating the time course of NGF delivery to tissue, and that modification of the NGF itself can improve penetration and retention in the brain.
High-dose CHOP as initial therapy for patients with poor-prognosis aggressive non-Hodgkin's lymphoma: a dose-finding pilot study. (1995)

The high-dose CHOP regimen may be an effective alternative for patients with poor-prognosis aggressive NHL.
Optical Interconnections Using Silica-Based Waveguide On Si Substrate (1988)

Guided-wave optical interconnections for interchip data transmissions and clock distributions are demonstrated. The optical interconnection circuit consists of a silica-based guided-wave circuit, laser diodes and photodiodes. The interconnection topology adopts the star coupler network used in Local Area Networks as a model. The laser diodes and photodiodes are integrated with the guided-wave circuit. Preliminary experiments on a 4-chip interconnection circuit yielded a 340 Mbps data rate and a 250 MHz clock frequency.
Molecular cloning of a novel melanocortin receptor. (1993)

Using the technique of the polymerase chain reaction primed with oligonucleotides based on the homologous transmembrane regions of seven transmembrane G protein-linked receptors, we isolated three full-length human genes that encode a novel subgroup of this receptor family. Recently, two of these receptors were identified as specific for alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone. We report the molecular cloning and pharmacologic characterization of a third member of this subgroup. The gene for this receptor encodes a protein of 361 amino acids in length. Its pharmacology characterizes it as an MSH receptor specific to the heptapeptide core common to adrenocorticotropic hormone and alpha-, beta-, and gamma-MSH. By Northern blot hybridization and polymerase chain reaction, it is expressed in brain, placental, and gut tissues but not in melanoma cells or in the adrenal gland. These findings may yield insight into the physiology of peptides derived from pro-opiomelanocortin post-translational processing.
Inhibition of Apoptosis in Chlamydia-infected Cells: Blockade of Mitochondrial Cytochrome c Release and Caspase Activation (1998)

We report that chlamydiae, which are obligate intracellular bacterial pathogens, possess a novel antiapoptotic mechanism. Chlamydia-infected host cells are profoundly resistant to apoptosis induced by a wide spectrum of proapoptotic stimuli including the kinase inhibitor staurosporine, the DNA-damaging agent etoposide, and several immunological apoptosis-inducing molecules such as tumor necrosis factor-alpha, Fas antibody, and granzyme B/perforin. The antiapoptotic activity was dependent on chlamydial but not host protein synthesis. These observations suggest that chlamydia may encode factors that interrupt many different host cell apoptotic pathways. We found that activation of the downstream caspase 3 and cleavage of poly (ADP-ribose) polymerase were inhibited in chlamydia-infected cells. Mitochondrial cytochrome c release into the cytosol induced by proapoptotic factors was also prevented by chlamydial infection. These observations suggest that chlamydial proteins may interrupt diverse apoptotic pathways by blocking mitochondrial cytochrome c release, a central step proposed to convert the upstream private pathways into an effector apoptotic pathway for amplification of downstream caspases. Thus, we have identified a chlamydial antiapoptosis mechanism(s) that will help define chlamydial pathogenesis and may also provide information about the central mechanisms regulating host cell apoptosis.
Arabidopsis , the Rosetta Stone of Flowering Time? (2002)

Multiple environmental and endogenous inputs regulate when plants flower. The molecular genetic dissection of flowering time control in Arabidopsis has identified an integrated network of pathways that quantitatively control the timing of this developmental switch. This framework provides the basis to understand the evolution of different reproductive strategies and how floral pathways interact through seasonal progression.
PET scanning of iodine-124-3F9 as an approach to tumor dosimetry during treatment planning for radioimmunotherapy in a child with neuroblastoma. (1992)

A patient with advanced neuroblastoma who had failed chemotherapy presented with a large abdominal mass and virtually total bone marrow replacement by tumor on repeated marrow biopsies. She was considered a candidate for a Phase I 131I-3F8 radioimmunotherapy trial, (MSKCC 89-141A). As a potential aid to treatment planning, a test dose of 124I-3F8 was injected and the patient was imaged over the 72 hr postinjection using two BGO based PET scanners of different designs. Time activity curves were obtained, and the cumulated activity concentration of radiolabeled 3F8 in tumor was determined. Based on MIRD, an estimated radiation absorbed dose for 131I-3F8 was 7.55 rad/mCi, in the most antibody avid lesions. Because of low uptake and unfavorable dosimetry in some bulky tumor sites, it was decided not to treat the patient with radiolabeled antibody. Positron emission tomography of 124I-labeled antibodies can be used to measure cumulated activity or residence time in tumor for more accurate estimates of radiation absorbed tumor dose from radioiodinated antibodies and can help guide management decisions in patients who are candidates for radioimmunotherapy.
Related Clones Containing SCC mec Type IV Predominate among Clinically Significant Staphylococcus epidermidis Isolates (2003)

SCCmec is a mobile genetic element that carries the gene (mecA) mediating methicillin resistance in staphylococci. For Staphylococcus aureus, four SCCmec types have been described, one (type IV) of which has been associated with newly identified community-acquired methicillin-resistant S. aureus. However, the distribution of SCCmec types among S. epidermidis is not known. SCCmec typing of a collection of 44 methicillin-resistant Staphylococcus epidermidis (MRSE) isolates recovered between 1973 and 1983 from the blood of patients with prosthetic valve endocarditis (PVE) was performed by PCR amplification of key genetic elements (mecA, mecI, IS1272, and ccrAB). Of the 44 isolates, 1 (2%) harbored SCCmec type I, 15 (34%) harbored type II, 12 (28%) harbored type III, and 16 (36%) harbored type IV. The complete nucleotide sequence of SCCmec type IV was determined for 16 isolates and found to be identical in size (24 kb) and 98% homologous to DNA sequences published for S. aureus. Type IV SCCmec was also common (5 of 10 isolates) among a geographically dispersed collection of 10 recent (1998 to 2001) S. epidermidis bloodstream isolates. Multilocus sequence typing (MLST) (using the same seven genes presently employed for S. aureus MLST) of these MRSE isolates and of 10 additional recent geographically dispersed methicillin-susceptible isolates demonstrated that all 16 PVE isolates and 2 of 5 recent isolates harboring type IV SCCmec were in three related clonal groups. All three MSSE PVE isolates recovered from patients between 1976 and 1979 were in the same clonal groups as type IV SCCmec MRSE isolates. These data support the hypothesis of intra- and interspecies transfer of type IV SCCmec and suggest that there are clonal associations in S. epidermidis that correlate with SCCmec type.
The GAL4 System (2008)

Over the past decade the adoption and refinement of the GAL4 system by the Drosophila field has resulted in a wide array of tools with which the researcher can drive transgene expression in a precise spatiotemporal pattern. The GAL4 system relies on two components: (1) GAL4, a transcriptional activator from yeast, which is expressed in a tissue-specific manner and (2) a transgene under the control of the upstream activation sequence that is bound by GAL4 (UASG). The two components are brought together in a simple genetic cross. In the progeny of the cross, the transgene is only transcribed in those cells or tissues expressing the GAL4 protein. Recent modifications of the GAL4 system have improved the control of both the initiation and the spatial restriction of transgene expression. Here we describe the GAL4 system highlighting the properties that make it a powerful tool for the analysis of gene function in Drosophila and higher organisms.