gebhart/patrepeval huggingface dataset:
Diurnal Fluctuations in Free and Total Steady‐State Plasma Levels of Carbamazepine and Correlation with Intermittent Side Effects (1984)

The relationship between diurnal fluctuations in free (unbound) and total plasma carbamazepine levels and the appearance of intermittent side effects was investigated in nine epileptic patients receiving chronic therapy with carbamazepine, alone or in combination with phenobarbital. On a three-times-daily or four-times-daily dosing schedule, both total and free carbamazepine levels fluctuated considerably (on an average, 41 and 45%, respectively, around the mean). Side effects (particularly diplopia and nystagmus) were observed in five patients and showed an intermittent pattern in four. Side effects were never found at total carbamazepine levels less than 34 mumol/L but invariably appeared at levels greater than 38 mumol/L. At levels between 34 and 38 mumol/L adverse effects were inconsistently observed. The correlation between plasma carbamazepine levels and manifestations of toxicity was slightly stronger when free rather than total levels were considered. Side effects were always apparent at free levels greater than 7.2 mumol/L. These data underline the limitations of relying on a single drug level determination during the monitoring of carbamazepine therapy and emphasize the necessity of carefully adjusting the dosing schedule, to minimize the appearance of intermittent adverse effects.
The HCV serum proteome: a search for fibrosis protein markers (2009)

Summary. Liver fibrosis/cirrhosis is a serious health issue in hepatitis C virus (HCV‐) infected patients and is currently diagnosed by the invasive liver biopsy. The aim of this study was to find useful fibrosis markers in HCV‐patients’ sera of different fibrosis degrees (METAVIR F0‐F4) based on proteomics. Serum proteome profiles were created by two‐dimensional gel electrophoresis. Profiles were analysed between different degrees of fibrosis (F0‐F4) and between early (F0F1) and late (F2F3F4) fibrosis by univariate analyses ( P ≤ 0.05). Differentially expressed proteins were subsequently identified by mass spectrometry. Mac‐2‐binding protein, α‐2‐macroglobulin and hemopexin were increased in F4 opposite F0/F1. A‐1‐antitrypsin, leucine‐rich α‐2‐glycoprotein and fetuin‐A were decreased in F4 opposite F0/F1. Late fibrosis was characterized by an increase in Mac‐2‐binding protein, α‐2‐macroglobulin and α‐1B‐glycoprotein expression and a decrease in haptoglobin expression. Mac‐2‐binding protein expression was confirmed by dot blot assay and enzyme‐linked immunosorbent assay in a secondary population. In conclusion, serum proteome analysis enabled the detection/identification of existing and new candidate markers in line with fibrosis progression in HCV‐patients.
Miniaturised nucleic acid analysis (2004)

The application of micro total analysis systems has grown exponentially over the past few years, particularly diversifying in disciplines related to bioassays. The primary focus of this review is to detail recent new approaches to sample preparation, nucleic acid amplification and detection within microfluidic devices or at the microscale level. We also introduce some applications that have as yet to be explored in a miniaturised environment, but should benefit from improvements in analytical efficiency and functionality when transferred to planar-chip formats. The studies described in this review were published in commonly available journals as well as in the proceedings of three major conferences relevant to microfluidics (Micro Total Analysis Systems, Transducers and The Nanotechnology Conference and Trade Show). Although an emphasis has been placed on papers published since 2002, pertinent articles preceding this publication year have also been included.
Effects of Electrical Muscle Stimulation on Body Composition, Muscle Strength, and Physical Appearance (2002)

Electrical muscle stimulation devices (EMS) have been advertised to increase muscle strength, to decrease body weight and body fat, and to improve muscle firmness and tone in healthy individuals. This study sought to test those claims. Twenty-seven college-aged volunteers were assigned to either an EMS (n = 16) or control group (n = 11). The EMS group underwent stimulation 3 times per week following the manufacturer's recommendations, whereas the control group underwent concurrent sham stimulation sessions. Bilaterally, the muscles stimulated included the biceps femoris, quadriceps, biceps, triceps, and abdominals (rectus abdominus and obliques). An identical pre- and posttesting battery included measurements of body weight, body fat (via skinfolds), girths, isometric and isokinetic strength (biceps, triceps, quadriceps, hamstrings), and appearance (via photographs from the front, side, and back). EMS had no significant effect on the any of the measured parameters. Thus, claims relative to the effectiveness of EMS for the apparently healthy individual are not supported by the findings of this study.
Vaccinia Virus Envelope D8L Protein Binds to Cell Surface Chondroitin Sulfate and Mediates the Adsorption of Intracellular Mature Virions to Cells (1999)

We previously showed that an envelope A27L protein of intracellular mature virions (IMV) of vaccinia virus binds to cell surface heparan sulfate during virus infection. In the present study we identified another viral envelope protein, D8L, that binds to chondroitin sulfate on cells. Soluble D8L protein interferes with the adsorption of wild-type vaccinia virions to cells, indicating a role in virus entry. To explore the interaction of cell surface glycosaminoglycans and vaccinia virus, we generated mutant viruses from a control virus, WR32-7/Ind14K (A27L(+) D8L(+)) to be defective in expression of either the A27L or the D8L gene (A27L(+) D8L(-) or A27L(-) D8L(+)) or both (A27L(-) D8L(-)). The A27L(+) D8L(+) and A27L(-) D8L(+) mutants grew well in BSC40 cells, consistent with previous observations. However, the IMV titers of A27L(+) D8L(-) and A27L(-) D8L(-) viruses in BSC40 cells were reduced, reaching only 10% of the level for the control virus. The data suggested an important role for D8L protein in WR32-7/Ind14K virus growth in cell cultures. A27L protein, on the other hand, could not complement the functions of D8L protein. The low titers of the A27L(+) D8L(-) and A27L(-) D8L(-) mutant viruses were not due to defects in the morphogenesis of IMV, and the mutant virions demonstrated a brick shape similar to that of the control virions. Furthermore, the infectivities of the A27L(+) D8L(-) and A27L(-) D8L(-) mutant virions were 6 to 10% of that of the A27L(+) D8L(+) control virus. Virion binding assays revealed that A27L(+) D8L(-) and A27L(-) D8L(-) mutant virions bound less well to BSC40 cells, indicating that binding of viral D8L protein to cell surface chondroitin sulfate could be important for vaccinia virus entry.
GC instrumentation for on‐column injection of large volumes: Automated optimization of conditions (1995)

Abstract Improved instrumentation facilitates on‐column injection of up to several hundreds of microliters onto GC capillary columns. It incorporates an autosampler with adjustable injection speed, a standardized precolumn system, an early vapor exit, and software that models evaporation of a given solvent at the flow and temperature conditions chosen by the user. The software calculates the appropriate injection speed, guides the autosampler correspondingly, and closes the vapor exit at a moment leaving in the precolumn the amount of unevaporated solvent that is selected by the user. © 1995 John Wiley &amp; Sons, Inc.
PNC/DOE Remote Monitoring Project at Japan`s Joyo Facility (1996)

The Power Reactor and Nuclear Fuel Development Corporation (PNC) of Japan and the US Department of Energy (DOE) are cooperating on the development of a remote monitoring system for nuclear nonproliferation efforts. This cooperation is part of a broader safeguards agreement between PNC and DOE. A remote monitoring system is being installed in a spent fuel storage area at PNC`s experimental reactor facility Joyo in Oarai. The system has been designed by Sandia National Laboratories (SNL) and is closely related to those used in other SNL remote monitoring projects. The Joyo project will particularly study the unique aspects of remote monitoring in contribution to nuclear nonproliferation. The project will also test and evaluate the fundamental design and implementation of the remote monitoring system in its application to regional and international safeguards efficiency. This paper will present a short history of the cooperation, the details of the monitoring system and a general schedule of activities.
Plasmid-associated virulence of Salmonella typhimurium (1987)

We investigated the role of the 100-kilobase (kb) plasmid of Salmonella typhimurium in the virulence of this organism for mice. Three strains, LT2-Z, SR-11, and SL1344, which possessed 100-kb plasmids with identical restriction enzyme digestion profiles, were cured of their respective 100-kb plasmids after Tnmini-tet was used to label plasmids. Curing wild-type virulent strains SR-11 and SL1344 raised peroral 50% lethal doses from 3 x 10(5) and 6 x 10(4) CFU, respectively, to greater than 10(8) CFU. Both wild-type strains had intraperitoneal 50% lethal doses of less than 50 CFU, whereas the intraperitoneal 50% lethal doses for cured SR-11 and SL1344 were less than 50 and 400 CFU, respectively. Reintroduction of the Tnmini-tet-labeled, 100-kb plasmid restored wild-type virulence. Invasion from Peyer's patches to mesenteric lymph nodes and spleens after peroral inoculation was the stage of pathogenesis most affected by curing S. typhimurium of the 100-kb plasmid. Wild-type S. typhimurium replicated in spleens of mice inoculated intravenously to a greater extent than did plasmid-cured derivatives. Wild-type and cured strains equally adhered to and invaded Henle-407, HEp-2, and CHO cells; furthermore, the presence of the 100-kb plasmid was not necessary for replication of S. typhimurium within CHO cells. The 100-kb plasmid had no effect on phagocytosis and killing of S. typhimurium by murine peritoneal macrophages in vitro and in vivo. Similarly, wild-type and plasmid-cured strains were resistant to killing by 90% normal human, rabbit, and guinea pig sera. All wild-type and plasmid-cured S. typhimurium strains possessed complete lipopolysaccharide, as determined by silver staining solubilized cells in sodium dodecyl sulfate-polyacrylamide gels. We have confirmed the role of the 100-kb plasmid of S. typhimurium in virulence, primarily in invasion to mesenteric lymph nodes and spleens after peroral inoculation of mice. Involvement of the 100-kb plasmid in infection of mesenteric lymph nodes and spleens suggests a role for the plasmid in the complex interaction of S. typhimurium with cells of the reticuloendothelial system.
Effect of Nitrogen on Polysaccharide Production in a Porphyridium sp (1988)

Porphyridium cultures grown on either nitrate or ammonium as the nitrogen source showed similar patterns of growth and cell wall polysaccharide production. The effect of nitrogen on growth and cell wall polysaccharide production was studied by applying three regimens of supply: batch mode, in which nitrate was supplied at the beginning of the experiment and became depleted at day 6; continual mode, in which nitrate was added daily; and deficient mode, in which the cells were cultured in a nitrate-free medium. Growth was similar in the batch- and continual-mode cultures, whereas it was totally inhibited in the deficient-mode culture. Polysaccharide content (per volume) was highest in the batch-mode culture and lowest in the deficient-mode culture. However, polysaccharide production per cell was similar in the continual- and deficient-mode cultures, the highest value being found in the batch-mode culture. In addition to its effect on polysaccharide content, nitrogen affected the polysaccharide distribution between soluble and bound polysaccharides. In the deficientmode culture, most of the cell wall polysaccharide was dissolved in the medium.
Trophic factors as modulators of motor neuron physiology and survival: implications for ALS therapy (2014)

Motor neuron physiology and development depend on a continuous and tightly regulated trophic support from a variety of cellular sources. Trophic factors guide the generation and positioning of motor neurons during every stage of the developmental process. As well, they are involved in axon guidance and synapse formation. Even in the adult spinal cord an uninterrupted trophic input is required to maintain neuronal functioning and protection from noxious stimuli. Among the trophic factors that have been demonstrated to participate in motor neuron physiology are vascular endothelial growth factor (VEGF), glial-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and insulin-like growth factor 1 (IGF-1). Upon binding to membrane receptors expressed in motor neurons or neighboring glia, these trophic factors activate intracellular signaling pathways that promote cell survival and have protective action on motor neurons, in both in vivo and in vitro models of neuronal degeneration. For these reasons these factors have been considered a promising therapeutic method for amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases, although their efficacy in human clinical trials have not yet shown the expected protection. In this minireview we summarize experimental data on the role of these trophic factors in motor neuron function and survival, as well as their mechanisms of action. We also briefly discuss the potential therapeutic use of the trophic factors and why these therapies may have not been yet successful in the clinical use.
The Penrose Transform for Complex Projective Space (2008)

Various complexes of differential operators are constructed on complex projective space via the Penrose transform, which also computes their cohomology.
Hydrolytically Stable Thiol–ene Networks for Flexible Bioelectronics (2015)

Hydrolytically stable, tunable modulus polymer networks are demonstrated to survive harsh alkaline environments and offer promise for use in long-term implantable bioelectronic medicines known as electroceuticals. Today's polymer networks (such as polyimides or polysiloxanes) succeed in providing either stiff or soft substrates for bioelectronics devices; however, the capability to significantly tune the modulus of such materials is lacking. Within the space of materials with easily modified elastic moduli, thiol-ene copolymers are a subset of materials that offer a promising solution to build next generation flexible bioelectronics but have typically been susceptible to hydrolytic degradation chronically. In this inquiry, we demonstrate a materials space capable of tuning the substrate modulus and explore the mechanical behavior of such networks. Furthermore, we fabricate an array of microelectrodes that can withstand accelerated aging environments shown to destroy conventional flexible bioelectronics.
THE ROLE OF THEhsp90-BASED CHAPERONE SYSTEM IN SIGNAL TRANSDUCTION BY NUCLEAR RECEPTORS AND RECEPTORS SIGNALING VIA MAP KINASE (1997)

The multicomponent heat-shock protein (hsp) 90-based chaperone system is an ubiquitous protein-folding system in the cytoplasm of eukaryotes. Several signal transduction systems utilize an interaction with hsp90 as an essential component of the signaling pathway. The steroid and dioxin receptors are bound to hsp90 through their hormone-binding domains, and several of them must be bound to hsp90 in order to have a ligand-binding site. The binding of ligands to these receptors promotes their dissociation from hsp90, an event that is the first step in their signaling pathways. Several protein kinases, including the Src and Raf components of the MAP kinase system, are also bound to hsp90. Genetic studies in yeast have demonstrated that hsp90 is required for normal signaling via steroid and dioxin receptors and for the activity of Src in vivo. The hsp90-based chaperone system has been reconstituted from purified components, permitting detailed analysis of the molecular basis of the chaperone's role in signal transduction.
Dinuclear vs. mononuclear complexes: accelerated, metal-dependent ring-opening polymerization of lactide (2013)

Dinuclear complexes of aluminum and indium with a bis(phenoxy-imine) platform have been synthesized and used in the polymerization of lactide. Kinetic studies demonstrate that the dialuminum precursor provides a more favorable reaction pathway in terms of activation free energy than that of directly related monoaluminum systems. No similar trend is observed with the corresponding diindium-monoindium systems, which is attributed to a dissimilar ROP mechanism.
SmartCanvas (2005)

This paper describes SmartCanvas, an intelligent desk system that allows a user to perform freehand drawing on a desk or similar surface with gestures. Our system requires one camera and no touch sensors. The key underlying technique is a vision-based method that distinguishes drawing gestures and transitional gestures in real time, avoiding the need for "artificial" gestures to mark the beginning and end of a drawing stroke. The method achieves an average classification accuracy of 92.17%. Pie-shaped menus and a "rotate-to-and-select" approach eliminate the need for a fixed menu display, resulting in an "invisible" interface.
Oral or parenteral iron supplementation to reduce deferral, iron deficiency and/or anaemia in blood donors (2014)

There is moderate quality evidence that rates of donor deferral due to low haemoglobin are considerably less in those taking iron supplements compared with those without iron supplementation, both at the first donation visit and at subsequent donation. Iron-supplemented donors also show elevated haemoglobin and iron stores. These beneficial effects are balanced by more frequent adverse events in donors who receive iron supplementation than in those who do not; this is likely to limit acceptability and compliance. The long-term effects of iron supplementation without measurement of iron stores are unknown. These considerations are likely to preclude widespread use of iron supplementation by tablets. Blood services may consider targeted use of supplementation in those at greatest risk of iron deficiency, personalised donation intervals and providing dietary advice.
Regulation of Heme Oxygenase-1 Expression through the Phosphatidylinositol 3-Kinase/Akt Pathway and the Nrf2 Transcription Factor in Response to the Antioxidant Phytochemical Carnosol (2004)

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway elicits a survival signal against multiple apoptotic insults. In addition, phase II enzymes such as heme oxygenase-1 (HO-1) protect cells against diverse toxins and oxidative stress. In this work, we describe a link between these defense systems at the level of transcriptional regulation of the antioxidant enzyme HO-1. The herb-derived phenol carnosol induced HO-1 expression at both mRNA and protein levels. Luciferase reporter assays indicated that carnosol targeted the mouse ho1 promoter at two enhancer regions comprising the antioxidant response elements (AREs). Moreover, carnosol increased the nuclear levels of Nrf2, a transcription factor governing AREs. Electrophoretic mobility shift assays and luciferase reporter assays with a dominant-negative Nrf2 mutant indicated that carnosol increased the binding of Nrf2 to ARE and induced Nrf2-dependent activation of the ho1 promoter. While investigating the signaling pathways responsible for HO-1 induction, we observed that carnosol activated the ERK, p38, and JNK pathways as well as the survival pathway driven by PI3K. Inhibition of PI3K reduced the increase in Nrf2 protein levels and activation of the ho1 promoter. Expression of active PI3K-CAAX (where A is aliphatic amino acid) was sufficient to activate AREs. The use of dominant-negative mutants of protein kinase Czeta and Akt1, two kinases downstream from PI3K, demonstrated a requirement for active Akt1, but not protein kinase Czeta. Moreover, the long-term antioxidant effect of carnosol was partially blocked by PI3K or HO-1 inhibitors, further demonstrating that carnosol attenuates oxidative stress through a pathway that involves PI3K and HO-1.
Physiological function and transplantation of scaffold-free and vascularized human cardiac muscle tissue (2009)

Success of human myocardial tissue engineering for cardiac repair has been limited by adverse effects of scaffold materials, necrosis at the tissue core, and poor survival after transplantation due to ischemic injury. Here, we report the development of scaffold-free prevascularized human heart tissue that survives in vivo transplantation and integrates with the host coronary circulation. Human embryonic stem cells (hESCs) were differentiated to cardiomyocytes by using activin A and BMP-4 and then placed into suspension on a rotating orbital shaker to create human cardiac tissue patches. Optimization of patch culture medium significantly increased cardiomyocyte viability in patch centers. These patches, composed only of enriched cardiomyocytes, did not survive to form significant grafts after implantation in vivo. To test the hypothesis that ischemic injury after transplantation would be attenuated by accelerated angiogenesis, we created "second-generation," prevascularized, and entirely human patches from cardiomyocytes, endothelial cells (both human umbilical vein and hESC-derived endothelial cells), and fibroblasts. Functionally, vascularized patches actively contracted, could be electrically paced, and exhibited passive mechanics more similar to myocardium than patches comprising only cardiomyocytes. Implantation of these patches resulted in 10-fold larger cell grafts compared with patches composed only of cardiomyocytes. Moreover, the preformed human microvessels anastomosed with the rat host coronary circulation and delivered blood to the grafts. Thus, inclusion of vascular and stromal elements enhanced the in vitro performance of engineered human myocardium and markedly improved viability after transplantation. These studies demonstrate the importance of including vascular and stromal elements when designing human tissues for regenerative therapies.
Future of Inertial Fusion Energy (2002)

In the past 50 years, fusion R&amp;D programs have made enormous technical progress. Projected billion-dollar scale research facilities are designed to approach net energy production. In this century, scientific and engineering progress must continue until the economics of fusion power plants improves sufficiently to win large scale private funding in competition with fission and non-nuclear energy systems. This economic advantage must be sustained: trillion dollar investments will be required to build enough fusion power plants to generate ten percent of the world's energy. For Inertial Fusion Energy, multi-billion dollar driver costs must be reduced by up to an order of magnitude, to a small fraction of the total cost of the power plant. Major cost reductions could be achieved via substantial improvements in target performance-both higher gain and reduced ignition energy. Large target performance improvements may be feasible through a combination of design innovations, e.g., ''fast ignition,'' propagation down density gradients, and compression of fusion fuel with a combination of driver and chemical energy. The assumptions that limit projected performance of fusion targets should be carefully examined. The National Ignition Facility will enable development and testing of revolutionary targets designed to make possible economically competitive fusion power plants.