gebhart/patrepeval huggingface dataset:
Detection of Mutated K‐ras DNA in Urine, Plasma, and Serum of Patients with Colorectal Carcinoma or Adenomatous Polyps (2008)

Our previous studies demonstrated that urine contains DNA derived from the circulation and that this DNA originated, in part, from organ sites and tumors distal to the urinary tract. To explore the potential use of DNA from urine as compared to other body fluids as a source for circulating DNA for cancer detection, the DNA concentration and the frequency of detection of mutated Kristin-ras (K-ras) DNA in serum, plasma, and urine were examined. The concentration of DNA in the urine was similar to that in the serum, but the DNA concentration in plasma was significantly lower than in either urine or serum (P < 0.05). When DNA derived from 10 muL of body fluid was used in each mutation assay, the detection frequency of mutated K-ras DNA was comparable among serum, plasma, and urine. However, when DNA derived from 200 muL of body fluid was used, the incidence of detecting mutated K-ras DNA in urine was significant higher (95%) than in either serum (35%) or plasma (40%) (P < 0.0005), suggesting that inhibitory factors in serum/plasma may be more limiting than in urine. The use and practicality of urine as a source of circulating DNA for cancer detection are discussed.
Mesenchymal Stem Cells: Biological Characteristics and Potential Clinical Applications (2004)

Mesenchymal stem cells (MSC) are clonogenic, non-hematpoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages, for example, osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages, for example, neuronal-like cells. Several methods are currently available for isolation of the MSC based on their physical and physico-chemical characteristics, for example, adherence to plastics or other extracellular matrix components. Because of the ease of their isolation and their extensive differentiation potential, MSC are among the first stem cell types to be introduced in the clinic. Several studies have demonstrated the possible use of MSC in systemic transplantation for systemic diseases, local implantation for local tissue defects, as a vehicle for genes in gene therapy protocols or to generate transplantable tissues and organs in tissue engineering protocols. Before their widespread use in therapy, methods allowing the generation of large number of cells without affecting their differentiation potential as well as technologies that overcome immunological rejection (in case allogenic transplantation) must be developed.
Performance Improvements for the Rasterization Pipeline (2009)

Performance improvements are always needed in computer graphics. Better performance frees up computational resources which can be used to increase the level of realism in the rendered images. Despite a very rapid development of graphics hardware, we are still far from the point where photo-realistic rendering can be done in real time. Therefore, better algorithms must be developed in order to advance the field. In this thesis, we present several new algorithms targeted for the rasterization pipeline, which is, at the time of writing, the de-facto standard rendering algorithm used in graphics hardware. We focus on three areas in the pipeline. The first is the rasterization step where we present efficient sampling strategies which can improve performance, or enable new algorithms to be implemented. This includes an investigation of very inexpensive, but relatively high quality, sampling schemes, an algorithm for conservative rasterization through area sampling, and an algorithm for efficiently rasterizing multiple views which can be useful for holographic displays, and other multi-view displays. The second area of focus is on compression algorithms. Compression is frequently used in graphics hardware in order to minimize memory traffic and thereby increase performance. We present efficient algorithms for high dynamic range texture compression, depth buffer compression, and color buffer compression. The inner workings of buffer compression have been kept secret by hardware vendors, and the only available information is available through patents. Therefore, we also present surveys of the prior art in buffer compression. The final area we focus on is programmable culling. Culling is an old concept in computer graphics, and it is often necessary to include some form of culling to make an algorithm truly efficient. However, current graphics hardware only has a few fixed function culling algorithms implemented. This often makes it impossible, or impractical, to implement culling in new rendering algorithms that rely on graphics hardware. We present a methodology for automatically deriving culling algorithms from shader programs, and we show how this can be used to perform culling both on a pixel level, and on a geometry or vertex level. In both cases, we show that our automatic culling can greatly improve rendering performance for a wide variety of scenes.
Hydrogen Production at <550°C Using a Low Temperature Thermochemical Cycle (2004)

A Department of Energy goal is to identify new technologies for producing hydrogen cost effectively without greenhouse gas emissions. Thermochemical cycles are one of the potential options under investigation. Thermochemical cycles consist of a series of reactions in which water is thermally decomposed and all other chemicals are recycled. Only heat and water are consumed. However, most thermochemical cycles require process heat at temperatures of 850-900°C. Argonne National Laboratory is developing low temperature cycles designed for lower temperature heat, 500-550°C, which is more readily available. For this temperature region, copper-chlorine (Cu-Cl) cycles are the most promising cycle. Several Cu-Cl cycles have been examined in the laboratory and the most promising cycle has been identified. Proof-of-principle experiments are nearly complete. A preliminary assessment of cycle efficiency is promising. Details of the experiments and efficiency calculations are discussed...
Synovial tissue macrophage populations and articular damage in rheumatoid arthritis (1996)

Synovial macrophage numbers correlated with articular destruction in RA. In addition, the study results provided further evidence that lining layer macrophages may represent a distinct subpopulation that is of importance in this process. These findings have implications for the development of new therapies for RA.
An aggrecan-degrading activity associated with chondrocyte membranes (1998)

The breakdown of aggrecan in cartilage is, in part, mediated by an enzyme named aggrecanase that cleaves within the interglobular domain of the molecule between a glutamic residue and an alanine residue. Although the enzyme cleavage site has been identified, the identity, characteristics and localization of this enzyme remain unclear. We have demonstrated that membranes isolated from stimulated chondrocytes are able to generate aggrecan fragments that are labelled by an antibody that recognizes the new N-terminus formed by aggrecanase activity. It was further shown that the membrane activity was a metalloproteinase but was not inhibited by the naturally occurring matrix metalloproteinase (MMP) inhibitors, TIMPs 1 and 2. These results show that an aggrecanase activity is associated with the membranes of the chondrocytes and is a metalloproteinase, but might not be a member of the MMP family.
Enhancement of Red Emission (4F9/2 → 4I15/2) via Upconversion in Bulk and Nanocrystalline Cubic Y2O3:Er3+ (2002)

In this paper, we investigate as a function of erbium concentration (1, 2, 5, 10 mol %) the upconversion properties of bulk and nanocrystalline Er3+ doped cubic Y2O3. After excitation at short wavelength (488 nm) or with upconversion pumping (815 nm), green and red emissions were observed for both nanocrystalline and bulk samples in the visible region of the spectrum, while blue emission was observed in bulk Y2O3:Er3+ only. The upconverted emission after 815 nm excitation revealed an enhancement of the red [4F9/2 → 4I15/2] emission with respect to the green [(2H11/2, 4S3/2) → 4I15/2] emission when the dopant concentration is increased. However, the magnitude of the red enhancement in the bulk material differs slightly from its nanocrystalline counterpart, with the nanocrystalline material showing a higher degree of dependence on the dopant Er3+ concentration. It is believed that two distinct mechanisms are responsible for populating the 4S3/2 and 4F9/2 levels, with the latter being more efficient at higher Er3+ ion concentration.
Cleavage at the amino and carboxyl termini of Alzheimer's amyloid-beta by cathepsin D (1994)

Amyloid beta (A beta) is a 39-43-residue protein that originates from proteolysis of the beta-protein precursor (beta PP) and accumulates in senile plaques in brains of Alzheimer's disease (AD) patients. Mutant beta PP, which incorporates an AD-causing double mutation at positions 687-688, has been shown to enhance A beta production in transfected cells. In this work we investigate the susceptibility of the mutant beta PP sequence to proteolytic cleavage by proteinases from human brain. Internally quenched fluorogenic substrates were used that encompass the NH2-terminal sequence of A beta from wild-type beta PP, the double mutant, and the two single substitutions. Proteinase activity in brain extract cleaved the mutant substrate 100-fold faster than the wild-type substrate and the partial mutants 25-fold faster. The major cleavage site in all substrates was at the amyloidogenic Asp1 site. The brain activity appeared to be cathepsin D (CD), as indicated by similarities to purified CD in 1) the rate and site of substrates cleavage, 2) the pH optima, and 3) the sensitivity to pepstatin A. The increased activity against the mutant substrate was not shared by cathepsins B and C, pepsin, HIV proteinase, and Candida albicans Asp-proteinase. Furthermore, CD cleaved a substrate that incorporates the COOH terminus of A beta at positions equivalent to Thr43 and Ala42, at ratios of 68% and 32%, respectively. CD degraded A beta 1-40 into six fragments but A beta 1-42 was completely resistant to digestion, probably because of its aggregation characteristics. These results indicate that CD is capable of producing the cleavages resulting in A beta production and that it may prove to be a suitable therapeutic target.
Meriolins, a New Class of Cell Death–Inducing Kinase Inhibitors with Enhanced Selectivity for Cyclin-Dependent Kinases (2007)

Protein kinases represent promising anticancer drug targets. We describe here the meriolins, a new family of inhibitors of cyclin-dependent kinases (CDK). Meriolins represent a chemical structural hybrid between meridianins and variolins, two families of kinase inhibitors extracted from various marine invertebrates. Variolin B is currently in preclinical evaluation as an antitumor agent. A selectivity study done on 32 kinases showed that, compared with variolin B, meriolins display enhanced specificity toward CDKs, with marked potency on CDK2 and CDK9. The structures of pCDK2/cyclin A/variolin B and pCDK2/cyclin A/meriolin 3 complexes reveal that the two inhibitors bind within the ATP binding site of the kinase, but in different orientations. Meriolins display better antiproliferative and proapoptotic properties in human tumor cell cultures than their parent molecules, meridianins and variolins. Phosphorylation at CDK1, CDK4, and CDK9 sites on, respectively, protein phosphatase 1alpha, retinoblastoma protein, and RNA polymerase II is inhibited in neuroblastoma SH-SY5Y cells exposed to meriolins. Apoptosis triggered by meriolins is accompanied by rapid Mcl-1 down-regulation, cytochrome c release, and activation of caspases. Meriolin 3 potently inhibits tumor growth in two mouse xenograft cancer models, namely, Ewing's sarcoma and LS174T colorectal carcinoma. Meriolins thus constitute a new CDK inhibitory scaffold, with promising antitumor activity, derived from molecules initially isolated from marine organisms.
A rapid bioassay for single bacterial cell quantitation using bioconjugated nanoparticles (2004)

The rapid and sensitive determination of pathogenic bacteria is extremely important in biotechnology, medical diagnosis, and the current fight against bioterrorism. Current methods either lack ultrasensitivity or take a long time for analysis. Here, we report a bioconjugated nanoparticle-based bioassay for in situ pathogen quantification down to single bacterium within 20 min. The bioconjugated nanoparticle provides an extremely high fluorescent signal for bioanalysis and can be easily incorporated with biorecognition molecules, such as antibody. The antibody-conjugated nanoparticles can readily and specifically identify a variety of bacterium, such as Escherichia coli O157:H7, through antibody-antigen interaction and recognition. The single-bacterium-detection capability within 20 min has been confirmed by the plate-counting method and realized by using two independent optical techniques. The two detection methods correlated extremely well. Furthermore, we were able to detect multiple bacterial samples with high throughput by using a 384-well microplate format. To show the usefulness of this assay, we have accurately detected 1-400 E. coli O157 bacterial cells in spiked ground beef samples. Our results demonstrate the potential for a broad application of bioconjugated nanoparticles in practical biotechnological and medical applications in various biodetection systems. The ultimate power of integrating bionanotechnology into complex biological systems will emerge as a revolutionary tool for ultrasensitive detection of disease markers and infectious agents.
Coordinate Copper- and Oxygen-responsive Cyc6 andCpx1 Expression in Chlamydomonas Is Mediated by the Same Element (2000)

Chlamydomonas reinhardtii activates the transcription of the Cyc6 and the Cpx1 genes (encoding cytochrome c(6) and coprogen oxidase) in response to copper deficiency. Mutational analysis of promoter regions of the Cyc6 and Cpx1 genes revealed a four nucleotide sequence, GTAC, which was absolutely essential for copper responsiveness. The Cyc6 promoter contains two copper response elements, each with a functionally important GTAC sequence, whereas the Cpx1 promoter contains only one. This may contribute to the stronger and more tightly regulated expression of the Cyc6 gene. Mutation or deletion of sequences flanking the GTACs implicates additional nucleotides contributing to copper-responsive expression, but none are absolutely essential. Metal ion selectivity of Cpx1 expression is identical to that described previously for Cyc6 and is restricted to the copper deficiency-induced Cpx1 transcript. The Cyc6 and Cpx1 genes are also induced by oxygen deficiency. Reporter gene constructs indicate that the induction occurs at the level of transcription and requires the same GTAC sequence that is critical for copper responsiveness. We suggest that components of the copper-responsive signal transduction pathway are used for some of the changes in gene expression in hypoxic cells.
l‐Threonine Deaminase of Rhodospirillum rubrum (1971)

A procedure for the purification of threonine deaminase from Rhodospirillum rubrum is described. The 2200‐fold purified enzyme was judged to be pure by disc‐gel electrophoresis and ultracentrifugation. Sedimentation velocity centrifugation yielded an s ° 20,w value of 8.1 S and a D 20,w of 4.65 × 10 −7 cm 2 × sec −1 . Assuming a partial specific volume of 0.74 g/ml the molecular weight of 164000 was calculated from the Svedberg equation. However, from calibrated Sephadex G‐200 columns, a D 20,w of 4.15 × 10 −7 cm 2 × sec −1 was obtained and using this equation, the molecular weight was calculated to be 180000. Electrophoresis of the enzyme on polyacrylamide gels in the presence of sodium dodecyl sulfate revealed that the native enzyme was composed of four subunits, each of about 46000 molecular weight. In addition to the native tetrameric molecule, an active octameric species was detected in polyacrylamide gel electrophoresis. The spectrum of the pure enzyme showed absorption maxima at 279 nm and 412 nm, characteristic of pyridoxal 5′‐phosphate‐containing enzymes. Analysis of the cofactor content revealed the presence of 4.2 moles of pyridoxal phosphate per 180000 g of protein. The enzyme displayed a normal Michaelis‐Menten substrate saturation curve in the absence of isoleucine. High concentrations of isoleucine inhibited the enzyme activity somewhat only at low levels of the substrate; the inhibition was weak as compared to all other biosynthetic threonine deaminases. No other amino acid or any nucleotide tested produced any significant activation or inhibition. In assays at pH values greater than 8.4, a transient build up of a 245 nm absorbing species was observed. It is suggested that this species corresponds to one of the two intermediates of the deamination reaction, α‐aminocrotonate or α‐iminobutyrate, and that at high pH the rate‐limiting step in the reaction is the hydrolysis of the intermediate to the final products, 2‐oxobutyrate and ammonia.
Pegbelfermin (BMS‐986036), PEGylated FGF21, in Patients with Obesity and Type 2 Diabetes: Results from a Randomized Phase 2 Study (2018)

Twelve-week pegbelfermin treatment did not impact HbA1c concentrations, but QW and higher daily doses were associated with improved metabolic parameters and fibrosis biomarkers in patients with obesity and T2DM predisposed to fatty liver. These results support evaluation of pegbelfermin in patients with obesity-related metabolic diseases (e.g., nonalcoholic steatohepatitis).
Novel yeast protein kinase (YPK1 gene product) is a 40-kilodalton phosphotyrosyl protein associated with protein-tyrosine kinase activity. (1990)

Extracts of bakers' yeast (Saccharomyces cerevisiae) contain protein-tyrosine kinase activity that can be detected with a synthetic Glu-Tyr copolymer as substrate (G. Schieven, J. Thorner, and G.S. Martin, Science 231:390-393, 1986). By using this assay in conjunction with ion-exchange and affinity chromatography, a soluble tyrosine kinase activity was purified over 8,000-fold from yeast extracts. The purified activity did not utilize typical substrates for mammalian protein-tyrosine kinases (enolase, casein, and histones). The level of tyrosine kinase activity at all steps of each preparation correlated with the content of a 40-kDa protein (p40). Upon incubation of the most highly purified fractions with Mn-ATP or Mg-ATP, p40 was the only protein phosphorylated on tyrosine. Immunoblotting of purified p40 or total yeast extracts with antiphosphotyrosine antibodies and phosphoamino acid analysis of 32P-labeled yeast proteins fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the 40-kDa protein is normally phosphorylated at tyrosine in vivo. 32P-labeled p40 immunoprecipitated from extracts of metabolically labeled cells by affinity-purified anti-p40 antibodies contained both phosphoserine and phosphotyrosine. The gene encoding p40 (YPK1) was cloned from a yeast genomic library by using oligonucleotide probes designed on the basis of the sequence of purified peptides. As deduced from the nucleotide sequence of YPK1, p40 is homologous to known protein kinases, with features that resemble known protein-serine kinases more than known protein-tyrosine kinases. Thus, p40 is a protein kinase which is phosphorylated in vivo and in vitro at both tyrosine and serine residues; it may be a novel type of autophosphorylating tyrosine kinase, a bifunctional (serine/tyrosine-specific) protein kinase, or a serine kinase that is a substrate for an associated tyrosine kinase.
Integration of a Field Surface and Production Network With a Reservoir Simulator (1997)

Summary Reservoir simulation studies allow engineers to identify development strategies that can maximize the economic recovery of hydrocarbon resources. During the life of a field, the reservoir engineer confronts numerous decisions about the placement and operation of wells for production or injection. Traditionally, engineers evaluate the costs and benefits associated with competing development strategies by using reservoir simulation tools in different scenarios. The numerical reservoir simulator is used in forecasting recovery of reserves under existing production schemes and in evaluating the effects of changing operating conditions. This approach limits the overall benefit of a field study because it does not consider the effects that flows in wellbores and surface facilities have on the economic performance of the recovery programs. Yet, the costs of compression, separation, fluid injection, or water treatment can have a significant effect on the success of production strategies. When the goal is to identify an optimal hydrocarbon-recovery scheme, a compelling case arises for the computational integration of subsurface- and surface-simulation technologies. In this paper, we discuss an integrated computational solution for management of reservoir-production strategies and field development. The approach is implemented by coupling a reservoir simulator (Eclipse) with a surface and production network simulator and optimizer (Netopt). Parallel Virtual Machine (PVM) interface provides the coupling communication mechanism that integrates the two simultaneously running simulators. At each timestep, the network simulator and the reservoir simulator provide a consistent integrated solution after rate and pressure convergence is achieved within a predetermined tolerance.
Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3. (1991)

The fibroblast growth factors are a family of polypeptide growth factors involved in a variety of activities including mitogenesis, angiogenesis, and wound healing. Fibroblast growth factor receptors (FGFRs) have previously been identified in chicken, mouse, and human and have been shown to contain an extracellular domain with either two or three immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tyrosine kinase domain. We have isolated a human cDNA for another tyrosine kinase receptor that is highly homologous to the previously described FGFR. Expression of this receptor cDNA in COS cells directs the expression of a 125-kDa glycoprotein. We demonstrate that this cDNA encodes a biologically active receptor by showing that human acidic and basic fibroblast growth factors activate this receptor as measured by 45Ca2+ efflux assays. These data establish the existence of an additional member of the FGFR family that we have named FGFR-3.
Pain Suppression by Transcutaneous Electronic Stimulation (1974)

Electrical stimulation applied to the skin has been observed to relieve pain. Although transcutaneous nerve stimulation devices are quite simple, certain constraints must be met, particularly in electrode design, in order to maximize effectiveness.
Oral oseltamivir treatment of influenza in children (2001)

Oral oseltamivir administration is an efficacious and well-tolerated therapy for influenza in children when given within 48 h of onset of illness.