gebhart/patrepeval huggingface dataset:
Acyl-coenzyme A: Cholesterol acyltransferase inhibitor, avasimibe, stimulates bile acid synthesis and cholesterol 7α-hydroxylase in cultured rat hepatocytes and in vivo in the rat (1999)

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitors are currently in clinical development as potential lipid-lowering and antiatherosclerotic agents. We investigated the effect of avasimibe (Cl- 1011), a novel ACAT inhibitor, on bile acid synthesis and cholesterol 7alpha-hydroxylase in cultured rat hepatocytes and rats fed different diets. Avasimibe dose-dependently decreased ACAT activity in rat hepatocytes in the presence and absence of beta-migrating very low-density lipoproteins (betaVLDL) (by 93% and 75% at 10 micromol/L) and reduced intracellular storage of cholesteryl esters. Avasimibe (3 micromol/L) increased bile acid synthesis (2.9-fold) after preincubation with betaVLDL and cholesterol 7alpha-hydroxylase activity (1.7- and 2.6-fold, with or without betaVLDL), the latter paralleled by a similar induction of its messenger RNA (mRNA). Hepatocytes treated with avasimibe showed a shift from storage and secretion of cholesteryl esters to conversion of cholesterol into bile acids. In rats fed diets containing different amounts of cholesterol and cholate, avasimibe reduced plasma cholesterol (by 52% to 71%) and triglyceride levels (by 28% to 62%). Avasimibe did not further increase cholesterol 7alpha-hydroxylase activity and mRNA in cholesterol-fed rats, but prevented down-regulation by cholate. Avasimibe did not affect sterol 27-hydroxylase and oxysterol 7alpha-hydroxylase, 2 enzymes in the alternative pathway in bile acid synthesis. No increase in the ratio of biliary excreted cholesterol to bile acids was found, indicating that ACAT inhibition does not result in a more lithogenic bile. Avasimibe increases bile acid synthesis in cultured hepatocytes by enhancing the supply of free cholesterol both as substrate and inducer of cholesterol 7alpha-hydroxylase. These effects may partially explain the potent cholesterol-lowering effects of avasimibe in the rat.
Treatment of Refractory Status Epilepticus with Pentobarbital, Propofol, or Midazolam: A Systematic Review (2002)

Despite the inherent limitations of a systematic review, our results suggest that treatment with PTB, or any cIV-AED infusion to attain EEG background suppression, may be more effective than other strategies for treating RSE. However, these interventions also were associated with an increased frequency of hypotension, and no effect on mortality was seen. A prospective randomized trial comparing different agents and titration goals for RSE with obligatory continuous EEG monitoring is needed.
Molecular microbial diversity of an anaerobic digestor as determined by small-subunit rDNA sequence analysis (1997)

The bacterial community structure of a fluidized-bed reactor fed by vinasses (wine distillation waste) was analyzed. After PCR amplification, four small-subunit (SSU) rDNA clone libraries of Bacteria, Archaea, Procarya, and Eucarya populations were established. The community structure was determined by operational taxonomic unit (OTU) phylogenetic analyses of 579 partial rDNA sequences (about 500 bp long). A total of 146 OTUs were found, comprising 133, 6, and 7 from the Bacteria, Archaea, and Eucarya domains, respectively. A total of 117 bacterial OTU were affiliated with major phyla: low-G+C gram-positive bacteria, Cytophaga-Flexibacter-Bacteroides, Proteobacteria, high-G+C gram-positive bacteria, and Spirochaetes, where the clone distribution was 34, 26, 17, 6, and 4%, respectively. The other 16 bacterial OTUs represent 13% of the clones. They were either affiliated with narrow phyla such as Planctomyces-Chlamydia, green nonsulfur bacteria, or Synergistes, or deeply branched on the phylogenetic tree. A large number of bacterial OTUs are not closely related to any other hitherto determined sequences. The most frequent bacterial OTUs represents less than 5% of the total bacterial SSU rDNA sequences. However, the 20 more frequent bacterial OTUs describe at least 50% of these sequences. Three of the six Archaea OTUs correspond to 95% of the Archaea population and are very similar to already known methanogenic species: Methanosarcina barkeri, Methanosarcina frisius, and Methanobacterium formicicum. In contrast, the three other Archaea OTUs are unusual and are related to thermophilic microorganisms such as Crenarchaea or Thermoplasma spp. Five percent of the sequences analyzed were chimeras and were removed from the analysis.
T‐cell hybridoma specific for myelin oligodendrocyte glycoprotein‐35–55 peptide produced from HLA‐DRB1*1501‐transgenic mice (2004)

The goal of this study was to establish an unlimited and standardized source of humanized myelin peptide-specific T cells for in vitro testing of biological function. Thus, we perpetuated myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide-specific T cells obtained from immunized HLA-DRB1*1501-transgenic (Tg) mice by somatic fusions with BW5147 thymoma cells or BW5147 T-cell receptor (TCR) alpha(-)beta(-) variant (BW5147 variant) cells. The resulting T-cell hybridomas responded strongly to both mouse MOG-35-55 (42S) and human MOG-35-55 peptide (42P), regardless of which peptide was used for initial immunization, and were DRB1*1501 restricted. The MOG-35-55-reactive T-cell hybridomas were CD3(+)CD4(+)CD8(-) and expressed intracellular Th1 cytokines upon concanavalin A stimulation. Clones from either human MOG-35-55- or mouse MOG-35-55-selected hybridomas uniquely expressed the TCR BV8 gene in combination with AV17 and AV11 genes. V gene analyses confirmed the expression of TCR AV1, AV11, AV16, BV1, and BV5 gene segments in the widely used fusion partner BW5147 and demonstrated deletion of TCR AV1, AV11, and BV1 in the BW5147 variant. T-cell hybridomas were positively stained with anti-TCR beta-chain antibody on the cell surface, whereas neither BW5147 nor its variant had positive TCR surface expression. For functional application, we found that a monomeric form of the human HLA-DR2-derived recombinant T-cell receptor ligand (RTL) covalently linked to human MOG-35-55 peptide specifically inhibited proliferation of a hybridoma clone selected with human MOG-35-55 but not a different hybridoma clone selected with myelin basic protein. The RTL-induced inhibition in vitro of the human MOG-35-55 peptide-specific hybridoma reflected the ability of the RTL to inhibit experimental autoimmune encephalomyelitis induced by human MOG-35-55 peptide in HLA-DR2 transgenic mice. Thus, the MOG-35-55 peptide-specific T-cell hybridoma from DR2-Tg mice represents a novel humanized T-cell reagent useful for standardized biological screening of both DR2-restricted stimulation and RTL-dependent inhibition of response to human MOG-35-55 peptide.
Self-Powered Gate Driver for Normally-ON SiC JFETs: Design Considerations and System Limitations (2014)

A circuit solution to the normally-ON property of the normally-ON silicon carbide junction field-effect transistor, namely the self-powered gate driver, has been recently proposed. This letter sheds some light on the design process of the self-powered gate driver concept as well as limitations from the system perspective. It is experimentally shown that the parameters of the self-powered gate driver must be chosen taking into account a tradeoff between a fast response and stable operation of the driver. Moreover, the influence of the shoot-through current in the fast activation of the self-powered gate driver is also presented.
Developing Fluorescent Hyaluronan Analogs for Hyaluronan Studies (2012)

Two kinds of fluorescent hyaluronan (HA) analogs, one serving as normal imaging agent and the other used as a biosensitive contrast agent, were developed for the investigation of HA uptake and degradation. Our approach of developing HA imaging agents depends on labeling HA with varying molar percentages of a near-infrared (NIR) dye. At low labeling ratios, the hyaluronan uptake can be directly imaged while at high labeling ratios, the fluorescent signal is quenched and signal generation occurs only after degradation. It is found that the conjugate containing 1%-2% NIR dye can be used as a normal optical imaging agent, while bioactivable imaging agents are formed at 6% to 17% dye loading. It was determined that the conjugation of dye to HA with different loading percentages does not impact HA biodegradation by hyaluronidase (Hyal). The feasibility of using these two NIR fluorescent hyaluronan analogs for HA investigation was evaluated in vivo with optical imaging. The data demonstrates that the 1% dye loaded fluorescent HA can be used to monitor the behavior of HA and its fragments, whereas bioactivatable HA imaging agent (17% dye in HA) is more suitable for detecting HA fragments.
Blocking Programmed Death-1 Ligand-PD-1 Interactions by Local Gene Therapy Results in Enhancement of Antitumor Effect of Secondary Lymphoid Tissue Chemokine (2004)

The negative signal provided by interactions of programmed death-1 (PD-1) and its ligands, costimulatory molecules PD-L1 (also B7-H1) and PD-L2 (also B7-DC), is involved in the mechanisms of tumor immune evasion. In this study, we found that this negative signal was also involved in immune evasion in tumor immunotherapy. When we used different doses of a constructed eukaryotic expression plasmid, pSLC, which expresses functional murine secondary lymphoid tissue chemokine (SLC, CCL21), to treat BALB/c mice inoculated with H22 murine hepatoma cells, the inhibitory effect was enhanced along with the increase of pSLC dosage. Unexpectedly, however, the best complete inhibition rate of tumor was reached when pSLC was used at the dosage of 50 microg but not 100 or 200 microg. RT-PCR and real-time PCR revealed that both PD-L1 and PD-L2 genes were expressed in tumor and vicinal muscle tissues of tumor-bearing mice and the expression level was significantly increased if a higher dosage of pSLC was administered. We then constructed a eukaryotic expression plasmid (pPD-1A) that expresses the extracellular domain of murine PD-1 (sPD-1). sPD-1 could bind PD-1 ligands, block PD-Ls-PD-1 interactions, and enhance the cytotoxicity of tumor-specific CTL. Local gene transfer by injection of pPD-1A mediated antitumor effect and improved SLC-mediated antitumor immunity. The combined gene therapy with SLC plus sPD-1 did not induce remarkable autoimmune manifestations. Our findings provide a potent method of improving the antitumor effects of SLC and possibly other immunotherapeutic methods by local blockade of negative costimulatory molecules.
High-density integration of functional modules using monolithic 3D-IC technology (2013)

Three dimensional integrated circuits (3D-ICs) have emerged as a promising solution to continue device scaling. They can be realized using Through Silicon Vias (TSVs), or monolithic integration using Monolithic Inter-tier vias (MIVs), an emerging alternative that provides much higher via densities. In this paper, we provide a framework for floorplanning existing 2D IP blocks into 3D-ICs using MIVs. We take the floorplanning solution all the way through place-and-route and report post-layout metrics for area, wirelength, timing, and power consumption. Results show that the wirelength of TSV-based 3D designs outperform 2D designs by upto 14% in large-scale circuits only. MIV-based 3D designs, however, offer an average wirelength improvement of 33% for a wide range of benchmark circuits. We also show that while TSV-based 3D cannot improve the performance and power unless the TSV capacitance is reduced, MIV-based 3D offers significant reduction of upto 33% in the longest path delay and 35% in the inter-block net power.
SELDI‐TOF Serum Profiling for Prognostic and Diagnostic Classification of Breast Cancers (2004)

Surface enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry has emerged as a successful tool for serum based detection and differentiation of many cancer types, including breast cancers. In this study, we have applied the SELDI technology to evaluate three potential applications that could extend the effectiveness of established procedures and biomarkers used for prognostication of breast cancers. Paired serum samples obtained from women with breast cancers prior to surgery and post-surgery (6-9 mos.) were examined. In 14/16 post-treatment patients, serum protein profiles could be used to distinguish these samples from the pre-treatment cancer samples. When compared to serum samples from normal healthy women, 11 of these post-treatment samples retained global protein profiles not found in healthy women, including five low-mass proteins that remained elevated in both pre-treatment and post-treatment serum groups. In another pilot study, serum profiles were compared for a group of 30 women who were known BRCA-1 mutation carriers, half of whom subsequently developed breast cancer within three years of the sample procurement. SELDI protein profiling accurately classified 13/15 women with BRCA-1 breast cancers from the 15 non-cancer BRCA-1 carriers. Additionally, the ability of SELDI to distinguish between the serum profiles from sentinel lymph node positive and sentinel lymph node negative patients was evaluated. In sentinel lymph node positive samples, 22/27 samples were correctly classified, in comparison to the correct classification of 55/71 sentinel lymph node negative samples. These initial results indicate the utility of protein profiling approaches for developing new diagnostic and prognostic assays for breast cancers.
Monolithic fluoride-fiber laser at 1480 nm using fiber Bragg gratings (2007)

We report what we believe is the first monolithic fluoride-fiber laser making use of fiber Bragg gratings written directly in the doped fluoride-fiber core. The Tm(3+):ZBLAN fiber laser is upconversion pumped at 1070 nm and emits at 1480 nm. Using two different all-fiber cavities, we observed a threshold as low as 75 mW and a conversion efficiency of up to 40% with respect to launched pump power.
Epstein–Barr virus-induced gene 3 and the p35 subunit of interleukin 12 form a novel heterodimeric hematopoietin (1997)

The Epstein-Barr virus-induced gene 3 (EBI3) is a novel soluble hematopoietin component related to the p40 subunit of interleukin 12 (IL-12). When EBI3 was expressed in cells, it accumulated in the endoplasmic reticulum and associated with the molecular chaperone calnexin, indicating that subsequent processing and secretion might be dependent on association with a second subunit. Coimmunoprecipitations from lysates and culture media of cells transfected with expression vectors for EBI3 and/or the p35 subunit of IL-12 now reveal a specific association of EBI3 with p35. Coexpression of EBI3 and p35 mutually facilitates their secretion. Most importantly, a large fraction of p35 in extracts of the trophoblast component of a human full-term normal placenta specifically coimmunoprecipitated with EBI3, indicating that EBI3 is in a heterodimer with p35, in vivo. Because EBI3 is expressed in EBV-transformed B lymphocytes, tonsil, spleen, and placental trophoblasts, the EBI3/p35 heterodimer is likely to be an important immunomodulator.
Overexpression of Escherichia coli oxidoreductases increases recombinant insulin-like growth factor-I accumulation (1998)

Transient overexpression of either DsbA or DsbC can double the yield of periplasmic insulin-like growth factor (IGF)-I in Escherichia coli to 8.5 g/liter. Strikingly, most of the overexpressed DsbA or DsbC is found in the reduced form, implying that enhanced disulfide isomerization is responsible for the substantial increase in IGF-I yield. All of the accumulated IGF-I has had the signal sequence removed, underscoring the secretion capacity of this organism as well as its utility for efficient production of polypeptide with the correct amino terminus. The overexpressed IGF-I constitutes approximately 30% of the total cell protein. Overproduction of active site mutants of DsbA instead of the wild-type gene do not produce this increase in yield. With wild-type levels of DsbA and DsbC, most of the secreted IGF-I is found in disulfide-linked aggregates, although 10% is soluble and about 5% is correctly folded. Contrary to expectations, overexpression of the disulfide oxidoreductases decreased the soluble fraction. Because the aggregated protein can be efficiently solubilized and refolded, the increased yield is a significant benefit for the production of IGF-I.
Automatable lipid bilayer formation for ion channel studies (2008)

Transmembrane proteins and ion channels are important drug targets and have been explored as single molecule sensors. For these proteins to function normally they must be integrated within lipid bilayers; however, the labor and skill required to create artificial lipid bilayers have the limited the possible applications utilizing these proteins. In order to reduce the complexity and cost of lipid bilayer formation and measurement, we have modified a previously published lipid bilayer formation technique using mechanically contacted monolayers so that the process is automatable, requiring minimal operator input. Measurement electronics are integrated with the fluid handling system, greatly reducing the time and operator feedback characteristically required of traditional bilayer experiments. To demonstrate the biological functionality of the resultant bilayers and the system's capabilities as a membrane platform, the ion channel gramicidin A was incorporated and measured with this system.
Characterization of two populations of mesenchymal progenitor cells in umbilical cord blood (2006)

Umbilical cord blood (UCB) is a valuable source for hematopoietic progenitor cell therapy. Moreover, it contains another subset of non-hematopoietic population referred to as mesenchymal progenitor cells (MPCs), which can be ex vivo expanded and differentiated into osteoblasts, chondrocytes and adipocytes. In this study, we successfully isolated the clonogenic MPCs from UCB by limiting dilution method. These cells exhibited two different morphologic phenotypes, including flattened fibroblasts (majority) and spindle-shaped fibroblasts (minority). Both types of MPCs shared similar cell surface markers except CD90 and had similar osteogenic and chondrogenic potentials. However, the spindle-shaped clones possessed the positive CD90 expression and showed a greater tendency in adipogenesis, while the flattened clones were CD90 negative cells and showed a lower tendency in adipogenesis. The high number of flattened MPCs might be linked to the less sensitivity of UCB-derived MPCs in adipogenic differentiation.
Inhibition of adhesion and induction of epithelial cell invasion by HAV-containing E-cadherin-specific peptides (1999)

The E-cadherin/catenin complex, an organizer of epithelial structure and function, is disturbed in invasive cancer. The HAV (histidine alanine valine) sequence in the first extracellular domain of E-cadherin is crucial for homophilic interactions between cadherins. We report that specific peptides containing an HAV sequence interfere with the functions of the E-cadherin/catenin complex. Cells either expressing specific cadherins or not were challenged with both cadherin and noncadherin peptides comprising a central HAV sequence. Specific E-cadherin peptides inhibited cell aggregation, disturbed the epithelial morphotype and were able to stimulate invasion of cells expressing E-cadherins. Conditioned medium, containing E-cadherin fragments, also stimulated invasion in contrast to conditioned medium from which the E-cadherin fragments were removed. Our studies show that E-cadherin functions are inhibited by homologous proteolytic HAV-containing fragments that are released in an autocrine manner and subsequently inhibit the E-cadherin/catenin complex. In this way such cadherin fragments may induce and support cancer invasion.
Mice humanised for the EGF receptor display hypomorphic phenotypes in skin, bone and heart (2003)

Mice lacking the epidermal growth factor receptor (EGFR) develop epithelial defects and a neurodegenerative disease and die within the first month of birth. By employing a conditional knock-in approach using the human EGFR cDNA mice humanised for EGFR (hEGFRKI/KI) were generated. Homozygous hEGFRKI/KI mice are viable and live up to six months. However, these mice are growth retarded and show skin and hair defects similar to Egfr-/- mutants. Interestingly, the neurodegeneration is fully rescued in hEGFRKI/KI mice, however, they develop a severe heart hypertrophy with semilunar valve abnormalities. Moreover, hEGFRKI/KI mice display accelerated chondrocyte and osteoblast differentiation, a phenotype that is also present in Egfr-/- mice and has not been previously described. The severity of the phenotypes correlates with the expression levels of the hEGFRKI allele, which is not efficiently expressed in epithelial and bone cells, but is expressed at similar and even higher levels as the endogenous Egfr in brain and heart. These results demonstrate that mice humanised for EGFR display tissue-specific hypomorphic phenotypes and describe a novel function for EGFR in bone development.
Protein-peptide interactions analyzed with the yeast two-hybrid system (1995)

The yeast two-hybrid system was used to screen a library of random peptides fused to a transcriptional activation domain in order to identify peptides capable of binding to the retinoblastoma protein (Rb). Seven peptides were identified, all of which contain the Leu-X-Cys-X-Glu motif found in Rb-binding proteins, although their activity in the yeast assay varied over a 40-fold range. Mutagenesis of the DNA encoding two of these peptides followed by screening in the two-hybrid system allowed the delineation of residues apart from the invariant Leu, Cys and Glu that affect binding to Rb. Binding affinities of a peptide and one of its variants to Rb, determined by surface plasmon resonance, correlated with results from the two-hybrid assay. This method offers several advantageous features compared to existing technology for screening peptide libraries: in vivo detection of protein-peptide interactions, high sensitivity, the capacity for rapid genetic screening to identify stronger and weaker binding peptide variants, and the use of a simple assay (transcriptional activity) as a means to assess binding affinity.
Solute Accumulation and Compartmentation during the Cold Acclimation of Puma Rye (1992)

During cold acclimation of Puma rye (Secale cereale L. cv Puma), the intracellular osmotic potential nearly doubles. During this period, the accumulation of glycinebetaine, proline, and soluble sugars was monitored. The amount of glycinebetaine increased from 290 to 1300 micrograms per gram fresh weight during the 4-week acclimation period. Proline content did not change during the first 3 weeks of acclimation but then increased from 27 to 580 micrograms per gram fresh weight during the next 3 weeks. The total soluble sugar content more than doubled by the second week of cold acclimation, increasing from 11 to 26 milligrams per gram fresh weight. Most of this increase can be attributed to the accumulation of sucrose and raffinose, whose levels increased from 2.4 and 0 to 11 and 5 milligrams per gram fresh weight, respectively. The content of monosaccharides, predominantly glucose, remained at a constant 10 milligrams per gram fresh weight throughout the acclimation period. A comparison of the sugar content of protoplasts versus vacuoles isolated from cold-acclimated leaves revealed that the extravacuolar volume contained monosaccharides, sucrose, and raffinose. Thus, the increased amounts of sucrose and raffinose that occur during cold acclimation are present in compartments external to the vacuole and may contribute to cryoprotection.