gebhart/patrepeval huggingface dataset:
Hepatocyte Growth Factor/Scatter Factor Differentially Regulates Expression of Proangiogenic Factors through Egr-1 in Head and Neck Squamous Cell Carcinoma (2005)

Hepatocyte growth factor/scatter factor (HGF) and the angiogenesis factors platelet-derived growth factors (PDGF), vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) are found in elevated concentrations in serum or tumor tissue of patients with head and neck squamous cell carcinomas (HNSCC), suggesting these factors may be coregulated. A cDNA microarray analysis for HGF-inducible genes revealed that HGF also modulates PDGFA expression, a gene recently shown to be inducible by the transcription factor, early growth response-1 (Egr-1). In the present study, we investigated the potential role of HGF-induced Egr-1 in expression of PDGF, VEGF, and IL-8. HGF induced expression of all three factors and Egr-1 expression and DNA-binding activity. The analysis of promoter sequences showed putative Egr-1 binding sites in the PDGFA or VEGF but not in the IL-8 promoter, and HGF-induced Egr-1-binding activity was confirmed by chromatin immunoprecipitation (ChIP) assay. The maximal basal and HGF-induced promoter activity for the PDGFA gene existed within -630 bp of the promoter region, and overexpression of Egr-1 significantly increased such activity. Consistent with this, expression of PDGFA and VEGF but not IL-8 showed corresponding differences with Egr-1 expression in HNSCC tumor specimens and were strongly suppressed by transfection of Egr-1-antisense or small interference RNA (siRNA) oligonucleotides. HGF-induced expression of Egr-1, PDGFA, and VEGF was suppressed by pharmacologic and siRNA inhibitors of mitogen-activated protein kinase kinase 1/2 (MEK1/2) and protein kinase C (PKC) pathways. We conclude that the HGF-induced activation of transcription factor Egr-1 by MEK1/2- and PKC-dependent mechanisms differentially contributes to expression of PDGF and VEGF, which are important angiogenesis factors and targets for HNSCC therapy.
Imidazo[1,2-b]Pyridazines. XVI. Synthesis and Central Nervous System Activities of Some 6-(Chloro, Alkylthio, Phenylthio, Benzylthio or Pyridinylmethylthio)-3-(unsubstituted, benzamidomethyl or methoxy)-2-(styryl or benzoyl)imidazo[1,2-b]pyridazines (1994)

Some 6-( chloro, alkylthio, phenylthio, benzylthio or pyridinylmethylthio )-3-( unsubstituted , benzamidomethyl or methoxy )-2-styrylimidazo[1,2-b] pyridazines and 6-chloro-3-( unsubstituted and benzamidomethyl )-2-benzoylimidazo[1,2-b] pyridazines have been prepared and tested for their ability to displace [3H]diazepam from rat brain plasma membranes. The structures of 6-chloro-2-benzoyl[and 6-fluoro-2-(4'-tolyl)] imidazo [1,2-b] pyridazine have been confirmed by X-ray analyses. The reactions of 6-methylthio(and 6-phenylthio)pyridazin-3-amines with 3-bromo-1-phenylpropane-1,2-dione also have been investigated. The 6-substituted 3-unsubstituted 2-styryl(and benzoyl ) imidazo [1,2-b] pyridazines did not bind strongly to rat brain benzodiazepine receptors; nor did the 3-benzamidomethyl or 3-methoxy derivatives (cf. the 2-phenyl analogues). However, 3-benzamidomethyl-6-(pyridin-3-ylmethylthio)-2-styrylimidazo[1,2-b] pyridazine was an exception with IC50 68 nM.
Gene Transfer as an Approach to Treating Hemophilia (2001)

Hemophilia is an X-linked bleeding diathesis caused by a deficiency of either factor VIII or factor IX. Present treatment for hemophilia involves intravenous infusion of either recombinant or plasma-derived clotting factor concentrates. Problems with this treatment method, including the expense, need for intravenous access, and risks of blood-borne disease transmission, have fueled an interest in developing a gene-transfer approach to treatment. On the basis of experience with protein concentrate therapy, it seems likely that even modest elevations in circulating levels of factor VIII or factor IX can prevent most of the mortality and much of the morbidity associated with the disease. Hemophilia has a number of advantages as a model system for working out strategies for gene transfer as an approach to the treatment of genetic diseases; these include wide latitude in choice of target tissue, a wide therapeutic window for levels of circulating factor, ease of determining therapeutic endpoints, and existence of excellent animal models of the disease. Preclinical studies over the last decade have recently culminated in the initiation of clinical trials of gene transfer for hemophilia A and B. Three trials, each using different vectors and target tissues, are presently underway, and two additional trials are in late planning stages. This report reviews the preclinical data underlying these strategies and the design of the ongoing and proposed clinical trials.
DCN+: Mixed Objective and Deep Residual Coattention for Question Answering (2017)

Traditional models for question answering optimize using cross entropy loss, which encourages exact answers at the cost of penalizing nearby or overlapping answers that are sometimes equally accurate. We propose a mixed objective that combines cross entropy loss with self-critical policy learning. The objective uses rewards derived from word overlap to solve the misalignment between evaluation metric and optimization objective. In addition to the mixed objective, we improve dynamic coattention networks (DCN) with a deep residual coattention encoder that is inspired by recent work in deep self-attention and residual networks. Our proposals improve model performance across question types and input lengths, especially for long questions that requires the ability to capture long-term dependencies. On the Stanford Question Answering Dataset, our model achieves state-of-the-art results with 75.1% exact match accuracy and 83.1% F1, while the ensemble obtains 78.9% exact match accuracy and 86.0% F1.
The 2001 Trading Agent Competition (2003)

The 2001 Trading Agent Competition was the second in a series of events aiming to shed light on research issues in automating trading strategies. Based on a challenging market scenario in the domain of travel shopping, the competition presents agents with difficult issues in bidding strategy, market prediction and resource allocation. Entrants in 2001 demonstrated substantial progress over the prior year, with the overall level of competence exhibited suggesting that trading in online markets is a viable domain for highly autonomous agents.
Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term (2014)

Prostaglandins PGE2 probably increase the chance of vaginal delivery in 24 hours, they increase uterine hyperstimulation with fetal heart changes but do not effect or may reduce caesarean section rates. They increase the likelihood of cervical change, with no increase in operative delivery rates. PGE2 tablets, gels and pessaries appear to be as effective as each other, any differences between formulations are marginal but may be important.
Effect of Estradiol and Ethynylestradiol on Microtubule Distribution in Chinese Hamster V79 Cells. (1992)

The effects of estradiol (E2) and ethynylestradiol (EE2) on the chromosome number and cellular microtubule architecture of Chinese hamster V79 cells were studied using fluorescent anti-tubulin antibody. Treatment with 20 microM E2 for 48 h induced only a small amount of tetraploid cells, but the normal microtubule network was disrupted completely by only 3 h of treatment. This data reveals that E2 has higher microtubule-disruptive activity than diethylstilbestrol in V79 cells.
Meta-q-plate for complex beam shaping (2016)

Optical beam shaping plays a key role in optics and photonics. In this work, meta-q-plate featured by arbitrarily space-variant optical axes is proposed and demonstrated via liquid crystal photoalignment based on a polarization-sensitive alignment agent and a dynamic micro-lithography system. Meta-q-plates with multiple-, azimuthally/radially variant topological charges and initial azimuthal angles are fabricated. Accordingly, complex beams with elliptical, asymmetrical, multi-ringed and hurricane transverse profiles are generated, making the manipulation of optical vortex up to an unprecedented flexibility. The evolution, handedness and Michelson interferogram of the hurricane one are theoretically analysed and experimentally verified. The design facilitates the manipulation of polarization and spatial degrees of freedom of light in a point-to-point manner. The realization of meta-q-plate drastically enhances the capability of beam shaping and may pave a bright way towards optical manipulations, OAM based informatics, quantum optics and other fields.
Paper-based smart microfluidics for education and low-cost diagnostics (2015)

Current centralised healthcare models pose many challenges, particularly for developing countries such as South Africa, where travel and time costs make it difficult for patients to seek healthcare, even when urgently needed. To address this issue, point-of-care (PoC) tests, which are performed at or near the site of clinical care, have gained popularity and are actively being developed. Microfluidic systems, in which small volumes of fluids can be processed, provide an ideal platform on which to develop PoC diagnostic solutions. Specifically, the emerging field of paper-based microfluidics, with advantages such as low-cost, disposability and minimal external equipment requirements, provides unique opportunities for addressing healthcare issues in developing countries. This work explores the field of paper-based microfluidics, with step-by-step instructions on the design, manufacture and testing processes to realise paper-based devices towards diagnostic applications. Paper-based microfluidic and electronic components are presented, as well as the integration of these components to provide smart paper-based devices. This serves as an educational tool, enabling both beginners and experts in the field to fast-track development of unique paper-based solutions towards PoC diagnostics, with emphasis on the South African context, where both the need for and impact of these solutions are great.
Infection enhancement of influenza A NWS virus in primary murine macrophages by anti‐hemagglutinin monoclonal antibody (1992)

Antibody-dependent enhancement (ADE) of influenza A NWS virus infection was investigated in primary murine macrophages (M phi) using anti-hemagglutinin(HA) monoclonal antibody (mAB). Contrary to previous reports of abortive influenza virus infection in primary M phi, this study demonstrated that the NWS virus replicated productively in both resident peritoneal M phi and thioglycolate-elicited peritoneal M phi providing cleavage of the HA was achieved by trypsin; 5 micrograms/ml of trypsin was the optimum concentration for the induction of infectivity. Under multiple-cycle growth conditions in the presence of mAB at various concentrations in trypsin-containing media, ADE was demonstrated in both M phi in the presence of subneutralizing concentrations of mAB. Flow cytometric analysis showed that the mechanism of virus entry into M phi could be through HA to specific virus receptors, or HA plus antibody to Fc receptors. These results indicate that ADE of the NWS virus infection actually occurs on Fc receptor-bearing primary murine M phi depending on the concentration of antibody in the presence of the appropriate protease for cleavage of viral HA.
Catabolic alanine racemase from Salmonella typhimurium: DNA sequence, enzyme purification, and characterization (1984)

The alanine racemase encoded by the Salmonella typhimurium dadB gene was purified to 90% homogeneity from an overproducing strain. At 37 degrees C the enzyme has a specific activity of 1400 units/mg (V max, L- to D-alanine). Active enzyme molecules are monomers of Mr 39 000 with one molecule of pyridoxal 5'-phosphate bound per subunit. The Km's for L- and D-alanine are 8.2 and 2.1 mM, respectively. Measurement of turnover numbers yielded the expected Keq value of 1.0. Determination of 22 of the 25 N-terminal amino acid residues of the purified polypeptide allowed localization of cloned DNA encoding the structural gene. Sequencing of subcloned DNA revealed that the dadB gene encodes a polypeptide of 356 amino acids whose calculated molecular weight (apoenzyme) was 39 044.
Is the Screening Method of Sacral Neuromodulation a Prognostic Factor for Long-Term Success? (2010)

The first stage tined lead procedure is a more sensitive screening tool than percutaneous nerve evaluation but long-term success seems to be independent of the screening method. Patients in whom percutaneous nerve evaluation initially failed but who responded to prolonged screening the with tined lead procedure appeared to be as successful as those who directly responded to percutaneous nerve evaluation or the tined lead procedure.
Review of recent progress in chemical stability of perovskite solar cells (2014)

The understanding of how the chemical stability of PSCs is affected by oxygen and moisture, UV light, the solution process, and temperature was reviewed.
Foundations of Time-Frequency Analysis (2001)

Time-frequency analysis is a modern branch of harmonic analysis. It com prises all those parts of mathematics and its applications that use the struc ture of translations and modulations (or time-freq
Nicotinic Acid Metabolism. Dimethylmaleate Hydratase (1984)

The partial enrichment of a new enzyme, dimethylmaleate hydratase from Clostridium barkeri and some of its characteristics are described. The unstable and oxygen-sensitive hydratase depends on ferrous ions and is induced during growth of C. barkeri on nicotinic acid. The enzyme uses both dimethylmaleate and the hydration product, 2,3-dimethylmalate, as substrates to establish an equilibrium that is 70% in favour of the latter acid; dimethylfumarate is not attacked. A 2,3-dimethyl[3-3H]malate specimen was prepared from dimethylmaleate with the hydratase in tritiated water. Based on proton attack at the re-face of the double bond, experimental results indicate the (2R,3S)-configuration for this malate. The hydration reaction takes an anti-course. The tritium label was lost in the sequence (2R,3S)-2,3-dimethyl[3-3H]malate----(R)-[2-3H1]-propionate----(2R) - [2-3H1]propionyl-CoA----(2S)-methylmalonyl-CoA. This result confirms the stereochemical course of the 2,3-dimethylmalate lyase reaction, inversion of configuration, by an independent approach. The hydratase reaction completes the degradation scheme of nicotinic acid by C. barkeri. The pathway is briefly reviewed.
CDDO-9,11-dihydro-trifluoroethyl amide (CDDO-dhTFEA) induces hepatic cytoprotective genes and increases bile flow in rats (2012)

1. The transcription factor Nrf2 is important for hepatoprotection against oxidative stress, as it regulates many cytoprotective genes, including several important for glutathione (GSH) homeostasis. In addition to being an important endogenous antioxidant, GSH is also critical for the maintenance of bile acid-independent bile flow. While it has been well-established that synthetic oleanane triterpenoids pharmacologically activate Nrf2, their effects on bile flow and hepatic cytoprotective capacity have not been fully explored. 2. The present studies were conducted to evaluate the effects of a compound in this class, CDDO-9,11-dihydro-trifluoroethyl amide (CDDO-dhTFEA), on these parameters. CDDO-dhTFEA at 3, 10 or 30 mg/kg was orally administered to bile duct-cannulated rats once daily for 7 days, with bile collected 5 h after each dose for 1 h. Livers were harvested after the final bile collection for the evaluation of histology and Nrf2 targets. 3. CDDO-dhTFEA did not affect liver histology. CDDO-dhTFEA markedly and dose-dependently increased bile flow, as well as the biliary excretion of GSH, cholesterol and phospholipids without affecting biliary excretion of bile acids. This was accompanied by dose-dependent increases in mRNA expression and/or enzyme activity of a broad panel of cytoprotective Nrf2 target genes, including NAD(P)H quinone oxidoreductase 1 (Nqo1), thioredoxin reductase (Txnrd), sulfiredoxin 1(Srxn1), glutamate cysteine ligase catalytic and modifier subunits (Gclc and Gclm), glutathione reductase (Gsr), gamma-glutamyl transpeptidase 1 (Ggt1), heme oxygenase-1 (Ho-1) and epoxide hydrolase-1 (Eh-1). 4. These data further demonstrate the important hepatobiliary attributes of oleanane synthetic triterpenoids and support their continued investigation for liver diseases.
Calnexin Phosphorylation Attenuates the Release of Partially Misfolded α1-Antitrypsin to the Secretory Pathway (2009)

Calnexin is a type I integral membrane phosphoprotein resident of the endoplasmic reticulum. Its intraluminal domain has been deduced to function as a lectin chaperone coordinating the timing of folding of newly synthesized N-linked glycoproteins of the secretory pathway. Its C-terminal cytosolic oriented extension has an ERK1 phosphorylation site at Ser(563) affecting calnexin association with the translocon. Here we find an additional function for calnexin phosphorylation at Ser(563) in endoplasmic reticulum quality control. A low dose of the misfolding agent l-azetidine 2-carboxylic acid slows glycoprotein maturation and diminishes the extent and rate of secretion of newly synthesized secretory alpha1-antitrypsin. Under these conditions the phosphorylation of calnexin is enhanced at Ser(563). Inhibition of this phosphorylation by the MEK1 inhibitor PD98059 enhanced the extent and rate of alpha1-antitrypsin secretion comparable with that achieved by inhibiting alpha-mannosidase activity with kifunensine. This is the first report in which the phosphorylation of calnexin is linked to the efficiency of secretion of a cargo glycoprotein.
T‐cell survival (1998)

Like other cells, T cells are dependent on signals from their environment for their survival. Resting T cells are supported in vitro by cytokines such as interleukin (IL)-4, IL-6 and IL-7. The latter two cytokines are made constitutively in animals and hence might affect the lifetimes of their resting T cells. Resting T cells are also kept alive by interaction with an as yet unidentified molecule on the surface of other cells. Activated T cells are also supported in vitro by members of two families of these proteins, the IL-2 family and the interferon-alpha beta family. Members of the latter family may have effects on activated cells in vivo. Thus although both resting and activated T cells require signals to keep themselves alive, the signals are different for the two types of cells. This perhaps allows the immune response to control the numbers of activated cells during infections without compromising its pool of precursor, resting T cells.
The Effects of interferons on the Activity of α -Glycerolphosphate Dehydrogenase in Benign Prostatic Hyperplasia Cells in Primary Culture (1987)

Human benign prostatic hyperplasia (BPH) tissues were obtained from patients undergoing transurethral resection of the prostate and viable cells from these were successfully maintained in primary cultures grown on collagen gel. The prostatic origin of the cells was confirmed by the measurement of prostate specific acid phosphatase and by scanning and transmission electron microscopy before and after immunostaining with human prostate specific antigen-antibody. The cell cultures were treated with various interferons (IFNs), both in the presence and absence of testosterone propionate (TP), for 72 hours and the activities of seven enzymes of carbohydrate metabolism were estimated in the cytosolic fraction of the cells. Treatment with TP induced a significant decrease in the activity of alpha-glycerolphosphate dehydrogenase (alpha-GPDH). Using this enzyme activity as a marker, the effects of various types of IFNs were investigated. IFN-alpha (wellferon) increased the activity of the enzyme both in the presence of one microgram./ml. of TP and in its absence whereas IFN-gamma inhibited the activity under similar conditions. The effect of treatment with IFN-beta in the presence of TP was biphasic in that there was an increase in the activity of the enzyme at the lowest concentration while at higher concentrations an inhibition of enzymic activity was observed. In the absence of TP IFN-beta inhibited the activity. The significance of these findings in terms of the clinical usefulness of IFNs is discussed and it is postulated that IFN-alpha (wellferon) might be effective in the treatment of metastatic carcinoma of the prostate in selected patients.
Reflection properties of pressed polytetrafluoroethylene powder (1981)

The reflection properties of pressed polytetrafluoroethylene powder have been under investigation by the Radiometric Physics Division at the National Bureau of Standards for the past five years. This material has a great potential use, both as a standard of diffuse reflectance and as a coating for integrating spheres for applications in reflectance spectrophotometry and other signal-averaging devices. It possesses certain physical and optical properties that make it ideal for use in these applications. Techniques are given for preparing reflection standards and coating integrating spheres with the pressed powder. The effects of powder density and thickness on its reflectance are reported, and observations of possible problems with fluorescence that are due to the presence of contaminants in the powder are discussed. The absolute reflectance (6°/hemispherical reflectance factor relative to a perfect diffuser) is reported for the spectral range of 200–2500 nm. The directional/hemispherical reflectance factor relative to 6°/hemispherical reflectance is given for several wavelengths in the ultraviolet and visible spectrum and for angles of incidence between 5 and 75°. The bidirectional reflectance factor is reported for 300, 600, and 1500 nm at angles of incidence of −10, −30, −50, and −70° and at viewing angles at 10° intervals from −80 to +80°.
Sinusoidal crossflow microfiltration device—experimental and computational flowfield analysis (2005)

We present an analysis of the flowfield inside a novel crossflow microfiltration device. The filter performance relies on shear focusing by means of a corrugated channel. The flow and shear stress characteristics inside the filter are studied by means of both micro Particle Image Velocimetry (micro-PIV) measurements and Computational Fluid Dynamics (CFD) analysis. We show that an increase of the shear rate by 55-85% as compared to a straight channel geometry is achieved for crossflow velocities ranging from 0.05 m s(-1)-0.8 m s(-1)(Re 5-70). This substantial increase in the local wall shear may improve filter performance in terms of reduced clogging and cell cake formation as compared to conventional crossflow filtration devices. Our current investigation, along with the fact that the filter employs no complex, three dimensional geometrical patterns, advanced pumping schemes, nor has a need for costly assembly and sealing procedures, indicates that the sinusoidal crossflow microfiltration module may serve as a technically and economically feasible solution for integrated lab-on-a-chip devices. Furthermore, the presented approach of shear-focusing may be beneficial in other bio-chemical contexts, such as cell lysis and surface chemistry.