gebhart/patrepeval huggingface dataset:
Pharmacological and Hemodynamic Profile of Nebivolol,* a Chemically Novel, Potent, and Selective β1-Adrenergic Antagonist (1988)

The pharmacological profile of nebivolol (N), a chemically novel beta-adrenergic antagonist, was assessed in investigations on isolated tissues, awake spontaneously hypertensive rats (SHR), closed-chest anesthetized dogs, and humans. In vitro, N was found to be a potent antagonist of beta 1-adrenergic receptors (A2 value, 5.8 X 10(-9) M) and only a weak beta 2-adrenergic antagonist (A2 value, 1.7 X 10(-6) M). The selectivity for the beta 1-adrenergic receptor was higher for N than for any of the reference compounds. In dogs--similarly with atenolol--N was more potent in blocking the isoprenaline (I)-induced increases in left ventricular performance than the I-induced decrease in arterial pressure. In dogs, as compared with propranolol, N (0.025 and 0.01 mg.kg-1 i.v.) increased cardiac output and stroke volume, lowered systemic vascular resistance, and had no significant effect on the variables related to left ventricular contraction. In contrast to other beta-adrenergic antagonists, N acutely lowered arterial blood pressure in SHR (1.25 mg.kg-1 i.p.) and in hypertensive patients (1 oral dose of 5 mg) for several hours. In healthy volunteers N (5 mg) lowered systemic vascular resistance during daily oral treatment and did not negatively affect left ventricular function. In conclusion, N is a potent and selective beta 1-adrenergic blocking agent with an interesting hemodynamic profile. In hypertensive subjects and SHR, a single dose lowers arterial blood pressure for substantial periods of time.
Reversible Conversion of Conducting Polymer Films from Superhydrophobic to Superhydrophilic (2005)

On-again, off-again personality: Superhydrophobic conducting polypyrrole (PPy) films are synthesized through a facile electrochemical process. The PPy films exhibit an extended porous structure with both coarse- and fine-scale roughness (see image). By controlling the electrical potential, PPy films can be switched between the oxidized state and the neutral state, resulting in reversibly switchable superhydrophobic and superhydrophilic properties. Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Blu-Iceand theDistributed Control System: software for data acquisition and instrument control at macromolecular crystallography beamlines (2002)

The Blu-Ice and Distributed Control System (DCS) software packages were developed to provide unified control over the disparate hardware resources available at a macromolecular crystallography beamline. Blu-Ice is a user interface that provides scientific experimenters and beamline support staff with intuitive graphical tools for collecting diffraction data and configuring beamlines for experiments. Blu-Ice communicates with the hardware at a beamline via DCS, an instrument-control and data-acquisition package designed to integrate hardware resources in a highly heterogeneous networked computing environment. Together, Blu-Ice and DCS provide a flexible platform for increasing the ease of use, the level of automation and the remote accessibility of beamlines. Blu-Ice and DCS are currently installed on four Stanford Synchrotron Radiation Laboratory crystallographic beamlines and are being implemented at sister light sources.
Quinap and Congeners: Atropos PN ligands for Asymmetric Catalysis (2014)

Among the range of P,N-chelating ligands that have been employed in asymmetric catalysis, those relying on atropisomerism for the stability of individual enantiomers form a definable class. These APN (atropos P,N) ligands require a specific type of biaryl, with one component carrying a pendant phosphine unit, most commonly diaryl substituted, and the other bearing an sp(2)-nitrogen adjacent to the biaryl link. When substituents in the biaryl inhibit rotation about the linking bond, stable nonracemizing six-membered ring chelates can be formed. This Perspective relates the background to the initial synthesis in 1993 of Quinap, the original member of the series, and initial observations on its effectiveness in asymmetric catalysis. The current state of play in development of syntheses of this and other members of the APN ligand family is assessed, and their applications in asymmetric catalysis are presented. These include hydroboration and diboration of alkenes, 1,3-dipolar cycloadditions, alkynylation of iminium salts in a three-component (A(3)) condensation, and conjugate additions of Cu acetylides.
The absolute number of circulating CD34+ cells predicts the number of hematopoietic stem cells that can be collected by apheresis. (1996)

We report our single institution's effort to standardize the method of collecting peripheral blood progenitor cells (PBPC) used for autologous transplantation. PBPC were mobilized by different types of chemotherapy followed by G-CSF (24 patients) or G-CSF alone (six patients) in 30 patients with various underlying neoplastic diseases. A median of three aphereses (range: 2-7), using the CS3000 cell separator was performed and a blood volume of 101 was processed. We studied the relationship between the absolute numbers of circulating leukocytes, mononuclear cells and CD34+ cells and the amount of PBPC collected during a single apheresis procedure. CD34+ cells were quantified by leukocyte subset analysis based on flow cytometry. Both CFU-GM and CD34+ cell contents of the apheresis products (69 procedures analyzed) correlated strongly: rho = 0.936, P = 0.0001). Regression analysis showed that the total number of CD34+ cells or CFU-GM content of the apheresis products could be predicted (r = 0.915, P = 0.0001) from the absolute number of CD34+ cells in the blood. A number of 10 circulating CD34+ cells per mm3 blood ensured a minimum of 0.5 x 10(6) CD34+ cells per kg, collected on the same day. Of the 30 patients, 17 received an autologous graft that contained only PBPC in 13. Long-term and complete hematological reconstitution was observed in all patients who had a minimum of 2 x 10(6) CD34+ cells per kg reinfused.
Klotho Contributes to Pravastatin Effect on Suppressing IL-6 Production in Endothelial Cells (2016)

Both statins and klotho have been shown to be beneficial in vascular diseases. Interleukin- (IL-) 6 is evidenced as an indicator reflecting the stability of atherosclerotic plaque and involved in the pathogenesis of artery atherosclerosis. However, the relationship between statin, klotho, and IL-6 under an inflammatory environment is unknown. Using primary human umbilical vein endothelial cells (HUVECs), pravastatin dose-dependently induced klotho expression in contrast to remarkable suppression to IL-6 expressions determined by qRT-PCR. Moreover, TNF-α-induced IL-6 was partly but significantly blunted by pravastatin detected by ELISA. To further study the role of klotho in modulating IL-6 expression, endothelial cells with klotho overexpression were treated with TNF-α. Importantly, TNF-α-induced IL-6 production was markedly attenuated in klotho-overexpressed cells. In agreement with in vitro data, a marked reduction of klotho mRNA expression was found in isolated peripheral blood mononuclear cells (PBMCs) from patients with atherosclerosis. Together, these data suggested that pravastatin could suppress IL-6 production via promoting klotho expression in endothelial cells under inflammatory stimuli.
Identification of Lectins in Snake Venoms (1984)

Venoms from 17 species of snakes representing the families Crotalidae, Elapidae and Viperidae were screened for hemagglutination activity. All venoms, with the exception of venom from Bitis arietans, contained an agglutinin which cross-linked trypsin-treated, formaldehyde-fixed erythrocytes. Venom agglutinins from snakes within the same family demonstrated similarities with regard to ligand specificity, requirements for divalent cations and sensitivity to reducing agent. There were few similarities detected for venom agglutinins from snakes belonging to dif- ferent families. Venoms from the family Crotalidae contained calcium-dependent lectins blockable by lactose and sensitive to reducing agent. The only crotalid venom agglutinin insensitive to re- ducing agent was found in the venom of Lachesis muta. Elapid venom agglutinins were calcium- independent and insensitive to reducing agent. The activity of only one of these agglutinins was blockable by lactose. The other three elapid agglutinins were inhibited by heparin. Agglutination activity was weak and variable or non-existent in venoms from snakes in the family Viperidae. Lectins are sugar-binding molecules of non-immune origin with the ability to agglutinate cells. These proteins or glycoproteins require two or more sug- ar-binding sites in order to cross-link cells (Goldstein et al., 1980). Lectin di- valency or polyvalency permits lectin interaction with sugar moieties on ad- jacent cell surfaces, thus resulting in cell agglutination. Some lectins are specific for simple sugars while others interact with complex carbohydrates (Sharon, 1972). The presence of an appropriate, specific sugar in a lectin assay inhibits lectin-mediated cell agglutination. The unbound sugar competes for binding sites on the lectin molecule, making
Theoretical Basis of Protocols for Seed Storage III. Optimum Moisture Contents for Pea Seeds Stored at Different Temperatures (1994)

In previous work, we demonstrated that there was an optimum moisture level for seed storage at a given temperature (Vertucci and Roos, 1990), and suggested, using thermodynamic considerations, that the optimum moisture content increased as the storage temperature decreased (Vertucci and Roos, 1993 b ). In this paper, we present data from a two year study of aging rates in pea ( Pisum sativum ) seeds supporting the hypothesis that the optimum moisture content for storage varies with temperature. Seed viability and vigour were monitored during storage under dark or lighted conditions at relative humidities between 1 and 90%, and temperatures between -5 and 65°C. The optimum moisture content varied from 0·015 g H 2 O g -1 d.wt at 65°C to 0·101 g H 2 O g -1 d.wt at 15°C under dark conditions and from 0·057 at 35°C to 0·092 g H 2 O g -1 d.wt at -5°C under lighted conditions. Our results suggest that optimum moisture contents cannot be considered independently of temperature. This conclusion has important implications for 'ultra-dry' and cryopreservation technologies. Copyright 1994, 1999 Academic Press
Series Introduction: JAK-STAT signaling in human disease (2002)

JAK-STAT signaling in human diseaseCytokines, a large family of extracellular ligands, stimulate biological responses in virtually all cell types.One important subfamily of cytokines, the hematopoietins, evolved largely to regulate host responses to exogenous stresses, especially infection with pathogens.They stimulate these responses by binding to and activating a family of structurally and functionally conserved receptors.As is the case for many types of receptor families, downstream signaling entails tyrosine phosphorylation.However, the activation of the Janus kinases (Jaks) and their downstream signal transducer and activator of transcription (Stat) proteins is both characteristic of and unique to this hematopoietin family.This signaling paradigm first appeared in invertebrates and has continued to grow in complexity through vertebrate and mammalian evolution.There are about 50 members of the hematopoietin family in mammals, and they transduce their signals through four Jaks and seven Stats.Consistent with their identity as ILs, many of these ligands play a critical role in regulating leukocyte maturation and activity.Others regulate more central aspects of cellular homeostasis, reflecting the role Stats play in invertebrates.This Perspective series will provide an overview of the Jak-Stat pathway (reviewed in more detail in refs.1-4) and will explore the important role this pathway plays in regulating immune responses and cellular homeostasis in human health and disease.The series will explore human ailments affected by this pathway, including immunodeficiency, asthma, and cancer.It will also examine the role Stats play in regulating innate immunity and the unique role Stat3 plays in regulating cellular homeostasis.
Borreliacidal activity of early Lyme disease sera against complement-resistant Borrelia afzelii FEM1 wild-type and an OspC-lacking FEM1 variant (2000)

Sera obtained from 14 Lyme borreliosis patients at early stages (stages I and II) of the disease were examined for their borreliacidal properties against Borrelia afzelii isolate FEM1 by use of a growth inhibition assay. Five of 14 immune sera exhibited borreliacidal activity against isolate FEM1. Heat-inactivated immune sera failed to kill the spirochaetes. Immunoblotting experiments with outer-membrane preparations showed that OspC and 11 additional proteins of 14.0, 16.0, 17.7, 19.3, 21.7, 27.5, 32.7, 40.7, 48.9, 51.3 and 53.6 kDa were recognised by borreliacidal immune sera. To analyse the borreliacidal properties of anti-OspC antibodies, two sera (EM4 and EM5), which beside antibodies against a 51.3-kDa protein contained exclusively anti-OspC antibodies, were further investigated by comparative analysis with a FEM1 wild-type and a FEM1 variant lacking OspC in a growth inhibition assay. Only FEM1 wild-type and not variant FEM1OspC(-) was killed by immune sera EM4 and EM5. Complement-dependent killing of FEM1 wild-type was mediated by formation of the terminal complement complex that was found to be attached directly to the outer membrane as confirmed by immuno-electron microscopy. No complement deposition was observed on the surface of variant FEM1OspC(-) after incubation with immune sera EM4 and EM5, thereby suggesting that only anti-OspC antibodies in these two immune sera were responsible for borreliacidal activity. These results provide direct evidence that anti-OspC antibodies, once developed during the immune response, are of critical importance for efficient killing of borreliae in the early phase of infection.
Sonogashira Coupling Using Bulky Palladium-Phenanthryl Imidazolium Carbene Catalysis (2003)

[structure: see text] Bulky phenanthracenyl imidazolium-derived carbene ligands were investigated for copper-free Sonogashira coupling with terminal acetylenes. Aryl bromides and iodides gave coupled products in excellent yields from the Pd(PPh(3))(2)Cl(2) complex with potassium t-butoxide and 18-crown-6 in THF. A remarkable dependence on the size of the ligand was found. The highest yields were obtained with the bulky 2,9-dicyclohexyl-10-phenanthryl ligand 5.
CTLA4Ig PROLONGS ALLOGRAFT SURVIVAL WHILE SUPPRESSING CELL-MEDIATED IMMUNITY (1994)

T cell activation is the result of antigen-specific interactions with the TCR/CD3 complex and costimulation via other T cell surface receptors. Prevention of costimulation can result in clonal anergy. CTLA4Ig is a fusion protein that binds with high-affinity to the B7/BB1 ligand and blocks the interaction of this ligand with CD28 and CTLA4. We explored the immunosuppressive effects of CTLA4Ig in a murine nonvascularized heterotopic cardiac transplant model and in a model of cell mediated immunity. CTLA4Ig administered in vivo for two days at the time of transplantation resulted in significant prolongation of allograft survival (55 +/- 2.0 vs. 12.2 +/- 0.5 days for control, P < 0.03). Administration at later times or to previously primed animals produced no prolongation of graft survival. CTLA4Ig administered during in vivo immunization to the hapten TNP suppressed the contact sensitivity response and inhibited the subsequent in vitro generation of secondary TNP-specific CTL. CTLA4Ig administered in vivo had no effect on subsequent primary alloantigen-specific CTL or MLR responses--however, when added to culture the fusion protein inhibited the MLR response by 80%, but not the alloantigen-specific CTL response. CTLA4Ig inhibited CD4+ and CD8+ proliferative and cytokine responses to alloantigen. Flow cytometry showed no changes in distribution of subpopulations of T cells. These results confirm the immunosuppressive activity of CTLA4Ig in vivo in an allograft model and show that both CD4+ and CD8+ T cells are suppressed by CTLA4Ig. The most efficacious time of administration is during priming of the immune response at the time of antigen presentation.
Nanometer-scale electrochemical deposition of silver on graphite using a scanning tunneling microscope (1992)

Silver pillars, 10–30 nm in diameter and 4–10 nm in height, were generated on graphite surfaces using a scanning tunneling microscope. These structures were produced following the application of tip(+), 6 V×50 μs bias pulses in dilute, aqueous silver fluoride. A pit on the graphite surface is formed during the first 5μs of the pulse, followed by nucleation and electrochemical deposition of silver at this pit. This two-step mechanism allows silver pillars to be located with a high lateral precision on the graphite surface−independent of the proximity of the tip to preexisting nucleation sites such as step edges.
DASD trends: cost, performance, and form factor (1993)

By examining trends in disk technology, performance, reliability, and price and comparing those trends to those of competing technologies, the authors conclude that magnetic disks will be useful for the foreseeable future. Key to the survival of magnetic disks is the use of low-cost logic and memory to enhance the performance and function of the disk subsystem, and rapid adaptation of disk technology to the changing requirements for storage.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Regulation of Maize Leaf Nitrate Reductase Activity Involves Both Gene Expression and Protein Phosphorylation (1994)

Nitrate reductase (NR; EC 1.6.6.1) activity increased at the beginning of the photoperiod in mature green maize (Zea mays L.) leaves as a result of increased enzyme protein level and protein dephosphorylation. In vitro experiments suggested that phosphorylation of maize leaf NR affected sensitivity to Mg2+ inhibition, as shown previously in spinach. When excised leaves were fed 32P-labeled inorganic phosphate, NR was phosphorylated on seryl residues in both the light and dark. Tryptic peptide mapping of NR labeled in vivo indicated three major 32P-phosphopeptide fragments, and labeling of all three was reduced when leaves were illuminated. Maize leaf NR mRNA levels that were low at the end of the dark period peaked within 2 h in the light and decreased thereafter, and NR activity generally remained high. It appears that light signals, rather than an endogenous rhythm, account primarily for diurnal variations in NR mRNA levels. Overall, regulation of NR activity in mature maize leaves in response to light signals appears to involve control of gene expression, enzyme protein synthesis, and reversible protein phosphorylation.
Convolutional Neural Networks for Classification and Segmentation of Medical Images (2017)

Automatic Detection, segmentation and classification of cancer plays an important role in the development of computer-aided diagnosis systems (CADs). This thesis investigates the application of convolutional and fully convolutional neural networks CNN/FCN for automatic detection, segmentation of liver and liver tumor in CT and MRI and classification of tumor malignancy of HCC in DW-MRI.
Abstract 5556: Combining adenosine receptor inhibition with AB928 and chemotherapy results in greater immune activation and tumor control (2018)

Abstract INTRODUCTION: Extracellular adenosine triphosphate (ATP) is efficiently hydrolyzed to adenosine by ecto-nucleotidases CD39 and CD73, which converts adenosine-monophosphate (AMP) into adenosine (ADO). ADO suppresses immune responses including those of T cells, natural killer (NK) cells, and dendritic cells (DC) through activation of A2aR and A2bR receptors. Treatment of cancer cells with platinum-based and anthracycline chemotherapy has been shown to induce immunogenic cell death (ICD), characterized by increased extracellular ATP levels, and upregulation of CD39 and CD73, leading to the enhanced generation of adenosine. METHODS: The ability of AB928 to inhibit adenosine-mediated suppression of immune cell function was assessed using human CD4 and CD8 cells. BALB/c mice were inoculated with AT-3-OVA tumors, which express the model antigen ovalbumin, and subsequently treated with chemotherapy or AB928 alone, or a combination of both. The growth rate and immune composition of the tumors were assessed (flow cytometry). RESULTS: Consistent with the ability of adenosine to suppress immune function, AB928 inhibited the ability of adenosine to suppress CD4 or CD8 T cell activation. Tumor-bearing mice that have been treated with either doxorubicin (DOX, an anthracycline) or oxaliplatin (OX) exhibit increased expression of CD39 and CD73. Established AT-3-OVA tumors treated with AB928 alone had a small but significant decrease in their growth rate; similarly, tumors treated with chemotherapy exhibited a reduction in growth rate. Consistent with the ICD hypothesis, treatment of AT-3-OVA-bearing mice with DOX or OX resulted in an increase in OVA-specific CD8 T cells in the tumor. Concurrent treatment with AB928 and chemotherapy resulted in significantly reduced tumor growth rates, when compared to chemotherapy alone. Analysis of the tumor-infiltrating cell populations showed a significant increase in OVA-specific CD8 T cells, relative to those treated with chemotherapy alone. CONCLUSIONS: Treatment of tumor-bearing mice with a combination of AB928, a dual A2aR and A2bR antagonist, and ICD-inducing chemotherapy results in increased tumor antigen-specific CD8 T cell responses and significantly reduced tumor growth. AB928 is currently undergoing clinical evaluation. Citation Format: Matt J. Walters, Dana Piovesan, Joanne Tan, Daniel DiRenzo, Fangfang Yin, Dillon Miles, Manmohan R. Leleti, Tim Park, Ferdie Soriano, Eshan Sharif, Ulrike Schindler, Jay P. Powers. Combining adenosine receptor inhibition with AB928 and chemotherapy results in greater immune activation and tumor control [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5556.
Inhibitors of the Salicylate Synthase (MbtI) from Mycobacterium tuberculosis Discovered by High‐Throughput Screening (2010)

A simple steady-state kinetic high-throughput assay was developed for the salicylate synthase MbtI from Mycobacterium tuberculosis, which catalyzes the first committed step of mycobactin biosynthesis. The mycobactins are small-molecule iron chelators produced by M. tuberculosis, and their biosynthesis has been identified as a promising target for the development of new antitubercular agents. The assay was miniaturized to a 384-well plate format and high-throughput screening was performed at the National Screening Laboratory for the Regional Centers of Excellence in Biodefense and Emerging Infectious Diseases (NSRB). Three classes of compounds were identified comprising the benzisothiazolones (class I), diarylsulfones (class II), and benzimidazole-2-thiones (class III). Each of these compound series was further pursued to investigate their biochemical mechanism and structure-activity relationships. Benzimidazole-2-thione 4 emerged as the most promising inhibitor owing to its potent reversible inhibition.