cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Changing Residue 338 in Human Factor IX from Arginine to Alanine Causes an Increase in Catalytic Activity
Creators: name: Straight, David L.
name: Lollar, Pete
name: Chang, Jinli
name: Bode, Wolfram
name: Jin, Jianping
name: Hamaguchi, Nobuko
name: Stafford, Darrel W.
name: Brandstetter, Hans
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1998

description: This study was designed to identify functionally important factor IX (FIX) residues. Using recombinant techniques and cell culture, we produced a mutant FIX with arginine at 338 changed to alanine (R338A-FIX). This molecule had approximately 3 times greater clotting activity than that of wild type FIX (wt-FIX) in the activated partial thromboplastin assay. R338A-FIX reacted normally with a panel of three FIX specific monoclonal antibodies and migrated on sodium dodecyl sulfate-polyacrylamide gels indistinguishably from wt-FIX. Using functional assays, we determined that R338A-FIXa's Kd for factor VIIIa (FVIIIa) was similar to that of wt-FIXa. Our kinetic analysis, using factor X as substrate, indicated that the mutation's major effects were a 3-fold increase in kcat and a 2-fold decrease in Km both manifested only in the presence of FVIIIa. R338A-FIXa's increased catalytic efficiency did not result from ablation of a thrombin sensitive site, reported to occur at arginine 338, since in our assays the thrombin inhibitor, hirudin, had no effect on activity of either wt-FIXa or R338A-FIXa. R338A-FIXa and wt-FIXa had equal activity, with or without FVIIIa, toward the synthetic substrate, methylsulfonyl-D-cyclohexylglycyl-arginine-p-nitroanilide. Interestingly, R338A-FIXa had reduced affinity for heparin. Therefore, we propose that R338A-FIXa's increased activity is not due to an allosteric effect on the active site, but that the Arg-338 residue is part of an exosite that binds both factor X and the mucopolysaccharide, heparin.
Implementation of quantum logic gates using coupled Bose-Einstein condensates
Creators: name: Luiz, F. S.
name: Duzzioni, E. I.
name: Sanz, L.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Quantum Physics (quant-ph)
subject: FOS: Physical sciences

description: In this work, we are interested on the implementation of single-qubit gates on coupled Bose-Einstein condensates (BECs). The system, a feasible candidate for a qubit, consists on condensed atoms of different hyperfine levels coupled by a two-photon transition. It is well established that the dynamics of coupled BECs can be described by the two-mode Hamiltonian which takes into account the confinement potential of the trap and the effects of collisions associated with each condensate. Other effects, as collisions between atoms belonging to different BECs and detuning are included in this approach. We demonstrate how to implement two types of quantum logic gates: \textit{transfer-population} gates (NOT, $\hat{Y}$, and Hadamard), which require inversion of population between hyperfine levels, and \textit{phase} gates ($\hat{Z}$, $\hat{S}$, and $\hat{T}$), which require self-trapping. We also discuss the experimental feasibility, checking the robustness of quantum gates against variations of physical parameters out of the ideal conditions for implementation of each quantum logic gate.
(1954) Joseph Sharp
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
Data and Methods from Metabolic rates, climate and macroevolution: a case study using Neogene molluscs.
Creators: name: Strotz, Luke C.
name: Saupe, Erin E.
name: Kimmig, Julien
name: Lieberman, Bruce S.
Publisher: name: The Royal Society
Year: 2018
Subjects: subject: Physiology
subject: FOS: Biological sciences
subject: Evolutionary Biology
subject: 40308 Palaeontology (incl. Palynology)
subject: FOS: Earth and related environmental sciences

description: Basal metabolic rate (BMR) is posited to be a fundamental control on the structure and dynamics of ecological networks, influencing organism resource use and rates of senescence. Differences in the maintenance energy requirements of individual species therefore potentially predict extinction likelihood. If validated, this would comprise an important link between organismic ecology and macroevolutionary dynamics. To test this hypothesis, the BMRs of organisms within fossil species were determined using body size and temperature data, and considered in the light of species' survival and extinction through time. Our analysis focused on the high-resolution record of Pliocene to recent molluscs (bivalves and gastropods) from the Western Atlantic. Species-specific BMRs were calculated by measuring the size range of specimens from museum collections, determining ocean temperature using the HadCM3 global climate model, and deriving values based on relevant equations. Intriguingly, a statistically significant difference in metabolic rate exists between those bivalve and gastropod taxa that went extinct and those that survived throughout the course of the Neogene. This indicates that there is a scaling up from organismic properties to species survival for these communities. Metabolic rate could therefore represent an important metric for predicting future extinction patterns, with changes in global climate potentially affecting the lifespan of individuals, ultimately leading to the extinction of the species they are contained within. We also find that, at the assemblage level, there are no significant differences in metabolic rates for different time intervals throughout the entire study period. This may suggest that Neogene mollusc communities have remained energetically stable, despite many extinctions.
Cortactin-Src Kinase Signaling Pathway Is Involved in N-syndecan-dependent Neurite Outgrowth
Creators: name: Kinnunen, Tarja
name: Kaksonen, Marko
name: Peng, H. Benjamin
name: Saarinen, Juhani
name: Kalkkinen, Nisse
name: Rauvala, Heikki
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1998

description: N-syndecan (syndecan-3) was previously isolated as a cell surface receptor for heparin-binding growth-associated molecule (HB-GAM) and suggested to mediate the neurite growth-promoting signal from cell matrix-bound HB-GAM to the cytoskeleton of neurites. However, it is unclear whether N-syndecan would possess independent signaling capacity in neurite growth or in related cell differentiation phenomena. In the present study, we have transfected N18 neuroblastoma cells with a rat N-syndecan cDNA and show that N-syndecan transfection clearly enhances HB-GAM-dependent neurite growth and that the transfected N-syndecan distributes to the growth cones and the filopodia of the neurites. The N-syndecan-dependent neurite outgrowth is inhibited by the tyrosine kinase inhibitors herbimycin A and PP1. Biochemical studies show that a kinase activity, together with its substrate(s), binds specifically to the cytosolic moiety of N-syndecan immobilized to an affinity column. Western blotting reveals both c-Src and Fyn in the active fractions. In addition, cortactin, tubulin, and a 30-kDa protein are identified in the kinase-active fractions that bind to the cytosolic moiety of N-syndecan. Ligation of N-syndecan in the transfected cells by HB-GAM increases phosphorylation of c-Src and cortactin. We suggest that N-syndecan binds a protein complex containing Src family tyrosine kinases and their substrates and that N-syndecan acts as a neurite outgrowth receptor via the Src kinase-cortactin pathway.
Coronal mass ejections from the same active region cluster: Two different perspectives
Creators: name: Cremades, H.
name: Mandrini, C. H.
name: Schmieder, B.
name: Crescitelli, A. M.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Solar and Stellar Astrophysics (astro-ph.SR)
subject: FOS: Physical sciences

description: The cluster formed by active regions (ARs) NOAA 11121 and 11123, approximately located on the solar central meridian on 11 November 2010, is of great scientific interest. This complex was the site of violent flux emergence and the source of a series of Earth-directed events on the same day. The onset of the events was nearly simultaneously observed by the Atmospheric Imaging Assembly (AIA) telescope aboard the Solar Dynamics Observatory (SDO) and the Extreme-Ultraviolet Imagers (EUVI) on the Sun-Earth Connection Coronal and Heliospheric Investigation (SECCHI) suite of telescopes onboard the Solar-Terrestrial Relations Observatory (STEREO) twin spacecraft. The progression of these events in the low corona was tracked by the Large Angle Spectroscopic Coronagraphs (LASCO) onboard the Solar and Heliospheric Observatory (SOHO) and the SECCHI/COR coronagraphs on STEREO. SDO and SOHO imagers provided data from the Earth's perspective, whilst the STEREO twin instruments procured images from the orthogonal directions. This spatial configuration of spacecraft allowed optimum simultaneous observations of the AR cluster and the coronal mass ejections that originated in it. Quadrature coronal observations provided by STEREO revealed a notably large amount of ejective events compared to those detected from Earth's perspective. Furthermore, joint observations by SDO/AIA and STEREO/SECCHI EUVI of the source region indicate that all events classified by GOES as X-ray flares had an ejective coronal counterpart in quadrature observations. These results have direct impact on current space weather forecasting because of the probable missing alarms when there is a lack of solar observations in a view direction perpendicular to the Sun-Earth line.
description: Solar Physics - Accepted for publication 2015-Apr-25 v2: Corrected metadata
Crystal Structure of Monoclonal 6B5 Fab Complexed with Phencyclidine
Creators: name: Arnold, Larry
name: Linthicum, D. Scott
name: Lim, Kap
name: Sacchettini, James C.
name: Owens, S. Michael
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1998

description: The crystal structure of monoclonal antibody (mAb) 6B5 Fab fragment complexed with 1-(1-phenylcyclohexyl)piperidine (PCP or phencyclidine) was determined at 2.2-A resolution. 6B5 was originally produced from a mouse immunized with a phencyclidine analogue hapten 5-[N-(1'phenylcyclohexyl)amino]pentanoic acid conjugated to bovine serum albumin. This mAb was selected for further study because of its high affinity (Kd = 2 x 10(-9) M/liter) for PCP and usefulness in reversing PCP-induced central nervous system toxicity in laboratory animals. The dominant feature of the 6B5 Fab.PCP complex is the deep binding site and hydrophobic nature of the interaction. The ligand binding pocket of 6B5 Fab has numerous aromatic side chains, as compared with other known Fab structures. The most notable feature of the binding site is a Trp at position 97H (H-chain), and the side chain of this residue appears to act as a hydrophobic umbrella on the ligand in the antigen binding pocket. There are only two other known Fabs found with a Trp at the 97H position in complementarity determining region (CDR) H3, but they do not play a major role in the interaction with their respective antigens; in both Fab TE33 and R6.5 the Trp 97H side chain is positioned away from the bound antigen. Comparison of the CDR residues of 6B5 with other Fab structures with similar CDR sizes and amino acid compositions reveals a number of important patterns of residue substitutions that appear to be critical for specific PCP ligand interactions.
A machine learning-based classification approach for phase diagram prediction
Creators: name: Deffrennes, Guillaume
name: Terayama, Kei
name: Abe, Taichi
name: Tamura, Ryo
Publisher: name: arXiv
Year: 2022
Subjects: subject: Materials Science (cond-mat.mtrl-sci)
subject: Computational Physics (physics.comp-ph)
subject: FOS: Physical sciences

description: Knowledge of phase diagrams is essential for material design as it helps in understanding microstructure evolution during processing. The determination of phase diagrams is thus one of the central tasks in materials science. When exploring new materials for which the phase diagram is unknown, experimentalists often try to determine the key experiments that should be performed by referencing known phase diagrams of similar systems. To enhance this practical strategy, we attempted to estimate unknown phase diagrams based on known phase diagrams using a machine learning-based classification approach. As a proof of concept, we focused on predicting the number of coexisting phases across the 800 K isothermal section of each of the 10 ternaries of the Al-Cu-Mg-Si-Zn system from the other 9 sections. To increase the prediction accuracy, we introduced new descriptors generated from the thermodynamic properties of the elements and CALPHAD extrapolations from lower-order systems. Using the random forest method, the presence of single-, two-, and three-phase domains was predicted with an average accuracy of 84% across all 10 considered sections with a standard deviation of 11%. The proposed approach represents a promising tool for assisting the investigator in developing new materials and determining phase equilibria efficiently.
description: Manuscript: 29 pages (double-spaced), 6 figures. Supplementary notes: 19 pages, 13 figures
(1950) George Buchanan
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
(1947) Mary [Harris]
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
(1948) William Harris
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
Normas e Rotinas do Serviço de Enfermagem: Cuidados em Feridas e Curativos
Creators: name: Martins, Leila Cristina da Silva
name: Miranda, Karol do socorro Pereira de
name: Meireles, Elizandra Silva de carvalho de
name: Santos, Kariny Veiga dos
Publisher: name: Zenodo
Year: 2023

description: Normas e Rotinas do Serviço de Enfermagem: Cuidados em Feridas e Curativos do Hospital Geral de Mosqueiro
Figure S2 from Metabolic rates, climate and macroevolution: a case study using Neogene molluscs.
Creators: name: Strotz, Luke C.
name: Saupe, Erin E.
name: Kimmig, Julien
name: Lieberman, Bruce S.
Publisher: name: The Royal Society
Year: 2018
Subjects: subject: Physiology
subject: FOS: Biological sciences
subject: Evolutionary Biology
subject: 40308 Palaeontology (incl. Palynology)
subject: FOS: Earth and related environmental sciences

description: Sample-size-based rarefaction (solid line) and extrapolation (dashed lines) of Western Atlantic bivalve and gastropod species richness (q= 0) for each of five separate time bins (early Pliocene, late Pliocene, early Pleistocene, middle Pleistocene, late Pleistocene). Reference sample for each sampling interval is indicated by a solid dot. Shaded areas equal rarefaction confidence intervals. For a fixed sample size, where confidence intervals for Hill number rarefaction/extrapolation do not overlap, significant difference (at a level of 5%) is guaranteed.
(1949) Mary Harris
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
Normas e Rotinas do Serviço de Enfermagem: Cuidados em Feridas e Curativos
Creators: name: Martins, Leila Cristina da Silva
name: Miranda, Karol do socorro Pereira de
name: Meireles, Elizandra Silva de carvalho de
Publisher: name: Zenodo
Year: 2023

description: Normas e Rotinas do Serviço de Enfermagem: Cuidados em Feridas e Curativos do Hospital Geral de Mosqueiro
Figure S1 from Metabolic rates, climate and macroevolution: a case study using Neogene molluscs.
Creators: name: Strotz, Luke C.
name: Saupe, Erin E.
name: Kimmig, Julien
name: Lieberman, Bruce S.
Publisher: name: The Royal Society
Year: 2018
Subjects: subject: Physiology
subject: FOS: Biological sciences
subject: Evolutionary Biology
subject: 40308 Palaeontology (incl. Palynology)
subject: FOS: Earth and related environmental sciences

description: Plot of Bspecies versus latitude for Neogene Western Atlantic bivalve and gastropod specimens. R2 for bivalves = 0.0021. R2 for gastropods = 0.0143. These results indicate negligible correlation between BMR and latitude.
Cyclic Peptides as Non-carboxyl-terminal Ligands of Syntrophin PDZ Domains
Creators: name: Kurakin, Alexei
name: Kay, Brian K.
name: Gee, Stephen H.
name: Froehner, Stanley C.
name: Sekely, Stacy A.
name: Lombardo, Christian
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1998

description: Syntrophins, a family of intracellular peripheral membrane proteins of the dystrophin-associated protein complex (DAPC), each contain a single PDZ domain. Syntrophin PDZ domains bind C-terminal peptide sequences with the consensus R/K-E-S/T-X-V-COOH, an interaction that mediates association of skeletal muscle sodium channels with the DAPC. Here, we have isolated cyclic peptide ligands for syntrophin PDZ domains from a library of combinatorial peptides displayed at the N terminus of protein III of bacteriophage M13. Affinity selection from a library of X10C peptides yielded ligands with the consensus X-(R/K)-E-T-C-L/M-A-G-X-Psi-C, where Psi represents any hydrophobic amino acid. These peptides contain residues (underlined) similar to the C-terminal consensus sequence for binding to syntrophin PDZ domains and bind to the same site on syntrophin PDZ domains as C-terminal peptides, but do not bind to other closely related PDZ domains. PDZ binding is dependent on the formation of an intramolecular disulfide bond in the peptides, since treatment with dithiothreitol, or substitution of either of the two cysteines with alanines, eliminated this activity. Furthermore, amino acid replacements revealed that most residues in the phage-selected peptides are required for binding. Our results define a new mode of binding to PDZ domains and suggest that proteins containing similar conformationally constrained sequences may be ligands for PDZ domains.
Data and Methods from Metabolic rates, climate and macroevolution: a case study using Neogene molluscs
Creators: name: Strotz, Luke C.
name: Saupe, Erin E.
name: Kimmig, Julien
name: Lieberman, Bruce S.
Publisher: name: The Royal Society
Year: 2018
Subjects: subject: Physiology
subject: FOS: Biological sciences
subject: Evolutionary Biology
subject: 40308 Palaeontology (incl. Palynology)
subject: FOS: Earth and related environmental sciences

description: Basal metabolic rate (BMR) is posited to be a fundamental control on the structure and dynamics of ecological networks, influencing organism resource use and rates of senescence. Differences in the maintenance energy requirements of individual species therefore potentially predict extinction likelihood. If validated, this would comprise an important link between organismic ecology and macroevolutionary dynamics. To test this hypothesis, the BMRs of organisms within fossil species were determined using body size and temperature data, and considered in the light of species' survival and extinction through time. Our analysis focused on the high-resolution record of Pliocene to recent molluscs (bivalves and gastropods) from the Western Atlantic. Species-specific BMRs were calculated by measuring the size range of specimens from museum collections, determining ocean temperature using the HadCM3 global climate model, and deriving values based on relevant equations. Intriguingly, a statistically significant difference in metabolic rate exists between those bivalve and gastropod taxa that went extinct and those that survived throughout the course of the Neogene. This indicates that there is a scaling up from organismic properties to species survival for these communities. Metabolic rate could therefore represent an important metric for predicting future extinction patterns, with changes in global climate potentially affecting the lifespan of individuals, ultimately leading to the extinction of the species they are contained within. We also find that, at the assemblage level, there are no significant differences in metabolic rates for different time intervals throughout the entire study period. This may suggest that Neogene mollusc communities have remained energetically stable, despite many extinctions.
(1945) Elizabeth Abbot
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
Cystic Fibrosis Transmembrane Regulator-independent Release of ATP: ITS IMPLICATIONS FOR THE REGULATION OF P2Y2RECEPTORS IN AIRWAY EPITHELIA
Creators: name: Boucher, Richard C.
name: Lazarowski, Eduardo R.
name: Watt, William C.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1998

description: The cystic fibrosis (CF) transmembrane regulator (CFTR) is a cyclic AMP-dependent Cl- channel that is defective in CF cells. It has been hypothesized that CFTR exhibits an ATP release function that controls the airway surface ATP concentrations. In airway epithelial cells, CFTR-independent Ca2+-activated Cl- conductance is regulated by the P2Y2 receptor. Thus, ATP may function as an autocrine signaling factor promoting Cl- secretion in normal but not CF epithelia if ATP release is defective. We have tested for CFTR-dependent ATP release using four independent detection systems. First, a luciferase assay detected no differences in ATP concentrations in the medium from control versus cyclic AMP-stimulated primary normal human nasal epithelial (HNE) cells. A marked accumulation of extracellular ATP resulted from mechanical stimulation effected by a medium displacement. Second, high pressure liquid chromatography analysis of 3H-labeled species released from [3H]adenine-loaded HNE cells revealed no differences between basal and cyclic AMP-stimulated cells. Mechanical stimulation of HNE cells again resulted in enhanced accumulation of extracellular [3H]ATP and [3H]ADP. Third, when measuring ATP concentrations via nucleoside diphosphokinase-catalyzed phosphorylation of [alpha-33P]dADP, equivalent formation of [33P]dATP was observed in the media of control and cyclic AMP-stimulated HNE cells and nasal epithelial cells from wild-type and CF mice. Mechanically stimulated [33P]dATP formation was similar in both cell types. Fourth, 1321N1 cells stably expressing the human P2Y2 receptor were used as a reporter system for detection of ATP via P2Y2 receptor-promoted formation of [3H]inositol phosphates. Basal [3H]inositol phosphate accumulation was of the same magnitude in control and CFTR-transduced cells, and no change was observed following addition of forskolin and isoproterenol. In both cell types, mechanical stimulation resulted in hexokinase-attenuable [3H]inositol phosphate formation. In summary, our data suggest that ATP release may be triggered by mechanical stimulation of cell surfaces. No evidence was found supporting a role for CFTR in the release of ATP.
Appunti sulla Biblioteca Warburg (1934)
Creators: name: Gertrud Bing, Giulia Zanon
Publisher: name: La Rivista di Engramma
Year: 2023
Subjects: The Warburg Institute
The Warburg Library
Gertrud Bing

description: In this text, written in the aftermath of the arrival of the Warburg Library in London, Assistant Director Gertrud Bing describes simply but fully the genesis, history, structure, mission, and meaning of the library conceived by Aby Warburg.
Differential Expression and Biological Effects of Insulin-like Growth Factor-binding Protein-4 and -5 in Vascular Smooth Muscle Cells
Creators: name: Duan, Cunming
name: Clemmons, David R.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1998

description: Insulin-like growth factor-I (IGF-I) plays an important role in regulating vascular smooth muscle cell (VSMC) proliferation, migration, and apoptosis. The bioactivity of IGF-I is modulated by a group of high affinity, specific binding proteins (IGF-binding proteins; IGFBPs) that are present in the interstitial fluid. Previously, we have reported that porcine VSMCs synthesize and secrete IGF-I and several forms of IGFBPs, including IGFBP-2, IGFBP-4, and IGFBP-5. In this study, we examined the role of autocrine/paracrine secreted IGF-I in controlling the expression of IGFBP-4 and IGFBP-5 as well as the effects of these IGFBPs in modulating the cellular replication response to IGF-I. The concentrations of IGFBP-4 in the conditioned medium increased significantly from <50 ng/ml to 742 +/- 105 ng/ml. This increase was associated with a decrease in the activity of an IGF-I-regulated IGFBP-4 protease. In contrast, the synthesis of IGFBP-5 was inversely correlated with culture density, and its concentration decreased from 792 +/- 91 to 44 +/- 14 ng/ml. IGFBP-5 mRNA in sparse cultures was 3-fold higher compared with those in confluent cultures. This culture density-dependent change in IGFBP-5 mRNA correlated closely with endogenous IGF-I levels. Since treatment of VSMC with exogenous IGF-I increased IGFBP-5 mRNA levels, we neutralized the effect of endogenously secreted IGF-I with an anti-IGF-I antibody to determine if it would alter IGFBP-5 mRNA abundance. This resulted in a 4.4-fold decrease in IGFBP-5 mRNA levels. When added together with IGF-I, exogenous IGFBP-4 inhibited IGF-I-induced DNA synthesis in a concentration-dependent manner. IGFBP-5, on the other hand, potentiated the effect of IGF-I. Therefore, IGFBP-4 and IGFBP-5 appear to be differentially regulated by autocrine/paracrine IGF-I through distinct mechanisms. These two proteins, in turn, play opposing roles in modulating IGF-I action in stimulating VSMC proliferation.
Direct Association of Protein-tyrosine Phosphatase PTP-PEST with Paxillin
Creators: name: Cloutier, Jean François
name: Shen, Yu
name: Schaller, Michael D.
name: Veillette, André
name: Schneider, Galen
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1998

description: Tyrosine phosphorylation of focal adhesion-associated proteins may be involved in the regulation of the cytoskeleton and in the control of signals for growth and survival. The focal adhesion kinase (FAK) functions in regulating tyrosine phosphorylation of several of these proteins, including paxillin, tensin, and p130(cas). Protein- tyrosine phosphatases, the counterparts of protein-tyrosine kinases, also presumably regulate phosphorylation of these proteins. We have tested the hypothesis that FAK intimately associates with a protein-tyrosine phosphatase. Protein-tyrosine phosphatase activity associated with the recombinant C-terminal domain of FAK in vitro and could be coimmunoprecipitated with both FAK and paxillin from lysates of chicken embryo cells. However, the interaction with FAK appeared to be indirect and mediated via paxillin. The protein-tyrosine phosphatase was subsequently identified as protein-tyrosine phosphatase-PEST, a nonreceptor protein-tyrosine phosphatase. The C-terminal noncatalytic domain of protein-tyrosine phosphatase-PEST directly bound to paxillin in vitro. The association of both a protein-tyrosine kinase and a protein-tyrosine phosphatase with paxillin suggests that paxillin may play a critical role in the regulation of the phosphotyrosine content of proteins in focal adhesions.
(1946) William Harris
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
Distinct Mechanisms Mediate the Initial and Sustained Phases of Integrin-mediated Activation of the Raf/MEK/Mitogen-activated Protein Kinase Cascade
Creators: name: Howe, Alan K.
name: Juliano, Rudy L.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1998

description: Integrin-mediated adhesion to the extracellular matrix activates the canonical mitogen-activated protein kinase cascade, although the exact mechanism is not fully resolved. We show that integrin-mediated activation of Raf-1, an upstream regulator of mitogen-activated protein kinase, occurs in two phases. Efficient early activation of Raf required Raf-Ras interaction but was not affected by protein kinase C (PKC) inhibitors, while a lower, sustained level of activity was independent of Raf-Ras interaction but was reduced by PKC inhibitors. The combination of PKC inhibition and lack of Ras binding completely blocked integrin-mediated Raf activity. The activity of a membrane-bound Raf mutant that is deficient in Ras binding (Raf-R89L-CAAX) was also regulated by adhesion. Raf-R89L-CAAX activity was low in nonadherent cells, was rapidly stimulated to wild-type levels by cell adhesion, and remained at nearly maximal levels longer than wild-type activity. The activation of wild-type and mutant Raf proteins was ablated by cytochalasin D, demonstrating that cytoskeletal organization is required for activation of Raf, even when targeted to the membrane. These data suggest distinct initial and sustained phases of integrin-mediated Raf activation that require Raf membrane localization and possibly PKC activity, respectively, and that integrin-mediated adhesion may regulate a cytoskeleton-associated factor(s) responsible for Raf activation.
Two Timers? Endogenous and Exogenous Alerting Types in an Intuitive Temporal Cueing Task
Creators: name: Redden, Ralph S.
name: Klein, Raymond M
name: McCormick, Colin R
Publisher: name: Open Science Framework
Year: 2023
Subjects: subject: Social and Behavioral Sciences

description: Data and code for manuscript " 'How does exogenous alerting impact endogenous preparation on a temporal cueing task''
Enhanced Binding of Altered H-NS Protein to Flagellar Rotor Protein FliG Causes Increased Flagellar Rotational Speed and Hypermotility in Escherichia coli
Creators: name: Donato, Gina M.
name: Kawula, Thomas H.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1998

description: H-NS is an Escherichia coli nucleoid protein known only to function as a modulator of gene expression. In this study, we found that specific single amino acid substitutions in H-NS caused an approximately 50% increase in flagellum rotational speed. In fluorescence anisotropy and chemical cross-linking assays, H-NS interacted with the flagellar torque-generating rotor protein FliG to form a complex with a Kd of 2.15 microM. Furthermore, one of the altered H-NS proteins that exhibited high speed flagellum rotation bound FliG 50% tighter than wild-type H-NS. These results demonstrate the first non-regulatory role for H-NS and provide a direct correlation between H-NS-FliG binding affinities, flagellar rotation, and motor torque generation.
Evidence for Dinucleotide Flipping by DNA Photolyase
Creators: name: Vande Berg, Brian J.
name: Sancar, Gwendolyn B.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1998

description: DNA photolyases repair pyrimidine dimers via a reaction in which light energy drives electron donation from a catalytic chromophore, FADH-, to the dimer. The crystal structure of Escherichia coli photolyase suggested that the pyrimidine dimer is flipped out of the DNA helix and into a cavity that leads from the surface of the enzyme to FADH-. We have tested this model using the Saccharomyces cerevisiae Phr1 photolyase which is >50% identical to E. coli photolyase over the region comprising the DNA binding domain. By using the bacterial photolyase as a starting point, we modeled the region encompassing amino acids 383-530 of the yeast enzyme. The model retained the cavity leading to FADH- as well as the band of positive electrostatic potential which defines the DNA binding surface. We found that alanine substitution mutations at sites within the cavity reduced both substrate binding and discrimination, providing direct support for the dinucleotide flip model. The roles of three residues predicted to interact with DNA flanking the dimer were also tested. Arg452 was found to be particularly critical to substrate binding, discrimination, and photolysis, suggesting a role in establishing or maintaining the dimer in the flipped state. A structural model for photolyase-dimer interaction is presented.
Non-equilibrium vibrational and electron energy distributions functions in atmospheric nitrogen ns pulsed discharges and \mus post-discharges: the role of electron molecule vibrational excitation scaling-laws
Creators: name: Colonna, Gianpiero
name: Laporta, Vincenzo
name: Celiberto, Roberto
name: Capitelli, Mario
name: Tennyson, Jonathan
Publisher: name: arXiv
Year: 2015
Subjects: subject: Plasma Physics (physics.plasm-ph)
subject: FOS: Physical sciences

description: The formation of the electron energy distribution function in nanosecond atmospheric nitrogen discharges is investigated by means of self-consistent solution of the chemical kinetics and the Boltzmann equation for free electrons. The post-discharge phase is followed to few microseconds. The model is formulated in order to investigate the role of the cross section set, focusing on the vibrational-excitation by electron-impact through resonant channel. Four different cross section sets are considered, one based on internally consistent vibrational-excitation calculations which extend to the whole vibrational ladder, and the others obtained by applying commonly used scaling-laws.
Evidence That IRS-2 Phosphorylation Is Required for Insulin Action in Hepatocytes
Creators: name: Formisano, Pietro
name: Beguinot, Francesco
name: Rother, Kristina I.
name: Accili, Domenico
name: Caruso, Matilde
name: Imai, Yumi
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1998

description: Insulin receptor substrates (IRSs) are tyrosine-phosphorylated following stimulation with insulin, insulin-like growth factors (IGFs), and interleukins. A key question is whether different IRSs play different roles to mediate insulin's metabolic and growth-promoting effects. In a novel system of insulin receptor-deficient hepatocytes, insulin fails to (i) stimulate glucose phosphorylation, (ii) enhance glycogen synthesis, (iii) suppress glucose production, and (iv) promote mitogenesis. However, insulin's ability to induce IRS-1 and gab-1 phosphorylation and binding to phosphatidylinositol (PI) 3-kinase is unaffected, by virtue of the compensatory actions of IGF-1 receptors. In contrast, phosphorylation of IRS-2 and generation of IRS-2/PI 3-kinase complexes are markedly reduced. Thus, absence of insulin receptors selectively reduces IRS-2, but not IRS-1 phosphorylation, and the impairment of IRS-2 activation is associated with lack of insulin effects. To address whether phosphorylation of additional IRSs is also affected, we analyzed phosphotyrosine-containing proteins in PI 3-kinase immunoprecipitates from insulin-treated cells. However, these experiments indicate that IRS-1 and IRS-2 are the main PI 3-kinase-bound proteins in hepatocytes. These data identify IRS-2 as the main effector of both the metabolic and growth-promoting actions of insulin through PI 3-kinase in hepatocytes, and IRS-1 as the main substrate mediating the mitogenic actions of IGF-1 receptors.
Expression of Interleukin-10 by in Vitro and in Vivo Activated Hepatic Stellate Cells
Creators: name: Ohata, Mitsuru
name: Tsukamoto, Hidekazu
name: Rippe, Richard A.
name: Schrum, Laura
name: Wang, Saixi C.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1998

description: Activated hepatic stellate cells (HSC) participate in matrix remodeling and deposition in liver fibrosis. The present study demonstrates that interleukin (IL)-10 is expressed by HSC upon activation in vitro or in vivo and that autocrine effects of this cytokine include inhibition of collagen production. Culture activation of HSC caused a distinct increase in IL-10 mRNA level compared with freshly isolated quiescent HSC. Treatment of cultured HSC with tumor necrosis factor-alpha, transforming growth factor-beta, or lipopolysaccharide further increased IL-10 mRNA by 2-fold and resulted in the release of IL-10 protein into the medium. HSC isolated from rats after bile duct ligation (BDL) showed prominent increases in IL-10 mRNA (x 100) and protein (x 30) levels at 7 days after BDL, but such induction disappeared in advanced liver fibrosis (19 days after BDL). IL-10 expression correlated positively with mRNA expression of interstitial collagenase and inversely with that of alpha1(I) collagen. Addition of anti-IL-10 IgG to cultured HSC caused enhanced collagen production under a basal or stimulated condition with TGF-beta, tumor necrosis factor-alpha, or lipopolysaccharide. These effects were associated with increased alpha1(I) collagen mRNA and reciprocally reduced collagenase mRNA levels. Co-transfection of HSC with an IL-10 expression vector and collagen reporter genes showed a 40% inhibition of alpha1(I) collagen promoter activity. These results demonstrate that activation of HSC causes enhanced autocrine expression of IL-10 which possesses a negative autoregulatory effect on HSC collagen production mediated at least in part by alpha1(I) collagen transcriptional inhibition and stimulation of collagenase expression. These findings, along with the demonstrated early induction of HSC IL-10 expression and its late disappearance during biliary liver fibrosis, suggest its in vivo role in matrix remodeling and a possibility that failure for HSC to sustain IL-10 expression underlies pathologic progression to liver cirrhosis.
Formation of a DNA Loop at the Replication Fork Generated by Bacteriophage T7 Replication Proteins
Creators: name: Tabor, Stanley
name: Park, Kyusung
name: Griffith, Jack D.
name: Richardson, Charles C.
name: Debyser, Zeger
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1998

description: Intermediates in the replication of circular and linear M13 double-stranded DNA by bacteriophage T7 proteins have been examined by electron microscopy. Synthesis generated double-stranded DNA molecules containing a single replication fork with a linear duplex tail. A complex presumably consisting of T7 DNA polymerase and gene 4 helicase/primase molecules was present at the fork together with a variable amount of single-stranded DNA sequestered by gene 2.5 single-stranded DNA binding protein. Analysis of the length distribution of Okazaki fragments formed at different helicase/primase concentrations was consistent with coupling of leading and lagging strand replication. Fifteen to forty percent of the templates engaged in replication have a DNA loop at the replication fork. The loops are fully double-stranded with an average length of approximately 1 kilobase. Labeling with biotinylated dCTP showed that the loops consist of newly synthesized DNA, and synchronization experiments using a linear template with a G-less cassette demonstrated that the loops are formed by active displacement of the lagging strand. A long standing feature of models for coupled leading/lagging strand replication has been the presence of a DNA loop at the replication fork. This study provides the first direct demonstration of such loops.
Emergence of granular-sized magnetic bubbles through the solar atmosphere. II. Non-LTE chromospheric diagnostics and inversions
Creators: name: Rodríguez, Jaime de la Cruz
name: Hansteen, Viggo
name: Bellot-Rubio, Luis
name: Ortiz, Ada
Publisher: name: arXiv
Year: 2015
Subjects: subject: Solar and Stellar Astrophysics (astro-ph.SR)
subject: FOS: Physical sciences

description: Magnetic flux emergence into the outer layers of the Sun is a fundamental mechanism for releasing energy into the chromosphere and the corona. In this paper, we study the emergence of granular-sized flux concentrations and the structuring of the corresponding physical parameters and atmospheric diagnostics in the upper photo- sphere and in the chromosphere. We make use of a realistic 3D MHD simulation of the outer layers of the Sun to study the formation of the Ca II 8542 line. We also derive semi-empirical 3D models from non-LTE inversions of our observations. These models contain depth-dependent information of the temperature and line-of-sight stratification. Our analysis explains the peculiar Ca II 8542 profiles observed in the flux-emerging region. In addition, we derive detailed temperature and velocity maps describing the ascent of magnetic bubbles from the photosphere to the chromosphere. The inversions suggest that, in active regions, granular-sized bubbles emerge up to the lower chromosphere where the existing large-scale field hinders their ascent. We report hints of heating when the field reaches the chromosphere.
description: Submitted to ApJ, 10 Figures
Spin Model of O2-based Magnet in a Nanoporous Metal Complex
Creators: name: Soda, M.
name: Honma, Y.
name: Takamizawa, S.
name: Ohira-Kawamura, S.
name: Nakajima, K.
name: Masuda, T.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Strongly Correlated Electrons (cond-mat.str-el)
subject: FOS: Physical sciences

description: Inelastic neutron scattering experiments are performed on a nanoporous metal complex Cu-Trans-1,4-Cyclohexanedicarboxylic Acid (Cu-CHD) adsorbing O2 molecules to identify the spin model of the O2-based magnet realized in the host complex. It is found that the magnetic excitations of Cu-CHDs adsorbing low- and high-concentration O2 molecules are explained by different spin models, the former by spin dimers and the latter by spin trimers. By using the obtained parameters and also by assuming that the levels of the higher energy states are reduced because of the non-negligible spin dependence of the molecular potential of oxygen, the magnetization curves are explained in quantitative level.
description: 11 pages, 7 figures
GAS6 Induces Axl-mediated Chemotaxis of Vascular Smooth Muscle Cells
Creators: name: Liu, Edison T.
name: Attar, Eyal C.
name: Villa Jr., Jacy
name: Fridell, Yih Woei C.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1998

description: Atherosclerosis and arterial restenosis are disease processes involving the accumulation of vascular smooth muscle cells following vascular injury. Key events leading to these processes are migration and proliferation of these cells. Here, we demonstrate that GAS6, encoded by the growth arrest-specific gene 6, induces a directed migration (chemotaxis) of both rat and human primary vascular smooth muscle cells while showing only marginal mitogenic potential in human vascular smooth muscle cells. GAS6 stimulation induces Axl autophosphorylation in human vascular smooth muscle cells, indicating that specific GAS6-Axl interactions may be associated with GAS6-directed chemotaxis. To test this hypothesis, vascular smooth muscle cells overexpressing Axl were generated by gene transfer and assessed for their ability to migrate along a GAS6 gradient. These Axl overexpressors exhibited 2-5-fold increased sensitivity to GAS6-induced chemotaxis. Furthermore, vascular smooth muscle cells expressing the kinase dead mutant of Axl or exposure to the soluble Axl extracellular domain showed attenuated GAS6-induced migration. Taken together, these results suggest that GAS6 is a novel chemoattractant that induces Axl-mediated migration of vascular smooth muscle cells. The separation of mitogenesis from migration provided by this study may enhance the molecular dissection of cell migration in vascular damage.