bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetic parameters for the generation of endothelins-1,-2 and -3 by human cathepsin E
Authors: Robinson P S , Lees W E , Kay J , Cook N D
Published: August 2015

The specific conversion of human endothelin (ET) precursors big ET-1, big ET-2 and big ET-3 into their respective ET by cathepsin E was examined. Comparable pH optima were obtained for ET-1 and ET-2 generation, whereas effective conversion of big ET-3 into ET-3 necessitated a lower pH value. Determination of kinetic parameters (Km, kcat.) for all three conversions indicated that the precursors were efficiently bound by cathepsin E. The significance of the values obtained for the catalytic-centre activities and the effect of a specific inhibitor are discussed.
Mutations altering substrate specificity in OHIO-1, and SHV-1 family β-lactamase
Authors: Shlaes D M , Currie-McCumber C
Published: August 2015

The OHIO-1 beta-lactamase does not normally hydrolyse oxyimino-beta-lactam substrates like cefotaxime, ceftriaxone, ceftazidime or aztreonam. We were able to select spontaneous mutants of an OHIO-1-bearing strain of Escherichia coli using the antibiotic substrates listed above by enrichment methods of frequencies of 10(-8)-10(-10) for all antibiotics except ceftazidime (frequency less than 10(-10)). Most mutants with increased resistance to the other beta-lactams were also more resistant to ceftazidime. Mutations identified by DNA sequencing included a Gly238----Ser238 substitution identical with the SHV-2 mutation previously described, cysteine and valine substitutions at the identical site, and a Gly242----Cys242 substitution. The Cys238 and Cys242 mutant enzymes had less affinity for aztreonam than had the other mutant enzymes. Hydrolysis of cefotaxime, but not cephaloridine, by the cysteine-substituted enzymes was inhibited by p-chloromercuribenzoate. The mutant enzymes had, in general, greater affinity for the mechanism-based inhibitors sulbactam, clavulanic acid and tazobactam. These results suggest two non-mutually exclusive hypotheses for the structural role of substitutions in this area of the enzyme. Either potential hydrogen-bond donors, such as serine and cysteine, interact directly with the beta-lactam molecules, or the steric bulk of these substitutions distorts the beta-pleated sheet such that the beta-lactam is held in a position favourable for stable binding and catalysis. Finally, our data raise questions about a strategy relying on oligonucleotide-probe technology to detect such mutations, because of the variety of substitutions that give rise to similar phenotypes.
The isolation and characterization of high-density-lipoprotein subfractions containing apolipoprotein E from human plasma
Authors: Wilson H M , Griffin B A , Watt C , Skinner E R
Published: August 2015

1. Plasma high-density lipoprotein (HDL) was separated by heparin-Sepharose affinity chromatography into a non-bound, apolipoprotein E-poor, and a bound, apolipoprotein E-rich, fraction through the binding effect of Mn2+ in the column buffer. 2. The application of a series of elution buffers in which the concentration of Mn2+ was progressively replaced by Mg2+ resulted in the separation of the bound HDL into five subfractions. 3. Each subfraction migrated a different distance on gradient-gel electrophoresis. Three of the subfractions had RF (relative migration compared with BSA) values within the range of HDL2b. One subfraction contained largely HDL2a, with some material in the regions of HDL2b and HDL3a, and one subfraction spanned the RF regions of HDL2a, HDL3a and HDL3b. 4. The number of molecules, per HDL particle, of cholesteryl ester, non-esterified cholesterol and phospholipid increased with particle size, whereas triacylglycerol passed through a maximum and the number of amino acid residues remained approximately the same. 5. Apolipoprotein (apo) A-I was the major apoprotein in all five subfractions, but the latter differed appreciably in their contents of apo A-II and apo E. 6. The major fatty acid component of each subfraction was linoleic acid, with moderate amounts of C16:0 and C18:1 fatty acids and a smaller content of C18:0, C20:4,n-6 and C22:6,n-3, with no significant difference in composition between the subfractions. 7. This paper provides the first description of a method for the isolation of three subfractions of HDL2b together with other subfractions in quantities that are sufficient for further analytical or metabolic studies.
Characterization of the interaction both in vitro and in vivo of tissue-type plasminogen activator (t-PA) with rat liver cells. Effects of monoclonal antibodies to t-PA
Authors: Otter M , Kuiper J , Bos R , Rijken D C , van Berkel T J
Published: August 2015

The interaction of 125I-labelled tissue-type plasminogen activator (125I-t-PA) with freshly isolated rat parenchymal and endothelial liver cells was studied. Binding experiments at 4 degrees C with parenchymal cells and endothelial liver cells indicated the presence of 68,000 and 44,000 high-affinity t-PA-binding sites, with an apparent Kd of 3.5 and 4 nM respectively. Association of 125I-t-PA with parenchymal cells was Ca(2+)-dependent and was not influenced by asialofetuin, a known ligand for the galactose receptor. Association of 125I-t-PA with liver endothelial cells was Ca(2+)-dependent and mannose-specific, since ovalbumin (a mannose-terminated glycoprotein) inhibited the cell association of t-PA. Association of 125I-t-PA with liver endothelial cells was inhibited by anti-(human mannose receptor) antiserum. Anti-(galactose receptor) IgG had no effect on 125I-t-PA association with either cell type. Degradation of 125I-t-PA at 37 degrees C by both cell types was inhibited by chloroquine or NH4Cl, indicating that t-PA is degraded lysosomally. in vitro experiments with three monoclonal antibodies (MAbs) demonstrated that anti-t-PA MAb 1-3-1 specifically decreased association of 125I-t-PA with the endothelial cells, and anti-t-PA Mab 7-8-4 inhibited association with the parenchymal cells. Results of competition experiments in rats in vivo with these antibodies were in agreement with findings in vitro. Both antibodies decreased the liver uptake of 125I-t-PA, while a combination of the two antibodies was even more effective in reducing the liver association of 125I-t-PA and increasing its plasma half-life. We conclude from these data that clearance of t-PA by the liver is regulated by at least two pathways, one on parenchymal cells (not galactose/mannose-mediated) and another on liver endothelial cells (mediated by a mannose receptor). Results with the MAbs imply that two distinct sites on the t-PA molecule are involved in binding to parenchymal cells and liver endothelial cells.
Gi3 does not contribute to the inhibition of adenylate cyclase when stimulation of an α2-adrenergic receptor causes activation of both Gi2 and Gi3
Authors: McClue S J , Selzer E , Freissmuth M , Milligan G
Published: August 2015

Agonist occupancy of the alpha 2-C10 adrenergic receptor in a stable clone (1C) of Rat 1 fibroblasts produced by transfection of cells with genomic DNA encoding this receptor causes the activation of both of the pertussis-toxin-sensitive G-proteins Gi2 and Gi3 [Milligan, Carr, Gould, Mullaney & Lavan (1991) J. Biol. Chem. 266, 6447-6455]. An IgG fraction from an antiserum (I3B) which identifies the C-terminal decapeptide of Gi3 alpha only was able to inhibit partially receptor stimulation of high-affinity GTPase activity. An equivalent fraction from an antiserum (AS7) able to identify the C-terminal decapeptide of Gi1 alpha + Gi2 alpha, but not Gi3 alpha, was also able to inhibit partially receptor stimulation of GTPase activity, and the effects of the two antisera were additive. By contrast, agonist-mediated inhibition of forskolin-amplified adenylate cyclase activity was abolished completely by the IgG fraction of antiserum AS7, but was not decreased by treatment with antiserum 13B. Based on the proportion of agonist-stimulated high-affinity GTPase which was prevented by each antiserum and on the measured membrane levels of Gi2 and Gi3, calculations indicated that essentially all of the cellular Gi3, but only 15% of the available Gi2, can be activated by the alpha 2-C10 adrenergic receptor in these cells. These results demonstrate that, although Gi3 is activated by alpha 2-adrenergic agonists in membranes of clone 1C cells, it does not contribute to the transduction of receptor-mediated inhibition of adenylate cyclase.
Insulin receptor and epidermal growth factor receptor dephosphorylation by three major rat liver protein-tyrosine phosphatases expressed in a recombinant bacterial system
Authors: Hashimoto N , Zhang W R , Goldstein B J
Published: August 2015

Protein-tyrosine phosphatases (PTPases) play an essential role in the regulation of signal transduction mediated by reversible protein-tyrosine phosphorylation. In order to characterize individual rat hepatic PTPases that might have specificity for autophosphorylated receptor tyrosine kinases, we isolated cDNA segments encoding three PTPases (PTPase 1B, LAR and LRP) that are expressed in insulin-sensitive liver and skeletal muscle tissue, and evaluated their catalytic activity in vitro. The intrinsic PTPase activities of the full-length PTPase 1B protein and the cytoplasmic domains of LAR and LRP were studied by expression of recombinant cDNA constructs in the inducible bacterial vector pKK233-2 using extracts of a host strain of Escherichia coli that lacks endogenous PTPase activity. Each of the cloned cDNAs dephosphorylated a cognate phosphopeptide derived from the regulatory region of the insulin receptor. Despite having only 30-39% sequence identity in their catalytic domains, LAR and PTPase 1B had similar relative activities between the peptide substrate and intact insulin receptors, and also displayed similar initial rates of simultaneous dephosphorylation of insulin and epidermal growth factor (EGF) receptors. In contrast, LRP exhibited a higher rate of dephosphorylation of both intact receptors relative to the peptide substrate, and also dephosphorylated EGF receptors more rapidly than insulin receptors. These studies indicate that three PTPases with markedly divergent structures have the catalytic potential to dephosphorylate both insulin and EGF receptors in intact cells and that redundant PTPase activity may occur in vivo. For these PTPases to have specific physiological actions in intact cells, they must be influenced by steric effects of the additional protein segments of the native transmembrane enzymes, cellular compartmentalization and/or interactions with regulatory proteins.
Leukoregulin down-regulates type I collagen mRNA levels and promoter activity in human dermal fibroblasts, and counteracts the up-regulation elicited by transforming growth factor-β
Authors: Mauviel A , Evans C H , Uitto J
Published: August 2015

Leukoregulin (LR), a T-cell-derived growth factor, modulates fibroblast functions in vitro [Mauviel, Rédini, Hartmann, Loyau & Pujol (1991) J. Cell Biol. 113, 1455-1462]. In the present study, incubation of human dermal fibroblasts with LR (0.1-2 units/ml) resulted in decreases in the mRNA steady-state levels for alpha 1(I), alpha 2(I) and alpha 1(III), but not alpha 2(V), collagen genes. LR also down-regulated alpha 2(I) collagen promoter activity in transient cell transfections of control cells as well as those incubated with transforming growth factor-beta, a potent up-regulator of collagen type I gene expression. Thus LR is a strong inhibitor of type I collagen gene expression, acting at the level of transcription.
Okadaic acid, an inhibitor of protein phosphatases 1 and 2A, inhibits induction of acute-phase proteins by interleukin-6 alone or in combination with interleukin-1 in human hepatoma cell lines
Authors: Ganapathi M K
Published: August 2015

Okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, inhibited in a dose-dependent manner (5-20 nM) the induction of C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen by interleukin-6 (IL-6) plus interleukin-1 (IL-1), and of fibrinogen by IL-6 alone, in Hep 3B cells. Induction of alpha 1-proteinase inhibitor (alpha 1-PI) by IL-6 plus IL-1 or IL-6 alone was not significantly affected by OA up to concentrations of 20 nM, above which concentration OA was toxic in Hep 3B cells. OA also inhibited the induction of CRP, fibrinogen and alpha 1-PI by IL-6 in the NPLC/PRF/5 cell line, albeit at a higher concentration (80 nM). These results suggest that the signal transduction mechanisms regulating induction of acute-phase proteins by IL-6, either alone or in combination with IL-1, are mediated by activation of protein phosphatases 1 and/or 2A.
Release and fixation of CO2 by guinea-pig kidney tubules metabolizing aspartate
Authors: Martin G , Michoudet C , Vincent N , Baverel G
Published: August 2015

1. The metabolism of L-[U-14C]aspartate, L-[1-14C]aspartate and L-[4-14C]aspartate was studied in isolated guinea-pig kidney tubules. 2. Oxidation of C-1 plus that of C-4 of aspartate accounted for 90-92% of the CO2 released from aspartate, whereas oxidation of the inner carbon atoms of aspartate (which occurs beyond the 2-oxoglutarate dehydrogenase step) represented only 8-10% of aspartate carbon oxidation. 3. The formation of [1-14C]glutamine and [1-14C]glutamate from [1-14C]aspartate and [4-14C]aspartate indicated that about one-third of the oxaloacetate synthesized from aspartate underwent randomization at the level of fumarate. 4. With [U-14C]aspartate as substrate, the percentage of the C-1 of glutamate and glutamine found radiolabelled after 60 min of incubation was 92.7% and 47.5% in the absence and the presence of bicarbonate respectively. 5. That CO2 fixation occurred at high rates in the presence of bicarbonate was demonstrated by incubating tubules with aspartate plus [14C]bicarbonate; under this condition, the label fixed was found in C-1 of glutamate, glutamine and aspartate, as well as in C-4 of aspartate, demonstrating not only randomization of aspartate carbon but also aspartate resynthesis secondary to oxaloacetate cycling via phosphoenolpyruvate carboxykinase, pyruvate kinase and pyruvate carboxylase. 6. The importance of CO2 fixation in glutamine synthesis from aspartate is discussed in relation to the possible role of the guinea-pig kidney in systemic acid-base regulation in vivo.
Effect of treatment in vivo of rats with bacterial endotoxin on fructose 2,6-bisphosphate metabolism and L-pyruvate kinase activity and flux in isolated liver cells
Authors: Ceppi E D , Knowles R G , Carpenter K M , Titheradge M A
Published: August 2015

The effect of treatment of rats with bacterial endotoxin on fructose 2,6-bisphosphate (Fru-2,6-P2) metabolism was investigated in isolated liver cells prepared from 18 h-starved animals. The results obtained support the hypothesis that a stimulation of 6-phosphofructo-1-kinase (PFK-1) activity and an inhibition of fructose-1,6-bisphosphatase (Fru-1,6-P2ase) may be one mechanism underlying the inhibition of gluconeogenesis from lactate and pyruvate by endotoxin. We suggest that the stimulation of PFK-1 and inhibition of Fru-1,6-P2ase activity is the result of a 2-3-fold increase in Fru-2,6-P2. The latter is not due to changes in the total activity or phosphorylation state of the bifunctional 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase, but appears to be the result of a decrease in the cytosolic concentration of phosphoenolpyruvate (PEP), an inhibitor of PFK-2 activity. The effect of endotoxin is resistant to the presence of glucagon, which has comparable effects in cells prepared from both control and endotoxin-treated animals. The mechanism by which endotoxin treatment of the rat decreases PEP and gluconeogenesis remains to be established. However, it does not involve alterations in either the total activity or the phosphorylation state of pyruvate kinase, nor does it involve increased flux through this enzyme in the intact cell, which is in fact decreased in this model of septic shock. It is suggested that the decreased flux may result from a lower rate of formation of PEP, suggesting that the prime lesion in sepsis is an inhibition of one or more of the steps leading to PEP formation.
Some properties of murine selenocysteine synthase
Authors: Mizutani T , Kurata H , Yamada K , Totsuka T
Published: August 2015

Selenocysteine (Scy) was synthesized on natural opal suppressor tRNA(Ser) by conversion from seryl-tRNA. We studied the mechanisms of the synthesis of mammalian Scy-tRNA using hydro[75Se]selenide (H75Se-). We found Scy synthase activity in the 105,000 g supernatant of a murine liver extract. The supernatant was chromatographed on DEAE-cellulose, and the activity was eluted at 0.12 M-KCl. The reaction mixture for synthesis of Scy-tRNA contained suppressor tRNA, serine, ATP, seryl-tRNA synthetase (SerRS), HSe- and the enzyme to synthesize Scy-tRNA. These are all essential for the synthesis of Scy-tRNA. Scy in the tRNA product was confirmed by five t.l.c. systems. The conversion from seryl-tRNA to Scy-tRNA was also confirmed with the use of [14C]- and [3H]-serine. The apparent Km values for the substrates serine, tRNA, ATP and HSe- were 30 microM, 140 nM, 2 mM and 40 nM respectively. The active eluates from DEAE-cellulose contained no tRNA kinase. This result showed that Scy-tRNA was not synthesized through phosphoseryl-tRNA. ATP was necessary when Scy-tRNA was synthesized from seryl-tRNA and HSe-. Therefore ATP is used for not only the synthesis of seryl-tRNA but also for the synthesis of Scy-tRNA from seryl-tRNA. The active fraction from DEAE-cellulose was chromatographed on Sephacryl S-300, but the activity disappeared. However, the activity was recovered by mixing the eluates corresponding to proteins of 500 kDa and 20 kDa. In order to examine the binding of HSe- to proteins, a mixture of the active fraction, H75Se- and ATP was analysed by chromatography on Sephacryl S-300. The 75Se radioactivity was found at the position of a 20 kDa protein in the presence of ATP. Thus the 20 kDa protein plays a role in binding HSe- in the presence of ATP. The 500 kDa protein must have a role in the synthesis of Scy-tRNA. There are two natural suppressor serine tRNAs, tRNA(NCA) and tRNA(CmCA), in cell cytosol. The present paper shows that the suppressor tRNA fraction, eluted later on benzoylated DEAE-(BD-)cellulose, is a better substrate with which to synthesize Scy-tRNA. Thus we consider that murine Scy-tRNA is synthesized from a suppressor seryl-tRNA on the 500 kDa protein with the activated HSe-, which is synthesized with ATP on the 20 kDa protein. This mammalian mechanism used to synthesize Scy is similar to that seen in Escherichia coli.
Epitope mapping reveals conserved regions of an auxin-binding protein
Authors: Napier R M , Venis M A
Published: August 2015

There is now good evidence that maize (Zea mays) auxin-binding protein (ABP) functions as a receptor. We have synthesized sequential overlapping hexapeptides to map the epitopes recognized by a number of antisera to ABP. Only a few regions of the protein are recognized, and these are shown to be exposed on the surface. Three epitopes predominate, and these are clustered around, but do not include, the glycosylation site. A comparison is made between these maps of sera against purified ABP, maps of sera raised against recombinant maize ABP expressed in Escherichia coli and computer antigenicity predictions. Our anti-(maize ABP) serum recognizes ABP counterparts in other plant species. We have used immunoblotting to affinity-purify the immunoglobulins which cross-react from the antiserum. Epitope mapping of these immunoglobulins suggests that two of the three predominant epitopes may be conserved in both monocotyledonous and dicotyledonous plants. The possible functional significance of these conserved epitopes is discussed.
Purification and partial identification of bone-inducing protein from a murine osteosarcoma
Authors: Ito Y
Published: August 2015

A highly purified fraction with bone-inducing potential was obtained from a murine osteosarcoma using initial fractionation, gel filtration on Sephacryl S-200, and cation-exchange, hydroxyapatite and reverse-phase h.p.l.c. Protein sequencing of the sample derived from this active fraction revealed the N-terminal amino acid sequence to be Ala-Ala-Leu-Arg-Pro-Leu-Val-Lys-Pro, which is identical to the N-terminal sequence of mouse, human and rat ribosomal protein L32, except for an additional methionine residue at the N-terminus of the three latter proteins. Amino acid analysis of the sample also showed its similarity to L32. Two lines of evidence using an antibody specific for the above peptide strongly suggest that this L32-related protein from a murine osteosarcoma has the potential to induce ectopic bone formation. First, the protein specifically detected by the antibody co-distributes with the bone-inducing active fraction. Secondly, a highly purified sample obtained using the antibody was shown to induce the formation of bone with active haematopoiesis.
Direct demonstration that increased phosphorylation of 3-hydroxy-3-methylglutaryl-CoA reductase does not increase its rate of degradation in isolated rat hepatocytes
Authors: Zammit V A , Caldwell A M
Published: August 2015

Increased phosphorylation of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase has been suggested to target the protein towards an increased rate of degradation. Our previous observations [Zammit & Caldwell (1990) Biochem. J. 269, 373-379] suggested that, although Ca(2+)-mobilizing hormones and other effectors can alter both the phosphorylation state of the enzyme and its total activity in isolated rat hepatocytes, there appears to be no causal correlation between the two parameters. In the present paper we set out to make direct measurements of the specific rate of degradation of 35S-labelled HMG-CoA reductase in hepatocytes treated with agents that produced very marked and prolonged increases in the degree of phosphorylation of the protein, through different mechanisms. Okadaic acid (which inhibits phosphatases 1 and 2A), fructose (which increases cellular AMP through its metabolism to fructose 1-phosphate) and the Ca2+ ionophore A23187 (which also raises cellular AMP through an unknown mechanism) were all unable to alter the rate of HMG-CoA reductase degradation. We conclude that the basal rate of degradation of HMG-CoA reductase is unaffected by its phosphorylation state and that a transiently increased degree of phosphorylation cannot be the mechanism through which mevalonate increases the rate of degradation of the enzyme in rat hepatocytes and other cell types.
G-protein-mediated activation of turkey erythrocyte phospholipase C by β-adrenergic and P2y-purinergic receptors
Authors: Vaziri C , Downes C P
Published: August 2015

Isoprenaline, previously known only to stimulate adenylate cyclase via the stimulatory G-protein, Gs, activates turkey erythrocyte ghost phospholipase C (PLC) in a dose-dependent manner when GTP or guanosine 5′-[gamma-thio]triphosphate (GTP[S]) is present. The effect is specific in that it is abolished by beta-adrenergic-receptor antagonists. Stimulation of adenosine receptors, which also couple to adenylate cyclase via Gs in turkey erythrocytes, does not activate PLC, indicating that the stimulation observed in the presence of isoprenaline is not due to Gs activation. Furthermore, the stimulation seen is independent of cyclic AMP production. Purified turkey erythrocyte PLC is activated in an adenosine 5′-[beta-thio]diphosphate (ADP[S]; a P2y-purinergic-receptor agonist)- or isoprenaline-regulated manner when reconstituted with turkey erythrocyte ghosts, demonstrating that a single species of PLC effector enzyme can be regulated by both the purinergic and the beta-adrenergic receptor populations present in turkey erythrocyte membranes. Pretreatment of intact turkey erythrocytes with the P2y agonist ADP[S] causes decreased PLC responsiveness of subsequent ghost preparations to ADP[S] stimulation, although responses to isoprenaline are unaffected (homologous desensitization). In contrast, pretreatment of intact erythrocytes with isoprenaline results in heterologous desensitization of both the P2y and the beta-adrenergic receptors. These effects occur at the level of receptor-G-protein coupling, since PLC stimulation by GTP[S] (which directly activates G-proteins) in the absence of agonists is unaffected.
Entwicklung und Periodizität humaner Expositionen in suizidaler Absicht im Einzugsbereich des Giftnotrufs Erfurt von 2004–2013
Authors: Hentschel H. , Prasa D. , Frimlova G. , Just S. , Liebetrau G. , Plenert B. , Stürzebecher A. , Deters M.
Published: August 2015

Ziel der Studie: Expositionen in suizidaler Absicht stellen besondere Anforderungen an Krankenhäuser und Giftinformationszentren. Deswegen wurden die zeitlichen Charakteristika ihrer Häufigkeit studiert.

Methodik: Retrospektive Analyse aller humanen Expositionen von Anfang 2004 bis Ende 2013 im Einzugsbereich des Giftnotrufs Erfurt nach Häufigkeit nach Jahren, Jahreszeiten, Monaten, Wochentagen, Tageszeiten sowie nach Expositionsumständen, Altersgruppen und Geschlecht.

Ergebnisse: 59,7% aller Expositionen (n=137 104) waren akzidentell, 23,4% in suizidaler und 3,3% in missbräuchlicher Absicht. 0,3% der Suizidversuche verliefen tödlich. Während die absolute Häufigkeit der Suizidversuche von 2 422 im Jahre 2004 auf 3 458 im Jahr 2013 anstieg, blieb die relative Häufigkeit konstant bei 23,4%. Die absolute Häufigkeit der Suizidversuche war am höchsten im Frühjahr und Sommer. Suizidversuche wurden am häufigsten im Juli und August und am seltensten im Februar und September beobachtet. Die meisten Suizidversuche wurden sonntags bis dienstags und die wenigsten freitags registriert. Die Tagesspitze der Suizidversuche wurde um 22 Uhr erreicht und der Tiefpunkt um 6 Uhr. Der Altersmedian war 39 Jahre (1. Quartil 24 Jahre, 3. Quartil 50 Jahre). Der Frauenanteil war fast doppelt so hoch wie der Männeranteil.

Schlussfolgerung: Kliniken im Einzugsbereich des Giftnotrufs Erfurt sollten im Frühjahr und Sommer, insbesondere im Juli und August, am Wochenanfang und kurz vor Mitternacht besonders auf Vergiftungsfälle in suizidaler Absicht vorbereitet sein.
Reduced entropic model for studies of multidimensional nonlocal transport in high-energy-density plasmas
Authors: Del Sorbo D. , Feugeas J.-L. , Nicolaï Ph. , Olazabal-Loumé M. , Dubroca B. , Guisset S. , Touati M. , Tikhonchuk V.
Published: August 2015

Hydrodynamic simulations of high-energy-density plasmas require a detailed description of energy fluxes. For low and intermediate atomic number materials, the leading mechanism is the electron transport, which may be a nonlocal phenomenon requiring a kinetic modeling. In this paper, we present and test the results of a nonlocal model based on the first angular moments of a simplified Fokker-Planck equation. This multidimensional model is closed thanks to an entropic relation (the Boltzman H-theorem). It provides a better description of the electron distribution function, thus enabling studies of small scale kinetic effects within the hydrodynamic framework. Examples of instabilities of electron plasma and ion-acoustic waves, driven by the heat flux, are presented and compared with the classical formula.
Flow of two immiscible fluids in a periodically constricted tube: Transitions to stratified, segmented, churn, spray, or segregated flow
Authors: Fraggedakis D. , Kouris Ch. , Dimakopoulos Y. , Tsamopoulos J.
Published: August 2015

We study the flow of two immiscible, Newtonian fluids in a periodically constricted tube driven by a constant pressure gradient. Our volume-of-fluid algorithm is used to solve the governing equations. First, the code is validated by comparing its predictions to previously reported results for stratified and pulsing flow. Then, it is used to capture accurately all the significant topological changes that take place. Initially, the fluids have a core-annular arrangement, which is found to either remain the same or change to a different arrangement depending on the fluid properties, the pressure driving the flow, or the flow geometry. The flow-patterns that appear are the core-annular, segmented, churn, spray, and segregated flow. The predicted scalings near pinching of the core fluid concur with similarity predictions and earlier numerical results [I. Cohen et al., “Two fluid drop snap-off problem: Experiments and theory,” Phys. Rev. Lett. 83, 1147–1150 (1999)]. Flow-pattern maps are constructed in terms of the Reynolds and Weber numbers. Our result provides deeper insights into the mechanism of the pattern transitions and is in agreement with previous studies on core-annular flow [Ch. Kouris and J. Tsamopoulos, “Core-annular flow in a periodically constricted circular tube, I. Steady state, linear stability and energy analysis,” J. Fluid Mech. 432, 31–68 (2001) and Ch. Kouris et al., “Comparison of spectral and finite element methods applied to the study of interfacial instabilities of the core-annular flow in an undulating tube,” Int. J. Numer. Methods Fluids 39(1), 41–73 (2002)], segmented flow [E. Lac and J. D. Sherwood, “Motion of a drop along the centreline of a capillary in a pressure-driven flow,” J. Fluid Mech. 640, 27–54 (2009)], and churn flow [R. Y. Bai et al., “Lubricated pipelining—Stability of core annular-flow. 5. Experiments and comparison with theory,” J. Fluid Mech. 240, 97–132 (1992)].
A novel parameter to describe the glass-forming ability of alloys
Authors: Park E. S. , Ryu C. W. , Kim W. T. , Kim D. H.
Published: August 2015

In this paper, we propose a new parameter for glass-forming ability (GFA) based on the combination of thermodynamic (stability of stable and metastable liquids by ΔTm = Tmmix − Tl and ΔTx = Tx − Tg, respectively) and kinetic (resistance to crystallization by Tx) aspects for glass formation. The parameter is defined as ε = (ΔTm + ΔTx + Tx)/Tmmix without directly adding Tg while considering the whole temperature range for glass formation up to Tmmix, which reflects the relative position of crystallization curve in continuous cooling transformation diagram. The relationship between the ε parameter and critical cooling rate (Rc) or maximum section thickness for glass formation (Zmax) clearly confirms that the ε parameter exhibits a better correlation with GFA than other commonly used GFA parameters, such as ΔTx (=Tx − Tg), K (=[Tx − Tg]/[Tl − Tx]), ΔT*(=(Tmmix − Tl)/Tmmix), Trg (=Tg/Tl), and γ (=[Tx]/[Tl + Tg]). The relationship between the ε parameter and Rc or Zmax is also formulated and evaluated in the study. The results suggest that the ε parameter can effectively predict Rc and Zmax for various glass-forming alloys, which would permit more widespread uses of these paradigm-shifting materials in a variety of industries.
Three-dimensional flow around two circular cylinders of different diameters in a close proximity
Authors: Thapa Jitendra , Zhao Ming , Cheng Liang , Zhou Tongming
Published: August 2015

Flow past two cylinders of different diameters in close proximity is simulated numerically for a constant diameter ratio of 0.45, a gap ratio of 0.0625, and a Reynolds number of 1000 (defined using the diameter of the main cylinder). The effect of the position angle α of the small cylinder relative to the large one on force coefficients and wake flow patterns are studied. Depending on the position angle α of the small cylinder, four wake flow modes are identified: the upstream interference mode for α = 0°, 22.5°, and 45°, the intermittent attached gap flow mode for α = 67.5° and 90°, the attached gap flow mode for α = 112.5° and 135°, and the wake interference mode for α = 157.5° and 180°. The RMS lift coefficients of both cylinders are reduced significantly compared with that of a single cylinder, regardless of the position angle of the small cylinder. Although the variation trends of the mean drag and lift coefficients with the position angle of the small cylinder obtained from the two-dimensional (2D) and three-dimensional (3D) simulations are similar, the 2D simulations overestimate the mean drag coefficient, the RMS drag and lift coefficients compared with those obtained from the 3D simulations.
Experimental investigations of the initial growth of flow asymmetries over a slender body of revolution at high angles of attack
Authors: Zhu Yiding , Yuan Huijing , Lee Cunbiao
Published: August 2015

This paper describes an experimental investigation of the initial growth of flow asymmetries over a slender body of revolution at high angles of attack with natural and disturbed noses. Time-resolved particle image velocimetry was used to investigate the flow field around the body. The experimental results show that initially different amplitudes of unsteady disturbances near the tip are established owing to the tip imperfections. These unsteady disturbances experience a super-exponential growth near the tip and continue to grow exponentially due to linear instabilities. Attachment of a piece to the tip brings a larger initial difference and extends the super-exponential growth region. Thus, the disturbance amplitudes and their differences are larger for the disturbed case than for the natural case before reaching the neutral point of linear instability. The amplified disturbances lead to different instability vortex strengths in the separated shear layers, which feed continuously into the two primary concentrated vortices. As a result, the primary vortex strengths differ, which result in the initial vortex asymmetry. The experiment results demonstrate that the initial flow asymmetry arises from an asymmetric development of the boundary layer instability.
Midplane neutral density profiles in the National Spherical Torus Experiment
Authors: Stotler D. P. , Scotti F. , Bell R. E. , Diallo A. , LeBlanc B. P. , Podestà M. , Roquemore A. L. , Ross P. W.
Published: August 2015

Atomic and molecular density data in the outer midplane of NSTX [Ono et al., Nucl. Fusion 40, 557 (2000)] are inferred from tangential camera data via a forward modeling procedure using the DEGAS 2 Monte Carlo neutral transport code. The observed Balmer-β light emission data from 17 shots during the 2010 NSTX campaign display no obvious trends with discharge parameters such as the divertor Balmer-α emission level or edge deuterium ion density. Simulations of 12 time slices in 7 of these discharges produce molecular densities near the vacuum vessel wall of 2–8 × 1017 m−3 and atomic densities ranging from 1 to 7 × 1016 m−3; neither has a clear correlation with other parameters. Validation of the technique, begun in an earlier publication, is continued with an assessment of the sensitivity of the simulated camera image and neutral densities to uncertainties in the data input to the model. The simulated camera image is sensitive to the plasma profiles and virtually nothing else. The neutral densities at the vessel wall depend most strongly on the spatial distribution of the source; simulations with a localized neutral source yield densities within a factor of two of the baseline, uniform source, case. The uncertainties in the neutral densities associated with other model inputs and assumptions are ≤50%.
Parametric study of a Schamel equation for low-frequency dust acoustic waves in dusty electronegative plasmas
Authors: Sabetkar Akbar , Dorranian Davoud
Published: August 2015

In this paper, our attention is first concentrated on obliquely propagating properties of low-frequency (ω ≪ ωcd) “fast” and “slow” dust acoustic waves, in the linear regime, in dusty electronegative plasmas with Maxwellian electrons, kappa distributed positive ions, negative ions (following the combination of kappa-Schamel distribution), and negatively charged dust particles. So, an explicit expression for dispersion relation is derived by linearizing a set of dust-fluid equations. The results show that wave frequency ω in long and short-wavelengths limit is conspicuously affected by physical parameters, namely, positive to negative temperature ion ratio (βp), trapping parameter of negative ions (μ), magnitude of the magnetic field B0 (via ωcd), superthermal index (κn,κp), and positive ion to dust density ratio (δp). The signature of the penultimate parameter (i.e., κn) on wave frequency reveals that the frequency gap between the modes reduces (escalates) for kkcr), where kcr is critical wave number. Alternatively, for weakly nonlinear analysis, reductive perturbation theory has been used to construct 1D and 3D Schamel Korteweg-de Vries (S-KdV) equations, whose nonlinearity coefficient prescribes only compressive soliton for all parameter values of interest. The survey manifests that deviation of ions from Maxwellian behavior leads intrinsic properties of solitary waves to be evolved in opposite trend. Additionally, at lower proportion of trapped negative ions, solitary wave amplitude mitigates, whilst the trapping parameter has no effect on both spatial width and the linear wave. The results are discussed in the context of the Earth's mesosphere of dusty electronegative plasma.
Ions lost on their first orbit can impact Alfvén eigenmode stability
Authors: Heidbrink W. W. , Fu Guo-Yong , Van Zeeland M. A.
Published: August 2015

Some neutral-beam ions are deflected onto loss orbits by Alfvén eigenmodes on their first bounce orbit. The resonance condition for these ions differs from the usual resonance condition for a confined fast ion. Estimates indicate that particles on single-pass loss orbits transfer enough energy to the wave to alter mode stability.
Thermodynamics of Yukawa fluids near the one-component-plasma limit
Authors: Khrapak Sergey A. , Semenov Igor L. , Couëdel Lénaïc , Thomas Hubertus M.
Published: August 2015

Thermodynamics of weakly screened (near the one-component-plasma limit) Yukawa fluids in two and three dimensions is analyzed in detail. It is shown that the thermal component of the excess internal energy of these fluids, when expressed in terms of the properly normalized coupling strength, exhibits the scaling pertinent to the corresponding one-component-plasma limit (the scalings differ considerably between the two- and three-dimensional situations). This provides us with a simple and accurate practical tool to estimate thermodynamic properties of weakly screened Yukawa fluids. Particular attention is paid to the two-dimensional fluids, for which several important thermodynamic quantities are calculated to illustrate the application of the approach.
First-principles study on phase transition and ferroelectricity in lithium niobate and tantalate
Authors: Toyoura Kazuaki , Ohta Masataka , Nakamura Atsutomo , Matsunaga Katsuyuki
Published: August 2015

The phase transitions and ferroelectricity of LiNbO3 and LiTaO3 have been investigated theoretically from first principles. The phonon analyses and the molecular dynamics simulations revealed that the ferroelectric phase transition is not conventional displacive type but order-disorder type with strong correlation between cation displacements. According to the evaluated potential energy surfaces around the paraelectric structures, the large difference in ferroelectricity between the two oxides results from the little difference in short-range interionic interaction between Nb-O and Ta-O. As the results of the crystal orbital overlap population analyses, the different short-range interaction originates from the difference in covalency between Nb4d-O2p and Ta5d-O2p orbitals, particularly dxz-px/dyz-py orbitals (π orbitals), from the electronic point of view.
Stability and ergodicity of moon billiards
Authors: Correia Maria F. , Zhang Hong-Kun
Published: August 2015

We construct a two-parameter family of moon-shaped billiard tables with boundary made of two circular arcs. These tables fail the defocusing mechanism and other known mechanisms that guarantee ergodicity and hyperbolicity. We analytically study the stability of some periodic orbits and prove there is a class of billiards in this family with elliptic periodic orbits. These moon billiards can be viewed as generalization of annular billiards, which all have Kolmogorov-Arnold-Moser islands. However, the novelty of this paper is that by varying the parameters, we numerically observe a subclass of moon-shaped billiards with a single ergodic component.
Note: Coherent resonances observed in the dissociative electron attachment to carbon monoxide
Authors: Wang Xu-Dong , Xuan Chuan-Jin , Luo Yi , Tian Shan Xi
Published: August 2015

Succeeding our previous finding about coherent interference of the resonant states of CO− formed by the low-energy electron attachment [Tian et al. Phys. Rev. A 88, 012708 (2013)], here we provide further evidence of the coherent interference. The completely backward distributions of the O− fragment of the temporary CO− are observed with anion velocity map imaging technique in an electron energy range of 11.3–12.6 eV and explained as the results of the coherent interferences of three resonant states. Furthermore, the state configuration of the interference is changed with the increase of electron attachment energy.
Small-molecule–directed, efficient generation of retinal pigment epithelium from human pluripotent stem cells
Authors: Maruotti Julien , Sripathi Srinivas R. , Bharti Kapil , Fuller John , Wahlin Karl J. , Ranganathan Vinod , Sluch Valentin M. , Berlinicke Cynthia A. , Davis Janine , Kim Catherine , Zhao Lijun , Wan Jun , Qian Jiang , Corneo Barbara , Temple Sally , Dubey Ramin , Olenyuk Bogdan Z. , Bhutto Imran , Lutty Gerard A. , Zack Donald J.
Published: August 2015

Significance

Cell-based approaches utilizing retinal pigment epithelial (RPE)-like cells derived from human pluripotent stem cells (hPSCs) are being developed for the treatment of retinal degeneration. In most research published to date, the choice of the factors used to induce RPE differentiation is based on data from developmental studies. Here, we developed an unbiased approach directed at identifying novel RPE differentiation-promoting factors using a high-throughput quantitative PCR screen complemented by a novel orthogonal human induced pluripotent stem cell (hiPSC)-based RPE reporter assay. We identified chetomin, a dimeric epidithiodiketopiperazine, as a strong inducer of RPE; combination with nicotinamide resulted in efficient RPE differentiation. Single passage of the whole culture yielded a highly pure hPSC-RPE cell population that displayed many of the morphological, molecular, and functional characteristics of native RPE.
Computational design and experimental verification of a symmetric protein homodimer
Authors: Mou Yun , Huang Po-Ssu , Hsu Fang-Ciao , Huang Shing-Jong , Mayo Stephen L.
Published: August 2015

Significance

Computational protein design tools use a bottom-up approach that allows for the testing of hypotheses on the relationships between amino acid sequence, protein structure and stability, and biological function. Here, we exploited two computational methods, protein docking and protein sequence optimization, to create a favorable protein–protein interaction between two identical proteins, resulting in a novel homodimer. A stepwise approach proved useful: scaffold stabilization followed by interface design to achieve homodimerization. Our results suggest that for some proteins, stabilization may be required for the successful design of functionality.
The spinor genus of the integral trace
Authors: Mantilla-Soler Guillermo
Published: August 2015

Let

K
K

be a number field of degree at least

3
3

. In this article we show that the genus of the integral trace form of

K
K

contains only one spinor genus. Additionally we show that exactly

43
43%

(resp.

29
29%

, resp.

58
58%

) of quadratic (resp. real quadratic, resp. imaginary quadratic) fields have the same property.
Single-cell analysis of circadian dynamics in tissue explants
Authors: Lande-Diner Laura , Stewart-Ornstein Jacob , Weitz Charles J. , Lahav Galit
Published: August 2015

Tracking molecular dynamics in single cells in vivo is instrumental to understanding how cells act and interact in tissues. Current tissue imaging approaches focus on short-term observation and typically nonendogenous or implanted samples. Here we develop an experimental and computational setup that allows for single-cell tracking of a transcriptional reporter over a period of >1 wk in the context of an intact tissue. We focus on the peripheral circadian clock as a model system and measure the circadian signaling of hundreds of cells from two tissues. The circadian clock is an autonomous oscillator whose behavior is well described in isolated cells, but in situ analysis of circadian signaling in single cells of peripheral tissues is as-yet uncharacterized. Our approach allowed us to investigate the oscillatory properties of individual clocks, determine how these properties are maintained among different cells, and assess how they compare to the population rhythm. These experiments, using a wide-field microscope, a previously generated reporter mouse, and custom software to track cells over days, suggest how many signaling pathways might be quantitatively characterized in explant models.
Blood Pressure Levels at the Time of Percutaneous Coronary Revascularization and Risk of Coronary In-Stent Restenosis
Authors: Tocci Giuliano , Barbato Emanuele , Coluccia Roberta , Modestino Anna , Pagliaro Beniamino , Mastromarino Vittoria , Giovannelli Francesca , Berni Andrea , Volpe Massimo
Published: August 2015

BACKGROUND

High blood pressure (BP) levels expose patients treated with percutaneous coronary interventions (PCI) to very high risk of 10-year cardiovascular morbidity and mortality.

OBJECTIVE

To investigate the role of BP levels at the time of PCI on the risk of in-stent restenosis (ISR).

METHODS

We retrospectively included 796 patients previously treated with PCI, who underwent repeated angiography for recurrent angina or reversible myocardial ischemia. Patients were stratified into either case ( n = 354) and control ( n = 442) groups in the presence or absence of ISR (defined as in-stent diameter stenosis ≥50%). BP levels were measured at the time of first and second procedures. Normal BP levels were defined for <140/90mm Hg.

RESULTS

Patients with normal BP showed significantly higher ISR-free survival (Log-rank: 5.937; P = 0.015). Both systolic (HR (95% CI): 0.731 (0.590–0.906)) and systolic/diastolic BP (HR (95% CI): 0.757 (0.611–0.939)) were significantly and independently associated with lower risk of ISR at Cox-regression analysis, adjusted for potential confounding factors, including stent type and concomitant medications. Patients with ISR showed lower rates of normal systolic/diastolic BP values (166 (47%) vs. 254 (57%); P = 0.003) compared to controls. They also received higher stent number (1.40±0.74 vs. 1.24±0.51; P < 0.001) with higher stent length (24.3±15.6 vs. 21.7±13.9mm; P = 0.012), and lower rate of drug-eluting stents (DESs) (210 (48%) vs. 139 (40%); P = 0.025) compared to controls.

CONCLUSIONS

Normal BP at the time of PCI is associated with nearly 24% risk reduction of ISR as evaluated in a new angiography in patients with coronary artery disease.