Structure and Function of the Splice Variants of TMPRSS2-ERG, a Prevalent Genomic Alteration in Prostate Cancer

Science.gov (United States)

2012-09-01

expression in prostate cancer (4). Lower or no ERG expression in a subset of aggressive tumors with TMPRSS2-ERG fusion may reflect attenuation of androgen...Services University of the Health Sciences, Bethesda MD 20814, USA 2. Cancer Vaccine Development Laboratory, Department of Surgery, United...negative for ERG. The ERG MAb did not show cross reactivity to FLI-1 in LNCaP cells infected with a FLI-1 adenovirus expression vector (Fig 1A

Bag1 Co-chaperone Promotes TRC8 E3 Ligase-dependent Degradation of Misfolded Human Ether a Go-Go-related Gene (hERG) Potassium Channels.

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Hantouche, Christine; Williamson, Brittany; Valinsky, William C; Solomon, Joshua; Shrier, Alvin; Young, Jason C

2017-02-10

Cardiac long QT syndrome type 2 is caused by mutations in the human ether a go-go-related gene (hERG) potassium channel, many of which cause misfolding and degradation at the endoplasmic reticulum instead of normal trafficking to the cell surface. The Hsc70/Hsp70 chaperones assist the folding of the hERG cytosolic domains. Here, we demonstrate that the Hsp70 nucleotide exchange factor Bag1 promotes hERG degradation by the ubiquitin-proteasome system at the endoplasmic reticulum to regulate hERG levels and channel activity. Dissociation of hERG complexes containing Hsp70 and the E3 ubiquitin ligase CHIP requires the interaction of Bag1 with Hsp70, but this does not involve the Bag1 ubiquitin-like domain. The interaction with Bag1 then shifts hERG degradation to the membrane-anchored E3 ligase TRC8 and its E2-conjugating enzyme Ube2g2, as determined by siRNA screening. TRC8 interacts through the transmembrane region with hERG and decreases hERG functional expression. TRC8 also mediates degradation of the misfolded hERG-G601S disease mutant, but pharmacological stabilization of the mutant structure prevents degradation. Our results identify TRC8 as a previously unknown Hsp70-independent quality control E3 ligase for hERG. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Modulation of ERG channels by XE991

DEFF Research Database (Denmark)

Elmedyb, Pernille; Calloe, Kirstine; Schmitt, Nicole

2007-01-01

In neuronal tissue, KCNQ2-5 channels conduct the physiologically important M-current. In some neurones, the M-current may in addition be conducted partly by ERG potassium channels, which have widely overlapping expression with the KCNQ channel subunits. XE991 and linopiridine are known to be stan......In neuronal tissue, KCNQ2-5 channels conduct the physiologically important M-current. In some neurones, the M-current may in addition be conducted partly by ERG potassium channels, which have widely overlapping expression with the KCNQ channel subunits. XE991 and linopiridine are known...... to be standard KCNQ potassium channel blockers. These compounds have been used in many different tissues as specific pharmacological tools to discern native currents conducted by KCNQ channels from other potassium currents. In this article, we demonstrate that ERG1-2 channels are also reversibly inhibited by XE......991 in the micromolar range (EC(50) 107 microM for ERG1). The effect has been characterized in Xenopus laevis oocytes expressing ERG1-2 and in the mammalian HEK293 cell line stably expressing ERG1 channels. The IC(50) values for block of KCNQ channels by XE991 range 1-65 microM. In conclusion, great...

Antineoplastic Effects of siRNA against TMPRSS2-ERG Junction Oncogene in Prostate Cancer.

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Giorgia Urbinati

Full Text Available TMPRSS2-ERG junction oncogene is present in more than 50% of patients with prostate cancer and its expression is frequently associated with poor prognosis. Our aim is to achieve gene knockdown by siRNA TMPRSS2-ERG and then to assess the biological consequences of this inhibition. First, we designed siRNAs against the two TMPRSS2-ERG fusion variants (III and IV, most frequently identified in patients' biopsies. Two of the five siRNAs tested were found to efficiently inhibit mRNA of both TMPRSS2-ERG variants and to decrease ERG protein expression. Microarray analysis further confirmed ERG inhibition by both siRNAs TMPRSS2-ERG and revealed one common down-regulated gene, ADRA2A, involved in cell proliferation and migration. The siRNA against TMPRSS2-ERG fusion variant IV showed the highest anti-proliferative effects: Significantly decreased cell viability, increased cleaved caspase-3 and inhibited a cluster of anti-apoptotic proteins. To propose a concrete therapeutic approach, siRNA TMPRSS2-ERG IV was conjugated to squalene, which can self-organize as nanoparticles in water. The nanoparticles of siRNA TMPRSS2-ERG-squalene injected intravenously in SCID mice reduced growth of VCaP xenografted tumours, inhibited oncoprotein expression and partially restored differentiation (decrease in Ki67. In conclusion, this study offers a new prospect of treatment for prostate cancer based on siRNA-squalene nanoparticles targeting TMPRSS2-ERG junction oncogene.

Mechanisms of IhERG/IKr Modulation by α1-Adrenoceptors in HEK293 Cells and Cardiac Myocytes

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Janire Urrutia

2016-12-01

Full Text Available Background: The rapid delayed rectifier K+ current (IKr, carried by the hERG protein, is one of the main repolarising currents in the human heart and a reduction of this current increases the risk of ventricular fibrillation. α1-adrenoceptors (α1-AR activation reduces IKr but, despite the clear relationship between an increase in the sympathetic tone and arrhythmias, the mechanisms underlying the α1-AR regulation of the hERG channel are controversial. Thus, we aimed to investigate the mechanisms by which α1-AR stimulation regulates IKr. Methods: α1-adrenoceptors, hERG channels, auxiliary subunits minK and MIRP1, the non PIP2-interacting mutant D-hERG (with a deletion of the 883-894 amino acids in the C-terminal and the non PKC-phosphorylable mutant N-terminal truncated-hERG (NTK-hERG were transfected in HEK293 cells. Cell membranes were extracted by centrifugation and the different proteins were visualized by Western blot. Potassium currents were recorded by the patch-clamp technique. IKr was recorded in isolated feline cardiac myocytes. Results: Activation of the α1-AR reduces the amplitude of IhERG and IKr through a positive shift in the activation half voltage, which reduces the channel availability at physiological membrane potentials. The intracellular pathway connecting the α1-AR to the hERG channel in HEK293 cells includes activation of the Gαq protein, PLC activation and PIP2 hydrolysis, activation of PKC and direct phosphorylation of the hERG channel N-terminal. The PKC-mediated IKr channel phosphorylation and subsequent IKr reduction after α1-AR stimulation was corroborated in feline cardiac myocytes. Conclusions: These findings clarify the link between sympathetic nervous system hyperactivity and IKr reduction, one of the best characterized causes of torsades de pointes and ventricular fibrillation.

Sedimentary record of erg migration

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Porter, M. L.

1986-06-01

The sedimentary record of erg (eolian sand sea) migration consists of an idealized threefold division of sand-sea facies sequences. The basal division, here termed the fore-erg, is composed of a hierarchy of eolian sand bodies contained within sediments of the flanking depositional environment. These sand bodies consist of eolian strata deposited by small dune complexes, zibars, and sand sheets. The fore-erg represents the downwind, leading edge of the erg and records the onset of eolian sedimentation. Basin subsidence coupled with erg migration places the medial division, termed the central erg, over the fore-erg strata. The central erg, represented by a thick accumulation of large-scale, cross-stratified sandstone, is the product of large draa complexes. Eolian influence on regional sedimentation patterns is greatest in the central erg, and most of the sand transported and deposited in the erg is contained within this region. Reduction in sand supply and continued erg migration will cover the central-erg deposits with a veneer of back-erg deposits. This upper division of the erg facies sequence resembles closely the fore-erg region. Similar types of eolian strata are present and organized in sand bodies encased in sediments of the upwind flanking depositional environment(s). Back-erg deposits may be thin due to limited eolian influence on sedimentation or incomplete erg migration, or they may be completely absent because of great susceptibility to postdepositional erosion. Tectonic, climatic, and eustatic influences on sand-sea deposition will produce distinctive variations or modifications of the idealized erg facies sequence. The resulting variants in the sedimentary record of erg migration are illustrated with ancient examples from western North America, Europe, southern Africa, and South America.

YK-4-279 inhibits ERG and ETV1 mediated prostate cancer cell invasion.

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Said Rahim

2011-04-01

Full Text Available Genomic rearrangements involving the ETS family of transcription factors occur in 40-70% of prostate cancer cases. ERG and ETV1 are the most common ETS members observed in these genetic alterations. The high prevalence of these rearrangements and their biological significance represents a novel therapeutic target for the treatment of prostate cancer.We recently reported the development of YK-4-279, a small molecule inhibitor of EWS-FLI1 oncoprotein in Ewing's Sarcoma. Since ERG and ETV1 belong to the same class of ETS factors as FLI1, we tested the ability of YK-4-279 to inhibit biological functions of ERG and ETV1 proteins in prostate cancer. YK-4-279 inhibited ERG and ETV1 mediated transcriptional activity in a luciferase assay. YK-4-279 also decreased ERG and ETV1 downstream target mRNA and protein expression in ETV1-fusion positive LNCaP and ERG fusion positive VCaP cells. YK-4-279 reduced the motility of LNCaP cells in a scratch assay and the invasive phenotype of both LNCaP and VCaP cells in a HUVEC invasion assay. Fusion-negative PC3 cells were unresponsive to YK-4-279. SiRNA mediated ERG knockdown in VCaP cells resulted in a loss of drug responsiveness. Concurrently, transient ERG expression in PC-3 cells resulted in increased invasive potential, which was reduced by YK-4-279.These data demonstrate that YK-4-279 inhibits ERG and ETV1 biological activity in fusion-positive prostate cancer cells leading to decreased motility and invasion. Therefore, YK-4-279 may have an impact on metastasis in prostate cancer and it may be further evaluated for its clinical applications in prostate cancer in addition to Ewing's sarcoma.

ELECTROOCULOGRAPHY AND PATTERN ERG IN THE DIAGNOSTICS OF BEST’S VITELLIFORM DISTROPHY

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Martina Jarc-Vidmar

2002-12-01

Full Text Available Background. The aim of the study was to develop electrooculography in accordance with ISCEV standards and to test its accuracy in the diagnosis of Best’s disease, where the EOG results should be invariably abnormal in all affected members. The pathophysiology of Best’s disease is not yet completely understood, so pattern and full field flash ERG responses compared to visual acuity and stage of the disease were used to asses the neurosensory retinal function in different stages of Best’s disease.Patients and methods. The EOG was recorded in accordance with ISCEV standards on 30 healthy individuals to determine normal values of our laboratory. Pattern as well as photopic and scotopic ERG were recorded on 24 eyes of 12 patients with typical Best’s disease with abnormal EOG responses. The results were compared to visual acuity and stage of the disease.Results. Our EOG normative data are comparable with results from other laboratories: the mean value of Arden ratio is 2.32, the range of 2 standard deviations from the mean value is from 1.6 to 3.04. The patients with Best’s disease have statisticaly significant lower values of Arden ratio (the mean value beeing 1.19. 12 patients (24 eyes with Best’s disease with abnormal EOG values were divided in two groups according to visual acuity. In the first group of 12 eyes with visual acuity > 0.5 PERG P50 and N95 responses were all in the normal range. In the second group of 12 eyes with visual acuity 0.5 or less PERG showed reduced both P50 and N95 responses in 5 eyes, and N95 solely, in two eyes.The photopic and scotopic electroretinographic responses were normal in all patients. Progression of the disease, seen in the deterioration of visual acuity, corresponded well with reduction of both PERG P50 and N95 responses. There was no correlation found between visual acuity and EOG responses.Conclusions. In the study on patients with Best’s disease, it was confirmed that EOG is a very sensitive

Antibody-Based Detection of ERG Rearrangement-Positive Prostate Cancer

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Kyung Park

2010-07-01

Full Text Available TMPRSS2-ERG gene fusions occur in 50% of prostate cancers and result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG product. Previous attempts to detect truncated ERG products have been hindered by a lack of specific antibodies. Here, we characterize a rabbit anti-ERG monoclonal antibody (clone EPR 3864; Epitomics, Burlingame, CA using immunoblot analysis on prostate cancer cell lines, synthetic TMPRSS2-ERG constructs, chromatin immunoprecipitation, and immunofluorescence. We correlated ERG protein expression with the presence of ERG gene rearrangements in prostate cancertissues using a combined immunohistochemistry(IHC and fluorescence in situ hybridization (FISH analysis. We independently evaluated two patient cohorts and observed ERG expression confined to prostate cancer cells and high-grade prostatic intraepithelial reoplasia associated with ERG-positive cancer, as well as vessels and lymphocytes (where ERG has a known biologic role. Image analysis of 131 cases demonstrated nearly 100% sensitivity for detecting ERG rearrangement prostate cancer, with only 2 (1.5% of 131 cases demonstrating strong ERG protein expression without any known ERG gene fusion. The combired pathology evaluation of 207 patient tumors for ERG protein expression had 95.7% sensitivity and 96.5% specificity for determining ERG rearrangement prostate cancer. Ir conclusion, this study qualifies a specific anti-ERG antibody and demonstrates exquisite association between ERG gene rearrangement and truncated ERG protein product expression. Giver the ease of performing IHC versus FISH, ERG protein expression may be useful for molecularly subtypirg prostate cancer based or ERG rearrangement status and suggests clinical utility it prostate needle biopsy evaluation.

THE 31 DEG{sup 2} RELEASE OF THE STRIPE 82 X-RAY SURVEY: THE POINT SOURCE CATALOG

Energy Technology Data Exchange (ETDEWEB)

LaMassa, Stephanie M.; Urry, C. Megan; Ananna, Tonima; Civano, Francesca; Marchesi, Stefano; Pecoraro, Robert [Yale Center for Astronomy and Astrophysics, Physics Department, P.O. Box 208120, New Haven, CT 06520 (United States); Cappelluti, Nico; Comastri, Andrea; Brusa, Marcella [INAF-Osservatorio Astronomico di Bologna, via Ranzani 1, I-40127 Bologna (Italy); Böhringer, Hans; Chon, Gayoung [Max-Planck-Institut für extraterrestrische Physik, D-85748 Garching (Germany); Glikman, Eilat [Department of Physics, Middlebury College, Middlebury, VT 05753 (United States); Richards, Gordon [Department of Physics, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Cardamone, Carie [Department of Math and Science, Wheelock College, 200 Riverway, Boston, MA 02215 (United States); Farrah, Duncan [Department of Physics MC 0435, Virginia Polytechnic Institute and State University, 850 West Campus Drive, Blacksburg, VA 24061 (United States); Gilfanov, Marat [Max-Planck Institut für Astrophysik, Karl-Schwarzschild-Str. 1, Postfach 1317, D-85741 Garching (Germany); Green, Paul [Smithsonian Astrophysical Observatory, 60 Garden Street, Cambridge, MA 02138 (United States); Komossa, S. [Max-Planck-Institut für Radioastronomie, Auf dem Hügel 69, D-53121 Bonn (Germany); Lira, Paulina [Departamento de Astronomia, Universidad de Chile, Camino del Observatorio 1515, Santiago (Chile); Makler, Martin [Centro Brasileiro de Pesquisas Fisicas, Rua Dr Xavier Sigaud 150, Rio de Janeiro, RJ 22290-180 (Brazil); and others

2016-02-01

We release the next installment of the Stripe 82 X-ray survey point-source catalog, which currently covers 31.3 deg{sup 2} of the Sloan Digital Sky Survey (SDSS) Stripe 82 Legacy field. In total, 6181 unique X-ray sources are significantly detected with XMM-Newton (>5σ) and Chandra (>4.5σ). This catalog release includes data from XMM-Newton cycle AO 13, which approximately doubled the Stripe 82X survey area. The flux limits of the Stripe 82X survey are 8.7 × 10{sup −16} erg s{sup −1} cm{sup −2}, 4.7 × 10{sup −15} erg s{sup −1} cm{sup −2}, and 2.1 × 10{sup −15} erg s{sup −1} cm{sup −2} in the soft (0.5–2 keV), hard (2–10 keV), and full bands (0.5–10 keV), respectively, with approximate half-area survey flux limits of 5.4 × 10{sup −15} erg s{sup −1} cm{sup −2}, 2.9 × 10{sup −14} erg s{sup −1} cm{sup −2}, and 1.7 × 10{sup −14} erg s{sup −1} cm{sup −2}. We matched the X-ray source lists to available multi-wavelength catalogs, including updated matches to the previous release of the Stripe 82X survey; 88% of the sample is matched to a multi-wavelength counterpart. Due to the wide area of Stripe 82X and rich ancillary multi-wavelength data, including coadded SDSS photometry, mid-infrared WISE coverage, near-infrared coverage from UKIDSS and VISTA Hemisphere Survey, ultraviolet coverage from GALEX, radio coverage from FIRST, and far-infrared coverage from Herschel, as well as existing ∼30% optical spectroscopic completeness, we are beginning to uncover rare objects, such as obscured high-luminosity active galactic nuclei at high-redshift. The Stripe 82X point source catalog is a valuable data set for constraining how this population grows and evolves, as well as for studying how they interact with the galaxies in which they live.

Structural refinement of the hERG1 pore and voltage-sensing domains with ROSETTA-membrane and molecular dynamics simulations.

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Subbotina, Julia; Yarov-Yarovoy, Vladimir; Lees-Miller, James; Durdagi, Serdar; Guo, Jiqing; Duff, Henry J; Noskov, Sergei Yu

2010-11-01

The hERG1 gene (Kv11.1) encodes a voltage-gated potassium channel. Mutations in this gene lead to one form of the Long QT Syndrome (LQTS) in humans. Promiscuous binding of drugs to hERG1 is known to alter the structure/function of the channel leading to an acquired form of the LQTS. Expectably, creation and validation of reliable 3D model of the channel have been a key target in molecular cardiology and pharmacology for the last decade. Although many models were built, they all were limited to pore domain. In this work, a full model of the hERG1 channel is developed which includes all transmembrane segments. We tested a template-driven de-novo design with ROSETTA-membrane modeling using side-chain placements optimized by subsequent molecular dynamics (MD) simulations. Although backbone templates for the homology modeled parts of the pore and voltage sensors were based on the available structures of KvAP, Kv1.2 and Kv1.2-Kv2.1 chimera channels, the missing parts are modeled de-novo. The impact of several alignments on the structure of the S4 helix in the voltage-sensing domain was also tested. Herein, final models are evaluated for consistency to the reported structural elements discovered mainly on the basis of mutagenesis and electrophysiology. These structural elements include salt bridges and close contacts in the voltage-sensor domain; and the topology of the extracellular S5-pore linker compared with that established by toxin foot-printing and nuclear magnetic resonance studies. Implications of the refined hERG1 model to binding of blockers and channels activators (potent new ligands for channel activations) are discussed. © 2010 Wiley-Liss, Inc.

Expression of ERG Protein and TMRPSS2-ERG Fusion in Prostatic Carcinoma in Egyptian Patients

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Ahmed Abdel-Hady

2017-03-01

CONCLUSION: Our findings emphasise that only malignant and pre-malignant cells and not benign cells from the prostate stain positive. ERG expression may offer a simpler, accurate and less costly alternative for evaluation of ERG fusion status in PCa.

Stereoselective inhibition of the hERG1 potassium channel

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Liliana eSintra Grilo

2010-11-01

Full Text Available A growing number of drugs have been shown to prolong cardiac repolarization, predisposing individuals to life-threatening ventricular arrhythmias known as Torsades de Pointes. Most of these drugs are known to interfere with the human ether à-gogo related gene 1 (hERG1 channel, whose current is one of the main determinants of action potential duration. Prolonged repolarization is reflected by lengthening of the QT interval of the electrocardiogram, as seen in the suitably named drug-induced long QT syndrome. Chirality (presence of an asymmetric atom is a common feature of marketed drugs, which can therefore exist in at least two enantiomers with distinct three-dimensional structures and possibly distinct biological fates. Both the pharmacokinetic and pharmacodynamic properties can differ between enantiomers, as well as also between individuals who take the drug due to metabolic polymorphisms. Despite the large number of reports about drugs reducing the hERG1 current, potential stereoselective contributions have only been scarcely investigated. In this review, we present a non-exhaustive list of clinically important molecules which display chiral toxicity that may be related to hERG1-blocking properties. We particularly focus on methadone cardiotoxicity, which illustrates the importance of the stereoselective effect of drug chirality as well as individual variations resulting from pharmacogenetics. Furthermore, it seems likely that, during drug development, consideration of chirality in lead optimization and systematic assessment of the hERG1 current block with all enantiomers could contribute to the reduction of the risk of drug-induced LQTS.

TMPRSS2- driven ERG expression in vivo increases self-renewal and maintains expression in a castration resistant subpopulation.

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Orla M Casey

Full Text Available Genomic rearrangements commonly occur in many types of cancers and often initiate or alter the progression of disease. Here we describe an in vivo mouse model that recapitulates the most frequent rearrangement in prostate cancer, the fusion of the promoter region of TMPRSS2 with the coding region of the transcription factor, ERG. A recombinant bacterial artificial chromosome including an extended TMPRSS2 promoter driving genomic ERG was constructed and used for transgenesis in mice. TMPRSS2-ERG expression was evaluated in tissue sections and FACS-fractionated prostate cell populations. In addition to the anticipated expression in luminal cells, TMPRSS2-ERG was similarly expressed in the Sca-1(hi/EpCAM(+ basal/progenitor fraction, where expanded numbers of clonogenic self-renewing progenitors were found, as assayed by in vitro sphere formation. These clonogenic cells increased intrinsic self renewal in subsequent generations. In addition, ERG dependent self-renewal and invasion in vitro was demonstrated in prostate cell lines derived from the model. Clinical studies have suggested that the TMPRSS2-ERG translocation occurs early in prostate cancer development. In the model described here, the presence of the TMPRSS2-ERG fusion alone was not transforming but synergized with heterozygous Pten deletion to promote PIN. Taken together, these data suggest that one function of TMPRSS2-ERG is the expansion of self-renewing cells, which may serve as targets for subsequent mutations. Primary prostate epithelial cells demonstrated increased post transcriptional turnover of ERG compared to the TMPRSS2-ERG positive VCaP cell line, originally isolated from a prostate cancer metastasis. Finally, we determined that TMPRSS2-ERG expression occurred in both castration-sensitive and resistant prostate epithelial subpopulations, suggesting the existence of androgen-independent mechanisms of TMPRSS2 expression in prostate epithelium.

ERG2 and ERG24 Are Required for Normal Vacuolar Physiology as Well as Candida albicans Pathogenicity in a Murine Model of Disseminated but Not Vaginal Candidiasis.

Science.gov (United States)

Luna-Tapia, Arturo; Peters, Brian M; Eberle, Karen E; Kerns, Morgan E; Foster, Timothy P; Marrero, Luis; Noverr, Mairi C; Fidel, Paul L; Palmer, Glen E

2015-10-01

Several important classes of antifungal agents, including the azoles, act by blocking ergosterol biosynthesis. It was recently reported that the azoles cause massive disruption of the fungal vacuole in the prevalent human pathogen Candida albicans. This is significant because normal vacuolar function is required to support C. albicans pathogenicity. This study examined the impact of the morpholine antifungals, which inhibit later steps of ergosterol biosynthesis, on C. albicans vacuolar integrity. It was found that overexpression of either the ERG2 or ERG24 gene, encoding C-8 sterol isomerase or C-14 sterol reductase, respectively, suppressed C. albicans sensitivity to the morpholines. In addition, both erg2Δ/Δ and erg24Δ/Δ mutants were hypersensitive to the morpholines. These data are consistent with the antifungal activity of the morpholines depending upon the simultaneous inhibition of both Erg2p and Erg24p. The vacuoles within both erg2Δ/Δ and erg24Δ/Δ C. albicans strains exhibited an aberrant morphology and accumulated large quantities of the weak base quinacrine, indicating enhanced vacuolar acidification compared with that of control strains. Both erg mutants exhibited significant defects in polarized hyphal growth and were avirulent in a mouse model of disseminated candidiasis. Surprisingly, in a mouse model of vaginal candidiasis, both mutants colonized mice at high levels and induced a pathogenic response similar to that with the controls. Thus, while targeting Erg2p or Erg24p alone could provide a potentially efficacious therapy for disseminated candidiasis, it may not be an effective strategy to treat vaginal infections. The potential value of drugs targeting these enzymes as adjunctive therapies is discussed. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

TMPRSS2-ERG gene fusion status in minute (minimal) prostatic adenocarcinoma.

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Albadine, Roula; Latour, Mathieu; Toubaji, Antoun; Haffner, Michael; Isaacs, William B; A Platz, Elizabeth; Meeker, Alan K; Demarzo, Angelo M; Epstein, Jonathan I; Netto, George J

2009-11-01

Minute prostatic adenocarcinomas are considered to be of insufficient virulence. Given recent suggestions of TMPRSS2-ERG gene fusion association with aggressive prostatic adenocarcinoma, we evaluated the incidence of TMPRSS2-ERG fusion in minute prostatic adenocarcinomas. A total of 45 consecutive prostatectomies with minute adenocarcinoma were used for tissue microarray construction. A total of 63 consecutive non-minimal, Gleason Score 6 tumors, from a separate PSA Era prostatectomy tissue microarray, were used for comparison. FISH was carried out using ERG break-apart probes. Tumors were assessed for fusion by deletion (Edel) or split (Esplit), duplicated fusions and low-level copy number gain in normal ERG gene locus. Minute adenocarcinomas: Fusion was evaluable in 32/45 tumors (71%). Fifteen out of 32 (47%) tumors were positive for fusion. Six (19%) were of the Edel class and 7 (22%) were classified as combined Edel+Esplit. Non-minute adenocarcinomas (pT2): Fusion was identified in 20/30 tumors (67%). Four (13%) were of Edel class and 5 (17%) were combined Edel+Esplit. Duplicated fusions were encountered in 5 (16%) tumors. Non-minute adenocarcinomas (pT3): Fusion was identified in 19/33 (58%). Fusion was due to a deletion in 6 (18%) tumors. Seven tumors (21%) were classified as combined Edel+Esplit. One tumor showed Esplit alone. Duplicated fusions were encountered in 3 (9%) cases. The incidence of duplicated fusions was higher in non-minute adenocarcinomas (13 vs 0%; P=0.03). A trend for higher incidence of low-level copy number gain in normal ERG gene locus without fusion was noted in non-minute adenocarcinomas (10 vs 0%; P=0.07). We found a TMPRSS2-ERG fusion rate of 47% in minute adenocarcinomas. The latter is not significantly different from that of grade matched non-minute adenocarcinomas. The incidence of duplicated fusion was higher in non-minute adenocarcinomas. Our finding of comparable rate of TMPRSS2-ERG fusion in minute adenocarcinomas may argue

Escitalopram block of hERG potassium channels.

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Chae, Yun Ju; Jeon, Ji Hyun; Lee, Hong Joon; Kim, In-Beom; Choi, Jin-Sung; Sung, Ki-Wug; Hahn, Sang June

2014-01-01

Escitalopram, a selective serotonin reuptake inhibitor, is the pharmacologically active S-enantiomer of the racemic mixture of RS-citalopram and is widely used in the treatment of depression. The effects of escitalopram and citalopram on the human ether-a-go-go-related gene (hERG) channels expressed in human embryonic kidney cells were investigated using voltage-clamp and Western blot analyses. Both drugs blocked hERG currents in a concentration-dependent manner with an IC50 value of 2.6 μM for escitalopram and an IC50 value of 3.2 μM for citalopram. The blocking of hERG by escitalopram was voltage-dependent, with a steep increase across the voltage range of channel activation. However, voltage independence was observed over the full range of activation. The blocking by escitalopram was frequency dependent. A rapid application of escitalopram induced a rapid and reversible blocking of the tail current of hERG. The extent of the blocking by escitalopram during the depolarizing pulse was less than that during the repolarizing pulse, suggesting that escitalopram has a high affinity for the open state of the hERG channel, with a relatively lower affinity for the inactivated state. Both escitalopram and citalopram produced a reduction of hERG channel protein trafficking to the plasma membrane but did not affect the short-term internalization of the hERG channel. These results suggest that escitalopram blocked hERG currents at a supratherapeutic concentration and that it did so by preferentially binding to both the open and the inactivated states of the channels and by inhibiting the trafficking of hERG channel protein to the plasma membrane.

High Charge-Carrier Mobility of 2.5 cm(2) V(-1) s(-1) from a Water-Borne Colloid of a Polymeric Semiconductor via Smart Surfactant Engineering.

Science.gov (United States)

Cho, Jangwhan; Cheon, Kwang Hee; Ahn, Hyungju; Park, Kwang Hun; Kwon, Soon-Ki; Kim, Yun-Hi; Chung, Dae Sung

2015-10-07

Semiconducting polymer nanoparticles dispersed in water are synthesized by a novel method utilizing non-ionic surfactants. By developing a smart surfactant engineering technique involving a selective post-removal process of surfactants, an unprecedentedly high mobility of 2.51 cm(2) V(-1) s(-1) from a water-borne colloid is demonstrated for the first time. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

EXTraS discovery of a 1.2-s X-ray pulsar in M31

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Esposito, P.; Israel, G.; Belfiore, A.; Novara, G.; Sidoli, L.; Rodriguez Castillo, G.; De Luca, A.; Tiengo, A.; Haberl, F.; Salvaterra, R.

2017-10-01

A systematic search for periodic signals in the XMM-Newton's EPIC archive carried out within the EXTraS project resulted in the discovery of a 1.2-s flux modulation in 3XMM J004301.4+413017. It is the first accreting neutron star in M31 for which the spin period has been detected. Besides this distinction, 3XMM J0043 proved to be an interesting system. Doppler shifts of the spin modulation revealed an orbital motion with period of 1.27 d and the analysis of optical data shows that, while the source is likely associated to a globular cluster, a counterpart with V ˜ 22 outside the cluster cannot be excluded. The emission of the pulsar appears rather hard (most data are described by a power law with photon index <1) and, assuming the distance to M31, the 0.3-10 keV luminosity was variable, from ˜3×10^{37} to 2×10^{38} erg/s. Based on this, we discuss two main possible scenarios for 3X J0043: a peculiar low-mass X-ray binary, perhaps similar to 4U 1822-37 or 4U 1626-67, or an intermediate-mass X-ray binary akin Her X-1.

Contribution of Interstitial Deletion of 21q22.2-3 per se to Prostate Cancer Progression in Tumors Harboring TMPRSS2-ERG Translocations

Science.gov (United States)

2015-12-01

harboring TMPRSS2- ERG translocations PRINCIPAL INVESTIGATOR: Yan Dong CONTRACTING ORGANIZATION: Tulane University New Orleans, LA 70112...0485 to prostate cancer progression in tumors harboring TMPRSS2- ERG translocations 5b. GRANT NUMBER W81XWH-14-1-0485 5c. PROGRAM ELEMENT NUMBER...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT TMPRSS2- ERG gene fusions are present in close to 50% of human prostate cancers. Approximately half of the

Swift and INTEGRAL observations of SAX J1747.0-2853

DEFF Research Database (Denmark)

Campana, S.; Chenevez, Jérôme; Kuulkers, E.

2009-01-01

on radius expansion Type I bursts). The 2-10 absorbed (unabsorbed) flux is 2.1(3.4) E-11 erg/cm^2/s. At 8 kpc this corresponds to 2E35 erg/s. Simultaneous observations with INTEGRAL between 11:42 and 15:24 UT confirm the faintness of the source, providing only upper limits: 8.E-11 erg/cm2/s (3-10 keV), 2.E......10-11 erg/cm^2/s (10-25 keV) and 1.E-10 erg/cm^2/s (15-40 keV) adopting a Crab like spectrum. Further observations and monitoring will assess if the source, after the bright Type I burst, is going to start a new outburst, remains in this quasi-persistent state or turns down to quiescence. We thank...

Analysis list: ERG [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ERG Blood,Breast,Prostate + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/ta...rget/ERG.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/ERG.5.tsv http://dbarchive.bioscienced...bc.jp/kyushu-u/hg19/target/ERG.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/ERG.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/ERG.Breast.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/ERG.Prostate.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/B

Voltage-Dependent Gating of hERG Potassium Channels

Science.gov (United States)

Cheng, Yen May; Claydon, Tom W.

2012-01-01

The mechanisms by which voltage-gated channels sense changes in membrane voltage and energetically couple this with opening of the ion conducting pore has been the source of significant interest. In voltage-gated potassium (Kv) channels, much of our knowledge in this area comes from Shaker-type channels, for which voltage-dependent gating is quite rapid. In these channels, activation and deactivation are associated with rapid reconfiguration of the voltage-sensing domain unit that is electromechanically coupled, via the S4–S5 linker helix, to the rate-limiting opening of an intracellular pore gate. However, fast voltage-dependent gating kinetics are not typical of all Kv channels, such as Kv11.1 (human ether-à-go-go related gene, hERG), which activates and deactivates very slowly. Compared to Shaker channels, our understanding of the mechanisms underlying slow hERG gating is much poorer. Here, we present a comparative review of the structure–function relationships underlying activation and deactivation gating in Shaker and hERG channels, with a focus on the roles of the voltage-sensing domain and the S4–S5 linker that couples voltage sensor movements to the pore. Measurements of gating current kinetics and fluorimetric analysis of voltage sensor movement are consistent with models suggesting that the hERG activation pathway contains a voltage independent step, which limits voltage sensor transitions. Constraints upon hERG voltage sensor movement may result from loose packing of the S4 helices and additional intra-voltage sensor counter-charge interactions. More recent data suggest that key amino acid differences in the hERG voltage-sensing unit and S4–S5 linker, relative to fast activating Shaker-type Kv channels, may also contribute to the increased stability of the resting state of the voltage sensor. PMID:22586397

Voltage-dependent gating of hERG potassium channels

Directory of Open Access Journals (Sweden)

Yen May eCheng

2012-05-01

Full Text Available The mechanisms by which voltage-gated channels sense changes in membrane voltage and energetically couple this with opening of the ion conducting pore has been the source of significant interest. In voltage-gated potassium (Kv channels, much of our knowledge in this area comes from Shaker-type channels, for which voltage-dependent gating is quite rapid. In these channels, activation and deactivation are associated with rapid reconfiguration of the voltage-sensing domain unit that is electromechanically coupled, via the S4-S5 linker helix, to the rate-limiting opening of an intracellular pore gate. However, fast voltage-dependent gating kinetics are not typical of all Kv channels, such as Kv11.1 (human ether-a-go-go related gene, hERG, which activates and deactivates very slowly. Compared to Shaker channels, our understanding of the mechanisms underlying slow hERG gating is much poorer. Here, we present a comparative review of the structure-function relationships underlying voltage-dependent gating in Shaker and hERG channels, with a focus on the roles of the voltage sensing domain and the S4-S5 linker that couples voltage sensor movements to the pore. Measurements of gating current kinetics and fluorimetric analysis of voltage sensor movement are consistent with models suggesting that the hERG activation pathway contains a voltage independent step, which limits voltage sensor transitions. Constraints upon hERG voltage sensor movement may result from loose packing of the S4 helices and additional intra-voltage sensor counter charge interactions. More recent data suggest that key amino acid differences in the hERG voltage sensing unit and S4-S5 linker, relative to fast activating Shaker-type Kv channels, may also contribute to the increased stability of the resting state of the voltage sensor.

``High energy Electron exPeriment (HEP)'' onboard the ERG satellite

Science.gov (United States)

Mitani, T.; Takashima, T.; Kasahara, S.; Miyake, W.; Hirahara, M.

2017-12-01

The Exploration of energization and Radiation in Geospace (ERG) satellite was successfully launched on December 20, 2016, and now explores how relativistic electrons in the radiation belts are generated during space storms. "High energy Electron exPeriment (HEP)" onboard the ERG satellite observes 70 keV - 2 MeV electrons and provides three-dimensional velocity distribution of electrons every spacecraft spin period. Electrons are observed by two types of camera designs, HEP-L and HEP-H, with regard to geometrical factor and energy range. HEP-L observes 0.1 - 1 MeV electrons and its geometrical factor (G-factor) is 10-3 cm2 str, and HEP-H observes 0.7 - 2 MeV and G-factor is 10-2 cm2 str. HEP-L and HEP-H each consist of three pin-hole type cameras, and each camera consist of mechanical collimator, stacked silicon semiconductor detectors and readout ASICs. HEP-H has larger opening angle of the collimator and more silicon detectors to observe higher energy electrons than HEP-L. The initial checkout in orbit was carried out in February 2017 and it was confirmed that there was no performance degradation by comparing the results of the initial checkout in orbit and the prelaunch function tests. Since late March, HEP has carried out normal observation. HEP observed losses and recovery of the outer radiation belt electrons several times up to now. In this presentation we introduce the HEP instrument design, prelaunch tests results and report the initial results in orbit.

Analysis list: Erg [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Erg Blood,Prostate + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Erg.1.tsv http:...//dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Erg.5.tsv http://dbarchive.biosciencedbc.jp/kyus...hu-u/mm9/target/Erg.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Erg.Blood.tsv,http://dbarchiv...e.biosciencedbc.jp/kyushu-u/mm9/colo/Erg.Prostate.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Prostate.gml ...

Deletion of the Candida glabrata ERG3 and ERG11 genes: effect on cell viability, cell growth, sterol composition, and antifungal susceptibility.

Science.gov (United States)

Geber, A; Hitchcock, C A; Swartz, J E; Pullen, F S; Marsden, K E; Kwon-Chung, K J; Bennett, J E

1995-01-01

We have cloned and sequenced the structural genes encoding the delta 5,6 sterol desaturase (ERG3 gene) and the 14 alpha-methyl sterol demethylase (ERG11 gene) from Candida glabrata L5 (leu2). Single and double mutants of these genes were created by gene deletion. The phenotypes of these mutants, including sterol profiles, aerobic viabilities, antifungal susceptibilities, and generation times, were studied. Strain L5D (erg3 delta::LEU2) accumulated mainly ergosta-7,22-dien-3 beta-ol, was aerobically viable, and remained susceptible to antifungal agents but had a slower generation time than its parent strain. L5LUD (LEU2 erg11 delta::URA3) strains required medium supplemented with ergosterol and an anaerobic environment for growth. A spontaneous aerobically viable mutant, L5LUD40R (LEU erg11 delta::URA3), obtained from L5LUD (LEU2 erg11 delta::URA3), was found to accumulate lanosterol and obtusifoliol, was resistant to azole antifungal agents, demonstrated some increase in resistance to amphotericin B, and exhibited a 1.86-fold increase in generation time in comparison with L5 (leu2). The double-deletion mutant L5DUD61 (erg3 delta::LEU2 erg11 delta::URA3) was aerobically viable, produced mainly 14 alpha-methyl fecosterol, and had the same antifungal susceptibility pattern as L5LUD40R (LEU2 erg11 delta::URA3), and its generation time was threefold greater than that of L5 (leu2). Northern (RNA) analysis revealed that the single-deletion mutants had a marked increase in message for the undeleted ERG3 and ERG11 genes. These results indicate that differences in antifungal susceptibilities and the restoration of aerobic viability exist between the C. glabrata ergosterol mutants created in this study and those sterol mutants with similar genetic lesions previously reported for Saccharomyces cerevisiae. PMID:8593007

Differential expression of hERG1 channel isoforms reproduces properties of native I(Kr and modulates cardiac action potential characteristics.

Directory of Open Access Journals (Sweden)

Anders Peter Larsen

Full Text Available BACKGROUND: The repolarizing cardiac rapid delayed rectifier current, I(Kr, is composed of ERG1 channels. It has been suggested that two isoforms of the ERG1 protein, ERG1a and ERG1b, both contribute to I(Kr. Marked heterogeneity in the kinetic properties of native I(Kr has been described. We hypothesized that the heterogeneity of native I(Kr can be reproduced by differential expression of ERG1a and ERG1b isoforms. Furthermore, the functional consequences of differential expression of ERG1 isoforms were explored as a potential mechanism underlying native heterogeneity of action potential duration (APD and restitution. METHODOLOGY/PRINCIPAL FINDINGS: The results show that the heterogeneity of native I(Kr can be reproduced in heterologous expression systems by differential expression of ERG1a and ERG1b isoforms. Characterization of the macroscopic kinetics of ERG1 currents demonstrated that these were dependent on the relative abundance of ERG1a and ERG1b. Furthermore, we used a computational model of the ventricular cardiomyocyte to show that both APD and the slope of the restitution curve may be modulated by varying the relative abundance of ERG1a and ERG1b. As the relative abundance of ERG1b was increased, APD was gradually shortened and the slope of the restitution curve was decreased. CONCLUSIONS/SIGNIFICANCE: Our results show that differential expression of ERG1 isoforms may explain regional heterogeneity of I(Kr kinetics. The data demonstrate that subunit dependent changes in channel kinetics are important for the functional properties of ERG1 currents and hence I(Kr. Importantly, our results suggest that regional differences in the relative abundance of ERG1 isoforms may represent a potential mechanism underlying the heterogeneity of both APD and APD restitution observed in mammalian hearts.

TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy

Science.gov (United States)

Gopalan, Anuradha; Leversha, Margaret A.; Satagopan, Jaya M.; Zhou, Qin; Al-Ahmadie, Hikmat A.; Fine, Samson W.; Eastham, James A.; Scardino, Peter T.; Scher, Howard I.; Tickoo, Satish K.; Reuter, Victor E.; Gerald, William L.

2009-01-01

A significant number of prostate cancers have been shown to have recurrent chromosomal rearrangements resulting in the fusion of the androgen regulated TMPRSS2 promoter to a member of the ETS transcription factor family, most commonly ERG. This results in ERG overexpression which may have a direct causal role in prostate tumorigenesis or progression. However, the clinical significance of the rearrangement is unclear and, in particular, relationship to outcome has been inconsistent in recent reports. We analyzed TMPRSS2-ERG gene rearrangement status by fluorescence in situ hybridization (FISH) in 521 cases of clinically localized surgically treated prostate cancer with 95 months median follow-up and also in 40 unmatched metastases. 42% of primary tumors and 40% of metastases had rearrangements. 11% had copy number increase (CNI) of the TMPRRS2-ERG region. Rearrangement alone was associated with lower grade, but not with stage, biochemical recurrence, metastases or death. CNI with and without rearrangement was associated with high grade and advanced stage. Further, a subgroup of cancers with CNI and rearrangement by deletion, with two or more copies of the deleted locus, tended to be more clinically aggressive. DNA index assessment revealed that the majority of tumors with CNI of TMPRSS2-ERG had generalized aneuploidy/ tetraploidy in contrast to tumors without TMPRSS2-ERG CNI, which were predominantly diploid. We therefore conclude that translocation of TMPRSS2-ERG is not associated with outcome and the aggressive clinical features associated with CNI of chromosome 21 reflect generalized aneuploidy and are not due to CNI specifically of rearranged TMPRSS2-ERG. PMID:19190343

Indexing molecules for their hERG liability.

Science.gov (United States)

Rayan, Anwar; Falah, Mizied; Raiyn, Jamal; Da'adoosh, Beny; Kadan, Sleman; Zaid, Hilal; Goldblum, Amiram

2013-07-01

The human Ether-a-go-go-Related-Gene (hERG) potassium (K(+)) channel is liable to drug-inducing blockage that prolongs the QT interval of the cardiac action potential, triggers arrhythmia and possibly causes sudden cardiac death. Early prediction of drug liability to hERG K(+) channel is therefore highly important and preferably obligatory at earlier stages of any drug discovery process. In vitro assessment of drug binding affinity to hERG K(+) channel involves substantial expenses, time, and labor; and therefore computational models for predicting liabilities of drug candidates for hERG toxicity is of much importance. In the present study, we apply the Iterative Stochastic Elimination (ISE) algorithm to construct a large number of rule-based models (filters) and exploit their combination for developing the concept of hERG Toxicity Index (ETI). ETI estimates the molecular risk to be a blocker of hERG potassium channel. The area under the curve (AUC) of the attained model is 0.94. The averaged ETI of hERG binders, drugs from CMC, clinical-MDDR, endogenous molecules, ACD and ZINC, were found to be 9.17, 2.53, 3.3, -1.98, -2.49 and -3.86 respectively. Applying the proposed hERG Toxicity Index Model on external test set composed of more than 1300 hERG blockers picked from chEMBL shows excellent performance (Matthews Correlation Coefficient of 0.89). The proposed strategy could be implemented for the evaluation of chemicals in the hit/lead optimization stages of the drug discovery process, improve the selection of drug candidates as well as the development of safe pharmaceutical products. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Choice of Surgical Procedure for Patients With Non-Small-Cell Lung Cancer ≤ 1 cm or > 1 to 2 cm Among Lobectomy, Segmentectomy, and Wedge Resection

DEFF Research Database (Denmark)

Dai, Chenyang; Shen, Jianfei; Ren, Yijiu

2016-01-01

PURPOSE: According to the lung cancer staging project, T1a (≤ 2 cm) non-small-cell lung cancer (NSCLC) should be additionally classified into ≤ 1 cm and > 1 to 2 cm groups. This study aimed to investigate the surgical procedure for NSCLC ≤ 1 cm and > 1 to 2 cm. METHODS: We identified 15...... multiple prognostic factors. RESULTS: OS and LCSS favored lobectomy compared with segmentectomy or wedge resection in patients with NSCLC ≤ 1 cm and > 1 to 2 cm. Multivariable analysis showed that segmentectomy and wedge resection were independently associated with poorer OS and LCSS than lobectomy...... for NSCLC ≤ 1 cm and > 1 to 2 cm. With sublobar resection, lower OS and LCSS emerged for NSCLC > 1 to 2 cm after wedge resection, whereas similar survivals were observed for NSCLC ≤ 1 cm. Multivariable analyses showed that wedge resection is an independent risk factor of survival for NSCLC > 1 to 2 cm...

IL-6 Overexpression in ERG-Positive Prostate Cancer Is Mediated by Prostaglandin Receptor EP2.

Science.gov (United States)

Merz, Constanze; von Mässenhausen, Anne; Queisser, Angela; Vogel, Wenzel; Andrén, Ove; Kirfel, Jutta; Duensing, Stefan; Perner, Sven; Nowak, Michael

2016-04-01

Prostate cancer is the most diagnosed cancer in men and multiple risk factors and genetic alterations have been described. The TMPRSS2-ERG fusion event and the overexpression of the transcription factor ERG are present in approximately 50% of all prostate cancer patients, however, the clinical outcome is still controversial. Prostate tumors produce various soluble factors, including the pleiotropic cytokine IL-6, regulating cellular processes such as proliferation and metastatic segregation. Here, we used prostatectomy samples in a tissue microarray format and analyzed the co-expression and the clinicopathologic data of ERG and IL-6 using immunohistochemical double staining and correlated the read-out with clinicopathologic data. Expression of ERG and IL-6 correlated strongly in prostate tissue samples. Forced expression of ERG in prostate tumor cell lines resulted in significantly increased secretion of IL-6, whereas the down-regulation of ERG decreased IL-6 secretion. By dissecting the underlying mechanism in prostate tumor cell lines we show the ERG-mediated up-regulation of the prostanoid receptors EP2 and EP3. The prostanoid receptor EP2 was overexpressed in human prostate cancer tissue. Furthermore, the proliferation rate and IL-6 secretion in DU145 cells was reduced after treatment with EP2-receptor antagonist. Collectively, our study shows that the expression of ERG in prostate cancer is linked to the expression of IL-6 mediated by the prostanoid receptor EP2. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

TMPRSS2-ERG -specific transcriptional modulation is associated with prostate cancer biomarkers and TGF-β signaling

International Nuclear Information System (INIS)

Brase, Jan C; Sirma, Hüseyin; Sauter, Guido; Simon, Ronald; Schlomm, Thorsten; Beißbarth, Tim; Korf, Ulrike; Kuner, Ruprecht; Sültmann, Holger; Johannes, Marc; Mannsperger, Heiko; Fälth, Maria; Metzger, Jennifer; Kacprzyk, Lukasz A; Andrasiuk, Tatjana; Gade, Stephan; Meister, Michael

2011-01-01

TMPRSS2-ERG gene fusions occur in about 50% of all prostate cancer cases and represent promising markers for molecular subtyping. Although TMPRSS2-ERG fusion seems to be a critical event in prostate cancer, the precise functional role in cancer development and progression is still unclear. We studied large-scale gene expression profiles in 47 prostate tumor tissue samples and in 48 normal prostate tissue samples taken from the non-suspect area of clinical low-risk tumors using Affymetrix GeneChip Exon 1.0 ST microarrays. Comparison of gene expression levels among TMPRSS2-ERG fusion-positive and negative tumors as well as benign samples demonstrated a distinct transcriptional program induced by the gene fusion event. Well-known biomarkers for prostate cancer detection like CRISP3 were found to be associated with the gene fusion status. WNT and TGF-β/BMP signaling pathways were significantly associated with genes upregulated in TMPRSS2-ERG fusion-positive tumors. The TMPRSS2-ERG gene fusion results in the modulation of transcriptional patterns and cellular pathways with potential consequences for prostate cancer progression. Well-known biomarkers for prostate cancer detection were found to be associated with the gene fusion. Our results suggest that the fusion status should be considered in retrospective and future studies to assess biomarkers for prostate cancer detection, progression and targeted therapy

X-ray detection with Micromegas with background levels below 10$^{-6}$ keV$^{-1}$cm$^{-2}$s$^{-1}$

CERN Document Server

Aune, S; Calvet, D.; Dafni, T.; Diago, A.; Druillole, F.; Fanourakis, G.; Ferrer-Ribas, E.; Galán, J.; García, J.A.; Gardikiotis, A.; Garza, J.G.; Geralis, T.; Giomataris, I.; Gómez, H.; González-Díaz, D.; Herrera, D.C.; Iguaz, F.J.; Irastorza, I.G.; Jourde, D.; Luzón, G.; Mirallas, H.; Mols, J.P.; Papaevangelou, T.; Rodríguez, A.; Seguí, L.; Tomás, A.; Vafeiadis, T.; Yildiz, S.C.

2013-01-01

Micromegas detectors are an optimum technological choice for the detection of low energy x-rays. The low background techniques applied to these detectors yielded remarkable background reductions over the years, being the CAST experiment beneficiary of these developments. In this document we report on the latest upgrades towards further background reductions and better understanding of the detectors' response. The upgrades encompass the readout electronics, a new detector design and the implementation of a more efficient cosmic muon veto system. Background levels below 10$^{-6}$keV$^{-1}$cm$^{-2}$s$^{-1}$ have been obtained at sea level for the first time, demonstrating the feasibility of the expectations posed by IAXO, the next generation axion helioscope. Some results obtained with a set of measurements conducted in the x-ray beam of the CAST Detector Laboratory will be also presented and discussed.

A radiolabeled peptide ligand of the hERG channel, [125I]-BeKm-1

DEFF Research Database (Denmark)

Angelo, Kamilla; Korolkova, Yuliya V; Grunnet, Morten

2003-01-01

The wild-type scorpion toxin BeKm-1, which selectively blocks human ether-a-go-go related (hERG) channels, was radiolabeled with iodine at tyrosine 11. Both the mono- and di-iodinated derivatives were found to be biologically active. In electrophysiological patch-clamp recordings mono-[127I]-BeKm-1...... had a concentration of half-maximal inhibition (IC50 value) of 27 nM, while wild-type BeKm-1 inhibited hERG channels with an IC50 value of 7 nM. Mono-[125I]-BeKm-1 was found to bind in a concentration-dependent manner and with picomolar affinity to hERG channel protein in purified membrane vesicles...... of [125I]-BeKm-1 to the hERG channel to an IC50 of 7 nM. In autoradiographic studies on rat hearts, binding of [125I]-BeKm-1 was dose-dependent and could partially be displaced by the addition of excess amounts of non-radioactive BeKm-1. The density of the radioactive signal was equally distributed...

Measurement of the 1S-2S frequency in atomic hydrogen

International Nuclear Information System (INIS)

Hildum, E.A.

1986-01-01

A first precise measurement of the 1S-2S energy interval in atomic hydrogen was obtained by observing the 1S-2S transition in an atomic beam by pulsed Doppler-free two-photon spectroscopy and using an interferometrically calibrated line of 130 Te 2 at 486 nm as the references. The measured 1S-2S frequency is 2,466,061 395.6(4.9)MHz. With the calculated 1S Lamb shift, the 1S-2S frequency yields a value for the Rydberg constant, R/sub ∞/ = 109,737.314 92(22) cm -1 , which is not in good agreement with the most recent previously measured value, 109,737.315 44(11) cm -1 , obtained by S.R. Amin et al. It is, however, in good agreement with a previous Rydberg value, 109,737.315 04(32) cm -1 , measured by J.E.M. Goldsmith. If the Rydberg constant is taken as given, the 1S-2S frequency determines a value for the 1S Lamb shift. With Amin's Rydberg, the measured Lamb shift is 8161.0(5.4) MHz, in poor agreement with the theoretical value of 8149.43(8) MHz. With Goldsmith's Rydberg, the measurement Lamb shift is 8151.0(8.7) MHz, in good agreement with theory

Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency

Science.gov (United States)

Yan, Meng; Zhang, Kaiping; Shi, Yanhui; Feng, Lifang; Lv, Lin; Li, Baoxin

2015-01-01

Berberine (BBR), an isoquinoline alkaloid mainly isolated from plants of Berberidaceae family, is extensively used to treat gastrointestinal infections in clinics. It has been reported that BBR can block human ether-a-go-go-related gene (hERG) potassium channel and inhibit its membrane expression. The hERG channel plays crucial role in cardiac repolarization and is the target of diverse proarrhythmic drugs. Dysfunction of hERG channel can cause long QT syndrome. However, the regulatory mechanisms of BBR effects on hERG at cell membrane level remain unknown. This study was designed to investigate in detail how BBR decreased hERG expression on cell surface and further explore its pharmacological rescue strategies. In this study, BBR decreases caveolin-1 expression in a concentration-dependent manner in human embryonic kidney 293 (HEK293) cells stably expressing hERG channel. Knocking down the basal expression of caveolin-1 alleviates BBR-induced hERG reduction. In addition, we found that aromatic tyrosine (Tyr652) and phenylalanine (Phe656) in S6 domain mediate the long-term effect of BBR on hERG by using mutation techniques. Considering both our previous and present work, we propose that BBR reduces hERG membrane stability with multiple mechanisms. Furthermore, we found that fexofenadine and resveratrol shorten action potential duration prolongated by BBR, thus having the potential effects of alleviating the cardiotoxicity of BBR. PMID:26543354

TMPRSS2-ERG gene fusions are infrequent in prostatic ductal adenocarcinomas.

Science.gov (United States)

Lotan, Tamara L; Toubaji, Antoun; Albadine, Roula; Latour, Mathieu; Herawi, Mehsati; Meeker, Alan K; DeMarzo, Angelo M; Platz, Elizabeth A; Epstein, Jonathan I; Netto, George J

2009-03-01

Ductal adenocarcinoma of the prostate is an unusual subtype that may be associated with a more aggressive clinical course, and is less responsive to conventional therapies than the more common prostatic acinar adenocarcinoma. However, given its frequent association with an acinar component at prostatectomy, some have challenged the concept of prostatic ductal adenocarcinoma as a distinct clinicopathologic entity. We studied the occurrence of the TMPRSS2-ERG gene fusion, in 40 surgically resected ductal adenocarcinoma cases, and in their associated acinar component using fluorescence in situ hybridization. A group of 38 'pure' acinar adenocarcinoma cases matched with the ductal adenocarcinoma group for pathological grade and stage was studied as a control. Compared with the matched acinar adenocarcinoma cases, the TMPRSS2-ERG gene fusion was significantly less frequently observed in ductal adenocarcinoma (45 vs 11% of cases, P=0.002, Fisher's exact test). Here, of the ductal adenocarcinoma cases with the gene fusion, 75% were fused through deletion, and the remaining case was fused through translocation. The TMPRSS2-ERG gene fusion was also rare in the acinar component of mixed ductal-acinar tumors when compared with the pure acinar adenocarcinoma controls (5 vs 45%, P=0.001, Fisher's exact test). In 95% of the ductal adenocarcinoma cases in which a concurrent acinar component was analyzed, there was concordance for presence/absence of the TMPRSS2-ERG gene fusion between the different histologic subtypes. In the control group of pure acinar adenocarcinoma cases, 59% were fused through deletion and 41% were fused through translocation. The presence of the TMPRSS2-ERG gene fusion in some cases of prostatic ductal adenocarcinoma supports the concept that ductal adenocarcinoma and acinar adenocarcinoma may be related genetically. However, the significantly lower rate of the gene fusion in pure ductal adenocarcinoma cases underscores the fact that genetic and biologic

The transcription factor ERG increases expression of neurotransmitter receptors on prostate cancer cells

International Nuclear Information System (INIS)

Kissick, Haydn T.; On, Seung T.; Dunn, Laura K.; Sanda, Martin G.; Asara, John M.; Pellegrini, Kathryn L.; Noel, Jonathan K.; Arredouani, Mohamed S.

2015-01-01

The TMPRSS2-ERG gene fusion occurs in about half of prostate cancer (PCa) cases and results in overexpression of the transcription factor ERG. Overexpression of ERG has many effects on cellular function. However, how these changes enhance cell growth and promote tumor development is unclear. To investigate the role of ERG, LNCaP and PC3 cells were transfected with ERG and gene expression and metabolic profile were analyzed. Our data show that expression of ERG induces overexpression of many nicotinicacetylcholine receptors (nAChRs). In addition, metabolic profiling by LC-MS/MS revealed elevated production of several neurotransmitters in cells expressing ERG. Consistently, treatment of ERG-expressing cells with nicotine induced elevated calcium influx, GSK3β (Ser9) phosphorylation and cell proliferation. Finally, we show that PCa patientswho are smokers have larger tumors if their tumors are TMPRSS2-ERG gene fusion positive. Collectively, our data suggest that ERG sensitizes prostate tumor cells to neurotransmitter receptor agonists like nicotine. The online version of this article (doi:10.1186/s12885-015-1612-3) contains supplementary material, which is available to authorized users

Targeting TMPRSS2 ERG in Prostate Cancer

Science.gov (United States)

2016-09-01

kinome library, using physiologic cell based assays of ERG activity. We made lentivirus expressing multiple shRNAs targeting each candidate 9...MDV3100 reverses the effect of R1881 (compare columns 2 and 3). Interestingly, PKCi inhibited a subset of androgen induced genes ( column 4...expenditures Nothing to report. Significant changes in use or care of human subjects, vertebrate animals, biohazards, and/or select agents Nothing to

Reduced Erg Dosage Impairs Survival of Hematopoietic Stem and Progenitor Cells.

Science.gov (United States)

Xie, Ying; Koch, Mia Lee; Zhang, Xin; Hamblen, Melanie J; Godinho, Frank J; Fujiwara, Yuko; Xie, Huafeng; Klusmann, Jan-Henning; Orkin, Stuart H; Li, Zhe

2017-07-01

ERG, an ETS family transcription factor frequently overexpressed in human leukemia, has been implicated as a key regulator of hematopoietic stem cells. However, how ERG controls normal hematopoiesis, particularly at the stem and progenitor cell level, and how it contributes to leukemogenesis remain incompletely understood. Using homologous recombination, we generated an Erg knockdown allele (Erg kd ) in which Erg expression can be conditionally restored by Cre recombinase. Erg kd/kd animals die at E10.5-E11.5 due to defects in endothelial and hematopoietic cells, but can be completely rescued by Tie2-Cre-mediated restoration of Erg in these cells. In Erg kd/+ mice, ∼40% reduction in Erg dosage perturbs both fetal liver and bone marrow hematopoiesis by reducing the numbers of Lin - Sca-1 + c-Kit + (LSK) hematopoietic stem and progenitor cells (HSPCs) and megakaryocytic progenitors. By genetic mosaic analysis, we find that Erg-restored HSPCs outcompete Erg kd/+ HSPCs for contribution to adult hematopoiesis in vivo. This defect is in part due to increased apoptosis of HSPCs with reduced Erg dosage, a phenotype that becomes more drastic during 5-FU-induced stress hematopoiesis. Expression analysis reveals that reduced Erg expression leads to changes in expression of a subset of ERG target genes involved in regulating survival of HSPCs, including increased expression of a pro-apoptotic regulator Bcl2l11 (Bim) and reduced expression of Jun. Collectively, our data demonstrate that ERG controls survival of HSPCs, a property that may be used by leukemic cells. Stem Cells 2017;35:1773-1785. © 2017 AlphaMed Press.

ERG review of waste package corrosion mechanisms

International Nuclear Information System (INIS)

Geisert, R.E.

1988-01-01

The Engineering Review Group (ERG) was established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate engineering-related issues in the US Department of Energy's nuclear waste repository program. The ERG reviewed the waste package corrosion mechanisms. This report documents the ERG's comments and recommendations on these subjects and the ONWI response to the specific points raised by the ERG. 1 ref

Differential expression of hERG1 channel isoforms reproduces properties of native I(Kr) and modulates cardiac action potential characteristics

DEFF Research Database (Denmark)

Larsen, Anders Peter; Olesen, Søren-Peter

2010-01-01

The repolarizing cardiac rapid delayed rectifier current, I(Kr), is composed of ERG1 channels. It has been suggested that two isoforms of the ERG1 protein, ERG1a and ERG1b, both contribute to I(Kr). Marked heterogeneity in the kinetic properties of native I(Kr) has been described. We hypothesized...

Structural implications of hERG K+ channel block by a high-affinity minimally structured blocker

Science.gov (United States)

Helliwell, Matthew V.; Zhang, Yihong; El Harchi, Aziza; Du, Chunyun; Hancox, Jules C.; Dempsey, Christopher E.

2018-01-01

Cardiac potassium channels encoded by human ether-à-go-go–related gene (hERG) are major targets for structurally diverse drugs associated with acquired long QT syndrome. This study characterized hERG channel inhibition by a minimally structured high-affinity hERG inhibitor, Cavalli-2, composed of three phenyl groups linked by polymethylene spacers around a central amino group, chosen to probe the spatial arrangement of side chain groups in the high-affinity drug-binding site of the hERG pore. hERG current (IhERG) recorded at physiological temperature from HEK293 cells was inhibited with an IC50 of 35.6 nm with time and voltage dependence characteristic of blockade contingent upon channel gating. Potency of Cavalli-2 action was markedly reduced for attenuated inactivation mutants located near (S620T; 54-fold) and remote from (N588K; 15-fold) the channel pore. The S6 Y652A and F656A mutations decreased inhibitory potency 17- and 75-fold, respectively, whereas T623A and S624A at the base of the selectivity filter also decreased potency (16- and 7-fold, respectively). The S5 helix F557L mutation decreased potency 10-fold, and both F557L and Y652A mutations eliminated voltage dependence of inhibition. Computational docking using the recent cryo-EM structure of an open channel hERG construct could only partially recapitulate experimental data, and the high dependence of Cavalli-2 block on Phe-656 is not readily explainable in that structure. A small clockwise rotation of the inner (S6) helix of the hERG pore from its configuration in the cryo-EM structure may be required to optimize Phe-656 side chain orientations compatible with high-affinity block. PMID:29545312

1ES 0033+595 found in a very high state by INTEGRAL

DEFF Research Database (Denmark)

Bassani, L.; Malizia, A.; Chenevez, Jérôme

2014-01-01

Crab (10^-10 erg/cm2/s) in the 18-40 keV band (13 sec, about 7 sigma) while a 3 sigma upper limit of 11 mCrab (10^-10 erg/cm2/s) is provided in the 40-100 keV band. Using data collected from the ASDC SED Builder tool (http://tools.asdc.asi.it/SED/) we notice that this is the highest X-ray flux so far...

A laser frequency comb that enables radial velocity measurements with a precision of 1 cm s(-1).

Science.gov (United States)

Li, Chih-Hao; Benedick, Andrew J; Fendel, Peter; Glenday, Alexander G; Kärtner, Franz X; Phillips, David F; Sasselov, Dimitar; Szentgyorgyi, Andrew; Walsworth, Ronald L

2008-04-03

Searches for extrasolar planets using the periodic Doppler shift of stellar spectral lines have recently achieved a precision of 60 cm s(-1) (ref. 1), which is sufficient to find a 5-Earth-mass planet in a Mercury-like orbit around a Sun-like star. To find a 1-Earth-mass planet in an Earth-like orbit, a precision of approximately 5 cm s(-1) is necessary. The combination of a laser frequency comb with a Fabry-Pérot filtering cavity has been suggested as a promising approach to achieve such Doppler shift resolution via improved spectrograph wavelength calibration, with recent encouraging results. Here we report the fabrication of such a filtered laser comb with up to 40-GHz (approximately 1-A) line spacing, generated from a 1-GHz repetition-rate source, without compromising long-term stability, reproducibility or spectral resolution. This wide-line-spacing comb, or 'astro-comb', is well matched to the resolving power of high-resolution astrophysical spectrographs. The astro-comb should allow a precision as high as 1 cm s(-1) in astronomical radial velocity measurements.

ERG review of containment failure probability and repository functional design criteria

International Nuclear Information System (INIS)

Gopal, S.

1986-06-01

The Engineering Review Group (ERG) was established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate engineering-related issues in the US Department of Energy's nuclear waste repository program. The June 1984 meeting of the ERG considered two topics: (1) statistical probability for containment of nuclides within the waste package and (2) repository design criteria. This report documents the ERG's comments and recommendations on these two subjects and the ONWI response to the specific points raised by ERG

ERG protein expression over time

DEFF Research Database (Denmark)

Berg, Kasper Drimer; Brasso, Klaus; Thomsen, Frederik Birkebæk

2015-01-01

AIMS: We evaluated the consistency in ERG protein expression from diagnostic specimens through rebiopsies to radical prostatectomies in patients with clinically localised prostate cancer to investigate the validity of ERG status in biopsies. METHODS: ERG expression was assessed by immunohistochem......AIMS: We evaluated the consistency in ERG protein expression from diagnostic specimens through rebiopsies to radical prostatectomies in patients with clinically localised prostate cancer to investigate the validity of ERG status in biopsies. METHODS: ERG expression was assessed...

Patch testing with 2.0% (0.60 mg/cm2) formaldehyde instead of 1.0% (0.30 mg/cm2) detects significantly more contact allerg

DEFF Research Database (Denmark)

Pontén, Ann; Aalto-Korte, Kristiina; Agner, Tove

2013-01-01

.To validate earlier patch test results for comparison of 1% (wt/vol) and 2% (wt/vol) formaldehyde in water, and to investigate co-reactivity with quaternium-15. Materials and methods.In 12 dermatology clinics, 3591 patients were routinely patch tested simultaneously with 2.0% (wt/vol) (0.60 mg/cm(2) ) and 1.......0% (wt/vol) (0.30 mg/cm(2) ) formaldehyde. Micropipettes were used for delivering the exact dosage of the allergen. Results.Significantly more patients reacted to 2.0% formaldehyde than to 1.0% (3.4% versus 1.8%, p

ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation by AML1-ETO in acute myeloid leukemia

NARCIS (Netherlands)

Martens, Joost H. A.; Mandoli, Amit; Simmer, Femke; Wierenga, Bart-Jan; Saeed, Sadia; Singh, Abhishek A.; Altucci, Lucia; Vellenga, Edo; Stunnenberg, Hendrik G.

2012-01-01

ERG and FLI1 are closely related members of the ETS family of transcription factors and have been identified as essential factors for the function and maintenance of normal hematopoietic stem cells. Here genome-wide analysis revealed that both ERG and FLI1 occupy similar genomic regions as AML1-ETO

Small nodules (1-2 cm) in liver cirrhosis: Characterization with contrast-enhanced ultrasound

Energy Technology Data Exchange (ETDEWEB)

Jang, Hyun-Jung [Department of Medical Imaging, Toronto General Hospital, University of Toronto, 585 University Avenue, Toronto, Ontario M5G 2N2 (Canada); Kim, Tae Kyoung [Department of Medical Imaging, Toronto General Hospital, University of Toronto, 585 University Avenue, Toronto, Ontario M5G 2N2 (Canada)], E-mail: taekyoung.kim@uhn.on.ca; Wilson, Stephanie R. [Department of Medical Imaging, Toronto General Hospital, University of Toronto, 585 University Avenue, Toronto, Ontario M5G 2N2 (Canada)

2009-12-15

Objective: To determine the diagnostic efficacy of arterial phase contrast-enhanced ultrasound (CEUS) for characterizing small hepatic nodules (1-2 cm) in patients with high-risk for hepatocellular carcinoma (HCC). Materials and methods: Over 12 months, CEUS was performed in 59 patients at high-risk for HCC with small hepatic nodules (1-2 cm; mean, 1.5 cm). Based only on arterial phase (<45 s) vascular intensity and pattern, lesions were prospectively diagnosed as HCC if there was hypervascularity without known features of hemangioma. The diagnosis of HCC was made regardless of the presence or absence of washout. Verification of diagnosis was made by liver transplantation (n = 13), biopsy (n = 12), resection (n = 3) or clinical and imaging follow-up for at least 12 months (n = 31). Results: At of the time of CEUS, the 59 nodules were diagnosed as HCC in 26 and benign lesions in 33, including 20 regenerative/dysplastic nodules (RN/DN), 11 hemangiomas, and 2 focal fat sparing. All 26 nodules with arterial phase hypervascularity without hemangioma-like features were HCC. However, CEUS misdiagnosed HCC as RN/DN in 4 cases with arterial iso- (n = 3) or hypovascularity (n = 1). CEUS correctly diagnosed all 11 hemangiomas. The sensitivity, specificity, and accuracy of CEUS for diagnosing HCC were 86.7, 100, and 93.2%. Conclusions: Arterial phase vascular intensity and pattern of CEUS are highly accurate for the diagnosis of small (1-2 cm) HCC and hemangioma in liver cirrhosis. On CEUS, arterial phase hypervascularity without a hemangioma-pattern alone may be sufficient for diagnosis of small HCC. Infrequent iso/hypovascular HCC may erroneously suggest RN/DN necessitating biopsy or close follow-up.

Pulsed WIP electron gun. Final report: design phase 1 x 70 cm cooled WIP electron gun, 1 December 1978--2 February 1979

International Nuclear Information System (INIS)

Wakalopulos, G.; Gresko, L.

1979-01-01

Presented here are design criteria for a full scale (70 cm) WIP electron gun system capable of long run operation with the following specifications: foil area approx. 70 x 1 cm, electron beam current density approx. 1 A/cm 2 , pulse length 2 , voltage -150 kV, voltage droop < 10%, Rep rate approx. 10 KHz, power approx. 20 kW, run time approx. 30 min, and jitter approx. 10 μs

Current State of ERG as Biomarker in Prostatic Adenocarcinoma.

Science.gov (United States)

Acs, Balazs; Szarvas, Tibor; Szekely, Nora; Nyirady, Peter; Szasz, A Marcell

2015-01-01

In this review we briefly discuss the possible biomarkers of prostate cancer among them we focus and analyze the relevance of TMPRSS2-ERG fusion gene in line with ERG expression in the diagnosis of prostate cancer. Starting at diagnosis and genetic alterations in prostate carcinomas, we examine the incidence and detection of the most common genetic aberration in this tumor and its protein product as well. We also examined the correlation of clinicopathological factors and prognosis with ERG and the TMPRSS2-ERG fusion oncogene and ERG expression as predictive markers.

ERG oncoprotein expression in prostate carcinoma patients of different ethnicities.

Science.gov (United States)

Kelly, Gregory M; Kong, Yink Heay; Dobi, Albert; Srivastava, Shiv; Sesterhenn, Isabell A; Pathmanathan, Rajadurai; Tan, Hui Meng; Tan, Shyh-Han; Cheong, Sok Ching

2015-01-01

Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 ( TMPRSS2 ) -ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed paraffin-embedded sections of transrectal ultrasound-guided prostate biopsy specimens, collected from 120 patients treated at the Sime Darby Medical Centre, Subang Jaya, Malaysia, were analyzed for ERG protein expression by immunohistochemistry using the anti-ERG monoclonal antibody 9FY as a surrogate for the detection of ERG fusion events. The overall frequency of ERG protein expression in the population evaluated in this study was 39.2%. Although seemingly similar to rates reported in other Asian communities, the expression of ERG was distinct amongst different ethnic groups (P=0.004). Malaysian Indian (MI) patients exhibited exceedingly high expression of ERG in their tumors, almost doubling that of Malaysian Chinese (MC) patients, whereas ERG expression was very low amongst Malay patients (12.5%). When collectively analyzing data, we observed a significant correlation between younger patients and higher ERG expression (P=0.04). The prevalence of ERG expression was significantly different amongst CaP patients of different ethnicities. The higher number of ERG-expressing tumors among MI patients suggested that the TMPRSS2-ERG fusion may be particularly important in the pathogenesis of CaP amongst this group of patients. Furthermore, the more frequent expression of ERG among the younger patients analyzed suggested an involvement of ERG in the early onset of CaP. The results of this study underline the value of using ERG status to better understand the differences in the

SPINK1 Overexpression in Localized Prostate Cancer: a Rare Event Inversely Associated with ERG Expression and Exclusive of Homozygous PTEN Deletion.

Science.gov (United States)

Huang, Kuo-Cheng; Evans, Andrew; Donnelly, Bryan; Bismar, Tarek A

2017-04-01

SPINK1 is proposed as potential prognostic marker in prostate cancer (PCA). However, its relation to PTEN and ERG in localized PCA remains unclear. The study population consisted of two independent cohorts of men treated by radical prostatectomy for localized PCA (discovery n = 218 and validation n = 129). Patterns of association between SPINK1 and each of ERG and PTEN were evaluated by immunohistochemistry and fluorescence in situ hybridization. Associations between SPINK1 expression and various pathologic parameters and clinical outcome were also investigated. SPINK1 was expressed in 15.3 % and 10.9 % of cases in the discovery and validation cohort, respectively. SPINK expression was observed in 5.56 % of high-grade prostatic intraepithelial neoplasia and 1.1 % of adjacent morphologically benign prostatic glands. SPINK1 and ERG expression were almost exclusive, with only 1.0 % of the cases co-expressing both in the same core sample. SPINK1 interfocal and within-core heterogeneity was noted in 29.2 % and 64.6 % of cases, respectively. SPINK1 expression was not significantly associated with PTEN deletion in the two cohorts (p = 0.871 for discovery cohort and p = 0.293 for validation cohort). While SPINK1 expression did occur with hemizygous PTEN deletion, there was a complete absence of SPINK1 expression in PCA showing homozygous PTEN deletion, which was confirmed in the validation cohort (p = 0.02). Despite SPINK1's association with higher Gleason score (>7) (p = 0.02), it was not associated with other pathological parameters or biochemical recurrence post-radical prostatectomy. We documented absolute exclusivity between SPINK1 overexpression and homozygous PTEN deletion in localized PCA. SPINK1 and ERG expressions are exclusive events in PCA. SPINK1 is not of added prognostic value in localized PCA.

An ERG channel inhibitor from the scorpion Buthus eupeus

DEFF Research Database (Denmark)

Korolkova, Y.V.; Kozlov, S.A.; Lipkin, A.V.

2001-01-01

and the three mutants partly inhibited the native M-like current in NG108-15 at 100 nm. The effect of the recombinant BeKm-1 on different K(+) channels was also studied. BeKm-1 inhibited hERG1 channels with an IC(50) of 3.3 nm, but had no effect at 100 nm on hEAG, hSK1, rSK2, hIK, hBK, KCNQ1/KCNE1, KCNQ2/KCNQ3......, KCNQ4 channels, and minimal effect on rELK1. Thus, BeKm-1 was shown to be a novel specific blocker of hERG1 potassium channels....

Quinoline-Flanked Diketopyrrolopyrrole Copolymers Breaking through Electron Mobility over 6 cm2 V-1 s-1 in Flexible Thin Film Devices.

Science.gov (United States)

Ni, Zhenjie; Dong, Huanli; Wang, Hanlin; Ding, Shang; Zou, Ye; Zhao, Qiang; Zhen, Yonggang; Liu, Feng; Jiang, Lang; Hu, Wenping

2018-03-01

Herein, the design and synthesis of novel π-extended quinoline-flanked diketopyrrolopyrrole (DPP) [abbreviated as QDPP] motifs and corresponding copolymers named PQDPP-T and PQDPP-2FT for high performing n-type organic field-effect transistors (OFETs) in flexible organic thin film devices are reported. Serving as DPP-flankers in backbones, quinoline is found to effectively tune copolymer optoelectric properties. Compared with TDPP and pyridine-flanked DPP (PyDPP) analogs, widened bandgaps and strengthened electron deficiency are achieved. Moreover, both hole and electron mobility are improved two orders of magnitude compared to those of PyDPP analogs (PPyDPP-T and PPyDPP-2FT). Notably, featuring an all-acceptor-incorporated backbone, PQDPP-2FT exhibits electron mobility of 6.04 cm 2 V -1 s -1 , among the highest value in OFETs fabricated on flexible substrates to date. Moreover, due to the widened bandgap and strengthened electron deficiency of PQDPP, n-channel on/off ratio over 10 5 with suppressed hole transport is first realized in the ambipolar DPP-based copolymers. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The prognostic value of SUMO1/Sentrin specific peptidase 1 (SENP1) in prostate cancer is limited to ERG-fusion positive tumors lacking PTEN deletion

International Nuclear Information System (INIS)

Burdelski, Christoph; Menan, Devi; Tsourlakis, Maria Christina; Kluth, Martina; Hube-Magg, Claudia; Melling, Nathaniel; Minner, Sarah; Koop, Christina; Graefen, Markus; Heinzer, Hans; Wittmer, Corinna; Sauter, Guido; Simon, Ronald; Schlomm, Thorsten; Steurer, Stefan; Krech, Till

2015-01-01

Posttranscriptional protein modification by SUMOylation plays an important role in tumor development and progression. In the current study we analyzed prevalence and prognostic impact of the de-SUMOylation enzyme SENP1 in prostate cancer. SENP1 expression was analyzed by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancer specimens. Results were compared to tumor phenotype, ERG status, genomic deletions of 3p, 5q, 6q and PTEN, and biochemical recurrence. SENP1 immunostaining was detectable in 34.5 % of 9,516 interpretable cancers and considered strong in 7.3 %, moderate in 14.9 % and weak in 12.3 % of cases. Strong SENP1 expression was linked to advanced pT stage (p < 0.0001), high Gleason grade (p < 0.0001), positive lymph node status (p = 0.0019), high pre-operative PSA levels (p = 0.0037), and PSA recurrence (p < 0.0001). SENP1 expression was strongly associated with positive ERG fusion status as determined by both in situ hybridization (FISH) and immunohistochemistry as well as with PTEN deletions. Detectable SENP1 immunostaining was found in 41 % of ERG positive and in 47 % of PTEN deleted cancers but in only 30 % of ERG negative and 30 % of PTEN non-deleted cancers (p < 0.0001 each). Deletions of 3p, 5q, and 6q were unrelated to SENP1 expression. Subset analyses revealed that the prognostic impact of SENP1 expression was solely driven by the subgroup of ERG positive, PTEN undeleted cancers. In this subgroup, the prognostic role of SENP1 expression was independent of the preoperative PSA level, tumor stage, Gleason grade, and the status of the resection margin. SENP1 expression has strong prognostic impact in a molecularly defined subset of cancers. This is per se not surprising as the biologic impact of each individual molecular event is likely to be dependent on its cellular environment. However, such findings challenge the concept of finding clinically relevant molecular signatures that are equally applicable to all

Magnetic domain structure and domain-wall energy in UFe8Ni2Si2 and UFe6Ni4Si2 intermetallic compounds

International Nuclear Information System (INIS)

Wyslocki, J.J.; Suski, W.; Wochowski, K.

1994-01-01

Magnetic domain structures in the UFe 8 Ni 2 Si 2 and UFe 6 Ni 4 Si 2 compounds were studied using the powder pattern method. The domain structure observed is typical for uniaxial materials. The domain-wall energy density γ was determined from the average surface domain width D s observed on surfaces perpendicular to the easy axis as equal to 16 erg/cm 2 for UFe 8 Ni 2 Si 2 and 10 erg/cm 2 for UFe 6 Ni 4 Si 2 . Moreover, the critical diameter for single domain particle D c was calculated for the studied compounds

[Follow-up on MEWDS by fundus perimetry and multifocal ERG with the SLO].

Science.gov (United States)

Bültmann, S; Martin, M; Rohrschneider, K

2002-09-01

Most conventional techniques for examination such as perimetry or ERG may not be sensitive enough to detect functional alterations due to MEWDS precisely. We report on a follow-up performed by fundus perimetry and the new technique of multifocal ERG using the scanning laser ophthalmoscope. A 24-year-old female patient (VA 0.2/0.8) was followed up for 7 weeks with these techniques as well as Octopus perimetry, fluorescence angiography, Ganzfeld ERG and biomicroscopy. Multifocal ERG stimulation (mfERG, Retiscan) was performed with the SLO. Visual acuity improved from 0.2 to 0.8 and the central relative scotoma disappeared while a relevant increase of P1-wave amplitudes in mfERG could be observed. Combining objective measurements from the fundus controlled SLO-mfERG and results from fundus perimetry enable good correlation of morphology and results, even for minor alterations of the macula only accessible by few established clinical examinations.

Crystallographic and magnetic structure of the novel compound ErGe 1.83

Science.gov (United States)

Oleksyn, O.; Schobinger-Papamantellos, P.; Ritter, C.; de Groot, C. H.; Buschow, K. H. J.

1997-02-01

The crystal structure and the magnetic ordering of the novel orthorhombic compound ErGe 2-x has been studied by neutron powder diffraction and magnetic measurements. The crystal structure belongs to the DyGe 1.85-type (space group Cmc2 1)·ErGe 2-x ( x = 0.17 (2)) orders antiferromagnetically below TN = 6 K and displays a metamagnetic behaviour. The magnetic cell has the same size as the chemical unit cell ( q = 0 ). The magnetic space group is Cmc2 1 (Sh 36173). At T = 1.5 K the magnetic moments of the two erbium sites have the same ordered magnetic moment values of 7.63 (6) μB/Er and are antiferromagnetically coupled leading to an uniaxial structure along the a direction.

GFDL CM2.1 Global Coupled Ocean-Atmosphere Model Water ...

Indian Academy of Sciences (India)

First page Back Continue Last page Overview Graphics. GFDL CM2.1 Global Coupled Ocean-Atmosphere Model Water Hosing Experiment with 1 Sv equivalent of Freshening Control Expt: 100 yrs After Hosing: 300 yrs.

Dynamics of hERG closure allow novel insights into hERG blocking by small molecules.

Science.gov (United States)

Schmidtke, Peter; Ciantar, Marine; Theret, Isabelle; Ducrot, Pierre

2014-08-25

Today, drug discovery routinely uses experimental assays to determine very early if a lead compound can yield certain types of off-target activity. Among such off targets is hERG. The ion channel plays a primordial role in membrane repolarization and altering its activity can cause severe heart arrhythmia and sudden death. Despite routine tests for hERG activity, rather little information is available for helping medicinal chemists and molecular modelers to rationally circumvent hERG activity. In this article novel insights into the dynamics of hERG channel closure are described. Notably, helical pairwise closure movements have been observed. Implications and relations to hERG inactivation are presented. Based on these dynamics novel insights on hERG blocker placement are presented, compared to literature, and discussed. Last, new evidence for horizontal ligand positioning is shown in light of former studies on hERG blockers.

Data on the construction of a recombinant HEK293 cell line overexpressing hERG potassium channel and examining the presence of hERG mRNA and protein expression

Directory of Open Access Journals (Sweden)

Yi Fan Teah

2017-10-01

Full Text Available The data presented in this article are related to the research article entitled “The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (IKr and human ether-a-go-go-related gene (hERG expression” (Y.F. Teah, M.A. Abduraman, A. Amanah, M.I. Adenan, S.F. Sulaiman, M.L. Tan [1], which the possible hERG blocking properties of deoxyelephantopin were investigated. This article describes the construction of human embryonic kidney 293 (HEK293 cells overexpressing HERG potassium channel and verification of the presence of hERG mRNA and protein expression in this recombinant cell line.

Functional recovery after experimental RPE debridement, mfERG studies in a porcine model

DEFF Research Database (Denmark)

Sørensen, Nina Buus; Lassota, Nathan; Kyhn, Maria Voss

2013-01-01

BACKGROUND: The correlation between histologically identified regeneration of retinal pigment epithelium (RPE) and functional outcome measured by multifocal electroretinography (mfERG) following surgical debridement is examined in a porcine model. In humans, visual acuity is reduced in diseases......, and by brushing the Bruch's membrane with a silicone catheter. Immediately following surgery (baseline) and after 2 and 6 weeks respectively, the animals were examined by mfERG, fundus photographs (FPs), fluorescein angiograms (FAs), and histopathology. RESULTS: The mfERG P1 amplitude was decreased 2 weeks (T2....... CONCLUSION: This is the first study to show that the histological regeneration of hypopigmented RPE correlates to a return of the retinal function, measured by mfERG....

Intrafocal heterogeneity of ERG protein expression and gene fusion pattern in prostate cancer.

Science.gov (United States)

Suh, Ja Hee; Park, Jeong Hwan; Lee, Cheol; Moon, Kyung Chul

2017-10-01

Prostate cancer is considered to be highly heterogeneous, with various morphologic features and biologic behaviors. The TMPRSS2-ERG gene fusion is the most frequently observed genetic aberration in prostate cancer. The aim of this study was to elucidate the intrafocal heterogeneity of ERG gene fusion status. ERG immunohistochemistry (IHC) was performed in samples from 168 prostate cancer patients who had undergone radical prostatectomy, and 40 cases showing ERG-positive IHC staining were selected for tissue microarray (TMA) construction. Two to six representative cores were selected from each tumor focus. In the cases with heterogeneous ERG IHC staining intensity, the areas showing different intensities were separately selected. Using the TMA blocks, IHC and fluorescence in situ hybridization (FISH) were conducted to evaluate the heterogeneity of ERG protein expression and ERG fusion gene patterns, respectively, in a single tumor focus. Heterogeneity of ERG IHC staining was defined as the simultaneous presence of negative and positive cores in the same tumor focus. Heterogeneity of ERG FISH was defined by the presence of cores with positive and negative FISH signals or cores with break-apart and interstitial deletion FISH signals in the same tumor focus. A total of 202 TMA cores were isolated from 40 ERG-positive cases. Of the 202 total cores, 19 were negative for ERG IHC staining, and 46 showed 1+, 52 showed 2+, and 85 showed 3+ ERG staining intensity. Eleven cores were negative for ERG FISH signal, 119 cores showed ERG break-apart FISH signals, and the remaining 72 cores revealed interstitial deletion. Intrafocal heterogeneity of ERG IHC staining was found in 20% (8/40) of cases, and intrafocal heterogeneity of ERG gene fusion pattern was found in 32.5% (13/40) of cases. In summary, this study showed significantly frequent intrafocal heterogeneity of ERG protein expression, gene fusion status and fusion pattern. This heterogeneity can be caused by the development

Effects of proton irradiation and temperature on 1 ohm-cm and 10 ohm-cm silicon solar cells

Science.gov (United States)

Nicoletta, C. A.

1973-01-01

The 1 ohm-cm and 10 ohm-cm silicon solar cells were exposed to 1.0 MeV protons at a fixed flux of 10 to the 9th power P/sq cm-sec and fluences of 10 to the 10th power, 10 to the 11th power, 10 to the 12th power and 3 X 10 to the 12th power P/sq cm. I-V curves of the cells were made at room temperature, 65 C and 165 C after each irradiation. A value of 139.5 mw/sq cm was taken as AMO incident energy rate per unit area. Degradation occurred for both uncovered 1 ohm-cm and 10 ohm-cm cells. Efficiencies are generally higher than those of comparable U.S. cells tested earlier. Damage (loss in maximum power efficiency) with proton fluence is somewhat higher for 10 ohm-cm cells, measured at the three temperatures, for fluences above 2 X 10 to the 11th power P/sq cm. Cell efficiency, as expected, changes drastically with temperature.

Highly accurate potential energy surface, dipole moment surface, rovibrational energy levels, and infrared line list for {sup 32}S{sup 16}O{sub 2} up to 8000 cm{sup −1}

Energy Technology Data Exchange (ETDEWEB)

Huang, Xinchuan, E-mail: Xinchuan.Huang-1@nasa.gov, E-mail: Timothy.J.Lee@nasa.gov [SETI Institute, 189 Bernardo Ave, Suite No. 100, Mountain View, California 94043 (United States); Schwenke, David W., E-mail: David.W.Schwenke@nasa.gov [MS T27B-1, NAS Facility, NASA Ames Research Center, Moffett Field, California 94035 (United States); Lee, Timothy J., E-mail: Xinchuan.Huang-1@nasa.gov, E-mail: Timothy.J.Lee@nasa.gov [MS 245-1, Space Science and Astrobiology Division, NASA Ames Research Center, Moffett Field, California 94035 (United States)

2014-03-21

A purely ab initio potential energy surface (PES) was refined with selected {sup 32}S{sup 16}O{sub 2} HITRAN data. Compared to HITRAN, the root-mean-squares error (σ{sub RMS}) for all J = 0–80 rovibrational energy levels computed on the refined PES (denoted Ames-1) is 0.013 cm{sup −1}. Combined with a CCSD(T)/aug-cc-pV(Q+d)Z dipole moment surface (DMS), an infrared (IR) line list (denoted Ames-296K) has been computed at 296 K and covers up to 8000 cm{sup −1}. Compared to the HITRAN and CDMS databases, the intensity agreement for most vibrational bands is better than 85%–90%. Our predictions for {sup 34}S{sup 16}O{sub 2} band origins, higher energy {sup 32}S{sup 16}O{sub 2} band origins and missing {sup 32}S{sup 16}O{sub 2} IR bands have been verified by most recent experiments and available HITRAN data. We conclude that the Ames-1 PES is able to predict {sup 32/34}S{sup 16}O{sub 2} band origins below 5500 cm{sup −1} with 0.01–0.03 cm{sup −1} uncertainties, and the Ames-296K line list provides continuous, reliable and accurate IR simulations. The K{sub a}-dependence of both line position and line intensity errors is discussed. The line list will greatly facilitate SO{sub 2} IR spectral experimental analysis, as well as elimination of SO{sub 2} lines in high-resolution astronomical observations.

Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer

International Nuclear Information System (INIS)

FitzGerald, Liesel M; Cox, Michael E; Ostrander, Elaine A; Stanford, Janet L; Huntsman, David G; Agalliu, Ilir; Johnson, Karynn; Miller, Melinda A; Kwon, Erika M; Hurtado-Coll, Antonio; Fazli, Ladan; Rajput, Ashish B; Gleave, Martin E

2008-01-01

The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer. In this study, fluorescent in situ hybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of four ERG and one TMPRSS2 SNPs using germline DNA was also performed in a sample of the cases (n = 127). Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22–3.93), nor was there a significant difference in cause-specific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23–3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = 0.45–3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of the TMPRSS2 SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03). If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer

Frequency of gamma-ray bursts greater than 3 x 10 to the -6th erg/sq cm

International Nuclear Information System (INIS)

Share, G.H.; Wood, K.; Meekins, J.; Yantis, D.J.

1982-01-01

Results are presented for gamma-ray burst observations with the Large Area Sky Survey instrument on HEAD-1. It is noted that during the time HEAD-1 was operational, the instrument detected at least 12 confirmed gamma-ray bursts with intensities greater than 3 microerg/sq cm and identified six additional unconfirmed bursts. The rates of gamma-ray bursts are estimated to be about 125 per yr for intensities greater than 3 microserg/sq cm and approximately 50 per yr for intensities preater than 10 microerg/yr. The data are shown to yield a log N - log S relation for gamma-ray bursts that is consistent with a spherical distrubution of sources within the Galaxy and having a broad range of intrinsic luminosities

NuSTAR and XMM-Newton observations of luminous, heavily obscured, WISE-selected quasars at z ∼ 2

Energy Technology Data Exchange (ETDEWEB)

Stern, D.; Eisenhardt, P. R. M. [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Mail Stop 169-221, Pasadena, CA 91109 (United States); Lansbury, G. B.; Alexander, D. M.; Del Moro, A.; Gandhi, P. [Department of Physics, University of Durham, South Road, Durham DH1 3LE (United Kingdom); Assef, R. J. [Núcleo de Astronomía de la Facultad de Ingeniería, Universidad Diego Portales, Av. Ejército Libertador 441, Santiago (Chile); Brandt, W. N.; Griffith, R. L. [Department of Astronomy and Astrophysics, The Pennsylvania State University, 525 Davey Lab, University Park, PA 16802 (United States); Ballantyne, D. R. [Center for Relativistic Astrophysics, School of Physics, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Baloković, M.; Bridge, C. [Cahill Center for Astronomy and Astrophysics, California Institute of Technology, Pasadena, CA 91125 (United States); Bauer, F. E. [Instituto de Astrofísica, Facultad de Física, Pontificia Universidad Católica de Chile, 306, Santiago 22 (Chile); Benford, D. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Blain, A. [Physics and Astronomy, University of Leicester, 1 University Road, Leicester, LE1 7RH (United Kingdom); Boggs, S. E.; Craig, W. W. [Space Sciences Laboratory, University of California, Berkeley, 7 Gauss Way, Berkeley, CA 94720-7450 (United States); Brightman, M. [Max-Planck-Institut für extraterrestrische Physik, Giessenbachstrasse 1, D-85748, Garching bei München (Germany); Christensen, F. E. [Danish Technical University, DK-2800 Lyngby (Denmark); Comastri, A., E-mail: daniel.k.stern@jpl.nasa.gov [INAF Osservatorio Astronomico di Bologna, via Ranzani 1, I-40127, Bologna (Italy); and others

2014-10-20

We report on a NuSTAR and XMM-Newton program that has observed a sample of three extremely luminous, heavily obscured WISE-selected active galactic nuclei (AGNs) at z ∼ 2 across a broad X-ray band (0.1 – 79 keV). The parent sample, selected to be faint or undetected in the WISE 3.4 μm (W1) and 4.6 μm (W2) bands but bright at 12 μm (W3) and 22 μm (W4), are extremely rare, with only ∼1000 so-called 'W1W2-dropouts' across the extragalactic sky. Optical spectroscopy reveals typical redshifts of z ∼ 2 for this population, implying rest-frame mid-IR luminosities of νL {sub ν}(6 μm) ∼ 6 × 10{sup 46} erg s{sup –1} and bolometric luminosities that can exceed L {sub bol} ∼ 10{sup 14} L {sub ☉}. The corresponding intrinsic, unobscured hard X-ray luminosities are L(2-10 keV) ∼ 4 × 10{sup 45} erg s{sup –1} for typical quasar templates. These are among the most AGNs known, though the optical spectra rarely show evidence of a broad-line region and the selection criteria imply heavy obscuration even at rest-frame 1.5 μm. We designed our X-ray observations to obtain robust detections for gas column densities N {sub H} ≤ 10{sup 24} cm{sup –2}. In fact, the sources prove to be fainter than these predictions. Two of the sources were observed by both NuSTAR and XMM-Newton, with neither being detected by NuSTAR (f {sub 3-24} {sub keV} ≲ 10{sup –13} erg cm{sup –2} s{sup –1}), and one being faintly detected by XMM-Newton (f {sub 0.5-10} {sub keV} ∼ 5 × 10{sup –15} erg cm{sup –2} s{sup –1}). A third source was observed only with XMM-Newton, yielding a faint detection (f {sub 0.5-10} {sub keV} ∼ 7 × 10{sup –15} erg cm{sup –2} s{sup –1}). The X-ray data imply these sources are either X-ray weak, or are heavily obscured by column densities N {sub H} ≳ 10{sup 24} cm{sup –2}. The combined X-ray and mid-IR analysis seems to favor this second possibility, implying the sources are extremely obscured, consistent with Compton

NuSTAR and XMM-Newton observations of luminous, heavily obscured, WISE-selected quasars at z ∼ 2

International Nuclear Information System (INIS)

Stern, D.; Eisenhardt, P. R. M.; Lansbury, G. B.; Alexander, D. M.; Del Moro, A.; Gandhi, P.; Assef, R. J.; Brandt, W. N.; Griffith, R. L.; Ballantyne, D. R.; Baloković, M.; Bridge, C.; Bauer, F. E.; Benford, D.; Blain, A.; Boggs, S. E.; Craig, W. W.; Brightman, M.; Christensen, F. E.; Comastri, A.

2014-01-01

We report on a NuSTAR and XMM-Newton program that has observed a sample of three extremely luminous, heavily obscured WISE-selected active galactic nuclei (AGNs) at z ∼ 2 across a broad X-ray band (0.1 – 79 keV). The parent sample, selected to be faint or undetected in the WISE 3.4 μm (W1) and 4.6 μm (W2) bands but bright at 12 μm (W3) and 22 μm (W4), are extremely rare, with only ∼1000 so-called 'W1W2-dropouts' across the extragalactic sky. Optical spectroscopy reveals typical redshifts of z ∼ 2 for this population, implying rest-frame mid-IR luminosities of νL ν (6 μm) ∼ 6 × 10 46 erg s –1 and bolometric luminosities that can exceed L bol ∼ 10 14 L ☉ . The corresponding intrinsic, unobscured hard X-ray luminosities are L(2-10 keV) ∼ 4 × 10 45 erg s –1 for typical quasar templates. These are among the most AGNs known, though the optical spectra rarely show evidence of a broad-line region and the selection criteria imply heavy obscuration even at rest-frame 1.5 μm. We designed our X-ray observations to obtain robust detections for gas column densities N H ≤ 10 24 cm –2 . In fact, the sources prove to be fainter than these predictions. Two of the sources were observed by both NuSTAR and XMM-Newton, with neither being detected by NuSTAR (f 3-24 keV ≲ 10 –13 erg cm –2 s –1 ), and one being faintly detected by XMM-Newton (f 0.5-10 keV ∼ 5 × 10 –15 erg cm –2 s –1 ). A third source was observed only with XMM-Newton, yielding a faint detection (f 0.5-10 keV ∼ 7 × 10 –15 erg cm –2 s –1 ). The X-ray data imply these sources are either X-ray weak, or are heavily obscured by column densities N H ≳ 10 24 cm –2 . The combined X-ray and mid-IR analysis seems to favor this second possibility, implying the sources are extremely obscured, consistent with Compton-thick, luminous quasars. The discovery of a significant population of heavily obscured, extremely luminous AGNs would not conform to the standard

Dipole polarizability of 2 3S1 and 2 1S0 metastable helium measured by the electric deflection time-of-flight method

International Nuclear Information System (INIS)

Crosby, D.A.; Zorn, J.C.

1977-01-01

The static dipole polarizability of helium atoms in the metastable 2 3 S 1 and 2 1 S 0 states has been determined by measuring the deflection of a beam of excited helium atoms that is caused by an inhomogeneous electric field of known properties. The necessary velocity distribution information is obtained from time-of-flight measurements, and a resonance quenching technique made it possible to distinguish the singlet and triplet components of the beam. The results, α(2 3 S 1 ) = (44.6 +- 3) x 10 -24 cm 3 and α(2 1 S 0 ) = (108 +- 13) x 10 -24 cm 3 , agree with the theoretical value that has been used to calibrate earlier polarizability measurements of the alkali metals and the heavier noble gases

Channel sialic acids limit hERG channel activity during the ventricular action potential.

Science.gov (United States)

Norring, Sarah A; Ednie, Andrew R; Schwetz, Tara A; Du, Dongping; Yang, Hui; Bennett, Eric S

2013-02-01

Activity of human ether-a-go-go-related gene (hERG) 1 voltage-gated K(+) channels is responsible for portions of phase 2 and phase 3 repolarization of the human ventricular action potential. Here, we questioned whether and how physiologically and pathophysiologically relevant changes in surface N-glycosylation modified hERG channel function. Voltage-dependent hERG channel gating and activity were evaluated as expressed in a set of Chinese hamster ovary (CHO) cell lines under conditions of full glycosylation, no sialylation, no complex N-glycans, and following enzymatic deglycosylation of surface N-glycans. For each condition of reduced glycosylation, hERG channel steady-state activation and inactivation relationships were shifted linearly by significant depolarizing ∼9 and ∼18 mV, respectively. The hERG window current increased significantly by 50-150%, and the peak shifted by a depolarizing ∼10 mV. There was no significant change in maximum hERG current density. Deglycosylated channels were significantly more active (20-80%) than glycosylated controls during phases 2 and 3 of action potential clamp protocols. Simulations of hERG current and ventricular action potentials corroborated experimental data and predicted reduced sialylation leads to a 50-70-ms decrease in action potential duration. The data describe a novel mechanism by which hERG channel gating is modulated through physiologically and pathophysiologically relevant changes in N-glycosylation; reduced channel sialylation increases hERG channel activity during the action potential, thereby increasing the rate of action potential repolarization.

The elusive 2s3s1S level in B II

International Nuclear Information System (INIS)

Martinson, I; Awaya, Y; Ekberg, J O; Kink, I; Mannervik, S; Ryabtsev, A N

2003-01-01

It has been known for nearly 30 years that the theoretical and experimental values for the energy of the 2s3s 1 S level in singly ionized boron, B II, differ strongly. Since there is much better agreement for other B II levels, it has been concluded that the experimental value for 2s3s 1 S must be revised. Despite a number of recordings over the years of sliding-spark, hollow cathode and beam-foil spectra, this level has not been located. We have now performed another beam-foil experiment, using higher resolution and sensitivity than in most previous studies. By combining these new data with previous results, we have identified transitions from the 2s4p, 2s5p and 2p3s 1 P levels to 2s3s 1 S, the excitation energy (137 622 ± 3 cm -1 ) of which is now well established and in excellent agreement with theoretical predictions

Dynamic regulation of canonical TGFβ signalling by endothelial transcription factor ERG protects from liver fibrogenesis.

Science.gov (United States)

Dufton, Neil P; Peghaire, Claire R; Osuna-Almagro, Lourdes; Raimondi, Claudio; Kalna, Viktoria; Chuahan, Abhishek; Webb, Gwilym; Yang, Youwen; Birdsey, Graeme M; Lalor, Patricia; Mason, Justin C; Adams, David H; Randi, Anna M

2017-10-12

The role of the endothelium in protecting from chronic liver disease and TGFβ-mediated fibrosis remains unclear. Here we describe how the endothelial transcription factor ETS-related gene (ERG) promotes liver homoeostasis by controlling canonical TGFβ-SMAD signalling, driving the SMAD1 pathway while repressing SMAD3 activity. Molecular analysis shows that ERG binds to SMAD3, restricting its access to DNA. Ablation of ERG expression results in endothelial-to-mesenchymal transition (EndMT) and spontaneous liver fibrogenesis in EC-specific constitutive hemi-deficient (Erg cEC-Het ) and inducible homozygous deficient mice (Erg iEC-KO ), in a SMAD3-dependent manner. Acute administration of the TNF-α inhibitor etanercept inhibits carbon tetrachloride (CCL 4 )-induced fibrogenesis in an ERG-dependent manner in mice. Decreased ERG expression also correlates with EndMT in tissues from patients with end-stage liver fibrosis. These studies identify a pathogenic mechanism where loss of ERG causes endothelial-dependent liver fibrogenesis via regulation of SMAD2/3. Moreover, ERG represents a promising candidate biomarker for assessing EndMT in liver disease.The transcription factor ERG is key to endothelial lineage specification and vascular homeostasis. Here the authors show that ERG balances TGFβ signalling through the SMAD1 and SMAD3 pathways, protecting the endothelium from endothelial-to-mesenchymal transition and consequent liver fibrosis in mice via a SMAD3-dependent mechanism.

The 590 cm-1 B_1g feature in underdoped Bi_2Sr_2CaCu_2O_8+δ

Science.gov (United States)

Hewitt, Kevin C.; Wang, N. L.; Irwin, J. C.; Pooke, D. M.; Pantoja, A. E.; Trodahl, H. J.

1999-05-01

Raman scattering studies have been performed on underdoped Bi_2Sr_2CaCu_2O_8+δ. In single crystals underdoped by oxygen removal, a 590 cm-1 peak is observed in the B_1g spectrum. The feature is observed to soften in frequency by 3.8% with isotopic exchange of ^16O by ^18O. In contrast, the 590 cm-1 peak is not observed in crystals underdoped by Y substitution which suggests that it corresponds to a disorder induced vibrational mode. We have also found that underdoping leads to a depletion of low energy spectral weight from regions of the Fermi surface located near the Brillouin zone axes.

On the 590cm-1 B1g feature in underdoped Bi2Sr2CaCu2O8+delta

OpenAIRE

Hewitt, Kevin C.; Wang, N. L.; Irwin, J. C.; Pooke, D. M.; Pantoja, A. E.; Trodahl, H. J.

1999-01-01

Raman scattering studies have been performed on underdoped Bi2Sr2CaCu2O8+delta. In single crystals underdoped by oxygen removal, a 590 cm-1 peak is observed in the B1g spectrum. The feature is observed to soften in frequency by 3.8% with isotopic exchange for 16-O by 18-O. In contrast, the 590cm-1 peak is not observed in crystals underdoped by Y substitution which suggests that it correspond to a disorder induced vibrational mode. We have also found that underdoping leads to a depletion of lo...

INTEGRAL/JEM-X detection of a type-I X-ray burst from MAXI J1421-613

DEFF Research Database (Denmark)

Bozzo, E.; Bazzano, A.; Kuulkers, Erik

2014-01-01

. The onset of the burst occurred on 2014 January 10 at 19:05 UTC, and the total event as observed by JEM-X lasted for about 20 s (3-25 keV). The average spectrum of the burst could be roughly described by using a black-body model with temperature kT~1 keV. The corresponding flux was 1.7E-9 erg/cm^2/s...... (translating into a luminosity of 1.3E37 erg/s at 8 kpc; 3-10 keV). We estimated a persistent flux outside the burst of 7E-10 erg/cm^2/s (3-25 keV). This detection reveals that MAXI J1421-613 is a newly discovered X-ray bursting transient source, thus hosting an accreting neutron star....

A novel assessment of nefazodone-induced hERG inhibition by electrophysiological and stereochemical method

Energy Technology Data Exchange (ETDEWEB)

Shin, Dae-Seop; Park, Myoung Joo [Drug Discovery Platform Technology Research Group, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of); Lee, Hyang-Ae [Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of); Lee, Joo Yun; Chung, Hee-Chung; Yoo, Dae Seok; Chae, Chong Hak [Drug Discovery Platform Technology Research Group, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of); Park, Sang-Joon [College of Veterinary Medicine, Kyungpook National University, Daegu (Korea, Republic of); Kim, Ki-Suk [Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of); Bae, Myung Ae, E-mail: mbae@krict.re.kr [Drug Discovery Platform Technology Research Group, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of)

2014-02-01

Nefazodone was used widely as an antidepressant until it was withdrawn from the U.S. market in 2004 due to hepatotoxicity. We have investigated methods to predict various toxic effects of drug candidates to reduce the failure rate of drug discovery. An electrophysiological method was used to assess the cardiotoxicity of drug candidates. Small molecules, including withdrawn drugs, were evaluated using a patch-clamp method to establish a database of hERG inhibition. Nefazodone inhibited hERG channel activity in our system. However, nefazodone-induced hERG inhibition indicated only a theoretical risk of cardiotoxicity. Nefazodone inhibited the hERG channel in a concentration-dependent manner with an IC{sub 50} of 45.3 nM in HEK-293 cells. Nefazodone accelerated both the recovery from inactivation and its onset. Nefazodone also accelerated steady-state inactivation, although it did not modify the voltage-dependent character. Alanine mutants of hERG S6 and pore region residues were used to identify the nefazodone-binding site on hERG. The hERG S6 point mutants Y652A and F656A largely abolished the inhibition by nefazodone. The pore region mutant S624A mildly reduced the inhibition by nefazodone but T623A had little effect. A docking study showed that the aromatic rings of nefazodone interact with Y652 and F656 via π–π interactions, while an amine interacted with the S624 residue in the pore region. In conclusion, Y652 and F656 in the S6 domain play critical roles in nefazodone binding. - Highlights: • Nefazodone inhibits hERG channels with an IC{sub 50} of 45.3 nM in HEK-293 cells. • Nefazodone blocks hERG channels by binding to the open channels. • Y652 and F656 are important for binding of nefazodone. • The aromatic rings of nefazodone interact with Y652 and F656 via π–π interactions.

MicroRNA-224 targets ERG2 and contributes to malignant progressions of meningioma

International Nuclear Information System (INIS)

Wang, Maomao; Deng, Xiaodong; Ying, Qi; Jin, Tingyan; Li, Ming; Liang, Chong

2015-01-01

MicroRNA-224 is overexpressed in various malignant tumors with poor prognosis, which plays a critical role in biological processes including cell proliferation, apoptosis and several developmental and physiological progressions. However, the potential association between miR-224 and clinical outcome in patients with meningiomas remains unknown. Here, we investigate miR-224 expression and biological functions in meningiomas. MiR-224 expression was measured by Northern blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in meningioma and normal brain tissues. Kaplan–Meier analysis and Cox regression analysis were used to exam its correlation with clinicopathological features and prognostic value. The biological effects of miR-224 on the cell proliferation and apoptosis in meningioma cells were examined by MTT assay and apoptosis assay. We found the expression levels of miR-224 were significantly higher in meningioma tissues than that in normal brain, positively correlated with advanced pathological grade. Kaplan–Meier analysis indicated that meningioma patients with low miR-224 expression exhibited significantly prolonged overall and recurrence-free survival. Furthermore, we demonstrated that ERG2 was an identical candidate target gene of MiR-224 in vitro. Our results indicated that downregulation of miR-224 suppressed cell growth and resulted in the enhancement of cell apoptosis through activation of the ERG2-BAK-induced apoptosis pathway. Our findings imply the miR-224 expression could predict the overall survival and recurrence-free survival of patients with meningioma and it might be a promising therapeutic target for treating malignant meningiomas. - Highlights: • MiR-224 expression is correlates with prognosis in meningioma patients. • ERG2 is a novel downstream target of miR-224. • MiR-224 suppressed cell growth and enhanced apoptosis in IOMM-Lee and CH157 cells. • MiR-224 is an upstream regulator of the ERG2

Role of the pH in state-dependent blockade of hERG currents

Science.gov (United States)

Wang, Yibo; Guo, Jiqing; Perissinotti, Laura L.; Lees-Miller, James; Teng, Guoqi; Durdagi, Serdar; Duff, Henry J.; Noskov, Sergei Yu.

2016-10-01

Mutations that reduce inactivation of the voltage-gated Kv11.1 potassium channel (hERG) reduce binding for a number of blockers. State specific block of the inactivated state of hERG block may increase risks of drug-induced Torsade de pointes. In this study, molecular simulations of dofetilide binding to the previously developed and experimentally validated models of the hERG channel in open and open-inactivated states were combined with voltage-clamp experiments to unravel the mechanism(s) of state-dependent blockade. The computations of the free energy profiles associated with the drug block to its binding pocket in the intra-cavitary site display startling differences in the open and open-inactivated states of the channel. It was also found that drug ionization may play a crucial role in preferential targeting to the open-inactivated state of the pore domain. pH-dependent hERG blockade by dofetilie was studied with patch-clamp recordings. The results show that low pH increases the extent and speed of drug-induced block. Both experimental and computational findings indicate that binding to the open-inactivated state is of key importance to our understanding of the dofetilide’s mode of action.

Evaluation of ERG and SPINK1 by Immunohistochemical Staining and Clinicopathological Outcomes in a Multi-Institutional Radical Prostatectomy Cohort of 1067 Patients.

Directory of Open Access Journals (Sweden)

James D Brooks

Full Text Available Distinguishing between patients with early stage, screen detected prostate cancer who must be treated from those that can be safely watched has become a major issue in prostate cancer care. Identification of molecular subtypes of prostate cancer has opened the opportunity for testing whether biomarkers that characterize these subtypes can be used as biomarkers of prognosis. Two established molecular subtypes are identified by high expression of the ERG oncoprotein, due to structural DNA alterations that encode for fusion transcripts in approximately ½ of prostate cancers, and over-expression of SPINK1, which is purportedly found only in ERG-negative tumors. We used a multi-institutional prostate cancer tissue microarray constructed from radical prostatectomy samples with associated detailed clinical data and with rigorous selection of recurrent and non-recurrent cases to test the prognostic value of immunohistochemistry staining results for the ERG and SPINK1 proteins. In univariate analysis, ERG positive cases (419/1067; 39% were associated with lower patient age, pre-operative serum PSA levels, lower Gleason scores (≤ 3+4=7 and improved recurrence free survival (RFS. On multivariate analysis, ERG status was not correlated with RFS, disease specific survival (DSS or overall survival (OS. High-level SPINK1 protein expression (33/1067 cases; 3% was associated with improved RFS on univariate and multivariate Cox regression analysis. Over-expression of either protein was not associated with clinical outcome. While expression of ERG and SPINK1 proteins was inversely correlated, it was not mutually exclusive since 3 (0.28% cases showed high expression of both. While ERG and SPINK1 appear to identify discrete molecular subtypes of prostate cancer, only high expression of SPINK1 was associated with improved clinical outcome. However, by themselves, neither ERG nor SPINK1 appear to be useful biomarkers for prognostication of early stage prostate

Evaluation of ERG and SPINK1 by Immunohistochemical Staining and Clinicopathological Outcomes in a Multi-Institutional Radical Prostatectomy Cohort of 1067 Patients.

Science.gov (United States)

Brooks, James D; Wei, Wei; Hawley, Sarah; Auman, Heidi; Newcomb, Lisa; Boyer, Hilary; Fazli, Ladan; Simko, Jeff; Hurtado-Coll, Antonio; Troyer, Dean A; Carroll, Peter R; Gleave, Martin; Lance, Raymond; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; Feng, Ziding; McKenney, Jesse K

2015-01-01

Distinguishing between patients with early stage, screen detected prostate cancer who must be treated from those that can be safely watched has become a major issue in prostate cancer care. Identification of molecular subtypes of prostate cancer has opened the opportunity for testing whether biomarkers that characterize these subtypes can be used as biomarkers of prognosis. Two established molecular subtypes are identified by high expression of the ERG oncoprotein, due to structural DNA alterations that encode for fusion transcripts in approximately ½ of prostate cancers, and over-expression of SPINK1, which is purportedly found only in ERG-negative tumors. We used a multi-institutional prostate cancer tissue microarray constructed from radical prostatectomy samples with associated detailed clinical data and with rigorous selection of recurrent and non-recurrent cases to test the prognostic value of immunohistochemistry staining results for the ERG and SPINK1 proteins. In univariate analysis, ERG positive cases (419/1067; 39%) were associated with lower patient age, pre-operative serum PSA levels, lower Gleason scores (≤ 3+4=7) and improved recurrence free survival (RFS). On multivariate analysis, ERG status was not correlated with RFS, disease specific survival (DSS) or overall survival (OS). High-level SPINK1 protein expression (33/1067 cases; 3%) was associated with improved RFS on univariate and multivariate Cox regression analysis. Over-expression of either protein was not associated with clinical outcome. While expression of ERG and SPINK1 proteins was inversely correlated, it was not mutually exclusive since 3 (0.28%) cases showed high expression of both. While ERG and SPINK1 appear to identify discrete molecular subtypes of prostate cancer, only high expression of SPINK1 was associated with improved clinical outcome. However, by themselves, neither ERG nor SPINK1 appear to be useful biomarkers for prognostication of early stage prostate cancer.

ERG oncoprotein expression in prostate carcinoma patients of different ethnicities

OpenAIRE

KELLY, GREGORY M.; KONG, YINK HEAY; DOBI, ALBERT; SRIVASTAVA, SHIV; SESTERHENN, ISABELL A.; PATHMANATHAN, RAJADURAI; TAN, HUI MENG; TAN, SHYH-HAN; CHEONG, SOK CHING

2014-01-01

Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 (TMPRSS2)-ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed para...

11.72-sq cm Active-Area Wafer Interconnected PiN Diode Pulsed at 64 kA Dissipates 382 J and Exhibits an Action of 1.7 MA(sup 2)-s

Science.gov (United States)

2012-01-30

calculated action exceeded 1.7 MA2 -s. Preliminary efforts on high voltage diode interconnection have produced quarter wafer interconnected PiN...was packaged in a “hockey-puck” configuration and pulsed to 64 kA, dissipating 382 J with a calculated action exceeding 1.7 MA2 -s. II. FULL...epitaxial layers are utilized. 11.72-cm2 Active-area Wafer Interconnected PiN Diode pulsed at 64 kA dissipates 382 J and exhibits an action of 1.7 MA2 -s

4-CM2 CuInGaSe2 based solar cells

International Nuclear Information System (INIS)

Devaney, W.E.; Stewart, J.M.; Chen, W.S.

1990-01-01

This paper reports that polycrystalline thin-film solar cells with the structure ZnO/CdZnS/CuInGaSe 2 have been fabricated with larger single cell areas than have been previously reported. A cell of area 4-cm 2 has been made with an Am1.5, 100 mW/cm 2 total area conversion efficiency of (11.1% 912.0% active area) and AMO conversion efficiency of 10.0% (10.9% active area). The CuInGaSe 2 layer had a gallium to indium ratio of 0.26:0.74 with a band gap of approximately 1.15 eV. The cells use an isolated tab design for the negative (grid) contact, demonstrating the ability to pattern the semiconductor layers. Such CuInGaSe 2 based cells may be suitable both for large area terrestrial applications and for single-junction space cell applications

Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis.

Science.gov (United States)

Iwamoto, Masahiro; Tamamura, Yoshihiro; Koyama, Eiki; Komori, Toshihisa; Takeshita, Nobuo; Williams, Julie A; Nakamura, Takashi; Enomoto-Iwamoto, Motomi; Pacifici, Maurizio

2007-05-01

Articular cartilage and synovial joints are critical for skeletal function, but the mechanisms regulating their development are largely unknown. In previous studies we found that the ets transcription factor ERG and its alternatively-spliced variant C-1-1 have roles in joint formation in chick. Here, we extended our studies to mouse. We found that ERG is also expressed in developing mouse limb joints. To test regulation of ERG expression, beads coated with the joint master regulator protein GDF-5 were implanted close to incipient joints in mouse limb explants; this led to rapid and strong ectopic ERG expression. We cloned and characterized several mammalian ERG variants and expressed a human C-1-1 counterpart (hERG3Delta81) throughout the cartilaginous skeleton of transgenic mice, using Col2a1 gene promoter/enhancer sequences. The skeletal phenotype was severe and neonatal lethal, and the transgenic mice were smaller than wild type littermates and their skeletons were largely cartilaginous. Limb long bone anlagen were entirely composed of chondrocytes actively expressing collagen IX and aggrecan as well as articular markers such as tenascin-C. Typical growth plates were absent and there was very low expression of maturation and hypertrophy markers, including Indian hedgehog, collagen X and MMP-13. The results suggest that ERG is part of molecular mechanisms leading chondrocytes into a permanent developmental path and become joint forming cells, and may do so by acting downstream of GDF-5.

Assessing the Contribution of the Oscillatory Potentials to the Genesis of the Photopic ERG with the Discrete Wavelet Transform.

Science.gov (United States)

Gauvin, Mathieu; Dorfman, Allison L; Trang, Nataly; Gauthier, Mercedes; Little, John M; Lina, Jean-Marc; Lachapelle, Pierre

2016-01-01

The electroretinogram (ERG) is composed of slow (i.e., a-, b-waves) and fast (i.e., oscillatory potentials: OPs) components. OPs have been shown to be preferably affected in some diseases (such as diabetic retinopathy), while the a- and b-waves remain relatively intact. The purpose of this study was to determine the contribution of OPs to the building of the ERG and to examine whether a signal mostly composed of OPs could also exist. DWT analyses were performed on photopic ERGs (flash intensities: -2.23 to 2.64 log cd·s·m -2 in 21 steps) obtained from normal subjects ( n = 40) and patients ( n = 21) affected with a retinopathy. In controls, the %OP value (i.e., OPs energy/ERG energy) is stimulus- and amplitude-independent (range: 56.6-61.6%; CV = 6.3%). In contrast, the %OPs measured from the ERGs of our patients varied significantly more (range: 35.4%-89.2%; p pathology, some presenting with ERGs that are almost solely composed of OPs. In conclusion, patients may present with a wide range of %OP values. Findings herein also support the hypothesis that, in certain conditions, the photopic ERG can be mostly composed of high-frequency components.

Assessing the Contribution of the Oscillatory Potentials to the Genesis of the Photopic ERG with the Discrete Wavelet Transform

Directory of Open Access Journals (Sweden)

Mathieu Gauvin

2016-01-01

Full Text Available The electroretinogram (ERG is composed of slow (i.e., a-, b-waves and fast (i.e., oscillatory potentials: OPs components. OPs have been shown to be preferably affected in some diseases (such as diabetic retinopathy, while the a- and b-waves remain relatively intact. The purpose of this study was to determine the contribution of OPs to the building of the ERG and to examine whether a signal mostly composed of OPs could also exist. DWT analyses were performed on photopic ERGs (flash intensities: −2.23 to 2.64 log cd·s·m−2 in 21 steps obtained from normal subjects (n=40 and patients (n=21 affected with a retinopathy. In controls, the %OP value (i.e., OPs energy/ERG energy is stimulus- and amplitude-independent (range: 56.6–61.6%; CV = 6.3%. In contrast, the %OPs measured from the ERGs of our patients varied significantly more (range: 35.4%–89.2%; p<0.05 depending on the pathology, some presenting with ERGs that are almost solely composed of OPs. In conclusion, patients may present with a wide range of %OP values. Findings herein also support the hypothesis that, in certain conditions, the photopic ERG can be mostly composed of high-frequency components.

Characterization of cucurbita maxima phloem serpin-1 (CmPS-1). A developmentally regulated elastase inhibitor.

Science.gov (United States)

Yoo, B C; Aoki, K; Xiang, Y; Campbell, L R; Hull, R J; Xoconostle-Cázares, B; Monzer, J; Lee, J Y; Ullman, D E; Lucas, W J

2000-11-10

We report on the molecular, biochemical, and functional characterization of Cucurbita maxima phloem serpin-1 (CmPS-1), a novel 42-kDa serine proteinase inhibitor that is developmentally regulated and has anti-elastase properties. CmPS-1 was purified to near homogeneity from C. maxima (pumpkin) phloem exudate and, based on microsequence analysis, the cDNA encoding CmPS-1 was cloned. The association rate constant (k(a)) of phloem-purified and recombinant His(6)-tagged CmPS-1 for elastase was 3.5 +/- 1.6 x 10(5) and 2.7 +/- 0.4 x 10(5) m(-)(1) s(-)(1), respectively. The fraction of complex-forming CmPS-1, X(inh), was estimated at 79%. CmPS-1 displayed no detectable inhibitory properties against chymotrypsin, trypsin, or thrombin. The elastase cleavage sites within the reactive center loop of CmPS-1 were determined to be Val(347)-Gly(348) and Val(350)-Ser(351) with a 3:2 molar ratio. In vivo feeding assays conducted with the piercing-sucking aphid, Myzus persicae, established a close correlation between the developmentally regulated increase in CmPS-1 within the phloem sap and the reduced ability of these insects to survive and reproduce on C. maxima. However, in vitro feeding experiments, using purified phloem CmPS-1, failed to demonstrate a direct effect on aphid survival. Likely roles of this novel phloem serpin in defense against insects/pathogens are discussed.

Remarkable strain-induced magnetic anisotropy in epitaxial Co2MnGa (0 0 1) films

International Nuclear Information System (INIS)

Pechan, Michael J.; Yu, Chengtao; Carr, David; Palmstroem, Chris J.

2005-01-01

Remarkably large, strain-induced anisotropy is observed in the thin-film Heusler alloy Co 2 MnGa. 30 nm Co 2 MnGa (0 0 1) films have been epitaxially grown on different interlayers/substrates with varied strain, and investigated with ferromagnetic resonance. The film grown on ErAs/InGaAs/InP experiences tension strain, resulting in an out-of-plane strain-induced anisotropy (∼1.1x10 6 erg/cm 3 ) adding to the effects of shape anisotropy. In contrast, the film grown on ScErAs/GaAs, experiences a compression strain, resulting in an out-of-plane strain-induced anisotropy (∼3.3x10 6 erg/cm 3 ) which almost totally cancels the effects of shape anisotropy, thus rendering the film virtually isotropic. This results in the formation of stripe domains in remanence. In addition, small, but well-defined 2-fold and 4-fold in-plane anisotropy coexist in each sample with weak, but interesting strain dependence. Transport measurement shows small (<1%) magnetoresistance effects in the compression film, but negligible magnetoresistance in the relaxed and tension strained samples

ERG voltage-gated K+ channels regulate excitability and discharge dynamics of the medial vestibular nucleus neurones.

Science.gov (United States)

Pessia, Mauro; Servettini, Ilenio; Panichi, Roberto; Guasti, Leonardo; Grassi, Silvarosa; Arcangeli, Annarosa; Wanke, Enzo; Pettorossi, Vito Enrico

2008-10-15

The discharge properties of the medial vestibular nucleus neurones (MVNn) critically depend on the activity of several ion channel types. In this study we show, immunohistochemically, that the voltage-gated K(+) channels ERG1A, ERG1B, ERG2 and ERG3 are highly expressed within the vestibular nuclei of P10 and P60 mice. The role played by these channels in the spike-generating mechanisms of the MVNn and in temporal information processing was investigated electrophysiologically from mouse brain slices, in vitro, by analysing the spontaneous discharge and the response to square-, ramp- and sinusoid-like intracellular DC current injections in extracellular and whole-cell patch-clamp studies. We show that more than half of the recorded MVNn were responsive to ERG channel block (WAY-123,398, E4031), displaying an increase in spontaneous activity and discharge irregularity. The response to step and ramp current injection was also modified by ERG block showing a reduction of first spike latency, enhancement of discharge rate and reduction of the slow spike-frequency adaptation process. ERG channels influence the interspike slope without affecting the spike shape. Moreover, in response to sinusoid-like current, ERG channel block caused frequency-dependent gain enhancement and phase-lead shift. Taken together, the data demonstrate that ERG channels control the excitability of MVNn, their discharge regularity and probably their resonance properties.

Widely bandgap tunable amorphous Cd–Ga–O oxide semiconductors exhibiting electron mobilities ≥10 cm{sup 2 }V{sup −1 }s{sup −1}

Energy Technology Data Exchange (ETDEWEB)

Yanagi, Hiroshi, E-mail: hyanagi@yamanashi.ac.jp [Graduate Faculty of Interdisciplinary Research, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi 400-8510 (Japan); Sato, Chiyuki; Kimura, Yota [Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi 400-8510 (Japan); Suzuki, Issei; Omata, Takahisa [Division of Material and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Kamiya, Toshio [Materials and Structures Laboratory, Tokyo Institute of Technology, Mailbox R3-4, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503 (Japan); Materials Research Center for Element Strategy, Tokyo Institute of Technology, Mailbox S2-16, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503 (Japan); Hosono, Hideo [Materials and Structures Laboratory, Tokyo Institute of Technology, Mailbox R3-4, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503 (Japan); Materials Research Center for Element Strategy, Tokyo Institute of Technology, Mailbox S2-16, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503 (Japan); Frontier Research Center, Tokyo Institute of Technology, Mailbox S2-16, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503 (Japan)

2015-02-23

Amorphous oxide semiconductors exhibit large electron mobilities; however, their bandgaps are either too large for solar cells or too small for deep ultraviolet applications depending on the materials system. Herein, we demonstrate that amorphous Cd–Ga–O semiconductors display bandgaps covering the entire 2.5–4.3 eV region while maintaining large electron mobilities ≥10 cm{sup 2 }V{sup −1 }s{sup −1}. The band alignment diagram obtained by ultraviolet photoemission spectroscopy and the bandgap values reveal that these semiconductors form type-II heterojunctions with p-type Cu{sub 2}O, which is suitable for solar cells and solar-blind ultraviolet sensors.

Magnetic phase diagram of ErGe 1-xSi x (01)

Science.gov (United States)

Thuéry, P.; El Maziani, F.; Clin, M.; Schobinger-Papamantellos, P.; Buschow, K. H. J.

1993-10-01

The composition-temperature magnetic phase diagram of ErGe 1- xSi x (0 0.40. For 0.17 ≥ x ≤ 0.55, a first-order transition occurs as function of the temperature between these two phases. For x ≥ 0.65, a lock-in transition takes place at TIC, leading from the wavevector ( k' x,0, k' z) to (1/2,0,1/2), as was already observed in ErSi. Finally, for x < 0.17 or 0.55 < x < 0.65, the wavevectors of the incommensurate phases characterized by (0,0, kz) or ( k' x,0, k' z) respectively remain unchanged in the whole temperature range below TN. For x≥0.65, a small amount of a magnetic phase characterized by the wavevector (0,0, 1/2) coexists with the main phases, below a Néel temperature T' N slightly lower than TN. In all cases, the erbium magnetic moments are colinear along the orthorhombic α-axis; the arrangement of the moments in the commensurate phases is the same as in ErSi and the incommensurate orderings correspond to sine-wave amplitude modulations. A brief account on the theoretical interpretation of this phase diagram is finally given.

Vacuum ultraviolet photoabsorption spectroscopy of CH2Cl2 and CD2Cl2 in the energy region 50,000-95,000 cm-1

Science.gov (United States)

Mandal, Anuvab; Singh, Param Jeet; Shastri, Aparna; Jagatap, B. N.

2014-12-01

A consolidated study of the VUV absorption spectra of CH2Cl2 and CD2Cl2 in the 50,000-95,000 cm-1 region using synchrotron radiation is presented. Rydberg series and vibronic analysis are carried out and supported by quantum chemical calculations. The broad absorption band of CH2Cl2 in the region 50,000-60,000 cm-1 is attributed to the valence states 11B2, 11B1 and 11A1. Most of the bands in the 60,000-95,000 cm-1 region are fitted to Rydberg series of ns, np and nd type converging to the first four ionization potentials 11.320, 11.357, 12.152 and 12.271 eV of CH2Cl2 arising from excitation of an electron from one of the four outermost Cl non-bonding orbitals (2b1, 3b2, 1a2 and 4a1). Vertical excited states of CH2Cl2 calculated using TDDFT are correlated with experimentally observed electronic states based on the symmetries of the initial and final MOs involved in a transition. A few Rydberg transitions viz. 2b1→5s, 4p, 5p, 6p; 3b2→4p, 5p; 1a2→4p are accompanied by vibronic features. Observed vibronic bands are assigned mainly to the CCl symmetric stretch (ν3‧) mode with smaller contributions from the CH symmetric stretch (ν1‧), CH2 bend (ν2‧) and CH2 wag (ν8‧) modes. Assignments are corroborated by comparison with the VUV absorption spectrum of the deuterated isotopologue CD2Cl2, reported here for the first time. The high underlying intensities seen in several sub-regions are explained by valence or valence-Rydberg mixed type transitions predicted with high oscillator strengths by the TDDFT calculations.

Determination of the 1s-2s two-photon excitation cross-section in atomic hydrogen

Energy Technology Data Exchange (ETDEWEB)

Bickel, G.A.; McRae, G.A

2000-07-01

Hydrogen atoms are ablated from zirconium alloys into the gas phase by a pulsed Nd:YAG laser and photo-ionized with three photons at 243 nm via the two-photon 1s {sup 2}S{sub 1/2}-2s {sup 2}S{sub 1/2} resonant transition. A determination of the effective 1s-2s two-photon excitation cross-section is necessary to quantify the hydrogen atom density in the ablation plume. A measurement of the ion signal vs photo-ionization beam energy is fitted to an expression derived from the rate equations. The temporal and spatial properties of the photo-ionization laser beam, transit of the H atoms through the beam, and detector geometry are taken into account. The effective two-photon cross-section for this experimental configuration, derived with the rate equation formalism, is 3.3 {+-} 0.8 X 10{sup -28} cm{sup 4} W{sup -1}. This compares well with the ab initio prediction of 5 {+-} 1 X 10{sup -28} cm{sup 4} W{sup -1} under these experimental conditions. (author)

Determination of the 1s-2s two-photon excitation cross-section in atomic hydrogen

International Nuclear Information System (INIS)

Bickel, G.A.; McRae, G.A.

2000-01-01

Hydrogen atoms are ablated from zirconium alloys into the gas phase by a pulsed Nd:YAG laser and photo-ionized with three photons at 243 nm via the two-photon 1s 2 S 1/2 -2s 2 S 1/2 resonant transition. A determination of the effective 1s-2s two-photon excitation cross-section is necessary to quantify the hydrogen atom density in the ablation plume. A measurement of the ion signal vs photo-ionization beam energy is fitted to an expression derived from the rate equations. The temporal and spatial properties of the photo-ionization laser beam, transit of the H atoms through the beam, and detector geometry are taken into account. The effective two-photon cross-section for this experimental configuration, derived with the rate equation formalism, is 3.3 ± 0.8 X 10 -28 cm 4 W -1 . This compares well with the ab initio prediction of 5 ± 1 X 10 -28 cm 4 W -1 under these experimental conditions. (author)

Functional characterization of Kv11.1 (hERG) potassium channels split in the voltage-sensing domain.

Science.gov (United States)

de la Peña, Pilar; Domínguez, Pedro; Barros, Francisco

2018-03-23

Voltage-dependent KCNH family potassium channel functionality can be reconstructed using non-covalently linked voltage-sensing domain (VSD) and pore modules (split channels). However, the necessity of a covalent continuity for channel function has not been evaluated at other points within the two functionally independent channel modules. We find here that by cutting Kv11.1 (hERG, KCNH2) channels at the different loops linking the transmembrane spans of the channel core, not only channels split at the S4-S5 linker level, but also those split at the intracellular S2-S3 and the extracellular S3-S4 loops, yield fully functional channel proteins. Our data indicate that albeit less markedly, channels split after residue 482 in the S2-S3 linker resemble the uncoupled gating phenotype of those split at the C-terminal end of the VSD S4 transmembrane segment. Channels split after residues 514 and 518 in the S3-S4 linker show gating characteristics similar to those of the continuous wild-type channel. However, breaking the covalent link at this level strongly accelerates the voltage-dependent accessibility of a membrane impermeable methanethiosulfonate reagent to an engineered cysteine at the N-terminal region of the S4 transmembrane helix. Thus, besides that of the S4-S5 linker, structural integrity of the intracellular S2-S3 linker seems to constitute an important factor for proper transduction of VSD rearrangements to opening and closing the cytoplasmic gate. Furthermore, our data suggest that the short and probably rigid characteristics of the extracellular S3-S4 linker are not an essential component of the Kv11.1 voltage sensing machinery.

Uranium sandwich targets of 0.1 to 100 mg.cm-2 prepared by electron beam gun evaporation

International Nuclear Information System (INIS)

Folger, H.; Klemm, J.

1978-01-01

Metallic uranium layers of 0.1 to 100 mg.cm -2 between different backings and protecting layers were prepared for bombardments with heavy ions such as argon, krypton, xenon, lead, or uranium at energies of up to 8 MeV/u at the UNILAC of the GSI. An experimental set-up for the preparation of thick and oxygen-free sandwich targets using a 6 kVA electron beam gun was installed in a high vacuum apparatus. Then deposition and evaporation rates for uranium were investigated as a function of the electron beam gun power. It turned out that reproducible evaporation rates of up to 7 mg.s -1 were achieved when uranium pieces of 20 to 40 grams were used. Specific evaporation rates and vapor pressures for different temperatures were calculated. Some of these data are compared to measured values, especially evaporation rates at the evaporation point. The preparation, composition, and usage of uranium sandwich targets is described in detail. It concerns uranium layers of 0.1 to 100 mg.cm -2 deposited onto backings of carbon, titanium, nickel, gold, or glass. Evaporated films of carbon, titanium, nickel, or gold of 0.01 to 0.2 mg.cm -2 are used to protect the uranium layers from oxidation

High-energy electron experiments (HEP) aboard the ERG (Arase) satellite

Science.gov (United States)

Mitani, Takefumi; Takashima, Takeshi; Kasahara, Satoshi; Miyake, Wataru; Hirahara, Masafumi

2018-05-01

This paper reports the design, calibration, and operation of high-energy electron experiments (HEP) aboard the exploration of energization and radiation in geospace (ERG) satellite. HEP detects 70 keV-2 MeV electrons and generates a three-dimensional velocity distribution for these electrons in every period of the satellite's rotation. Electrons are detected by two instruments, namely HEP-L and HEP-H, which differ in their geometric factor (G-factor) and range of energies they detect. HEP-L detects 70 keV-1 MeV electrons and its G-factor is 9.3 × 10-4 cm2 sr at maximum, while HEP-H observes 0.7-2 MeV electrons and its G-factor is 9.3 × 10-3 cm2 sr at maximum. The instruments utilize silicon strip detectors and application-specific integrated circuits to readout the incident charge signal from each strip. Before the launch, we calibrated the detectors by measuring the energy spectra of all strips using γ-ray sources. To evaluate the overall performance of the HEP instruments, we measured the energy spectra and angular responses with electron beams. After HEP was first put into operation, on February 2, 2017, it was demonstrated that the instruments performed normally. HEP began its exploratory observations with regard to energization and radiation in geospace in late March 2017. The initial results of the in-orbit observations are introduced briefly in this paper.[Figure not available: see fulltext.

Cone responses in Usher syndrome types 1 and 2 by microvolt electroretinography.

Science.gov (United States)

Zein, Wadih M; Falsini, Benedetto; Tsilou, Ekaterina T; Turriff, Amy E; Schultz, Julie M; Friedman, Thomas B; Brewer, Carmen C; Zalewski, Christopher K; King, Kelly A; Muskett, Julie A; Rehman, Atteeq U; Morell, Robert J; Griffith, Andrew J; Sieving, Paul A

2014-11-25

Progressive decline of psychophysical cone-mediated measures has been reported in type 1 (USH1) and type 2 (USH2) Usher syndrome. Conventional cone electroretinogram (ERG) responses in USH demonstrate poor signal-to-noise ratio. We evaluated cone signals in USH1 and USH2 by recording microvolt level cycle-by-cycle (CxC) ERG. Responses of molecularly genotyped USH1 (n = 18) and USH2 (n = 24) subjects (age range, 15-69 years) were compared with those of controls (n = 12). A subset of USH1 (n = 9) and USH2 (n = 9) subjects was examined two to four times over 2 to 8 years. Photopic CxC ERG and conventional 30-Hz flicker ERG were recorded on the same visits. Usher syndrome subjects showed considerable cone flicker ERG amplitude losses and timing phase delays (P Usher subjects showed abnormal ERG response latency, but this changed less than amplitude with time. In USH syndrome, CxC ERG is more sensitive than conventional ERG and warrants consideration as an outcome measure in USH treatment trials. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Fourier Transform Spectroscopy of Carbonyl Sulfide from 4800 to 8000 cm -1and New Global Analysis of 16O 12C 32S

Science.gov (United States)

Rbaihi, E.; Belafhal, A.; Vander Auwera, J.; Naı̈m, S.; Fayt, A.

1998-09-01

We have measured the FT spectrum of natural OCS from 4800 to 8000 cm-1with a near Doppler resolution and a line-position accuracy between 2 and 8 × 10-4cm-1. For the normal isotopic species16O12C32S, 37 vibrational transitions have been analyzed for both frequencies and intensities. We also report six bands of16O12C34S, five bands of16O13C32S, two bands of16O12C33S, and two bands of18O12C32S. Important effective Herman-Wallis terms are explained by the anharmonic resonances between closely spaced states. As those results complete the study of the Fourier transform spectra of natural carbonyl sulfide from 1800 to 8000 cm-1, a new global rovibrational analysis of16O12C32S has been performed. We have determined a set of 148 molecular parameters, and a statistical agreement is obtained with all the available experimental data.

Oxygen isotope systematics of chondrules in the Murchison CM2 chondrite and implications for the CO-CM relationship

Science.gov (United States)

Chaumard, Noël; Defouilloy, Céline; Kita, Noriko T.

2018-05-01

High-precision oxygen three-isotope measurements of olivine and pyroxene were performed on 29 chondrules in the Murchison CM2 chondrite by secondary ion mass spectrometry (SIMS). The oxygen isotope ratios of analyzed chondrules all plot very close to the primitive chondrule minerals (PCM) line. In each of 24 chondrules, the olivine and/or pyroxene grains analyzed show indistinguishable oxygen isotope ratios. Exceptions are minor occurrences of isotopically distinguished relict olivine grains, which were found in nine chondrules. The isotope homogeneity of these phenocrysts is consistent with a co-magmatic crystallization of olivine and pyroxene from the final chondrule melts and a significant oxygen isotope exchange between the ambient gas and the melts. Homogeneous type I chondrules with Mg#'s of 98.9-99.5 have host chondrule Δ17O values ranging from -6.0‰ to -4.1‰, with one exception (Δ17O: -1.2‰; Mg#: 99.6). Homogeneous chondrules with Mg#'s poor H2O ice (∼0.3-0.4× the CI dust; Δ17O > 0‰) and at dust enrichments of ∼300-2000×. Regarding the Mg# and oxygen isotope ratios, the chondrule populations sampled by CM and CO chondrites are similar and indistinguishable. The similarity of these 16O-rich components in CO and CM chondrites is also supported by the common Fe/Mn ratio of olivine in type II chondrules. Although they accreted similar high-temperature silicates, CO chondrites are anhydrous compared to CM chondrites, suggesting they derived from different parent bodies formed inside and outside the snow line, respectively. If chondrules in CO and CM chondrites formed at the same disk locations but the CM parent body accreted later than the CO parent body, the snow line might have crossed the common chondrule-forming region towards the Sun between the time of the CO and CM parent bodies accretion.

Potential of ultraviolet radiation for control of American cockroach populations

International Nuclear Information System (INIS)

Gingrich, J.B.; Pratt, J.J. Jr.; Mandels, G.R.

1977-01-01

Populations of Periplaneta americana (L.) were exposed for 8-20 week periods in specially designed rooms to 254 nm UV radiation at low intensity (50-115 ergs s -1 cm -2 ), high intensity (160-220 ergs s -1 cm -2 ), or to white light. The rooms contained tables and chairs to simulate occupied space, with food and water placed in positions exposed to UV radiation. 'General' irradiation (where the whole room was exposed to UV) at 115 ergs s -1 cm -2 and above was effective in producing high mortality in all stages except 8-10th instar nymphs and adults. 'Hot-spots' irradiation (where UV lamps were placed behind table and chair harborages) produced high mortality only in 1st-3rd instar nymphs which would result in slower elimination of a population. Crude aggregation pheromone was not successful in holding cockroaches close to radiation sources or substantially increasing mortality under the conditions of the experiments

Overexpression of erg1 gene in Trichoderma harzianum CECT 2413: effect on the induction of tomato defence-related genes.

Science.gov (United States)

Cardoza, R E; Malmierca, M G; Gutiérrez, S

2014-09-01

To investigate the effect of the overexpression of erg1 gene of Trichoderma harzianum CECT 2413 (T34) on the Trichoderma-plant interactions and in the biocontrol ability of this fungus. Transformants of T34 strain overexpressing erg1 gene did not show effect on the ergosterol level, although a drastic decrease in the squalene level was observed in the transformants at 96 h of growth. During interaction with plants, the erg1 overexpression resulted in a reduction of the priming ability of several tomato defence-related genes belonging to the salicylate pathway, and also of the TomLoxA gene, which is related to the jasmonate pathway. Interestingly, other jasmonate-related genes, such as PINI and PINII, were slightly induced. The erg1 overexpressed transformants also showed a reduced ability to colonize tomato roots. The ergosterol biosynthetic pathway might play an important role in regulating Trichoderma-plant interactions, although this role does not seem to be restricted to the final product; instead, other intermediates such as squalene, whose role in the Trichoderma-plant interaction has not been characterized, would also play an important role. The functional analysis of genes involved in the synthesis of ergosterol could provide additional strategies to improve the ability of biocontrol of the Trichoderma strains and their interaction with plants. © 2014 The Society for Applied Microbiology.

The role of hERG1 ion channels in epithelial-mesenchymal transition and the capacity of riluzole to reduce cisplatin resistance in colorectal cancer cells.

Science.gov (United States)

Fortunato, Angelo

2017-08-01

The transition of cells from the epithelial to the mesenchymal state (EMT) plays an important role in tumor progression. EMT allows cells to acquire mobility, stem-like behavior and resistance to apoptosis and drug treatment. These features turn EMT into a central process in tumor biology. Ion channels are attractive targets for the treatment of cancer since they play critical roles in controlling a wide range of physiological processes that are frequently deregulated in cancer. Here, we investigated the role of ether-a-go-go-related 1 (hERG1) ion channels in the EMT of colorectal cancer cells. We studied the epithelial-mesenchymal profile of different colorectal cancer-derived cell lines and the expression of hERG1 potassium channels in these cell lines using real-time PCR. Next, we knocked down hERG1 expression in HCT116 cells using lentivirus mediated RNA interference and characterized the hERG1 silenced cells in vitro and in vivo. Finally, we investigated the capacity of riluzole, an ion channel-modulating drug used in humans to treat amyotrophic lateral sclerosis, to reduce the resistance of the respective colorectal cancer cells to the chemotherapeutic drug cisplatin. We found that of the colorectal cancer-derived cell lines tested, HCT116 showed the highest mesenchymal profile and a high hERG1 expression. Subsequent hERG1 expression knockdown induced a change in cell morphology, which was accompanied by a reduction in the proliferative and tumorigenic capacities of the cells. Notably, we found that hERG1expression knockdown elicited a reversion of the EMT profile in HCT116 cells with a reacquisition of the epithelial-like profile. We also found that riluzole increased the sensitivity of HCT116 cisplatin-resistant cells to cisplatin. Our data indicate that hERG1 plays a role in the EMT of colorectal cancer cells and that its knockdown reduces the proliferative and tumorigenic capacities of these cells. In addition, we conclude that riluzole may be used in

Web 2.0 Dienste als Ergänzung zu algorithmischen Suchmaschinen

CERN Document Server

Deutschland. Bundesministerium für Wirtschaft und Technologie; Maas, Christian

2008-01-01

Dokumentiert die Ergebnisse des Fachprojekts "Einbingung von Frage-Antwort-Diensten in die Web-Suche", Wintersemester 2007/2008, Dept. Information, Hochschule für angewandte Wissenschaften Hamburg. Mit sozialen Suchdiensten - wie z.B. Yahoo Clever, Lycos iQ oder Mister Wong - ist eine Ergänzung zu den bisherigen Ansätzen in der Web-Suche entstanden. Während Google und Co. automatisch generierte Trefferlisten bieten, binden soziale Suchdienste die Anwender zur Generierung der Suchergebnisse in den Suchprozess ein. Vor diesem Hintergrund wird in diesem Buch der Frage nachgegangen, inwieweit soziale Suchdienste mit traditionellen Suchmaschinen konkurrieren oder diese qualitativ ergänzen können. Der vorliegende Band beleuchtet die hier aufgeworfene Fragestellung aus verschiedenen Perspektiven, um auf die Bedeutung von sozialen Suchdiensten zu schließen.

A 4Σ1/2-X2Π1/2 transition in the electronic spectrum of the CuS molecule

International Nuclear Information System (INIS)

Lefebvre, Y.; Delaval, J.M.; Schamps, J.

1991-01-01

The (0-0) band of a new 4 Σ 1/2 -X 2 Π 1/2 transition has been observed in the hollow cathode emission spectra of the CuS molecule. Rotational analysis provides the following molecular constants (in cm -1 ) for the D 4 Σ 1/2 state: T 0 = 23112.88; B 0 = 0.17453; p 0 = 0.858; p 0j = 3.3x10 -6 ; D 0 = 0.11x10 -6 . Pulsed dye laser fluorescence experiments confirm the general diagram of the observed CuS electronic states. (orig.)

INTEGRAL detects Swift J1910.2-0546 (= MAXI J1910-057) in the hard X-rays

DEFF Research Database (Denmark)

Bodaghee, A.; Bozzo, E.; Tomsick, J. A.

2012-01-01

.2-0546 is detected up to ~200 keV. Fitting this spectrum (9.1 ks of effective exposure time) with a power-law model yields a photon index of 1.8+/-0.3 (at 90% confidence) for a reduced chi^2/d.o.f.=1.0/9; adding an exponential cutoff does not improve the fit. The observed 20--100-keV flux is 1.5e-9 ergs/cm^2/s...

Carma 1 CM Line Survey of Orion-Kl

Science.gov (United States)

Friedel, Douglas; Looney, Leslie; Corby, Joanna F.; Remijan, Anthony

2015-06-01

We have conducted the first 1 cm (27-35 GHz) line survey of the Orion-KL region by an array. With a primary beam of ˜4.5 arcminutes, the survey looks at a region ˜166,000 AU (0.56 pc) across. The data have a resolution of ˜6 arcseconds on the sky and 97.6 kHz(1.07-0.84 km/s) in frequency. This region of frequency space is much less crowded than at 3mm or 1mm frequencies and contains the fundamental transitions of several complex molecular species, allowing us to probe the largest extent of the molecular emission. We present the initial results, and comparison to 3mm results, from several species including, dimethyl ether [(CH_3)_2O], ethyl cyanide [C_2H_5CN], acetone [(CH_3)_2CO], SO, and SO_2.

High Glucose Represses hERG K+ Channel Expression through Trafficking Inhibition

Directory of Open Access Journals (Sweden)

Yuan-Qi Shi

2015-08-01

Full Text Available Background/Aims: Abnormal QT prolongation is the most prominent cardiac electrical disturbance in patients with diabetes mellitus (DM. It is well known that the human ether-ago-go-related gene (hERG controls the rapid delayed rectifier K+ current (IKr in cardiac cells. The expression of the hERG channel is severely down-regulated in diabetic hearts, and this down-regulation is a critical contributor to the slowing of repolarization and QT prolongation. However, the intracellular mechanisms underlying the diabetes-induced hERG deficiency remain unknown. Methods: The expression of the hERG channel was assessed via western blot analysis, and the hERG current was detected with a patch-clamp technique. Results: The results of our study revealed that the expression of the hERG protein and the hERG current were substantially decreased in high-glucose-treated hERG-HEK cells. Moreover, we demonstrated that the high-glucose-mediated damage to the hERG channel depended on the down-regulation of protein levels but not the alteration of channel kinetics. These discoveries indicated that high glucose likely disrupted hERG channel trafficking. From the western blot and immunoprecipitation analyses, we found that high glucose induced trafficking inhibition through an effect on the expression of Hsp90 and its interaction with hERG. Furthermore, the high-glucose-induced inhibition of hERG channel trafficking could activate the unfolded protein response (UPR by up-regulating the expression levels of activating transcription factor-6 (ATF-6 and the ER chaperone protein calnexin. In addition, we demonstrated that 100 nM insulin up-regulated the expression of the hERG channel and rescued the hERG channel repression caused by high glucose. Conclusion: The results of our study provide the first evidence of a high-glucose-induced hERG channel deficiency resulting from the inhibition of channel trafficking. Furthermore, insulin promotes the expression of the hERG channel

The multifocal electroretinogram (mfERG) in the pig

DEFF Research Database (Denmark)

Voss Kyhn, Maria; Kiilgaard, Jens Folke; Lopez, Ana Garcia

2007-01-01

To establish a method allowing multifocal electroretinography (mfERG) recording with simultaneous fundus monitoring on anaesthetized pigs. In addition we characterize the peaks of the porcine mfERG trace, and compare the visual streak area with the optic nerve head, a known non-response area....... Finally we illustrate the feasibility of the method by performing mfERG after an induced laser burn in the visual streak....

Influence of Cu(In,Ga)(Se,S)2 surface treatments on the properties of 30 × 30 cm2 large area modules with atomic layer deposited Zn(O,S) buffers

International Nuclear Information System (INIS)

Merdes, S.; Steigert, A.; Ziem, F.; Lauermann, I.; Klenk, R.; Hergert, F.; Kaufmann, C.A.; Schlatmann, R.

2015-01-01

We report the effect of Cu(In,Ga)(Se,S) 2 absorber surface treatments on the properties of atomic layer deposited-Zn(O,S) buffered 30 × 30 cm 2 large area modules. The absorber is prepared by the sequential process. H 2 O and KCN solution treatments are investigated. The absorber surface treatment is found to influence significantly the open circuit voltage and the fill factor of the full modules. Light soaking related metastabilities are also found to depend on the type of treatment. While both H 2 O and KCN treatments are efficient at removing Se-oxides and Na 2 HCO 3 , the KCN treatment is found to remove additionally Ga-oxides and elemental Se that are detected on the surface of the absorber. A 30 × 30 cm 2 module aperture efficiency up to 12.3% could be achieved with KCN surface treatment of the absorber. - Highlights: • The Cu(In,Ga)(Se,S) 2 surface influences the Zn(O,S)-buffered module performance. • Surface treatment by H 2 O efficiently removes Se-oxides and sodium compounds. • KCN treatment of the absorber removes Se-oxides, Ga-oxides and elemental Se. • The devices' light soaking behavior depends on the absorber's surface chemistry. • A 30 × 30 cm 2 module efficiency of 12.3% is achieved with KCN treatment

Absorption spectrum and absorption cross sections of the 2ν1 band of HO2 between 20 and 760 Torr air in the range 6636 and 6639 cm-1

Science.gov (United States)

Assaf, Emmanuel; Liu, Lu; Schoemaecker, Coralie; Fittschen, Christa

2018-05-01

The absorption spectrum of HO2 radicals has been measured in the range 6636-6639 cm-1 at several pressures between 20 and 760 Torr of air. Absolute absorption cross sections of the strongest line at around 6638.2 cm-1 have been determined from kinetic measurements, taking advantage of the well known rate constant of the self-reaction. Peak absorption cross sections of 22.6, 19.5, 14.4, 7.88, 5.12 and 3.23 × 10-20 cm2 were obtained at 20, 50, 100, 200, 400 and 760 Torr, respectively. By fitting these data, an empirical expression has been obtained for the absorption cross section of HO2 in the range 20-760 Torr air: σ6638.2cm-1 = 1.18 × 10-20 + (2.64 × 10-19 × (1-exp (-63.1/p (Torr))) cm2.

Analysis of ν2 of D 2S

Science.gov (United States)

Gillis, James R.; Blatherwick, Ronald D.; Bonomo, Francis S.

1985-11-01

The infrared spectrum of ν2 of D 2S was recorded from 740 to 1100 cm -1 on the University of Denver 50-cm FTIR spectrometer system. We have assigned 655 transitions from D 232S and 129 from D 234S, and have analyzed them using Watson's A-reduced Hamiltonian evaluated in the I r representation. We used the recently published D 232S and D 234S ground state Hamiltonian constants [C. Camy-Peyret, J. M. Flaud, L. Lechuga-Fossat and J. W. C. Johns, J. Mol. Spectrosc.109, 300-333 (1985)]. Upper state Hamiltonian constants were obtained from a fit of the ν2 transitions, keeping the ground state constants fixed while varying the upper state constants. The standard deviation of the D 232S ν2 fit is 0.0025 cm -1. The standard deviation of the D 234S ν2 fit is 0.0041 cm -1.

CALET UPPER LIMITS ON X-RAY AND GAMMA-RAY COUNTERPARTS OF GW151226

Energy Technology Data Exchange (ETDEWEB)

Adriani, O.; Bongi, M.; Castellini, G. [University of Florence, Via Sansone, 1, I-50019 Sesto, Fiorentino (Italy); Akaike, Y. [Universities Space Research Association, 7178 Columbia Gateway Drive, Columbia, MD 21046 (United States); Asano, K. [Institute for Cosmic Ray Research, The University of Tokyo, 5-1-5 Kashiwa-no-Ha, Kashiwa, Chiba 277-8582 (Japan); Asaoka, Y. [JEM Mission Operations and Integration Center, Human Spaceflight Technology Directorate, Japan Aerospace Exploration Agency, 2-1-1 Sengen, Tsukuba, Ibaraki 305-8505 (Japan); Bagliesi, M. G.; Bigongiari, G.; Bonechi, S.; Brogi, P.; Felice, V. Di [National Institute for Nuclear Physics (INFN), Piazza dei Caprettari, 70, I-00186 Rome (Italy); Binns, W. R.; Buckley, J. H. [Department of Physics, Washington University, One Brookings Drive, St. Louis, MO 63130-4899 (United States); Cannady, N.; Cherry, M. L.; Guzik, T. G. [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803 (United States); Checchia, C.; Collazuol, G. [Department of Physics and Astronomy, University of Padova, Via Marzolo, 8, I-35131 Padova (Italy); Ebisawa, K.; Fuke, H., E-mail: nakahira@crab.riken.jp, E-mail: yoichi.asaoka@aoni.waseda.jp, E-mail: tsakamoto@phys.aoyama.ac.jp [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency, 3-1-1 Yoshinodai, Chuo, Sagamihara, Kanagawa 252-5210 (Japan); and others

2016-09-20

We present upper limits in the hard X-ray and gamma-ray bands at the time of the Laser Interferometer Gravitational-wave Observatory (LIGO) gravitational-wave event GW151226 derived from the CALorimetric Electron Telescope ( CALET ) observation. The main instrument of CALET , CALorimeter (CAL), observes gamma-rays from ∼1 GeV up to 10 TeV with a field of view of ∼2 sr. The CALET gamma-ray burst monitor (CGBM) views ∼3 sr and ∼2 π sr of the sky in the 7 keV–1 MeV and the 40 keV–20 MeV bands, respectively, by using two different scintillator-based instruments. The CGBM covered 32.5% and 49.1% of the GW151226 sky localization probability in the 7 keV–1 MeV and 40 keV–20 MeV bands respectively. We place a 90% upper limit of 2 × 10{sup −7} erg cm{sup −2} s{sup −1} in the 1–100 GeV band where CAL reaches 15% of the integrated LIGO probability (∼1.1 sr). The CGBM 7 σ upper limits are 1.0 × 10{sup −6} erg cm{sup −2} s{sup −1} (7–500 keV) and 1.8 × 10{sup −6} erg cm{sup −2} s{sup −1} (50–1000 keV) for a 1 s exposure. Those upper limits correspond to the luminosity of 3–5 × 10{sup 49} erg s{sup −1}, which is significantly lower than typical short GRBs.

MiR-17-5p impairs trafficking of H-ERG K+ channel protein by targeting multiple er stress-related chaperones during chronic oxidative stress.

Directory of Open Access Journals (Sweden)

Qi Wang

Full Text Available BACKGROUND: To investigate if microRNAs (miRNAs play a role in regulating h-ERG trafficking in the setting of chronic oxidative stress as a common deleterious factor for many cardiac disorders. METHODS: We treated neonatal rat ventricular myocytes and HEK293 cells with stable expression of h-ERG with H2O2 for 12 h and 48 h. Expression of miR-17-5p seed miRNAs was quantified by real-time RT-PCR. Protein levels of chaperones and h-ERG trafficking were measured by Western blot analysis. Luciferase reporter gene assay was used to study miRNA and target interactions. Whole-cell patch-clamp techniques were employed to record h-ERG K(+ current. RESULTS: H-ERG trafficking was impaired by H2O2 after 48 h treatment, accompanied by reciprocal changes of expression between miR-17-5p seed miRNAs and several chaperones (Hsp70, Hsc70, CANX, and Golga2, with the former upregulated and the latter downregulated. We established these chaperones as targets for miR-17-5p. Application miR-17-5p inhibitor rescued H2O2-induced impairment of h-ERG trafficking. Upregulation of endogenous by H2O2 or forced miR-17-5p expression either reduced h-ERG current. Sequestration of AP1 by its decoy molecule eliminated the upregulation of miR-17-5p, and ameliorated impairment of h-ERG trafficking. CONCLUSIONS: Collectively, deregulation of the miR-17-5p seed family miRNAs can cause severe impairment of h-ERG trafficking through targeting multiple ER stress-related chaperones, and activation of AP1 likely accounts for the deleterious upregulation of these miRNAs, in the setting of prolonged duration of oxidative stress. These findings revealed the role of miRNAs in h-ERG trafficking, which may contribute to the cardiac electrical disturbances associated with oxidative stress.

MiR-17-5p impairs trafficking of H-ERG K+ channel protein by targeting multiple er stress-related chaperones during chronic oxidative stress.

Science.gov (United States)

Wang, Qi; Hu, Weina; Lei, Mingming; Wang, Yong; Yan, Bing; Liu, Jun; Zhang, Ren; Jin, Yuanzhe

2013-01-01

To investigate if microRNAs (miRNAs) play a role in regulating h-ERG trafficking in the setting of chronic oxidative stress as a common deleterious factor for many cardiac disorders. We treated neonatal rat ventricular myocytes and HEK293 cells with stable expression of h-ERG with H2O2 for 12 h and 48 h. Expression of miR-17-5p seed miRNAs was quantified by real-time RT-PCR. Protein levels of chaperones and h-ERG trafficking were measured by Western blot analysis. Luciferase reporter gene assay was used to study miRNA and target interactions. Whole-cell patch-clamp techniques were employed to record h-ERG K(+) current. H-ERG trafficking was impaired by H2O2 after 48 h treatment, accompanied by reciprocal changes of expression between miR-17-5p seed miRNAs and several chaperones (Hsp70, Hsc70, CANX, and Golga2), with the former upregulated and the latter downregulated. We established these chaperones as targets for miR-17-5p. Application miR-17-5p inhibitor rescued H2O2-induced impairment of h-ERG trafficking. Upregulation of endogenous by H2O2 or forced miR-17-5p expression either reduced h-ERG current. Sequestration of AP1 by its decoy molecule eliminated the upregulation of miR-17-5p, and ameliorated impairment of h-ERG trafficking. Collectively, deregulation of the miR-17-5p seed family miRNAs can cause severe impairment of h-ERG trafficking through targeting multiple ER stress-related chaperones, and activation of AP1 likely accounts for the deleterious upregulation of these miRNAs, in the setting of prolonged duration of oxidative stress. These findings revealed the role of miRNAs in h-ERG trafficking, which may contribute to the cardiac electrical disturbances associated with oxidative stress.

Isotope shift of the 590-cm-1 Raman feature in underdoped Bi2Sr2CaCu2O8+δ

Science.gov (United States)

Hewitt, K. C.; Wang, N. L.; Irwin, J. C.; Pooke, D. M.; Pantoja, A. E.; Trodahl, H. J.

1999-10-01

Raman-scattering studies have been performed on underdoped Bi2Sr2CaCu2O8+δ. In single crystals underdoped by oxygen removal, a 590-cm-1 peak is observed in the B1g spectrum. The feature is observed to soften in frequency by 3.8% with isotopic exchange of 16O by 18O. In contrast, the 590-cm-1 peak is not observed in crystals underdoped by Y substitution which suggests that it is a vibrational mode activated by oxygen deficency. We have also found that underdoping leads to a depletion of low-energy spectral weight from regions of the Fermi surface located near the Brillouin-zone axes.

ERG review of waste package container materials selection and corrosion

International Nuclear Information System (INIS)

Moak, D.P.; Perrin, J.S.

1986-07-01

The Engineering Review Group (ERG) was established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate engineering-related issues in the US Department of Energy's nuclear waste repository program. The October 1984 meeting of the ERG reviewed the waste package container materials selection and corrosion. This report documents the ERG's comments and recommendations on these subjects and the ONWI response to the specific points raised by the ERG

Measurements of NH3 linestrengths and collisional broadening coefficients in N2, O2, CO2, and H2O near 1103.46cm-1

KAUST Repository

Owen, Kyle

2013-05-01

Laser-based ammonia gas sensors have useful applications in many fields including combustion, atmospheric monitoring, and medical diagnostics. Calibration-free trace gas sensors require the spectroscopic parameters including linestrengths and collisional broadening coefficients to be known. Ammonia\\'s strong ν2 vibrational band between 9 - 12 μm has the high absorption strength needed for sensing small concentrations. Within this band, the 1103.46cm-1 feature is one of the strongest and has minimal interference from CO2 and H2O. However, the six rotational transitions that make up this feature have not been studied previously with absorption spectroscopy due to their small line spacing ranging from 0.004 to 0.029cm-1. A tunable quantum cascade laser was used to accurately study these six transitions. A retrieval program was used to determine the linestrengths and collisional broadening coefficients based on Voigt and Galatry profiles. The experiments were performed with ammonia mixtures in nitrogen, oxygen, water vapor, and carbon dioxide at room temperature in an optical cell. These data are going to aid in the development of quantitative ammonia sensors utilizing this strong absorption feature. © 2013 Elsevier Ltd.

A comparison of two patient friendly ERG electrodes

International Nuclear Information System (INIS)

Hidajat, R.; McLay, J.; Elder, M.; Burley, C.; Goode, D.; Morton, J.

2000-01-01

Full text: The ideal electroretinography (ERG) electrode should provide reproducible waveforms, maximal amplitudes and minimal irritation of the patient's eyes. Contact lens electrodes (e.g. Burian-Allen, ERG jet) generate large amplitudes but are very uncomfortable and quite intimidating for the patient. Two other types, the gold foil and the H-K loop, provide a much more patient friendly alternative at the cost of somewhat reduced amplitudes. With the purchase of a new Nicolet Bravo electrodiagnostic system we had to select a suitable type of ERG electrode and establish the normal range for each ERG test with that electrode. It was decided to trial two electrodes, the gold foil (CH Electronics, UK) and the H-K loop (Avanta, Slovenia) before making the final choice. Seventeen normal volunteers, ranging in age from 14 to 56 years, were subjected to three standard measurements namely the flash photopic, white flash scotopic and transient pattern (PERG) ERG. Each test followed the guidelines set by the International Society for Clinical Electrophysiology of Vision (ISCEV). Before starting the measurements both eyes were anaesthetised with Ophthetic and for the flash ERG's the pupils were dilated with 1% Tropicamide. Immediately after the measurements each subject was asked which electrode was most comfortable. As specified by ISCEV the amplitudes were measured between adjacent troughs and peaks. The mean and standard deviation of the flash ERG b wave and the PERG P 50 amplitudes for each electrode are shown m the accompanying table together with the mean and standard deviation of the ratios of the amplitudes (gold foil/H-K loop) from each subject. It can be seen that the amplitudes measured with the gold foil electrodes are approximately twice those from the H-K loop and that the fractional variation (standard deviation/mean) of the gold foil amplitudes is also lower. In addition nearly all the subjects (13/17) felt less discomfort with the gold foil electrodes, only

hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia.

Science.gov (United States)

Nogawa, Hisashi; Kawai, Tomoyuki

2014-10-15

Acquired long QT syndrome induced by non-cardiovascular drugs can cause lethal cardiac arrhythmia called torsades de points and is a significant problem in drug development. The prolongation of QT interval and cardiac action potential duration are mainly due to reduced physiological function of the rapidly activating voltage-dependent potassium channels encoded by human ether-a-go-go-related gene (hERG). Structurally diverse groups of drugs are known to directly inhibit hERG channel conductance. Therefore, the ability of acute hERG inhibition is routinely assessed at the preclinical stages in pharmaceutical testing. Recent findings indicated that chronic treatment with various drugs not only inhibits hERG channels but also decreases hERG channel expression in the plasma membrane of cardiomyocytes, which has become another concern in safety pharmacology. The mechanisms involve the disruption of hERG trafficking to the surface membrane or the acceleration of hERG protein degradation. From this perspective, we present a brief overview of mechanisms of drug-induced trafficking inhibition and pathological regulation. Understanding of drug-induced hERG trafficking inhibition may provide new strategies for predicting drug-induced QT prolongation and lethal cardiac arrhythmia in pharmaceutical drug development. Copyright © 2014 Elsevier B.V. All rights reserved.

Ga2O3 Schottky rectifiers with 1 ampere forward current, 650 V reverse breakdown and 26.5 MW.cm-2 figure-of-merit

Science.gov (United States)

Yang, Jiancheng; Ren, F.; Tadjer, Marko; Pearton, S. J.; Kuramata, A.

2018-05-01

A key goal for Ga2O3 rectifiers is to achieve high forward currents and high reverse breakdown voltages. Field-plated β-Ga2O3 Schottky rectifiers with area 0.01 cm2, fabricated on 10 μm thick, lightly-doped drift regions (1.33 x 1016 cm-3) on heavily-doped (3.6 x 1018 cm-3) substrates, exhibited forward current density of 100A.cm-2 at 2.1 V, with absolute current of 1 A at this voltage and a reverse breakdown voltage (VB) of 650V. The on-resistance (RON) was 1.58 x 10-2 Ω.cm2, producing a figure of merit (VB2/RON) of 26.5 MW.cm-2. The Schottky barrier height of the Ni was 1.04 eV, with an ideality factor of 1.02. The on/off ratio was in the range 3.3 x 106 - 5.7 x 109 for reverse biases between 5 and 100V. The reverse recovery time was ˜30 ns for switching from +2V to -5V. The results show the capability of β-Ga2O3 rectifiers to achieve exceptional performance in both forward and reverse bias conditions.

Common variants in the hERG (KCNH2) voltage-gated potassium channel are associated with altered fasting and glucose-stimulated plasma incretin and glucagon responses

DEFF Research Database (Denmark)

Engelbrechtsen, Line; Mahendran, Yuvaraj; Jonsson, Anna

2018-01-01

BACKGROUND: Patients with long QT syndrome due to rare loss-of-function mutations in the human ether-á-go-go-related gene (hERG) have prolonged QT interval, risk of arrhythmias, increased secretion of insulin and incretins and impaired glucagon response to hypoglycemia. This is caused by a dysfun......BACKGROUND: Patients with long QT syndrome due to rare loss-of-function mutations in the human ether-á-go-go-related gene (hERG) have prolonged QT interval, risk of arrhythmias, increased secretion of insulin and incretins and impaired glucagon response to hypoglycemia. This is caused...... by a dysfunctional Kv11.1 voltage-gated potassium channel. Based on these findings in patients with rare variants in hERG, we hypothesized that common variants in hERG may also lead to alterations in glucose homeostasis. Subsequently, we aimed to evaluate the effect of two common gain-of-function variants in hERG...... in hERG on QT-interval and circulation levels of incretins, insulin and glucagon. The Danish population-based Inter99 cohort (n = 5895) was used to assess the effect of common variants on QT-interval. The Danish ADDITION-PRO cohort was used (n = 1329) to study genetic associations with levels of GLP-1...

Rehabilitating drug-induced long-QT promoters: in-silico design of hERG-neutral cisapride analogues with retained pharmacological activity.

Science.gov (United States)

Durdagi, Serdar; Randall, Trevor; Duff, Henry J; Chamberlin, Adam; Noskov, Sergei Y

2014-03-08

The human ether-a-go-go related gene 1 (hERG1), which codes for a potassium ion channel, is a key element in the cardiac delayed rectified potassium current, IKr, and plays an important role in the normal repolarization of the heart's action potential. Many approved drugs have been withdrawn from the market due to their prolongation of the QT interval. Most of these drugs have high potencies for their principal targets and are often irreplaceable, thus "rehabilitation" studies for decreasing their high hERG1 blocking affinities, while keeping them active at the binding sites of their targets, have been proposed to enable these drugs to re-enter the market. In this proof-of-principle study, we focus on cisapride, a gastroprokinetic agent withdrawn from the market due to its high hERG1 blocking affinity. Here we tested an a priori strategy to predict a compound's cardiotoxicity using de novo drug design with molecular docking and Molecular Dynamics (MD) simulations to generate a strategy for the rehabilitation of cisapride. We focused on two key receptors, a target interaction with the (adenosine) receptor and an off-target interaction with hERG1 channels. An analysis of the fragment interactions of cisapride at human A2A adenosine receptors and hERG1 central cavities helped us to identify the key chemical groups responsible for the drug activity and hERG1 blockade. A set of cisapride derivatives with reduced cardiotoxicity was then proposed using an in-silico two-tier approach. This set was compared against a large dataset of commercially available cisapride analogs and derivatives. An interaction decomposition of cisapride and cisapride derivatives allowed for the identification of key active scaffolds and functional groups that may be responsible for the unwanted blockade of hERG1.

Internal hydration H{sub 2}/O{sub 2} 100 cm{sup 2} polymer electrolyte membrane fuel cell

Energy Technology Data Exchange (ETDEWEB)

Miachon, S [CEA, Dept. de Recherche Fondamentale sur la Matiere Condensee, SESAM/PCM, 38 - Grenoble (France); Aldebert, P [CEA, Dept. de Recherche Fondamentale sur la Matiere Condensee, SESAM/PCM, 38 - Grenoble (France)

1995-07-01

This work deals with a new arrangement of a polymer electrolyte membrane fuel cell (PEMFC) support which allows the operation of a 100 cm{sup 2} surface area fuel cell with cold and unhumidified gases. Hydrogen is not recycled. Both gases (pure hydrogen and oxygen) are heated and humidified internally, each one crossing a porous carbon block. This allows a simplified water management. Classical low platinum loading E-Tek{sup R} electrodes, hot-pressed on Nafion{sup R} 117 and 112 membranes, are used. Performances are then a little higher than those of comparable PEMFCs in the literature: 0.7 V at 0.7 A/cm{sup 2} for Nafion{sup R} 117, and 0.724 V at 1 A/cm{sup 2} for Nafion{sup R} 112, under 4/6 bar (absolute) of H{sub 2}/O{sub 2} at 100 C. The values of PEMFC resistance obtained in fitting the data were found to be R=0.254 (with Nafion{sup R} 117) and 0.108 {Omega} cm{sup 2} (with Nafion{sup R} 112). The membrane contribution to the cell resistance was then estimated to be R{sub m}=0.204 and 0.058 {Omega} cm{sup 2}, respectively (with Nafion{sup R} conductivity estimated at 0.103 S/cm at 100 C in working fuel cell conditions). This membrane is therefore the major contributor to the total cell resistance. (orig.)

Rapid detection of ERG11 gene mutations in clinical Candida albicans isolates with reduced susceptibility to fluconazole by rolling circle amplification and DNA sequencing

Directory of Open Access Journals (Sweden)

Ellis David

2009-08-01

Full Text Available Abstract Background Amino acid substitutions in the target enzyme Erg11p of azole antifungals contribute to clinically-relevant azole resistance in Candida albicans. A simple molecular method for rapid detection of ERG11 gene mutations would be an advantage as a screening tool to identify potentially-resistant strains and to track their movement. To complement DNA sequencing, we developed a padlock probe and rolling circle amplification (RCA-based method to detect a series of mutations in the C. albicans ERG11 gene using "reference" azole-resistant isolates with known mutations. The method was then used to estimate the frequency of ERG11 mutations and their type in 25 Australian clinical C. albicans isolates with reduced susceptibility to fluconazole and in 23 fluconazole-susceptible isolates. RCA results were compared DNA sequencing. Results The RCA assay correctly identified all ERG11 mutations in eight "reference" C. albicans isolates. When applied to 48 test strains, the RCA method showed 100% agreement with DNA sequencing where an ERG11 mutation-specific probe was used. Of 20 different missense mutations detected by sequencing in 24 of 25 (96% isolates with reduced fluconazole susceptibility, 16 were detected by RCA. Five missense mutations were detected by both methods in 18 of 23 (78% fluconazole-susceptible strains. DNA sequencing revealed that mutations in non-susceptible isolates were all due to homozygous nucleotide changes. With the exception of the mutations leading to amino acid substitution E266D, those in fluconazole-susceptible strains were heterozygous. Amino acid substitutions common to both sets of isolates were D116E, E266D, K128T, V437I and V488I. Substitutions unique to isolates with reduced fluconazole susceptibility were G464 S (n = 4 isolates, G448E (n = 3, G307S (n = 3, K143R (n = 3 and Y123H, S405F and R467K (each n = 1. DNA sequencing revealed a novel substitution, G450V, in one isolate. Conclusion The sensitive RCA

Chemically deposited In2S3–Ag2S layers to obtain AgInS2 thin films by thermal annealing

International Nuclear Information System (INIS)

Lugo, S.; Peña, Y.; Calixto-Rodriguez, M.; López-Mata, C.; Ramón, M.L.; Gómez, I.; Acosta, A.

2012-01-01

Highlights: ► We obtained polycrystalline silver indium sulfide thin films through the annealing of chemically deposited In 2 S 3 –Ag 2 S films. ► According to XRD chalcopyrite structure of AgInS 2 was obtained. ► AgInS 2 thin film has a band gap of 1.86 eV and a conductivity value of 1.2 × 10 −3 (Ω cm) −1 . - Abstract: AgInS 2 thin films were obtained by the annealing of chemical bath deposited In 2 S 3 –Ag 2 S layers at 400 °C in N 2 for 1 h. According to the XRD and EDX results the chalcopyrite structure of AgInS 2 has been obtained. These films have an optical band gap, E g , of 1.86 eV and an electrical conductivity value of 1.2 × 10 −3 (Ω cm) −1 .

Infrared spectroscopy of the NO3 radical from 2000 to 3000 cm-1

Science.gov (United States)

Kawaguchi, Kentarou; Fujimori, Ryuji; Tang, Jian; Ishiwata, Takashi

2018-02-01

The present paper reports high-resolution spectroscopic study of the 14NO3 radical in the 2000-3000 cm-1 region, where eight E‧-A2‧ bands from the ground state are observed. Three bands at 2206, 2246, and 2377 cm-1 are analyzed for the first time, and assigned to the ν1 + 3ν4, 2ν2 + 2ν4, and ν3 + 3ν4 bands, respectively. Bands at 2024, 2155, 2518, and 2585 cm-1 are reassigned to the ν1 + ν3, 2ν3, ν1 + ν3 + ν4, and 2ν3 + ν4 bands, respectively, by adopting the new ν3 vibrational frequency of 1055 cm-1 lower than the previous ν3 = 1492 cm-1. The band at 2902 cm-1 is observed for the first time and assigned to the ν1 + ν3 + 2ν4 band which is the ν1 combined band with the 1927 cm-1 band. Band intensities observed in the 2000-3000 cm-1 region are attributed to the intensity borrowing from the B˜2E‧ -X˜2 A2‧ electronic transition through the vibronic interaction. Although the ν3 fundamental band has not been observed due to the cancelation of vibrational intensity and borrowed intensity, the 2ν3 band becomes stronger than ν3 by a factor of more than 50. Perturbation effects are recognized for the bands observed except for the 2206 cm-1 and 2377 cm-1 bands, and are analyzed by taking into account the Coriolis interaction in the most cases. However, the 2024 cm-1 band is free from the Coriolis interaction, and the v1-v3 interaction is incorporated in the analysis, leading to the 2ν1 frequency of 2008.8 cm-1, which is close to the energy value of 2010 cm-1 observed by a laser induced fluorescence study.

An empirical spectroscopic database for acetylene in the regions of 5850-6341 cm-1 and 7000-9415 cm-1

Science.gov (United States)

Lyulin, O. M.; Campargue, A.

2017-12-01

Six studies have been recently devoted to a systematic analysis of the high-resolution near infrared absorption spectrum of acetylene recorded by Cavity Ring Down spectroscopy (CRDS) in Grenoble and by Fourier-transform spectroscopy (FTS) in Brussels and Hefei. On the basis of these works, in the present contribution, we construct an empirical database for acetylene in the 5850-9415 cm-1 region excluding the 6341-7000 cm-1 interval corresponding to the very strong ν1+ν3 manifold. Our database gathers and extends information included in our CRDS and FTS studies. In particular, the intensities of about 1700 lines measured by CRDS in the 7244-7920 cm-1 region are reported for the first time together with those of several bands of 12C13CH2 present in natural isotopic abundance in the acetylene sample. The Herman-Wallis coefficients of most of the bands are derived from a fit of the measured intensity values. A recommended line list is provided with positions calculated using empirical spectroscopic parameters of the lower and upper energy vibrational levels and intensities calculated using the derived Herman-Wallis coefficients. This approach allows completing the experimental list by adding missing lines and improving poorly determined positions and intensities. As a result the constructed line list includes a total of 11113 transitions belonging to 150 bands of 12C2H2 and 29 bands of 12C13CH2. For comparison the HITRAN database in the same region includes 869 transitions of 14 bands, all belonging to 12C2H2. Our weakest lines have an intensity on the order of 10-29 cm/molecule, about three orders of magnitude smaller than the HITRAN intensity cut off. Line profile parameters are added to the line list which is provided in HITRAN format. The comparison of the acetylene database to the HITRAN2012 line list or to results obtained using the global effective operator approach is discussed in terms of completeness and accuracy.

Photoassociation spectroscopy of 87Rb2 (5s1/2+5p1/2)0u+ long-range molecular states: Coupling with the (5s1/2+5p3/2)0u+ series analyzed using the Lu-Fano approach

International Nuclear Information System (INIS)

Jelassi, H.; Viaris de Lesegno, B.; Pruvost, L.

2006-01-01

We report on photoassociation of cold 87 Rb atoms providing the spectroscopy of (5s 1/2 +5p 1/2 )0 u + long-range molecular states, in the energy range of [-12.5, -0.7 cm -1 ] below the dissociation limit. A Lu-Fano approach coupled to the LeRoy-Bernstein formula is used to analyze the data. The Lu-Fano graph exhibits the coupling of the molecular series with the (5s 1/2 +5p 3/2 )0 u + one, which is due to spin effects in the molecule. A two-channel model involving an improved LeRoy-Bernstein formula allows us to characterize the molecular series, to localize (5s 1/2 +5p 3/2 )0 u + levels, to evaluate the coupling, and to predict the energy and width of the first predissociated level of (5s 1/2 +5p 3/2 )0 u + series. An experimental spectrum confirms the prediction

Fourier Transform Spectroscopy of 18O-Enriched Carbonyl Sulfide from 1825 to 2700 cm -1

Science.gov (United States)

Strugariu, T.; Naı̈m, S.; Fayt, A.; Bredohl, H.; Blavier, J.-F.; Dubois, I.

1998-06-01

We have measured the Fourier transform spectrum of carbonyl sulfide from 1825 to 2700 cm-1, using a sample enriched in both18O (94.0%) and17O (1.54%). A careful calibration yields a line-position accuracy between 1.5 and 3.0 10-5cm-1. We have observed and analyzed 118 infrared bands of which 93 are measured for the first time: 55 for18O12C32S, 20 for18O12C34S, 11 for18O12C33S, 1 for18O12C36S, 12 for17O12C32S, 4 for17O12C34S, 2 for17O12C33S, and 13 for18O13C32S. Intensities are also reported and analyzed for all those bands. The intensity accuracy is better than 10%, and the precision of approximately 1% allows us to determine some Herman-Wallis coefficients.

Early identification of hERG liability in drug discovery programs by automated patch clamp

Directory of Open Access Journals (Sweden)

Timm eDanker

2014-09-01

Full Text Available Blockade of the cardiac ion channel coded by hERG can lead to cardiac arrhythmia, which has become a major concern in drug discovery and development. Automated electrophysiological patch clamp allows assessment of hERG channel effects early in drug development to aid medicinal chemistry programs and has become routine in pharmaceutical companies. However, a number of potential sources of errors in setting up hERG channel assays by automated patch clamp can lead to misinterpretation of data or false effects being reported. This article describes protocols for automated electrophysiology screening of compound effects on the hERG channel current. Protocol details and the translation of criteria known from manual patch clamp experiments to automated patch clamp experiments to achieve good quality data are emphasized. Typical pitfalls and artifacts that may lead to misinterpretation of data are discussed. While this article focuses on hERG channel recordings using the QPatch (Sophion A/S, Copenhagen, Denmark technology, many of the assay and protocol details given in this article can be transferred for setting up different ion channel assays by automated patch clamp and are similar on other planar patch clamp platforms.

X-ray Transients in M31

Science.gov (United States)

Kong, A. K. H.; Garcia, M. R.; Primini, F. A.; Murray, S. S.; McClintock, J. E.

2002-06-01

A bright X-ray transient was detected by Chandra on 2002 June 2 with a series of 5 HRC-I snapshots. The new source CXOU J004154.6+405648 (R.A.=00h41m54s.64, Dec.=+40d56m48s.0, +/- 1", J2000) is discovered at a luminosity (0.3-10 keV) of 1.5 x 1038 erg/s (assuming an absorbed power-law model with photon index = 2 and NH = 1021 cm-2 at a distance of 780 kpc).

X-ray surface brightness of Kepler's supernova remnant

International Nuclear Information System (INIS)

White, R.L.; Long, K.S.

1983-01-01

We have observed Kepler's supernova remnant (SNR) with the imaging instruments on board the Einstein Observatory. The 0.15-4.5 keV flux incident on the Earth is 1.2 x 10 - 10 ergs cm - 2 s - 1 ; the flux corrected for interstellar absorption is 3.4 x 10 - 10 ergs cm - 2 s - 1 (L/sub x/ = 1.0 x 10 36 ergs s - 1 at D = 5 kpc) if the absorbing column density is N/sub H/ = 2.8 x 10 21 cm - 2 . The remnant is circular and shows a strong shell which is at least 5 times brighter in the north than in the south. The X-ray observations do not unambiguously determine whether the remnant is in the adiabatic or the free expansion phase. If the remnant is in the adiabatic phase, the density of the interstellar medium (ISM) ( 2 /sub e/>/sup 1/2/) surrounding Kepler's SNR must be about 5 cm - 3 . If the remnant is in the free expansion phase, where most of the emission arises from shock-heated ejecta, the ISM density must still be relatively high, n/sub i/> or approx. =0.1 cm - 3 . Even if the ISM is very inhomogeneous, with very many small, dense clouds, we show that the mean density of the ISM must be greater than approx.0.1 cm - 3 . In any case, the density of the x-ray emitting gas must be high ( 2 /sub e/>/sup 1/2/ > or approx. =10 cm - 3 ), and the temperature must be fairly low (T/sub e/ 7 K). The relatively high ISM density which is required is surprising in view of Kepler's distance above the galactic plane, approx.600 pc. Possibly the ISM around Kepler's SNR and around other type i SNRs is dominated by the mass lost from the presupernova star

The NAP flux at mountain altitude 725 g cm-2

International Nuclear Information System (INIS)

Hazama, M.

1977-01-01

The energy spectrum of nuclear active particles (NAP) with energy ΣEsub(γ) greater than 3 TeV is obtained from an analysis of a thick emulsion chamber (140 cu of Pb) exposed on Mount Norikura at 2770 m above sea level and the vertical flux is estimated to be (1.4 +- 0.1) x 10 -10 cm -2 s -1 sr -1 . Assuming that the energy spectrum and the zenith angle distribution of NAP are expressed by power functions proportional to Esup(-(γ + 1)) and cossup(n-2) theta respectively in differential form, the exponents γ and n are obtained as 2.3 +- 0.1 and 7.3 +- 0.5 respectively. The collision mean free path and the ratio of constituents of NAP are discussed. (author)

PASS Reference Set Application: Lin UW (2010) TMPRSS2-ERG-PCA-PASS — EDRN Public Portal

Science.gov (United States)

Active surveillance is used to manage low-risk prostate cancer. Both PCA3 and TMPRSS2:ERG are promising biomarkers that may be associated with aggressive disease. This study examines the correlation of these biomarkers with higher cancer volume and grade determined at the time of biopsy in an active surveillance cohort.

Interaction between the cardiac rapidly (IKr) and slowly (IKs) activating delayed rectifier potassium channels revealed by low K+-induced hERG endocytic degradation.

Science.gov (United States)

Guo, Jun; Wang, Tingzhong; Yang, Tonghua; Xu, Jianmin; Li, Wentao; Fridman, Michael D; Fisher, John T; Zhang, Shetuan

2011-10-07

Cardiac repolarization is controlled by the rapidly (I(Kr)) and slowly (I(Ks)) activating delayed rectifier potassium channels. The human ether-a-go-go-related gene (hERG) encodes I(Kr), whereas KCNQ1 and KCNE1 together encode I(Ks). Decreases in I(Kr) or I(Ks) cause long QT syndrome (LQTS), a cardiac disorder with a high risk of sudden death. A reduction in extracellular K(+) concentration ([K(+)](o)) induces LQTS and selectively causes endocytic degradation of mature hERG channels from the plasma membrane. In the present study, we investigated whether I(Ks) compensates for the reduced I(Kr) under low K(+) conditions. Our data show that when hERG and KCNQ1 were expressed separately in human embryonic kidney (HEK) cells, exposure to 0 mM K(+) for 6 h completely eliminated the mature hERG channel expression but had no effect on KCNQ1. When hERG and KCNQ1 were co-expressed, KCNQ1 significantly delayed 0 mM K(+)-induced hERG reduction. Also, hERG degradation led to a significant reduction in KCNQ1 in 0 mM K(+) conditions. An interaction between hERG and KCNQ1 was identified in hERG+KCNQ1-expressing HEK cells. Furthermore, KCNQ1 preferentially co-immunoprecipitated with mature hERG channels that are localized in the plasma membrane. Biophysical and pharmacological analyses indicate that although hERG and KCNQ1 closely interact with each other, they form distinct hERG and KCNQ1 channels. These data extend our understanding of delayed rectifier potassium channel trafficking and regulation, as well as the pathology of LQTS.

ERG and GRG review of the draft of ''preliminary test plan for in situ testing from an exploratory shaft in salt - October 1983''

International Nuclear Information System (INIS)

Kalia, H.N.

1986-03-01

The Engineering Review Group (ERG) and Geologic Review Group (GRG) were established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate engineering- and geologic-related issues in the US Department of Energy's nuclear waste repository program. The January 1984 meeting of the ERG and GRG reviewed the In Situ Test Plan (ISTP) titled ''Preliminary Test Plan for In Situ Testing From an Exploratory Shaft in Salt - October 1983.'' This report documents the ERG's and GRG's comments and recommendations on this subject and the ONWI responses to the specific points raised by the ERG and GRG. 6 refs., 2 figs., 1 tab

Electron-impact excitation of multiply-charged ions using energy loss in merged beams: e + Si3+(3s2S1/2) → e + Si3+(3p2P1/2,3/2)

International Nuclear Information System (INIS)

Wahlin, E.K.; Thompson, J.S.; Dunn, G.H.; Phaneuf, R.A.; Gregory, D.C.; Smith, A.C.H.

1990-01-01

For the first time absolute total cross sections for electron-impact excitation of a multiply-charged ion have been measured using an electron-energy-loss technique. Measurements were made near threshold for the process e + Si 3+ (3s 2 S 1/2 ) → e + Si 3+ (3p 2 P 1/2 , 3/2 ) -- 8.88 eV. The 10 -15 cm 2 measured cross section agrees with results of 7-state close coupling calculations to better than the ±20% (90% CL) total uncertainty of the measurements. Convoluting the theoretical curve with a Gaussian energy distribution indicates an energy width of 0.15 approx-lt ΔE approx-lt 0.20 eV. 12 refs., 2 figs

Synthesis and Characterisation of Tris(1-carboxyl-2-phenyl-1,2-ethyl eno dithiol enic-S,S') Tungsten Complex as Photo catalyst for Photolysis of H2O Molecules

International Nuclear Information System (INIS)

Fadhli Hadana Rahman; Rusli Daik; Mohammad Kassim; Khuzaimah; Wan Ramli Wan Daud

2008-01-01

Tris(1-carboxyl-2-phenyl-1,2-ethylenodithiolenic-S,S ' ) tungsten complex is one of the most promising photo catalyst to be used in photolysis of water to produce hydrogen. The first step of the synthesis involves a metathesis reaction of tetrapropylammonium bromide [((C 3 H 7 ) 4 N)Br] and ammonium tetrathiotungstate [(NH 4 ) 2 WS 4 ] to form a tetrapropylammonium tetrathiotungstate [((C 3 H 7 ) 4 N) 2 WS 4 ] (precursor). Then, the precursor was reacted with phenyl acetylenecarboxylic acid (C 9 H 6 O 2 ) to form tris(1-carboxyl-2-phenyl-1,2-ethylenodithiolenic-S,S ' ) tungsten complex (C 27 H 18 O 2 S 6 W). The infra-red, ultra violet/ visible (UV/ Vis) spectrum, nuclear magnetic resonance (NMR) and elemental micro-analysis of C, H, N and S agreed with the characteristic of the tris(1-carboxyl-2-phenyl-1,2-ethylenodithiolenic-S,S ' ) tungsten complex. The (W-S), (C-S) and (C=O) stretching frequencies were detected at 511, (1470 and 1035) and 1655 cm -1 , respectively. The 1 H NMR spectrum showed six protons in the complex. The 13 C NMR showed only 7 signals for carbon atom in the benzene ring, ethylene groups and carboxylic acid pendant group due to the symmetry of the molecules. The reaction yield was about 50 percent. Photolysis of acetone spiked H 2 O showed that the catalyst was able to produced 1.8 μmol/ h hydrogen. (author)

Fourier transform infrared spectroscopy of D212CO in the 2500-4500 cm-1 region and the first rovibrational analysis of its v2 = 2 state

Science.gov (United States)

A'dawiah, Rabia'tul; Tan, T. L.; Ng, L. L.

2018-03-01

A low-resolution (0.5 cm-1) Fourier transform infrared (FTIR) spectrum of formaldehyde-d2 (D212CO) in the 2500-4500 cm-1 region was recorded to study the combination bands in this region. The bands ν2 +ν4,ν2 +ν6 , ν2 +ν3 , ν1 +ν2 , ν2 +ν5 , 3ν3 , 2ν2 and 2ν5 were identified and their band centers (with an uncertainty of ± 0.1 cm-1) and band types were determined. Furthermore, the high-resolution FTIR spectrum of the 2ν2 overtone band (3315-3440 cm-1) of D212CO was recorded at an unapodized resolution of 0.0063 cm-1 and its infrared lines were analyzed. A total of 970 rovibrational transitions have been assigned and fitted up to J‧ = 35 and Ka‧ = 14 using the Watson's A-reduced Hamiltonian in the Ir representation. Upper state (v2 = 2) rovibrational constants inclusive of three rotational and five quartic centrifugal distortion constants were accurately determined for the first time. The band center of the 2ν2 band was determined as 3385.200666 ± 0.000035 cm-1. The rms deviation of the rovibrational fit was 0.00093 cm-1. From the fitting of 451 ground state combination differences (GSCDs) of D212CO which were derived from the infrared transitions of the 2ν2 band of this work, together with 360 microwave frequencies from a previous study, new and accurate ground state constants of D212CO up to three octic terms were obtained. The combination and overtone bands and the newly assigned high-resolution infrared lines of the 2ν2 band in the 2500-4500 cm-1 region can be used to detect D212CO in this infrared region. In addition, the results derived from this study give information on the rovibrational molecular structure of D212CO.

FeS2-doped MoS2 nanoflower with the dominant 1T-MoS2 phase as an excellent electrocatalyst for high-performance hydrogen evolution

International Nuclear Information System (INIS)

Zhao, Xue; Ma, Xiao; Lu, Qingqing; Li, Qun; Han, Ce; Xing, Zhicai; Yang, Xiurong

2017-01-01

Well-established methods to improve the hydrogen evolution reaction (HER) performances include, but are not limited to, tailoring the morphology and electronic structure of transition metal dichalcogenides (TMDs), and doping of earth abundant chemicals such as iron pyrite FeS 2 into existing TMDs. In this work, MoS 2 nanoflowers with the majority being octahedral MoS 2 (1T-MoS 2 ) and doped with FeS 2 were prepared and applied to HER. The as-prepared catalysts were characterized by X-ray absorption fine structure at the K-edge of Mo, S, and Fe to probe the local electronic structures. The resulting nanomaterial was identified to be FeS 2 doped MoS 2 nanoflower (denoted as Fe-MoS 2 NF) with 66% 1T-MoS 2 which was the metallic phase and could drastically boost the HER properties. The Fe-MoS 2 NF exhibited high HER performance with a Tafel slope of 82 mV dec −1 and it needs 136 mV to achieve a current density of 10 mA cm −2 . The synthesis of Fe-MoS 2 NF with refined morphology and active electronic structure is expected to open a new era for improving the catalytic activity and stability of MoS 2 .

X-linked retinoschisis: RS1 mutation severity and age affect the ERG phenotype in a cohort of 68 affected male subjects.

Science.gov (United States)

Bowles, Kristen; Cukras, Catherine; Turriff, Amy; Sergeev, Yuri; Vitale, Susan; Bush, Ronald A; Sieving, Paul A

2011-11-29

To assess the effect of age and RS1 mutation on the phenotype of X-linked retinoschisis (XLRS) subjects using the clinical electroretinogram (ERG) in a cross-sectional analysis. Sixty-eight XLRS males 4.5 to 55 years of age underwent genotyping, and the retinoschisis (RS1) mutations were classified as less severe (27 subjects) or more severe (41 subjects) based on the putative impact on the protein. ERG parameters of retinal function were analyzed by putative mutation severity with age as a continuous variable. The a-wave amplitude remained greater than the lower limit of normal (mean, -2 SD) for 72% of XLRS males and correlated with neither age nor mutation class. However, b-wave and b/a-ratio amplitudes were significantly lower in the more severe than in the less severe mutation groups and in older than in younger subjects. Subjects up to 10 years of age with more severe RS1 mutations had significantly greater b-wave amplitudes and faster a-wave trough implicit times than older subjects in this group. RS1 mutation putative severity and age both had significant effects on retinal function in XLRS only in the severe mutation group, as judged by ERG analysis of the b-wave amplitude and the b/a-ratio, whereas the a-wave amplitude remained normal in most. A new observation was that increasing age (limited to those aged 55 and younger) caused a significant delay in XLRS b-wave onset (i.e., a-wave implicit time), even for those who retained considerable b-wave amplitudes. The delayed b-wave onset suggested that dysfunction of the photoreceptor synapse or of bipolar cells increases with age of XLRS subjects.

Pharmacologic Approach to Defective Protein Trafficking in the E637K-hERG Mutant with PD-118057 and Thapsigargin.

Directory of Open Access Journals (Sweden)

Haiyan Mao

Full Text Available Treatment of LQT2 is inadequate. Many drugs which can pharmacologically rescue defective protein trafficking in LQT2 also result in potent blockade of HERG current, negating their therapeutic benefit. It is reported that PD-118057 and thapsigargin can rescue LQT2 without hERG channel blockade, but the precise mechanism of action is unknown. Furthermore, the effect of PD-118057 and thapsigargin on the dominant negative E637K-hERG mutant has not been previously investigated.IN THIS STUDY, WE INVESTIGATED: (a the effect of PD-118057 and thapsigargin on the current amplitudes of WT-hERG and WT/E637K-hERG channels; (b the effect of PD-118057 and thapsigargin on the biophysical properties of WT-hERG and WT/E637K-hERG channels; (c whether drug treatment can rescue channel processing and trafficking defects of the WT/E637K-hERG mutant.The whole-cell Patch-clamp technique was used to assess the effect of PD-118057 and thapsigargin on the electrophysiological characteristics of the rapidly activating delayed rectifier K(+ current (Ikr of the hERG protein channel. Western blot was done to investigate pharmacological rescue on hERG protein channel function.In our study, PD-118057 was shown to significantly enhance both the maximum current amplitude and tail current amplitude, but did not alter the gating and kinetic properties of the WT-hERG channel, with the exception of accelerating steady-state inactivation. Additionally, thapsigargin shows a similar result as PD-118057 for the WT-hERG channel, but with the exception of attenuating steady-state inactivation. However, for the WT/E637K-hERG channel, PD-118057 had no effect on either the current or on the gating and kinetic properties. Furthermore, thapsigargin treatment did not alter the current or the gating and kinetic properties of the WT/E637K-hERG channel, with the exception of opening at more positive voltages.Our findings illustrate that neither PD-118057 nor thapsigargin play a role in correcting

Performance of Machine Learning Algorithms for Qualitative and Quantitative Prediction Drug Blockade of hERG1 channel.

Science.gov (United States)

Wacker, Soren; Noskov, Sergei Yu

2018-05-01

Drug-induced abnormal heart rhythm known as Torsades de Pointes (TdP) is a potential lethal ventricular tachycardia found in many patients. Even newly released anti-arrhythmic drugs, like ivabradine with HCN channel as a primary target, block the hERG potassium current in overlapping concentration interval. Promiscuous drug block to hERG channel may potentially lead to perturbation of the action potential duration (APD) and TdP, especially when with combined with polypharmacy and/or electrolyte disturbances. The example of novel anti-arrhythmic ivabradine illustrates clinically important and ongoing deficit in drug design and warrants for better screening methods. There is an urgent need to develop new approaches for rapid and accurate assessment of how drugs with complex interactions and multiple subcellular targets can predispose or protect from drug-induced TdP. One of the unexpected outcomes of compulsory hERG screening implemented in USA and European Union resulted in large datasets of IC 50 values for various molecules entering the market. The abundant data allows now to construct predictive machine-learning (ML) models. Novel ML algorithms and techniques promise better accuracy in determining IC 50 values of hERG blockade that is comparable or surpassing that of the earlier QSAR or molecular modeling technique. To test the performance of modern ML techniques, we have developed a computational platform integrating various workflows for quantitative structure activity relationship (QSAR) models using data from the ChEMBL database. To establish predictive powers of ML-based algorithms we computed IC 50 values for large dataset of molecules and compared it to automated patch clamp system for a large dataset of hERG blocking and non-blocking drugs, an industry gold standard in studies of cardiotoxicity. The optimal protocol with high sensitivity and predictive power is based on the novel eXtreme gradient boosting (XGBoost) algorithm. The ML-platform with XGBoost

CHANDRA OBSERVATION OF THE RELATIVISTIC BINARY J1906+0746

International Nuclear Information System (INIS)

Kargaltsev, O.; Pavlov, G. G.

2009-01-01

PSR J1906+0746 is a young radio pulsar (τ = 112 kyr, P = 144 ms) in a tight binary (P orb = 3.98 hr) with a compact high-mass companion (M comp ≅ 1.36 M sun ), at the distance of about 5 kpc. We observed this unique relativistic binary with the Chandra Advanced CCD Imaging Spectrometer detector for 31.6 ks. Surprisingly, not a single photon was detected within the 3'' radius from the J1906+0746 radio position. For a plausible range of hydrogen column densities, n H = (0.5-1) x 10 22 cm -2 , the nondetection corresponds to the 90% upper limit of (3-5) x 10 30 erg s -1 on the unabsorbed 0.5-8 keV luminosity for the power-law model with Γ = 1.0-2.0, and ∼10 32 erg s -1 on the bolometric luminosity of the thermal emission from the neutrons star surface. The inferred limits are the lowest known for pulsars with spin-down properties similar to those of PSR J1906+0746. We have also tentatively detected a puzzling extended structure which looks like a tilted ring with a radius of 1.'6 centered on the pulsar. The measured 0.5-8 keV flux of the feature, ∼3.1 x 10 -14 erg cm -2 s -1 , implies an unabsorbed luminosity of 1.2 x 10 32 erg s -1 (4.5 x 10 -4 of the pulsar's E-dot) for n H = 0.7 x 10 22 cm -2 . If the ring is not a peculiar noise artifact, the pulsar wind nebula around an unusually underluminous pulsar would be the most plausible interpretation.

In vitro chronic effects on hERG channel caused by the marine biotoxin Yessotoxin.

Directory of Open Access Journals (Sweden)

Sara Fernández Ferreiro

2014-06-01

Currently, published evidence indicates that hERG channel dysfunction can be due to more than one mechanism for many drugs (Guth, 2007. Alterations of hERG channel trafficking are considered an important factor in hERG-related cardiotoxicity. Actually, a screening study revealed that almost 40% of the drugs that block Ikr have also trafficking effects (Wible et al., 2005. Although YTX does not block hERG channels, it has been historically described as cardiotoxic due to in vivo damage to cardiomyocytes. Our results show that YTX induces a significant increase of hERG channel levels on the extracellular side of the plasma membrane in vitro. YTX causes cell death in many cell lines (Korsnes and Espenes, 2011 and the alterations of surface hERG levels might be related to the apoptotic process. However, annexin-V, a relatively early marker of apoptosis (Vermes et al., 1995, occurs later than the increase of surface hERG. Additionally, staurosporine triggered apoptosis without a simultaneous increase of surface hERG, so events are not necessarily related. Therefore YTX-induced elevated hERG in the plasma membrane seem to be independent of apoptosis. Functional implications of hERG currents have been described after alterations of cell surface hERG density (Guth, 2007. YTX did not cause significant alterations of hERG currents. Furthermore the hERG levels after YTX treatment were duplicated, so the effect on currents should be clearly evidenced if these channels were functional. The hERG channels on the cell surface are regulated by its production, translocation to the plasma membrane and degradation. The increase of extracellular channel could be a consequence of a higher production and externalization or a slower degradation. Higher synthesis in our cell model would not be physiologically relevant but our results demonstrated that the amount of immature hERG is reduced instead of increased. Fully glycosylated hERG seems slightly increased in these conditions but it is

Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer

Science.gov (United States)

2017-10-01

performed exploratory data analysis on all clinically annotated prostate cancer datasets available from the public domain and through the collaboration...with GenomeDX. We used statistical summaries and data visualizations techniques (e.g., principal component analysis , hierarchical clustering) to...associated with PTEN loss on genetically homogeneous ERG-positive and ERG- negative backgrounds. Timeline (Months) Major Task 2: Perform CAGE analysis

ZO-1 expression is suppressed by GM-CSF via miR-96/ERG in brain microvascular endothelial cells.

Science.gov (United States)

Zhang, Hu; Zhang, Shuhong; Zhang, Jilin; Liu, Dongxin; Wei, Jiayi; Fang, Wengang; Zhao, Weidong; Chen, Yuhua; Shang, Deshu

2018-05-01

The level of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases in some disorders such as vascular dementia, Alzheimer's disease, and multiple sclerosis. We previously reported that in Alzheimer's disease patients, a high level of GM-CSF in the brain parenchyma downregulated expression of ZO-1, a blood-brain barrier tight junction protein, and facilitated the infiltration of peripheral monocytes across the blood-brain barrier. However, the molecular mechanism underlying regulation of ZO-1 expression by GM-CSF is unclear. Herein, we found that the erythroblast transformation-specific (ETS) transcription factor ERG cooperated with the proto-oncogene protein c-MYC in regulation of ZO-1 transcription in brain microvascular endothelial cells (BMECs). The ERG expression was suppressed by miR-96 which was increased by GM-CSF through the phosphoinositide-3 kinase (PI3K)/Akt pathway. Inhibition of miR-96 prevented ZO-1 down-regulation induced by GM-CSF both in vitro and in vivo. Our results revealed the mechanism of ZO-1 expression reduced by GM-CSF, and provided a potential target, miR-96, which could block ZO-1 down-regulation caused by GM-CSF in BMECs.

DNA repair genes RAD52 and SRS2, a cell wall synthesis regulator gene SMI1, and the membrane sterol synthesis scaffold gene ERG28 are important in efficient Agrobacterium-mediated yeast transformation with chromosomal T-DNA.

Science.gov (United States)

Ohmine, Yuta; Satoh, Yukari; Kiyokawa, Kazuya; Yamamoto, Shinji; Moriguchi, Kazuki; Suzuki, Katsunori

2016-04-02

Plant pathogenic Agrobacterium strains can transfer T-DNA regions of their Ti plasmids to a broad range of eukaryotic hosts, including fungi, in vitro. In the recent decade, the yeast Saccharomyces cerevisiae is used as a model host to reveal important host proteins for the Agrobacterium-mediated transformation (AMT). Further investigation is required to understand the fundamental mechanism of AMT, including interaction at the cell surface, to expand the host range, and to develop new tools. In this study, we screened a yeast mutant library for low AMT mutant strains by advantage of a chromosome type T-DNA, which transfer is efficient and independent on integration into host chromosome. By the mutant screening, we identified four mutant strains (srs2Δ, rad52Δ, smi1Δ and erg28Δ), which showed considerably low AMT efficiency. Structural analysis of T-DNA product replicons in AMT colonies of mutants lacking each of the two DNA repair genes, SRS2 and RAD52, suggested that the genes act soon after T-DNA entry for modification of the chromosomal T-DNA to stably maintain them as linear replicons and to circularize certain T-DNA simultaneously. The cell wall synthesis regulator SMI1 might have a role in the cell surface interaction between the donor and recipient cells, but the smi1Δ mutant exhibited pleiotropic effect, i.e. low effector protein transport as well as low AMT for the chromosomal T-DNA, but relatively high AMT for integrative T-DNAs. The ergosterol synthesis regulator/enzyme-scaffold gene ERG28 probably contributes by sensing a congested environment, because growth of erg28Δ strain was unaffected by the presence of donor bacterial cells, while the growth of the wild-type and other mutant yeast strains was suppressed by their presence. RAD52 and the DNA helicase/anti-recombinase gene SRS2 are necessary to form and maintain artificial chromosomes through the AMT of chromosomal T-DNA. A sterol synthesis scaffold gene ERG28 is important in the high

Chemically deposited In{sub 2}S{sub 3}-Ag{sub 2}S layers to obtain AgInS{sub 2} thin films by thermal annealing

Energy Technology Data Exchange (ETDEWEB)

Lugo, S. [Universidad Autonoma de Nuevo Leon, UANL, Fac. de Ciencias Quimicas, Av. Universidad S/N Ciudad Universitaria San Nicolas de Los Garza Nuevo Leon, C.P. 66451 (Mexico); Pena, Y., E-mail: yolapm@gmail.com [Universidad Autonoma de Nuevo Leon, UANL, Fac. de Ciencias Quimicas, Av. Universidad S/N Ciudad Universitaria San Nicolas de Los Garza Nuevo Leon, C.P. 66451 (Mexico); Calixto-Rodriguez, M. [Centro de Investigacion en Energia-Universidad Nacional Autonoma de Mexico, 62580, Temixco, Morelos (Mexico); Lopez-Mata, C. [Instituto Tecnologico de Chetumal, Av. Insurgentes No. 330, C.P. 77013, Col. David Gustavo Gtz., Chetumal, Quintana Roo (Mexico); Ramon, M.L. [Centro de Investigacion en Energia-Universidad Nacional Autonoma de Mexico, 62580, Temixco, Morelos (Mexico); Gomez, I.; Acosta, A. [Universidad Autonoma de Nuevo Leon, UANL, Fac. de Ciencias Quimicas, Av. Universidad S/N Ciudad Universitaria San Nicolas de Los Garza Nuevo Leon, C.P. 66451 (Mexico)

2012-12-15

Highlights: Black-Right-Pointing-Pointer We obtained polycrystalline silver indium sulfide thin films through the annealing of chemically deposited In{sub 2}S{sub 3}-Ag{sub 2}S films. Black-Right-Pointing-Pointer According to XRD chalcopyrite structure of AgInS{sub 2} was obtained. Black-Right-Pointing-Pointer AgInS{sub 2} thin film has a band gap of 1.86 eV and a conductivity value of 1.2 Multiplication-Sign 10{sup -3} ({Omega} cm){sup -1}. - Abstract: AgInS{sub 2} thin films were obtained by the annealing of chemical bath deposited In{sub 2}S{sub 3}-Ag{sub 2}S layers at 400 Degree-Sign C in N{sub 2} for 1 h. According to the XRD and EDX results the chalcopyrite structure of AgInS{sub 2} has been obtained. These films have an optical band gap, E{sub g}, of 1.86 eV and an electrical conductivity value of 1.2 Multiplication-Sign 10{sup -3} ({Omega} cm){sup -1}.

Inhibitory effects and mechanism of dihydroberberine on hERG channels expressed in HEK293 cells.

Directory of Open Access Journals (Sweden)

Dahai Yu

Full Text Available The human ether-a-go-go-related gene (hERG potassium channel conducts rapid delayed rectifier potassium currents (IKr and contributes to phase III cardiac action potential repolarization. Drugs inhibit hERG channels by binding to aromatic residues in hERG helixes. Berberine (BBR has multiple actions, and its hydrogenated derivative dihydroberberine (DHB is a potential candidate for developing new drugs. Previous studies have demonstrated that BBR blocks hERG channels and prolongs action potential duration (APD. Our present study aimed to investigate the effects and mechanism of DHB on hERG channels. Protein expression and the hERG current were analyzed using western blotting and patch-clamp, respectively. DHB inhibited the hERG current concentration-dependently after instantaneous perfusion, accelerated channel inactivation by directly binding tyrosine (Tyr652 and phenylalanine (Phe656, and decreased mature (155-kDa and simultaneously increased immature (135-kDa hERG expression, respectively. This suggests disruption of forward trafficking of hERG channels. Besides, DHB remarkably reduced heat shock protein 90 (Hsp90 expression and its interaction with hERG, indicating that DHB disrupted hERG trafficking by impairing channel folding. Meanwhie, DHB enhanced the expression of cleaved activating transcription factor-6 (ATF-6, a biomarker of unfolded protein response (UPR. Expression of calnexin and calreticulin, chaperones activated by ATF-6 to facilitate channel folding, were also increased, which indicating UPR activation. Additionally, the degradation rate of mature 155-kDa hERG increased following DHB exposure. In conclusion, we demonstrated that DHB acutely blocked hERG channels by binding the aromatic Tyr652 and Phe656. DHB may decrease hERG plasma membrane expression through two pathways involving disruption of forward trafficking of immature hERG channels and enhanced degradation of mature hERG channels. Furthermore, forward trafficking was

Gating mechanism of Kv11.1 (hERG) K+ channels without covalent connection between voltage sensor and pore domains.

Science.gov (United States)

de la Peña, Pilar; Domínguez, Pedro; Barros, Francisco

2018-03-01

Kv11.1 (hERG, KCNH2) is a voltage-gated potassium channel crucial in setting the cardiac rhythm and the electrical behaviour of several non-cardiac cell types. Voltage-dependent gating of Kv11.1 can be reconstructed from non-covalently linked voltage sensing and pore modules (split channels), challenging classical views of voltage-dependent channel activation based on a S4-S5 linker acting as a rigid mechanical lever to open the gate. Progressive displacement of the split position from the end to the beginning of the S4-S5 linker induces an increasing negative shift in activation voltage dependence, a reduced z g value and a more negative ΔG 0 for current activation, an almost complete abolition of the activation time course sigmoid shape and a slowing of the voltage-dependent deactivation. Channels disconnected at the S4-S5 linker near the S4 helix show a destabilization of the closed state(s). Furthermore, the isochronal ion current mode shift magnitude is clearly reduced in the different splits. Interestingly, the progressive modifications of voltage dependence activation gating by changing the split position are accompanied by a shift in the voltage-dependent availability to a methanethiosulfonate reagent of a Cys introduced at the upper S4 helix. Our data demonstrate for the first time that alterations in the covalent connection between the voltage sensor and the pore domains impact on the structural reorganizations of the voltage sensor domain. Also, they support the hypothesis that the S4-S5 linker integrates signals coming from other cytoplasmic domains that constitute either an important component or a crucial regulator of the gating machinery in Kv11.1 and other KCNH channels.

On the nature of the ultraluminous X-ray transient in Cen~A (NGC 5128)

OpenAIRE

Ghosh, Kajal K.; Finger, Mark H.; Swartz, Douglas A.; Tennant, Allyn F.; Wu, Kinwah

2005-01-01

We combine 9 ROSAT, 9 Chandra, and 2 XMM-Newton observations of the Cen~A galaxy to obtain the X-ray light curve of 1RXH J132519.8-430312 (=CXOU J132519.9$-$430317) spanning 1990 to 2003. The source reached a peak 0.1-2.4 keV flux F_X>10^{-12} ergs cm^{-2} s^{-1} during a 10~day span in 1995 July. The inferred peak isotropic luminosity of the source therefore exceeded 3 10^{39} ergs s^{-1}, which places the source in the class of ultra-luminous X-ray sources. Coherent pulsations at 13.264 Hz ...

Facultative Sterol Uptake in an Ergosterol-Deficient Clinical Isolate of Candida glabrata Harboring a Missense Mutation in ERG11 and Exhibiting Cross-Resistance to Azoles and Amphotericin B

Science.gov (United States)

Hull, Claire M.; Parker, Josie E.; Bader, Oliver; Weig, Michael; Gross, Uwe; Warrilow, Andrew G. S.; Kelly, Diane E.

2012-01-01

We identified a clinical isolate of Candida glabrata (CG156) exhibiting flocculent growth and cross-resistance to fluconazole (FLC), voriconazole (VRC), and amphotericin B (AMB), with MICs of >256, >256, and 32 μg ml−1, respectively. Sterol analysis using gas chromatography-mass spectrometry (GC-MS) revealed that CG156 was a sterol 14α-demethylase (Erg11p) mutant, wherein 14α-methylated intermediates (lanosterol was >80% of the total) were the only detectable sterols. ERG11 sequencing indicated that CG156 harbored a single-amino-acid substitution (G315D) which nullified the function of native Erg11p. In heterologous expression studies using a doxycycline-regulatable Saccharomyces cerevisiae erg11 strain, wild-type C. glabrata Erg11p fully complemented the function of S. cerevisiae sterol 14α-demethylase, restoring growth and ergosterol synthesis in recombinant yeast; mutated CG156 Erg11p did not. CG156 was culturable using sterol-free, glucose-containing yeast minimal medium (glcYM). However, when grown on sterol-supplemented glcYM (with ergosta 7,22-dienol, ergosterol, cholestanol, cholesterol, Δ7-cholestenol, or desmosterol), CG156 cultures exhibited shorter lag phases, reached higher cell densities, and showed alterations in cellular sterol composition. Unlike comparator isolates (harboring wild-type ERG11) that became less sensitive to FLC and VRC when cultured on sterol-supplemented glcYM, facultative sterol uptake by CG156 did not affect its azole-resistant phenotype. Conversely, CG156 grown using glcYM with ergosterol (or with ergosta 7,22-dienol) showed increased sensitivity to AMB; CG156 grown using glcYM with cholesterol (or with cholestanol) became more resistant (MICs of 2 and >64 μg AMB ml−1, respectively). Our results provide insights into the consequences of sterol uptake and metabolism on growth and antifungal resistance in C. glabrata. PMID:22615281

Ultrasonographic criteria for fine needle aspiration of nonpalpable thyroid nodules 1–2 cm in diameter

Energy Technology Data Exchange (ETDEWEB)

Kim, Ji Yang, E-mail: j0kim040@louisville.edu [Department of Radiology, University of Louisville, 530 South Jackson Street, Louisville, KY 40242 (United States); Department of Healthcare System Gangnam Center, Department of Radiology, Seoul National University Hospital, 737 Star tower, 40 floor, Yeoksam-dong, Gangnam-gu, Seoul 135-080 (Korea, Republic of); Kim, Soo Young; Yang, Ki Ra [Department of Healthcare System Gangnam Center, Department of Radiology, Seoul National University Hospital, 737 Star tower, 40 floor, Yeoksam-dong, Gangnam-gu, Seoul 135-080 (Korea, Republic of)

2013-02-15

Purpose: To investigate the ultrasonographic (US) characteristics for nonpalpable thyroid nodules 1–2 cm in diameter and to evaluate the guideline for fine needle aspiration (FNA) in terms of US findings. Materials and methods: Between June 2005 and November 2006, FNA was performed in 919 thyroid nodules by radiologists. Of these nodules, 51 malignant nodules and 72 benign nodules were finally included. All 123 nodules were analyzed by 3 radiologists if there were the following US characteristics: marked hypoechogenecity, hypoechogenecity, isoechogenecity, hyperechogenecity, microcalcification, coarse calcification, rim calcification, spiculated margin, taller-than-wide shape, irregular shape, hypoechoic rim and honeycomb appearance. The maximum diameters of nodules and thickness of hypoechoic rim were measured. US characteristics relevant as predictors were identified using a Chi-square or Fisher's exact test and odds ratio. We compared the diagnostic efficacy of 3 US criteria for FNA indication. Results: Microcalcification, taller-than-wide shape, marked hypoechogenecity, hypoechogenecity, coarse calcification, irregular shape and spiculated margin were significant characteristics of malignant nodules. Isoechogenecity, hypoechoic rim and honeycomb appearance was significant characteristics of benign nodules. Rim or arc calcification, hyperechogenecity and thickness of hypoechoic rim were insignificant. Among 3 US criteria for FNA indication, NFI showed the highest diagnostic efficacy, 98.0% in sensitivity, 75.0% in specificity and 150.0 in odds ratio. Conclusion: As for nonpalpable thyroid nodules 1–2 cm in diameter, US characteristics are useful for differentiating between malignant and benign nodules. Malignant US characteristics and honeycombing appearance have significant value in selecting nodules for biopsy and reducing the frequency of the FNA procedure.

Tubin: Sinfonie nr. 11 (ergänzt von Kaljo Raid) / Christoph Schlüren

Index Scriptorium Estoniae

Schlüren, Christoph

1997-01-01

Uuest heliplaadist "Tubin: Sinfonie nr. 11 (ergänzt von Kaljo Raid); Pärt: Nekrolog op. 5, Sinfonie nr. 1; Tüür: Searching for Roots, Insula deserta, Zeitraum. Königliches Philharmonisches Orchester Stockholm, Paavo Järvi". Virgin/EMI CD 5 45212 2 (WD:71'34") DDD

GFDL's CM2 global coupled climate models. Part I: Formulation and simulation characteristics

Science.gov (United States)

Delworth, T.L.; Broccoli, A.J.; Rosati, A.; Stouffer, R.J.; Balaji, V.; Beesley, J.A.; Cooke, W.F.; Dixon, K.W.; Dunne, J.; Dunne, K.A.; Durachta, J.W.; Findell, K.L.; Ginoux, P.; Gnanadesikan, A.; Gordon, C.T.; Griffies, S.M.; Gudgel, R.; Harrison, M.J.; Held, I.M.; Hemler, R.S.; Horowitz, L.W.; Klein, S.A.; Knutson, T.R.; Kushner, P.J.; Langenhorst, A.R.; Lee, H.-C.; Lin, S.-J.; Lu, J.; Malyshev, S.L.; Milly, P.C.D.; Ramaswamy, V.; Russell, J.; Schwarzkopf, M.D.; Shevliakova, E.; Sirutis, J.J.; Spelman, M.J.; Stern, W.F.; Winton, M.; Wittenberg, A.T.; Wyman, B.; Zeng, F.; Zhang, R.

2006-01-01

The formulation and simulation characteristics of two new global coupled climate models developed at NOAA's Geophysical Fluid Dynamics Laboratory (GFDL) are described. The models were designed to simulate atmospheric and oceanic climate and variability from the diurnal time scale through multicentury climate change, given our computational constraints. In particular, an important goal was to use the same model for both experimental seasonal to interannual forecasting and the study of multicentury global climate change, and this goal has been achieved. Tw o versions of the coupled model are described, called CM2.0 and CM2.1. The versions differ primarily in the dynamical core used in the atmospheric component, along with the cloud tuning and some details of the land and ocean components. For both coupled models, the resolution of the land and atmospheric components is 2?? latitude ?? 2.5?? longitude; the atmospheric model has 24 vertical levels. The ocean resolution is 1?? in latitude and longitude, with meridional resolution equatorward of 30?? becoming progressively finer, such that the meridional resolution is 1/3?? at the equator. There are 50 vertical levels in the ocean, with 22 evenly spaced levels within the top 220 m. The ocean component has poles over North America and Eurasia to avoid polar filtering. Neither coupled model employs flux adjustments. The co ntrol simulations have stable, realistic climates when integrated over multiple centuries. Both models have simulations of ENSO that are substantially improved relative to previous GFDL coupled models. The CM2.0 model has been further evaluated as an ENSO forecast model and has good skill (CM2.1 has not been evaluated as an ENSO forecast model). Generally reduced temperature and salinity biases exist in CM2.1 relative to CM2.0. These reductions are associated with 1) improved simulations of surface wind stress in CM2.1 and associated changes in oceanic gyre circulations; 2) changes in cloud tuning and

Development of Peptidomimetic Inhibitors of the ERG Gene Fusion Product in Prostate Cancer.

Science.gov (United States)

Wang, Xiaoju; Qiao, Yuanyuan; Asangani, Irfan A; Ateeq, Bushra; Poliakov, Anton; Cieślik, Marcin; Pitchiaya, Sethuramasundaram; Chakravarthi, Balabhadrapatruni V S K; Cao, Xuhong; Jing, Xiaojun; Wang, Cynthia X; Apel, Ingrid J; Wang, Rui; Tien, Jean Ching-Yi; Juckette, Kristin M; Yan, Wei; Jiang, Hui; Wang, Shaomeng; Varambally, Sooryanarayana; Chinnaiyan, Arul M

2017-04-10

Transcription factors play a key role in the development of diverse cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the gene encoding the transcription factor ERG is recurrently rearranged and plays a critical role in prostate oncogenesis. Here, we identified a series of peptides that interact specifically with the DNA binding domain of ERG. ERG inhibitory peptides (EIPs) and derived peptidomimetics bound ERG with high affinity and specificity, leading to proteolytic degradation of the ERG protein. The EIPs attenuated ERG-mediated transcription, chromatin recruitment, protein-protein interactions, cell invasion and proliferation, and tumor growth. Thus, peptidomimetic targeting of transcription factor fusion products may provide a promising therapeutic strategy for prostate cancer as well as other malignancies. Copyright © 2017 Elsevier Inc. All rights reserved.

ERG Protein Expression in Diagnostic Specimens Is Associated with Increased Risk of Progression During Active Surveillance for Prostate Cancer

DEFF Research Database (Denmark)

Berg, Kasper Drimer; Vainer, Ben; Thomsen, Frederik Birkebæk

2014-01-01

with a ready-to-use kit (anti-ERG, EPR3864). Men were characterised as ERG positive if a minimum of one tumour focus demonstrated ERG expression. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall AS progression was defined as clinical progression: increased clinical tumour category ≥cT2b by digital rectal...

Patients with Long QT Syndrome Due to Impaired hERG-encoded Kv11.1 Potassium Channel Have Exaggerated Endocrine Pancreatic and Incretin Function Associated with Reactive Hypoglycemia

DEFF Research Database (Denmark)

Hyltén-Cavallius, Louise; Iepsen, Eva W; Wewer Albrechtsen, Nicolai J

2017-01-01

Background -Loss-of-function mutations in hERG (encoding the Kv11.1 voltage-gated potassium channel) cause long QT syndrome (LQT2) due to prolonged cardiac repolarization. However, Kv11.1 is also present in pancreatic α and β cells and intestinal L and K cells, secreting glucagon, insulin, and th...

ERG and other discriminators between advanced hydroxychloroquine retinopathy and retinitis pigmentosa.

Science.gov (United States)

Nair, Archana A; Marmor, Michael F

2017-06-01

To study whether the ERG and other clinical findings help to distinguish between advanced hydroxychloroquine (HCQ) retinopathy and pericentral or diffuse retinitis pigmentosa (RP) with similar fundus appearance. We conducted a retrospective analysis of patients with advanced HCQ retinopathy (n = 11), pericentral RP (n = 8) and diffuse RP (n = 8). Pericentral RP was defined as having limited fundus damage and relatively normal flicker ERG time-to-peak. Diffuse RP had typical loss of the rod ERG and flicker timing delay. All patients showed reduced amplitude of the ISCEV responses in the full-field electroretinogram (ERG). Aspects of history, visual field results, fundus appearance, fundus autofluorescence and ocular coherence tomography were also compared. Relative to pericentral RP, patients with HCQ toxicity showed delayed flicker ERG time-to-peak and lower ERG amplitudes, particularly combined rod-cone responses. Relative to diffuse RP, most HCQ toxicity patients had some preserved rod ERG response, and there was no obvious predilection for rod over cone damage. In addition, patients with HCQ toxicity usually lacked markers of long-standing degeneration such as bone spicule figures or severe loss of peripheral field. History of familial disease and long-standing night blindness were specific to RP. While the early signs of HCQ damage are typically regional in the posterior pole, advanced disease is characteristically diffuse (unlike pericentral RP). This is appropriate for a systemic toxin, as is the finding that rods and cones were both affected in the ERG to a similar degree (unlike genetic rod-cone dystrophies). For patients with severe HCQ exposure and some of our discriminatory findings, and no family history or prior night blindness, HCQ toxicity is a sufficient diagnosis without invoking a second rare disease (Occam's razor).

Striation Free Doped Silicon.

Science.gov (United States)

1984-12-01

34 .. - .- . *- * - * 14079- "- UPPERFURNACE CHAMBER 4 in. QUARTZ TUBE RF WORK COIL MAGNET COIL 4 in POLE PIECE IRON YOKEj ALUMINUM SPACER LOWER FURNACE CHAMBER Fi;uru 3...cal/(cm*K) =3.2 lO 6erg/(cm*K) A-I thermometric cond. K =0.15 cm2/s (used Pr .~{=.023) A-I K melting point Tm =1410*C A-2 el. conductivity a =1.29-1O

2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial

DEFF Research Database (Denmark)

Gillgren, Peter; Drzewiecki, Krzysztof T; Niin, Marianne

2011-01-01

Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin.......Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin....

Effects of electron irradiation and temperature on 1 ohm-cm and 10 ohm-cm silicon solar cells

Science.gov (United States)

Nicoletta, C. A.

1973-01-01

One OHM-cm and 10 OHM-cm silicon solar cells were exposed to 1.0 MeV electrons at a fixed flux of 10 to the 11th power e/sq cm/sec and fluences of 10 to the 13th power, 10 to the 14th power and 10 to the 15th power e/sq.cm. 1-V curves of the cells were made at room temperature, - 63 C and + or - 143 C after each irradiation. A value of 139.5 mw/sq cm was used as AMO incident energy rate per unit area. The 10 OHM-cm cells appear more efficient than 1 OHM-cm cells after exposure to a fluence greater than 10 to the 14th power e/sq cm. The 1.0 MeV electron damage coefficients for both 1 OHM-cm and 10 OHM-cm cells are somewhat less than those for previously irradiated cells at room temperature. The values of the damage coefficients increase as the cell temperatures decrease. Efficiencies pertaining to maximum power output are about the same as those of n on p silicon cells evaluated previously.

Identification of the 1s2s2p 4P5/2-->1s22s 2S1/2 magnetic quadrupole inner-shell satellite line in the Ar16+ K-shell x-ray spectrum

Science.gov (United States)

Beiersdorfer, P.; Bitter, M.; Hey, D.; Reed, K. J.

2002-09-01

We have identified the dipole-forbidden 1s2s2p 4P5/2-->1s22s 2S1/2 transition in lithiumlike Ar15+ in high-resolution K-shell x-ray emission spectra recorded at the Livermore EBIT-II electron-beam ion trap and the Princeton National Spherical Tokamak Experiment. Unlike other Ar15+ satellite lines, which can be excited by dielectronic recombination, the line is exclusively excited by electron-impact excitation. Its predicted radiative rate is comparable to that of the well-known 1s2p 3P1-->1s2 1S0 magnetic quadrupole transition in heliumlike Ar16+. As a result, it can also only be observed in low-density plasma. We present calculations of the electron-impact excitation cross sections of the innershell excited Ar15+ satellite lines, including the magnetic sublevels needed for calculating the linear line polarization. We compare these calculations to the relative magnitudes of the observed 1s2s2p-->1s22s transitions and find good agreement, confirming the identification of the lithiumlike 1s2s2p 4P5/2-->1s22s 2S1/2 magnetic quadrupole line.

Magnetic and structural properties of L1{sub 1} type CoPt-C ordered alloy perpendicular films as a function of C content

Energy Technology Data Exchange (ETDEWEB)

Shimatsu, T; Kataoka, H; Aoi, H [Research Institute of Electrical Communication, Tohoku University, Sendai, 980-8577 (Japan); Sato, H; Okamoto, S; Kitakami, O, E-mail: shimatsu@riec.tohoku.ac.j [Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, 980-8577 (Japan)

2010-01-01

Magnetic and structural properties of L1{sub 1} type (Co{sub 0.5}Pt{sub 0.5}){sub 100-X}-C{sub X} ordered alloy perpendicular films, fabricated on 2.5 inch size glass disks by sputter deposition, were examined as a function of C content, X. L1{sub 1} type Co{sub 0.5}Pt{sub 0.5}-C polycrystalline films (10 nm thickness), with <111> axis (the easy axis) perpendicular to the film plane, were successfully fabricated even for a 30 vol% C content. Structural analysis indicated the segregation of C to the grain boundaries. Uniaxial magnetic anisotropy, K{sub u}, of Co{sub 0.5}Pt{sub 0.5} films without C addition was relatively low, about 1.5x10{sup 7} erg/cm{sup 3} under the present deposition conditions. However, the addition of 5 vol.% C to Co-Pt films enhanced the ordering, resulting in an increase in K{sub u} to around 2.5 x10{sup 7} erg/cm{sup 3}. A further increase in C content reduced K{sub u}; however, K{sub u} maintained a relatively large value of about 1.8x10{sup 7} erg/cm{sup 3} even for a 20vol% C content, without degrading the easy axis orientation perpendicular to the film plane. Experimental results demonstrated the potential of the L1{sub 1} type Co{sub 0.5}Pt{sub 0.5}-C films for use in granular media applications, due to their very high K{sub u}, the relatively low fabrication temperature, and good controllability of the grain orientation.

Low-frequency 1/f noise in MoS2 transistors: Relative contributions of the channel and contacts

Science.gov (United States)

Renteria, J.; Samnakay, R.; Rumyantsev, S. L.; Jiang, C.; Goli, P.; Shur, M. S.; Balandin, A. A.

2014-04-01

We report on the results of the low-frequency (1/f, where f is frequency) noise measurements in MoS2 field-effect transistors revealing the relative contributions of the MoS2 channel and Ti/Au contacts to the overall noise level. The investigation of the 1/f noise was performed for both as fabricated and aged transistors. It was established that the McWhorter model of the carrier number fluctuations describes well the 1/f noise in MoS2 transistors, in contrast to what is observed in graphene devices. The trap densities extracted from the 1/f noise data for MoS2 transistors, are 2 × 1019 eV-1cm-3 and 2.5 × 1020 eV-1cm-3 for the as fabricated and aged devices, respectively. It was found that the increase in the noise level of the aged MoS2 transistors is due to the channel rather than the contact degradation. The obtained results are important for the proposed electronic applications of MoS2 and other van der Waals materials.

Fixation of chiral smectic liquid crystal (S)-(+)-4-(2-methyl-1-butyloyloxy)phenyl 4-[1-(propenoyloxy) butiloxy] benzoate using UV curing techniques

Energy Technology Data Exchange (ETDEWEB)

Afrizal,, E-mail: rizalunj04@yahoo.com; Nurdelima,; Umeir [Faculty of Mathemathics and Natural Science, University of State Jakarta, Jakarta (Indonesia); Hikam, Muhammad; Soegiyono, Bambang [Department of Materials Science, University of Indonesia, Depok (Indonesia); Riswoko, Asep [Center for Material Technology, BPPT, Jl. MH.Thamrin 8 Jakarta (Indonesia)

2014-03-24

Chiral Smectic Liquid Crystal (S)-(+)-4-(2-methyl-1-butyloyloxy)phenyl 4-[1-(propenoyloxy) butiloxy] benzoate has been synthesized using method of steglich esterification at room temperature. The mesomorphic behavior of chiral smectic at 55°C that showed schlieren texture in POM analysis. Fixation of structure chiral smectic liquid crystal by means of photopolymerization of monomer (S)-(+)-4-(2-methyl-1-butyloyloxy)phenyl 4-[1-(propenoyloxy) butiloxy] benzoate under UV irradiation which called UV curing techniques. The curing process using UV 3 lamps 100 volt at 60°C for an hour. The product of photopolymerization could be seen by analysis of FTIR spectra both monomer and polymer. FTIR spectra of monomer, two peaks for ester carbonyl and C-C double bond groups appeared at 1729.09 cm-1and 3123.46 cm{sup −1}. After UV curing process, peak for the carbonyl group at 1729.09 cm{sup −1} decreased and a new peak at 1160.21 cm{sup −1} appeared due to the carbonyl group attached to a C-C bond group and then peak at 3123.46 cm{sup −1} for C-C double bond group was disappeared.

Multifocal ERG wavelet packet decomposition applied to glaucoma diagnosis

Directory of Open Access Journals (Sweden)

Rodríguez-Ascariz José M

2011-05-01

Full Text Available Abstract Background Glaucoma is the second-leading cause of blindness worldwide and early diagnosis is essential to its treatment. Current clinical methods based on multifocal electroretinography (mfERG essentially involve measurement of amplitudes and latencies and assume standard signal morphology. This paper presents a new method based on wavelet packet analysis of global-flash multifocal electroretinogram signals. Methods This study comprised twenty-five patients diagnosed with OAG and twenty-five control subjects. Their mfERG recordings data were used to develop the algorithm method based on wavelet packet analysis. By reconstructing the third wavelet packet contained in the fourth decomposition level (ADAA4 of the mfERG recording, it is possible to obtain a signal from which to extract a marker in the 60-80 ms time interval. Results The marker found comprises oscillatory potentials with a negative-slope basal line in the case of glaucomatous recordings and a positive-slope basal line in the case of normal signals. Application of the optimal threshold calculated in the validation cases showed that the technique proposed achieved a sensitivity of 0.81 and validation specificity of 0.73. Conclusions This new method based on mfERG analysis may be reliable enough to detect functional deficits that are not apparent using current automated perimetry tests. As new stimulation and analysis protocols develop, mfERG has the potential to become a useful tool in early detection of glaucoma-related functional deficits.

Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-16-1-0737 TITLE: Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer PRINCIPAL...AND SUBTITLE 5a. CONTRACT NUMBER Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer 5b. GRANT NUMBER W81XWH...that there exist distinctive molecular correlates of PTEN loss in the context of ETS-negative versus ETS-positive human prostate cancers and that

Accuracy of free energies of hydration using CM1 and CM3 atomic charges.

Science.gov (United States)

Udier-Blagović, Marina; Morales De Tirado, Patricia; Pearlman, Shoshannah A; Jorgensen, William L

2004-08-01

Absolute free energies of hydration (DeltaGhyd) have been computed for 25 diverse organic molecules using partial atomic charges derived from AM1 and PM3 wave functions via the CM1 and CM3 procedures of Cramer, Truhlar, and coworkers. Comparisons are made with results using charges fit to the electrostatic potential surface (EPS) from ab initio 6-31G* wave functions and from the OPLS-AA force field. OPLS Lennard-Jones parameters for the organic molecules were used together with the TIP4P water model in Monte Carlo simulations with free energy perturbation theory. Absolute free energies of hydration were computed for OPLS united-atom and all-atom methane by annihilating the solutes in water and in the gas phase, and absolute DeltaGhyd values for all other molecules were computed via transformation to one of these references. Optimal charge scaling factors were determined by minimizing the unsigned average error between experimental and calculated hydration free energies. The PM3-based charge models do not lead to lower average errors than obtained with the EPS charges for the subset of 13 molecules in the original study. However, improvement is obtained by scaling the CM1A partial charges by 1.14 and the CM3A charges by 1.15, which leads to average errors of 1.0 and 1.1 kcal/mol for the full set of 25 molecules. The scaled CM1A charges also yield the best results for the hydration of amides including the E/Z free-energy difference for N-methylacetamide in water. Copyright 2004 Wiley Periodicals, Inc.

Cm3+-F- interaction in a mixed system of methanol and water

International Nuclear Information System (INIS)

Satoh, I.; Watanabe, T.; Ishii, Y.; Kawasaki, M.; Suganuma, H.

2003-01-01

The stability constants (β 1 ) of the monofluoro complex of Cm(III) have been determined in mixed solvents of methanol and water using the solvent extraction technique. The values of Inβ 1 increase as the molar fraction of methanol (X s ) in the mixed solvent increases. The variation in the stability constants mainly depends on the solvation of F - and slightly depends on both (1) the solvation of cations in connection with the complexation of CmF 2+ and (2) the electrostatic attraction of Cm 3+ -F - . The variation in Inβ 1 for Cm(III) due to the effect of both (1) and (2) is similar to that for Sm(III). By variation of Inβ 1 the coordination number in the primary hydration sphere (CN) of Cm(III) decreased from a value between CN = 9 and CN = 8 to CN = 8, at about X s = 0.02. The X s value of the inflection point of the CN for Cm is slightly lower than X s = 0.06 for Sm(III) and X s = 0.03 for Eu(III), previously obtained. (author)

On the possibility of auroral remote sensing with the Viking ultraviolet imager

International Nuclear Information System (INIS)

Steele, D.P.; McEwen, D.J.; Murphree, J.S.

1992-01-01

An investigation was carried out to assess the value of ultraviolet auroral images for remote sensing of electron precipitation. The authors compared auroral images, obtained by both cameras of the Viking Ultraviolet Imager during April and early May 1986, with simultaneous measurements of electron precipitation from the DMSP F7 and HiLat satellites at low altitudes above the auroral zone. The electron data were averaged over the image pixels and were used to normalize the imager signals to unit electron energy flux. The resulting quantity, here termed the effective sensitivity, showed large scatter about the mean values for both cameras that tended to mask any energy dependence except a decrease at electron energies above 6 keV. The mean effective sensitivities were 11.3 ± 1.1 digitization numbers (DN)/(erg cm -2 s -1 ) for the Lyman-Birge-Hopfield (LBH) camera and 15.9 ± 2.5 DN/(erg cm -2 s -1 ) for the 1304 camera. The signal ratio in simultaneous images from both cameras was insensitive to electron energy in the two cases examined, consistent with the weak energy dependences of the effective sensitivities. Unusually high LBH camera effective sensitivities of 45-60 DN/(erg cm -2 s -1 ) were obtained during several orbits on May 2 and 3. They conclude that images from either Viking camera may be used to infer the instantaneous distribution of electron energy deposition, with roughly 50% accuracy

An ultrasoft X-ray source in Coma Berenices

International Nuclear Information System (INIS)

Margon, B.; Malina, R.; Bowyer, S.; Cruddace, R.; Lampton, M.

1976-01-01

We have observed an intense soft X-ray source with an extraordinary spectrum in Coma Berenices, 4 0 northeast of and unassociated with the Coma cluster of galaxies. Two spectra, obtained at different times in a sounding rocket flight, indicate that the source temperature in thermal models is less than 10 6 K; a power-law model requires photon power-law indices steeper than n=-3. The intensity in the 44--165 A band is of the order of 5x10 -10 ergs cm -2 s -1 , but no flux is present at energies 0.3--2.1 keV to a limit of 1x10 -10 ergs cm -2 s -1 . The lack of bright stars or a supernova remnant in the error box implies that this may be a new class of soft X-ray sources

Interactions between charged residues in the transmembrane segments of the voltage-sensing domain in the hERG channel.

Science.gov (United States)

Zhang, M; Liu, J; Jiang, M; Wu, D-M; Sonawane, K; Guy, H R; Tseng, G-N

2005-10-01

Studies on voltage-gated K channels such as Shaker have shown that positive charges in the voltage-sensor (S4) can form salt bridges with negative charges in the surrounding transmembrane segments in a state-dependent manner, and different charge pairings can stabilize the channels in closed or open states. The goal of this study is to identify such charge interactions in the hERG channel. This knowledge can provide constraints on the spatial relationship among transmembrane segments in the channel's voltage-sensing domain, which are necessary for modeling its structure. We first study the effects of reversing S4's positive charges on channel activation. Reversing positive charges at the outer (K525D) and inner (K538D) ends of S4 markedly accelerates hERG activation, whereas reversing the 4 positive charges in between either has no effect or slows activation. We then use the 'mutant cycle analysis' to test whether D456 (outer end of S2) and D411 (inner end of S1) can pair with K525 and K538, respectively. Other positive charges predicted to be able, or unable, to interact with D456 or D411 are also included in the analysis. The results are consistent with predictions based on the distribution of these charged residues, and confirm that there is functional coupling between D456 and K525 and between D411 and K538.

Synthesis and crystal structures of two α-bromoamides, (2'R,1S,2S)-N(2-bromopropanoyl)-2-amino-1-phenylpropane-1,3-diol and (2'S,5S,6S)-N(2-bromopropanoyl)-5-amino-6-phenyl-2-oxo-1,3,2-dioxathiane

International Nuclear Information System (INIS)

English, R.B.; Liddell, R.J.; Whiteley, C.G.

1987-01-01

One pair of diastereomeric bromoamides, (2'R,1S,2S)- and (2'S,1S,2S)-N(2-bromopropanoyl)-2-amino-1-phenylpropane-1,3-diol have been synthesized from ethyl 2-bromopropionate and an optically active amino-diol. The crystal structures of both were determined from single-crystal X-ray analyses. Both compounds are orthorhombic with space group P2 1 2 1 2 1 with Z = 4 in a unit cell of dimensions a 22,124(5),b 12,812(5), and c 4,886(5)A and a 15,510(5), b 9,707(5), and c 9,457(5)A. The proton chemical shifts of the groups attached to the asymmetric centre C(2'), and consequently, the identification of the configuration of the molecules, were resolved with the help of high-resolution nuclear magnetic resonance

Changes in cortical cytoskeletal and extracellular matrix gene expression in prostate cancer are related to oncogenic ERG deregulation

International Nuclear Information System (INIS)

Schulz, Wolfgang A; Ingenwerth, Marc; Djuidje, Carolle E; Hader, Christiane; Rahnenführer, Jörg; Engers, Rainer

2010-01-01

The cortical cytoskeleton network connects the actin cytoskeleton to various membrane proteins, influencing cell adhesion, polarity, migration and response to extracellular signals. Previous studies have suggested changes in the expression of specific components in prostate cancer, especially of 4.1 proteins (encoded by EPB41 genes) which form nodes in this network. Expression of EPB41L1, EPB41L2, EPB41L3 (protein: 4.1B), EPB41L4B (EHM2), EPB41L5, EPB49 (dematin), VIL2 (ezrin), and DLG1 (summarized as „cortical cytoskeleton' genes) as well as ERG was measured by quantitative RT-PCR in a well-characterized set of 45 M0 prostate adenocarcinoma and 13 benign tissues. Hypermethylation of EPB41L3 and GSTP1 was compared in 93 cancer tissues by methylation-specific PCR. Expression of 4.1B was further studied by immunohistochemistry. EPB41L1 and EPB41L3 were significantly downregulated and EPB41L4B was upregulated in cancer tissues. Low EPB41L1 or high EPB41L4B expression were associated with earlier biochemical recurrence. None of the other cortical cytoskeleton genes displayed expression changes, in particular EPB49 and VIL2, despite hints from previous studies. EPB41L3 downregulation was significantly associated with hypermethylation of its promoter and strongly correlated with GSTP1 hypermethylation. Protein 4.1B was detected most strongly in the basal cells of normal prostate epithelia. Its expression in carcinoma cells was similar to the weaker one in normal luminal cells. EPB41L3 downregulation and EPB41L4B upregulation were essentially restricted to the 22 cases with ERG overexpression. Expression changes in EPB41L3 and EPB41L4B closely paralleled those previously observed for the extracellular matrix genes FBLN1 and SPOCK1, respectively. Specific changes in the cortical cytoskeleton were observed during prostate cancer progression. They parallel changes in the expression of extracellular matrix components and all together appear to be associated with

Improved wavelengths for the 1s2s3S1-1s2p3P0,2 transitions in helium-like Si12+

International Nuclear Information System (INIS)

Armour, I.A.; Myers, E.G.; Silver, J.D.; Traebert, E.; Oxford Univ.

1979-01-01

The wavelengths of the 1s2s 3 S 1 -1s2p 3 P 0 , 2 transitions in He-like Si 12+ have been remaesured to be 87.86 +- 0.01 nm and 81.48 +- 0.01 nm. The use of Rydberg lines for the calibration of fast beam spectra is discussed. (orig.)

An electrochemical study of the systems Li1+-xV2O4 and Li1-xVO2 (0≤x≤1)

International Nuclear Information System (INIS)

De Picciotto, L.A.; Thackeray, M.M.; Pistoia, G.

1988-01-01

Electrochemical properties of the systems Li 1±x V 2 O 4 (0≤x≤1), Li 1-x VO 2 (0≤x 2 O 4 is reversible, which confirms that lithium may be cycled, topotactically, in and out of the Li 1+x V 2 O 4 spinel structure. Delithiation of the LiV 2 O 4 spinel is irreversible; during this process the vanadium ions migrate through the oxide layers. This results in a defect rocksalt phase, which can, in turn, be relithiated by a different mechanism. Lithium extraction for the layered compound LiVO 2 yields a structure similar to the delithiated LiV 2 O 4 product. The spinel-derived compounds Li 1 +-x/V 2 O 4 (0 -3 Ω -1 cm -1 at x=0 and 10 -6 Ω -1 cm -1 at x=1. Lithium diffusion rates in Li 1±x V 2 O 4 samples increase with lithiation from D=4x10 -10 cm 2 /s in LiV 2 O 4 to D=6x10 -8 cm 2 /s in Li 2 V 2 O 4 . Intermediate values of D are obtained in the delithiated compound Li 0.28 V 2 O 4 and in the layered oxide LiVO 2 ; significantly lower values of D, viz. 1x10 -11 cm 2 /s and 4x10 -11 cm 2 /s , are found in the spinels LiMn 2 O 4 and Fe 3 O 4 respectively. 28 refs.; 5 figs.; 1 table

Influence of CSN1S2 protein from Caprine milk Etawah Breed (EB) on histology of microglial cells in rat (Rattus norvegicus) Type-2 diabetes mellitus (T2DM)

Science.gov (United States)

Rika, Margareth; Fatchiyah

2017-11-01

Type-2 diabetes mellitus (T2DM) is a degenerative disease that causes an imbalance in the metabolism. The aim of this research is to determine the influences of CSN1S2 on the structure of microglial cells in T2DM. Rats (Rattus norvegicus) were divided into eight groups of treatment with looping three times each between treatment groups (CM) Control. The control is given a milk treatment with doses of 375 mg/kg (CM375), 750 mg/kg (CM750), and 1500 mg/kg (CM1500), T2DM (DMK), and T2DM with CSN1S2 375 mg/kg dose (DM375), 750mg/kg (DM750), and 1500 mg/kg (DM1500). The animal model T2DM was induced by a high-fat diet in the form of feed followed by injection of STZ (dose of 25 mg/kg of animal treatment) and treatment of CSN1S2 for 28 days. Brain organs were taken and analysed in histopathology stained by Hematoxylin-eosin (HE) and observed using Olympus BX53. Based on the results, it was concluded that CSN1S2 protein is influential for induction of microglial cell proliferation in animal models of T2DM, as immunity responds to the inflammatory condition in T2DM.

Low-frequency 1/f noise in MoS2 transistors: Relative contributions of the channel and contacts

International Nuclear Information System (INIS)

Renteria, J.; Jiang, C.; Samnakay, R.; Rumyantsev, S. L.; Goli, P.; Balandin, A. A.; Shur, M. S.

2014-01-01

We report on the results of the low-frequency (1/f, where f is frequency) noise measurements in MoS 2 field-effect transistors revealing the relative contributions of the MoS 2 channel and Ti/Au contacts to the overall noise level. The investigation of the 1/f noise was performed for both as fabricated and aged transistors. It was established that the McWhorter model of the carrier number fluctuations describes well the 1/f noise in MoS 2 transistors, in contrast to what is observed in graphene devices. The trap densities extracted from the 1/f noise data for MoS 2 transistors, are 2 × 10 19  eV −1 cm −3 and 2.5 × 10 20  eV −1 cm −3 for the as fabricated and aged devices, respectively. It was found that the increase in the noise level of the aged MoS 2 transistors is due to the channel rather than the contact degradation. The obtained results are important for the proposed electronic applications of MoS 2 and other van der Waals materials

X-ray variability of the BL Lacertae object PKS 2155 - 304 in the 0.1-6 keV range

International Nuclear Information System (INIS)

Morini, M.; Chiappetti, L.; Maccagni, D.; Maraschi, L.; Molteni, D.; CNR, Istituto di Fisica Cosmica, Milan, Italy; CNR, Istituto di Fisica Cosmica; Milano Universita, Italy; Palermo Universita, Italy)

1986-01-01

Observations of the bright BL Lac object PKS 2155 - 304 obtained at 1-6 keV using the ME argon counters and channel-multiplier array at the focus of the Exosat LE telescope, in conjunction with the 0.05-2-keV-bandpass 3000-A Lexan filter, during a total of 30 h in October-November 1983 and November 1984 are reported. The data are presented in tables and graphs and characterized. Findings discussed include an overall variation of a factor of 10, one factor-of-four increase over 4 h, and maximum luminosity variation dL/dt = 2 x 10 to the 42nd erg/s sq for H = 100 km/s Mpc (corresponding to a lower limit of mass of 10 to the 8th solar mass and a gravitational radius of 3 x 10 to the 13th cm). The implications of these results for theoretical models of the X-ray emission source are considered. 17 references

Comparative evaluation of urinary PCA3 and TMPRSS2: ERG scores and serum PHI in predicting prostate cancer aggressiveness.

Science.gov (United States)

Tallon, Lucile; Luangphakdy, Devillier; Ruffion, Alain; Colombel, Marc; Devonec, Marian; Champetier, Denis; Paparel, Philippe; Decaussin-Petrucci, Myriam; Perrin, Paul; Vlaeminck-Guillem, Virginie

2014-07-30

It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2) scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume≥0.5 mL. Only PHI predicted Gleason score≥7. T2 score and PHI were both independent predictors of extracapsular extension(≥pT3), while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy), the addition of both PCA3 score and PHI to the base model induced a significant increase (+12%) when predicting tumor volume>0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

Comparative Evaluation of Urinary PCA3 and TMPRSS2: ERG Scores and Serum PHI in Predicting Prostate Cancer Aggressiveness

Directory of Open Access Journals (Sweden)

Lucile Tallon

2014-07-01

Full Text Available It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2 scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume ≥0.5 mL. Only PHI predicted Gleason score ≥7. T2 score and PHI were both independent predictors of extracapsular extension (≥pT3, while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy, the addition of both PCA3 score and PHI to the base model induced a significant increase (+12% when predicting tumor volume >0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

A DNA methylation microarray-based study identifies ERG as a gene commonly methylated in prostate cancer.

Science.gov (United States)

Schwartzman, Jacob; Mongoue-Tchokote, Solange; Gibbs, Angela; Gao, Lina; Corless, Christopher L; Jin, Jennifer; Zarour, Luai; Higano, Celestia; True, Lawrence D; Vessella, Robert L; Wilmot, Beth; Bottomly, Daniel; McWeeney, Shannon K; Bova, G Steven; Partin, Alan W; Mori, Motomi; Alumkal, Joshi

2011-10-01

DNA methylation of promoter regions is a common event in prostate cancer, one of the most common cancers in men worldwide. Because prior reports demonstrating that DNA methylation is important in prostate cancer studied a limited number of genes, we systematically quantified the DNA methylation status of 1505 CpG dinucleotides for 807 genes in 78 paraffin-embedded prostate cancer samples and three normal prostate samples. The ERG gene, commonly repressed in prostate cells in the absence of an oncogenic fusion to the TMPRSS2 gene, was one of the most commonly methylated genes, occurring in 74% of prostate cancer specimens. In an independent group of patient samples, we confirmed that ERG DNA methylation was common, occurring in 57% of specimens, and cancer-specific. The ERG promoter is marked by repressive chromatin marks mediated by polycomb proteins in both normal prostate cells and prostate cancer cells, which may explain ERG's predisposition to DNA methylation and the fact that tumors with ERG DNA methylation were more methylated, in general. These results demonstrate that bead arrays offer a high-throughput method to discover novel genes with promoter DNA methylation such as ERG, whose measurement may improve our ability to more accurately detect prostate cancer.

The Influence of Brightness on Functional Assessment by mfERG

DEFF Research Database (Denmark)

Christiansen, A T; Kiilgaard, J F; Smith, M

2012-01-01

To determine the effect of membrane brightness on multifocal electroretinograms (mfERGs), we implanted poly lactic-co-glycolic acid (PLGA) membranes in the subretinal space of 11 porcine eyes. We compared membranes with their native shiny white color with membranes that were stained with a blue dye...... (Brilliant Blue). Histological and electrophysiological evaluation of the overlying retina was carried out 6 weeks after implantation. Histologically, both white and blue membranes degraded in a spongiform manner leaving a disrupted outer retina with no preserved photoreceptor segments. Multifocal ERG...... when the adjacent photoreceptors are missing. Functional assessment with mfERG in scaffold implant studies should therefore be evaluated with care....

Intermediate-duration burst from AX J1754.2-2754 detected by INTEGRAL

DEFF Research Database (Denmark)

Chenevez, Jérôme; Beeck, Sarah; Brandt, Søren

2017-01-01

any emission from the source, and we infer a 3-σ upper limit on the persistent flux of 10-10 erg/cm2/s between 3-40 keV. We tentatively interpret this as an intermediate-duration burst (see, e.g., Cumming et al., ApJ 646, 429, 2006) with a superexpansion phase (see in 't Zand & Weinberg, A&A 520, 81...... is not detected outside the burst interval, with a 3-σ upper limit of 4 mCrab in the JEM-X range, and the burst is only marginally detected by the IBIS/ISGRI instrument in the 20-40 keV energy band. Previous observations regularly taken since February 13, when the region became visible by INTEGRAL, do not reveal....... At this distance, the upper-limit on the persistent emission translates to a 3-40 keV luminosity of 5.2×1035 erg/s, which is consistent with previous values measured when the source was observed in outburst with Chandra (Jonker & Keek 2008, ATel #1643) and Swift (Maccarone et al. 2012, ATel #4109). INTEGRAL...

Increased vulnerability of human ventricle to re-entrant excitation in hERG-linked variant 1 short QT syndrome.

Directory of Open Access Journals (Sweden)

Ismail Adeniran

2011-12-01

Full Text Available The short QT syndrome (SQTS is a genetically heterogeneous condition characterized by abbreviated QT intervals and an increased susceptibility to arrhythmia and sudden death. This simulation study identifies arrhythmogenic mechanisms in the rapid-delayed rectifier K(+ current (I(Kr-linked SQT1 variant of the SQTS. Markov chain (MC models were found to be superior to Hodgkin-Huxley (HH models in reproducing experimental data regarding effects of the N588K mutation on KCNH2-encoded hERG. These ionic channel models were then incorporated into human ventricular action potential (AP models and into 1D and 2D idealised and realistic transmural ventricular tissue simulations and into a 3D anatomical model. In single cell models, the N588K mutation abbreviated ventricular cell AP duration at 90% repolarization (APD(90 and decreased the maximal transmural voltage heterogeneity (δV during APs. This resulted in decreased transmural heterogeneity of APD(90 and of the effective refractory period (ERP: effects that are anticipated to be anti-arrhythmic rather than pro-arrhythmic. However, with consideration of transmural heterogeneity of I(Kr density in the intact tissue model based on the ten Tusscher-Noble-Noble-Panfilov ventricular model, not only did the N588K mutation lead to QT-shortening and increases in T-wave amplitude, but δV was found to be augmented in some local regions of ventricle tissue, resulting in increased tissue vulnerability for uni-directional conduction block and predisposing to formation of re-entrant excitation waves. In 2D and 3D tissue models, the N588K mutation facilitated and maintained re-entrant excitation waves due to the reduced substrate size necessary for sustaining re-entry. Thus, in SQT1 the N588K-hERG mutation facilitates initiation and maintenance of ventricular re-entry, increasing the lifespan of re-entrant spiral waves and the stability of scroll waves in 3D tissue.

Theory, modeling, and integrated studies in the Arase (ERG) project

Science.gov (United States)

Seki, Kanako; Miyoshi, Yoshizumi; Ebihara, Yusuke; Katoh, Yuto; Amano, Takanobu; Saito, Shinji; Shoji, Masafumi; Nakamizo, Aoi; Keika, Kunihiro; Hori, Tomoaki; Nakano, Shin'ya; Watanabe, Shigeto; Kamiya, Kei; Takahashi, Naoko; Omura, Yoshiharu; Nose, Masahito; Fok, Mei-Ching; Tanaka, Takashi; Ieda, Akimasa; Yoshikawa, Akimasa

2018-02-01

Understanding of underlying mechanisms of drastic variations of the near-Earth space (geospace) is one of the current focuses of the magnetospheric physics. The science target of the geospace research project Exploration of energization and Radiation in Geospace (ERG) is to understand the geospace variations with a focus on the relativistic electron acceleration and loss processes. In order to achieve the goal, the ERG project consists of the three parts: the Arase (ERG) satellite, ground-based observations, and theory/modeling/integrated studies. The role of theory/modeling/integrated studies part is to promote relevant theoretical and simulation studies as well as integrated data analysis to combine different kinds of observations and modeling. Here we provide technical reports on simulation and empirical models related to the ERG project together with their roles in the integrated studies of dynamic geospace variations. The simulation and empirical models covered include the radial diffusion model of the radiation belt electrons, GEMSIS-RB and RBW models, CIMI model with global MHD simulation REPPU, GEMSIS-RC model, plasmasphere thermosphere model, self-consistent wave-particle interaction simulations (electron hybrid code and ion hybrid code), the ionospheric electric potential (GEMSIS-POT) model, and SuperDARN electric field models with data assimilation. ERG (Arase) science center tools to support integrated studies with various kinds of data are also briefly introduced.[Figure not available: see fulltext.

Lithium Superionic Conductor Li9.42Si1.02P2.1S9.96O2.04 with Li10GeP2S12-Type Structure in the Li2S–P2S5–SiO2 Pseudoternary System: Synthesis, Electrochemical Properties, and Structure–Composition Relationships

International Nuclear Information System (INIS)

Hori, Satoshi; Suzuki, Kota; Hirayama, Masaaki; Kato, Yuki; Kanno, Ryoji

2016-01-01

Lithium superionic conductors with the Li 10 GeP 2 S 12 (LGPS)-type structure are promising materials for use as solid electrolytes in the next-generation lithium batteries. A novel member of the LGPS family, Li 9.42 Si 1.02 P 2.1 S 9.96 O 2.04 (LSiPSO), and its solid solutions were synthesized by quenching from 1273 K in the Li 2 S–P 2 S 5 –SiO 2 pseudoternary system. The material exhibited an ionic conductivity as high as 3.2 × 10 −4 S cm −1 at 298 K, as well as the high electrochemical stability to lithium metal, which was improved by the introduction of oxygen into the LGPS-type structure. An all-solid-state cell with a lithium metal anode and LSiPSO as the separator showed excellent performance with a high reversibility of 100%. Thus, oxygen doping is an effective way of improving the electrochemical stability of LGPS-type structure.

Energies and E1, M1, E2, and M2 transition rates for states of the 2s{sup 2}2p{sup 3}, 2s2p{sup 4}, and 2p{sup 5} configurations in nitrogen-like ions between F III and Kr XXX

Energy Technology Data Exchange (ETDEWEB)

Rynkun, P., E-mail: pavel.rynkun@gmail.com [Department of Physics and Information Technologies, Lithuanian University of Educational Science, Studentu 39, LT-08106 Vilnius (Lithuania); Jönsson, P. [Group for Materials Science and Applied Mathematics, Malmö University, 20506 Malmö (Sweden); Gaigalas, G. [Department of Physics and Information Technologies, Lithuanian University of Educational Science, Studentu 39, LT-08106 Vilnius (Lithuania); Vilnius University, Institute of Theoretical Physics and Astronomy, A. Goštauto 12, LT-01108 Vilnius (Lithuania); Froese Fischer, C. [National Institute of Standards and Technology, Gaithersburg, MD 20899-8420 (United States)

2014-03-15

Based on relativistic wavefunctions from multiconfiguration Dirac–Hartree–Fock and configuration interaction calculations, E1, M1, E2, and M2 transition rates, weighted oscillator strengths, and lifetimes are evaluated for the states of the (1s{sup 2})2s{sup 2}2p{sup 3},2s2p{sup 4}, and 2p{sup 5} configurations in all nitrogen-like ions between F III and Kr XXX. The wavefunction expansions include valence, core–valence, and core–core correlation effects through single–double multireference expansions to increasing sets of active orbitals. The computed energies agree very well with experimental values, with differences of only 300–600 cm{sup −1} for the majority of the levels and ions in the sequence. Computed transitions rates are in close agreement with available data from MCHF-BP calculations by Tachiev and Froese Fischer [G.I. Tachiev, C. Froese Fischer, A and A 385 (2002) 716].

Interstellar matter near the Pleiades. III. A search for H2 2.4-micron vibration-rotation emission

International Nuclear Information System (INIS)

White, R.E.

1988-01-01

Results are reported from a search for 2.4-micron v = 1-0 H2 emission near five stars in the Pleiades, performed using a cooled InSb photometer and a 10-arcsec entrance aperture on the 2.3-m telescope at Wyoming IR Observatory. The calibration and data-reduction procedures are described, and the results are presented in a table. No emission is detected, and upper limits in the range 0.000026-0.000072 erg/sec sq cm sr are obtained, corresponding to limiting column densities of (1.3-3.7) x 10 to the 15th/sq cm and H2 densities of 400-1100/cu cm (assuming fluorescence and dissociation of the gas as it passes the stars). 16 references

Self-Driven Photoelectrochemical Splitting of H2S for S and H2 Recovery and Simultaneous Electricity Generation.

Science.gov (United States)

Luo, Tao; Bai, Jing; Li, Jinhua; Zeng, Qingyi; Ji, Youzhi; Qiao, Li; Li, Xiaoyan; Zhou, Baoxue

2017-11-07

A novel, facile self-driven photoelectrocatalytic (PEC) system was established for highly selective and efficient recovery of H 2 S and simultaneous electricity production. The key ideas were the self-bias function between a WO 3 photoanode and a Si/PVC photocathode due to their mismatched Fermi levels and the special cyclic redox reaction mechanism of I - /I 3 - . Under solar light, the system facilitated the separation of holes in the photoanode and electrons in the photocathode, which then generated electricity. Cyclic redox reactions were produced in the photoanode region as follows: I - was transformed into I 3 - by photoholes or hydroxyl radicals, H 2 S was oxidized to S by I 3 - , and I 3 - was then reduced to I - . Meanwhile, H + was efficiently converted to H 2 in the photocathode region. In the system, H 2 S was uniquely oxidized to sulfur but not to polysulfide (S x n- ) because of the mild oxidation capacity of I 3 - . High recovery rates for S and H 2 were obtained up to ∼1.04 mg h -1 cm -1 and ∼0.75 mL h -1 cm -1 , respectively, suggesting that H 2 S was completely converted into H 2 and S. In addition, the output power density of the system reached ∼0.11 mW cm -2 . The proposed PEC-H 2 S system provides a self-sustaining, energy-saving method for simultaneous H 2 S treatment and energy recovery.

Improved functional expression of recombinant human ether-a-go-go (hERG K+ channels by cultivation at reduced temperature

Directory of Open Access Journals (Sweden)

Hamilton Bruce

2007-12-01

Full Text Available Abstract Background HERG potassium channel blockade is the major cause for drug-induced long QT syndrome, which sometimes cause cardiac disrhythmias and sudden death. There is a strong interest in the pharmaceutical industry to develop high quality medium to high-throughput assays for detecting compounds with potential cardiac liability at the earliest stages of drug development. Cultivation of cells at lower temperature has been used to improve the folding and membrane localization of trafficking defective hERG mutant proteins. The objective of this study was to investigate the effect of lower temperature maintenance on wild type hERG expression and assay performance. Results Wild type hERG was stably expressed in CHO-K1 cells, with the majority of channel protein being located in the cytoplasm, but relatively little on the cell surface. Expression at both locations was increased several-fold by cultivation at lower growth temperatures. Intracellular hERG protein levels were highest at 27°C and this correlated with maximal 3H-dofetilide binding activity. In contrast, the expression of functionally active cell surface-associated hERG measured by patch clamp electrophysiology was optimal at 30°C. The majority of the cytoplasmic hERG protein was associated with the membranes of cytoplasmic vesicles, which markedly increased in quantity and size at lower temperatures or in the presence of the Ca2+-ATPase inhibitor, thapsigargin. Incubation with the endocytic trafficking blocker, nocodazole, led to an increase in hERG activity at 37°C, but not at 30°C. Conclusion Our results are consistent with the concept that maintenance of cells at reduced temperature can be used to boost the functional expression of difficult-to-express membrane proteins and improve the quality of assays for medium to high-throughput compound screening. In addition, these results shed some light on the trafficking of hERG protein under these growth conditions.

X-ray evidence for ultra-fast outflows in Seyfert galaxies

Science.gov (United States)

Tombesi, Francesco; Braito, Valentina; Reeves, James; Cappi, Massimo; Dadina, Mauro

2012-07-01

X-ray evidence for massive, highly ionized, ultra-fast outflows (UFOs) has been recently reported in a number of AGNs through the detection of blue-shifted Fe XXV/XXVI absorption lines. We present the results of a comprehensive spectral analysis of a large sample of 42 local Seyferts observed with XMM-Newton. Similar results are also obtained from a Suzaku analysis of 5 radio galaxies. We find that UFOs are common phenomena, being present in >40% of the sources. Their outflow velocity distribution is in the range ˜0.03--0.3c, with mean value of ˜0.14c. The ionization parameter is very high, in the range logξ˜3--6 erg~s^{-1}~cm, and the associated column densities are also large, in the range ˜10^{22}--10^{24} cm^{-2}. Their location is constrained at ˜0.0003--0.03pc (˜10^2--10^4 r_s) from the central black hole, consistent with what is expected for accretion disk winds/outflows. The mass outflow rates are in the interval ˜0.01--1M_{⊙}~yr^{-1}. The associated mechanical power is also high, in the range ˜10^{43}--10^{45} erg/s, which indicates that UFOs are capable to provide a significant contribution to the AGN cosmological feedback.

Achievement of 900kgf/cm[sup 2] super workable high strength concrete with belite portland cement. (elevator building of cement silo in Chichibu cement). Part 1. ; Development of cement for super workable high strength concrete. Ko belite kei cement de 900kgf/cm[sup 2] wo tassei (Chichibu cement cement sairo no elevaor to). 1. ; Koryudo kokyodo concrete yo no cement no kaihatsu

Energy Technology Data Exchange (ETDEWEB)

Tanaka, M.; Fukaya, Y.; Nawa, T. (Chichibu Cement Co. Ltd., Tokyo (Japan))

1993-08-01

This paper describes the features of high belite Portland cement which can make the super workable high strength concrete, and the properties of concrete using this. The super workable concrete is required an excellent segregation resistance property as well as high flow property. Since the high belite Portland cement contains a small amount of C[sub 3]S in the clinker, the amounts of C[sub 3]A and C[sub 4]AF can be reduced without hindering the calcination of clinker. Additionally, since it contains a large amount of C[sub 2]S with low heat of hydration, an increase in the temperature of members can be suppressed. 'Chichibu High Flow Cement' having characteristics of this high belite Portland cement was developed for the super workable high strength concrete. The concrete using the High Flow Cement exhibited the maximum flow value of 70cm. It also exhibited the strength of 1,075 kgf/cm[sup 2] at the age of 91 days, and 1,100 kgf/cm[sup 2] at the age of 14 days under insulating. 4 refs., 8 figs., 2 tabs.

Discovery of an Energetic Pulsar Associated with SNR G76.9+1.0

Science.gov (United States)

Arzoumanian, Zaven; Gotthelf, E. V.; Ransom, S. M.; Safi-Harb, S.; Kothes, R.; Landecker, T. L.

2012-01-01

We report the discovery of PSR J2022-pulsar in the supernova remnant G76.9+i.0, in observations with the Chandra X-ray telescope, the Robert C. Byrd Green Bank Radio Telescope, and the Rossi X-ray Timing Explorer (RXTE). The pulsar's spin-down rate implies a rotation-powered luminosity E = 1.2 X 10(exp 38) erg/s, a surface dipole magnetic field strength B(sub S), = 1.0 X 10(exp 12) G, and a characteristic age of 8.9 kyr. PSR J2022+3842 is thus the second-most energetic Galactic pulsar known, after the Crab, as well as the most rapidly-rotating young, radio-bright pulsar known. The radio pulsations are highly dispersed and broadened by interstellar scattering, and we find that a large (delta f/f approximates 1.9 x 10(exp -6)) spin glitch must have occurred between our discovery and confirmation observations. The X-ray pulses are narrow (0.06 cycles FWHM) and visible up to 20 keV, consistent with magnetospheric emission from a rotation-powered pulsar. The Chandra X-ray image identifies the pulsar with a hard, unresolved source at the midpoint of the double-lobed radio morphology of G76.9+ 1.0 and embedded within faint, compact X-ray nebulosity. The spatial relationship of the X-ray and radio emissions is remarkably similar to extended structure seen around the Vela pulsar. The combined Chandra and RXTE pulsar spectrum is well-fitted by an absorbed power-law model with column density N(sub H) = (1.7 +/- 0.3) x 10(exp 22) / sq cm and photon index Gamma = 1.0 +/- 0.2; it implies that the Chandra point-source flux is virtually 100% pulsed. For a distance of 10 kpc, the X-ray luminosity of PSR J2022+3842 is L(sub x){2-1O keV) = 7.0 x 10(exp 33) erg/s. Despite being extraordinarily energetic, PSR J2022+3842 lacks a bright X-ray wind nebula and has an unusually low conversion efficiency of spin-down power to X-ray luminosity, Lx/E = 5.9 X 10(exp-5).

Risk stratification of gallbladder polyps (1-2 cm) for surgical intervention with 18F-FDG PET/CT.

Science.gov (United States)

Lee, Jaehoon; Yun, Mijin; Kim, Kyoung-Sik; Lee, Jong-Doo; Kim, Chun K

2012-03-01

We assessed the value of (18)F-FDG uptake in the gallbladder polyp (GP) in risk stratification for surgical intervention and the optimal cutoff level of the parameters derived from GP (18)F-FDG uptake for differentiating malignant from benign etiologies in a select, homogeneous group of patients with 1- to 2-cm GPs. Fifty patients with 1- to 2-cm GPs incidentally found on the CT portion of PET/CT were retrospectively analyzed. All patients had histologic diagnoses. GP (18)F-FDG activity was visually scored positive (≥liver) or negative (L ratio) were also measured. Univariate and multivariate logistic regression analyses were performed to determine the utility of patient and clinical variables--that is, sex, age, gallstone, polyp size, and three (18)F-FDG-related parameters in risk stratification. Twenty GPs were classified as malignant and 30 as benign. Multivariate analyses showed that the age and all parameters (visual criteria, SUVgp, and GP/L) related to (18)F-FDG uptake were significant risk factors, with the GP/L being the most significant. The sex, size of GPs, and presence of concurrent gallstones were found to be insignificant. (18)F-FDG uptake in a GP is a strong risk factor that can be used to determine the necessity of surgical intervention more effectively than other known risk factors. However, all criteria derived from (18)F-FDG uptake presented in this series may be applicable to the assessment of 1- to 2-cm GPs.

Rab11-dependent Recycling of the Human Ether-a-go-go-related Gene (hERG) Channel*

Science.gov (United States)

Chen, Jeffery; Guo, Jun; Yang, Tonghua; Li, Wentao; Lamothe, Shawn M.; Kang, Yudi; Szendrey, John A.; Zhang, Shetuan

2015-01-01

The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel (IKr). A reduction in the hERG current causes long QT syndrome, which predisposes affected individuals to ventricular arrhythmias and sudden death. We reported previously that hERG channels in the plasma membrane undergo vigorous internalization under low K+ conditions. In the present study, we addressed whether hERG internalization occurs under normal K+ conditions and whether/how internalized channels are recycled back to the plasma membrane. Using patch clamp, Western blot, and confocal imaging analyses, we demonstrated that internalized hERG channels can effectively recycle back to the plasma membrane. Low K+-enhanced hERG internalization is accompanied by an increased rate of hERG recovery in the plasma membrane upon reculture following proteinase K-mediated clearance of cell-surface proteins. The increased recovery rate is not due to enhanced protein synthesis, as hERG mRNA expression was not altered by low K+ exposure, and the increased recovery was observed in the presence of the protein biosynthesis inhibitor cycloheximide. GTPase Rab11, but not Rab4, is involved in the recycling of hERG channels. Interfering with Rab11 function not only delayed hERG recovery in cells after exposure to low K+ medium but also decreased hERG expression and function in cells under normal culture conditions. We concluded that the recycling pathway plays an important role in the homeostasis of plasma membrane-bound hERG channels. PMID:26152716

An XMM-Newton study of the hard X-ray sky

Science.gov (United States)

Piconcelli, E.; Cappi, M.; Bassani, L.; Di Cocco, G.; Dadina, M.

2003-12-01

We report on the spectral properties of a sample of 90 hard X-ray selected serendipitous sources detected in 12 XMM-Newton observations with 1 law modified by Galactic absorption offers an acceptable fit to ~ 65% of the source spectra. This fit yields an average photon index of ≈ 1.55 over the whole sample. We also find that the mean slope of the QSOs in our sample turns out to remain nearly constant ( (≈ 1.8-1.9) between 0 1022 cm-2) is ~ 30%, with little evolution in the range 2 <≈ F2-10˜< 80 x 10-14 erg cm-2 s-1. Interestingly, this value is a factor ~ 2 lower than predicted by the synthesis models of the CXB. This finding, detected for the first time in this survey, therefore suggests that most of the heavily obscured objects which make up the bulk of the CXB will be found at lower fluxes (F2-10< 10-14 erg cm-2 s-1). This mismatch together with other recent observational evidences which contrast with CXB model predictions suggest that one (or more) of the assumptions usually included in these models need to be revised.

Measurement of total hadronic cross section σ(e+e-→hadrons) in the continuum at the c.m. energy W=9.39 GeV and determination of Γee of the Υ(1S) and Υ(2S) resonances

International Nuclear Information System (INIS)

Jakubowski, Z.

1990-01-01

This work is based on a study of e + e - collisions in the energy region of Υ(1S) and Υ(2S) resonances. Using the data taken by the Crystal Ball Detector in the continuum below Υ(1S) we have determined the value of R, the ratio of the hadronic cross section to the Born cross section of μ pair production, at c.m. energy W = 9.39 GeV to be R = 3.48±0.04±0.14. This is the most precise measurement of R below the Υ(1S) threshold. Resonance scan data were used to determine the leptonic partial widths Γ ee of Υ(1S) and Υ(2S). We find Γ ee (Υ(1S))=(1.34±0.03±0.06) keV, Γ ee (Υ(2S))=(0.56±0.03±0.02) keV. The method of obtaining Γ ee from the measured excitation curve is not unique. Our results are ∝10% higher than those already published mainly because we used an internally consistent treatment of the radiative corrections. We discuss the effect of applying different theoretical prescriptions for the radiative corrections on Γ ee . Both results presented here require the knowledge of the absolute cross sections to a high precision. Uncertainties in the corrections to the cross section due to detector efficiency constitute the main source of the systematic error. To minimize these uncertainties substantial modifications of the detector simulation program GHEISHA were necessary to obtain a satisfactory description of the data. The modifications may be of importance for other calorimetric experiments. (orig.)

X-Ray Emission from a Merger Remnant, NGC 7252 (the ``Atoms-for-Peace'' Galaxy)

Science.gov (United States)

Awaki, Hisamitsu; Matsumoto, Hironori; Tomida, Hiroshi

2002-03-01

We observed a nearby merger remnant NGC 7252 with the X-ray satellite ASCA and detected X-ray emission with the X-ray flux of (1.8+/-0.3)×10-13 ergs s-1 cm-2 in the 0.5-10 keV band. This corresponds to the X-ray luminosity of 8.1×1040 ergs s-1. The X-ray emission is well described with a two-component model: a soft component with kT=0.72+/-0.13 keV and a hard component with kT>5.1 keV. Although NGC 7252 is referred to as a dynamically young protoelliptical, the 0.5-4 keV luminosity of the soft component is about 2×1040 ergs s-1, which is low for an early-type galaxy. The ratio of LX/LFIR suggests that the soft component originated from the hot gas due to star formation. Its low luminosity can be explained by the gas ejection from the galaxy as galaxy winds. Our observation reveals the existence of hard X-ray emission with the 2-10 keV luminosity of 5.6×1040 ergs s-1. This may indicate the existence of nuclear activity or an intermediate-mass black hole in NGC 7252.

Concurrent nuclear ERG and MYC protein overexpression defines a subset of locally advanced prostate cancer: Potential opportunities for synergistic targeted therapeutics.

Science.gov (United States)

Udager, Aaron M; DeMarzo, Angelo M; Shi, Yang; Hicks, Jessica L; Cao, Xuhong; Siddiqui, Javed; Jiang, Hui; Chinnaiyan, Arul M; Mehra, Rohit

2016-06-01

Recurrent ERG gene fusions, the most common genetic alterations in prostate cancer, drive overexpression of the nuclear transcription factor ERG, and are early clonal events in prostate cancer progression. The nuclear transcription factor MYC is also frequently overexpressed in prostate cancer and may play a role in tumor initiation and/or progression. The relationship between nuclear ERG and MYC protein overexpression in prostate cancer, as well as the clinicopathologic characteristics and prognosis of ERG-positive/MYC high tumors, is not well understood. Immunohistochemistry (IHC) for ERG and MYC was performed on formalin-fixed, paraffin-embedded tissue from prostate cancer tissue microarrays (TMAs), and nuclear staining was scored semi-quantitatively (IHC product score range = 0-300). Correlation between nuclear ERG and MYC protein expression and association with clinicopathologic parameters and biochemical recurrence after radical prostatectomy was assessed. 29.1% of all tumor nodules showed concurrent nuclear ERG and MYC protein overexpression (i.e., ERG-positive/MYC high), including 35.0% of secondary nodules. Overall, there was weak positive correlation between ERG and MYC expression across all tumor nodules (rpb  = 0.149, P = 0.045), although this correlation was strongest in secondary nodules (rpb  = 0.520, P = 0.019). In radical prostatectomy specimens, ERG-positive/MYC high tumors were positively associated with the presence of extraprostatic extension (EPE), relative to all other ERG/MYC expression subgroups, however, there was no significant association between concurrent nuclear ERG and MYC protein overexpression and time to biochemical recurrence. Concurrent nuclear ERG and MYC protein overexpression is common in prostate cancer and defines a subset of locally advanced tumors. Recent data indicates that BET bromodomain proteins regulate ERG gene fusion and MYC gene expression in prostate cancer, suggesting possible synergistic

糖尿病视网膜1期病变多焦视网膜图变化分析%A Study in the Changes of mfERG in Stage 1 Diabetic Retinopathyn

Institute of Scientific and Technical Information of China (English)

张聪; 刘哲丽; 徐丽; 郭敬斌

2009-01-01

目的 通过检测糖尿病视网膜1期病变患者多焦视网膜电图(multifocal electroretino-gram,mfERG),评价1期糖尿病视网膜病变患者早期视功能的变化.方法 检测正常对照组31只眼,1期糖尿病视网膜病变组46只眼的mtERG在视野30°的测试范围内6个不同离心度的环形区N1、P1波潜伏期、P1波反应密度改变.结果 在视野30°的测试范围内6个不同离心度的环形区,1期糖尿病视网膜病变组(DR组)与正常对照组之间比较N1、P1波潜伏期显著延长;环1、2区DR组与正常对照组之间比较P1波反应密度显著降低.结论 尚未出现肉眼可见眼底改变的1期糖尿病视网膜病变即可出现视功能的异常,mfERG能够定量的检测1期糖尿病视网膜病变的局部视功能变化,为糖尿病视网膜病变的早期诊断提供有效方法.%Objective To investigate the changes of retinal function in stage 1 of diabetic retinopathy detected by multifoeal electroretinogram (mfERG).Methods The responses of mfERG were recorded and analyzed from eyes of 31 normal control subjects and 46 diabetic patients with stage 1 of diabetic retinopathy. Results In eyes of diabetic patients with stage 1 of diabetic retinopathy (DR), the lateneies of N1, P1 were delayed obviously compared to normal control subjects, in the field of about 30 degrees of six rings with different eccentricities; the response densities of the P1 ring1, 2 was significantly decreased in diabetic patients with stagel of diabetic retinopathy compared to normal control subjects.Conclusions The abnormalities of retinal function may occur in stagel of diabetic retinopathy, when there is no abnormality of ocular fundus.As a new objective and quantitative examination for visual function, mfERG may be valuable in early diagnosis of diabetic retinopathy.

Measuring patchy reionization with kSZ2-21 cm correlations

Science.gov (United States)

Ma, Q.; Helgason, K.; Komatsu, E.; Ciardi, B.; Ferrara, A.

2018-05-01

We study cross-correlations of the kinetic Sunyaev-Zel'dovich effect (kSZ) and 21 cm signals during the epoch of reionization (EoR) to measure the effects of patchy reionisation. Since the kSZ effect is proportional to the line-of-sight velocity, the kSZ-21 cm cross correlation suffers from cancellation at small angular scales. We thus focus on the correlation between the kSZ-squared field (kSZ2) and 21 cm signals. When the global ionization fraction is low (xe ≲ 0.7), the kSZ2 fluctuation is dominated by rare ionized bubbles, which leads to an anticorrelation with the 21 cm signal. When 0.8 ≲ xe primary cosmic microwave background (CMB) anisotropy. The expected signal-to-noise ratios for a ˜10-h integration of upcoming Square Kilometre Array data cross-correlated with maps from the current generation of CMB observatories with 3.4μK arcmin noise and 1.7 arcmin beam over 100 deg2 are 51, 60, and 37 for xe = 0.2, 0.5, and 0.9, respectively.

Exclusion of aldose reductase as a mediator of ERG deficits in a mouse model of diabetic eye disease.

Science.gov (United States)

Samuels, Ivy S; Lee, Chieh-Allen; Petrash, J Mark; Peachey, Neal S; Kern, Timothy S

2012-11-01

Streptozotocin (STZ)-induced diabetes is associated with reductions in the electrical response of the outer retina and retinal pigment epithelium (RPE) to light. Aldose reductase (AR) is the first enzyme required in the polyol-mediated metabolism of glucose, and AR inhibitors have been shown to improve diabetes-induced electroretinogram (ERG) defects. Here, we used control and AR -/- mice to determine if genetic inactivation of this enzyme likewise inhibits retinal electrophysiological defects observed in a mouse model of type 1 diabetes. STZ was used to induce hyperglycemia and type 1 diabetes. Diabetic and age-matched nondiabetic controls of each genotype were maintained for 22 weeks, after which ERGs were used to measure the light-evoked components of the RPE (dc-ERG) and the neural retina (a-wave, b-wave). In comparison to their nondiabetic controls, wildtype (WT) and AR -/- diabetic mice displayed significant decreases in the c-wave, fast oscillation, and off response components of the dc-ERG but not in the light peak response. Nondiabetic AR -/- mice displayed larger ERG component amplitudes than did nondiabetic WT mice; however, the amplitude of dc-ERG components in diabetic AR -/- animals were similar to WT diabetics. ERG a-wave amplitudes were not reduced in either diabetic group, but b-wave amplitudes were lower in WT and AR -/-diabetic mice. These findings demonstrate that the light-induced responses of the RPE and outer retina are disrupted in diabetic mice, but these defects are not due to photoreceptor dysfunction, nor are they ameliorated by deletion of AR. This latter finding suggests that benefits observed in other studies utilizing pharmacological inhibitors of AR might have been secondary to off-target effects of the drugs.

The predictive value of ERG protein expression for development of castration-resistant prostate cancer in hormone-naïve advanced prostate cancer treated with primary androgen deprivation therapy

DEFF Research Database (Denmark)

Berg, Kasper Drimer; Røder, Martin A; Thomsen, Frederik B

2015-01-01

BACKGROUND: Biomarkers predicting response to primary androgen deprivation therapy (ADT) and risk of castration-resistant prostate cancer (CRPC) is lacking. We aimed to analyse the predictive value of ERG expression for development of CRPC. METHODS: In total, 194 patients with advanced and....../or metastatic prostate cancer (PCa) treated with first-line castration-based ADT were included. ERG protein expression was analysed in diagnostic specimens using immunohistochemistry (anti-ERG, EPR3864). Time to CRPC was compared between ERG subgroups using multiple cause-specific Cox regression stratified......-negative group, respectively. Compared to a model omitting ERG-status, the ERG-stratified model showed comparable AUC values 1 year (77.6% vs. 78.0%, P = 0.82), 2 years (71.7% vs. 71.8%, P = 0.85), 5 years (68.5% vs. 69.9%, P = 0.32), and 8 years (67.9% vs. 71.4%, P = 0.21) from ADT initiation. No differences...

Characterization of three types of silicon solar cells for SEPS deep space missions. Volume 1: Current-voltage characteristics of OCLI BSF/BSR 10 ohm-cm, and BSR 2 ohm-cm cells as a function of temperature and intensity

Science.gov (United States)

Whitaker, A. F.; Little, S. A.; Smith, C. F., Jr.; Wooden, V. A.

1979-01-01

Three types of high performance silicon solar cells, BSF/BSR 10 ohm-cm, BSR 10 ohm-cm, and BSR 2 ohm-cm, were evaluated for their low temperature and low intensity performance. Sixteen cells of each type were subjected to ten temperatures and nine intensities. The BSF/BSR 10 ohm-cm cells provided the best performance at 1 solar constant and +25 C with an efficiency of 14.1% while the BSR 2 ohm-cm cells had the highest low temperature and low intensity performance with an efficiency of 22.2% at 0.04 solar constant and -170 C and the most consistent cell-to-cell characteristics.

Detection of gamma rays from the supernova remnant RX J0852.0-4622 with H.E.S.S

International Nuclear Information System (INIS)

Komin, N.R.

2005-01-01

This work reports on the observations of γ-rays from the shell-type supernova remnant RXJ0852.0-4622 carried out with the High Energy Stereoscopic System in February 2004. H.E.S.S., a system of four imaging Cherenkov telescopes, is dedicated to the observation of γ-rays of energies between 100 GeV and several tens of TeV. Emission of -rays from RXJ0852.0-4622 was detected with a significance of 12σ within a live time of 3.2 h. The morphology of the emission region is clearly extended and correlated with the morphology of the X-ray emission. A differential energy spectrum of the photon flux between 0.5 and 10TeV was reconstructed. It is found to follow a power law dN/dE ∝E -Γ with a spectral index of Γ=2.1 ±0.1 stat ±0.2 syst . The integral photon flux above 1 TeV from the entire remnant is (1.9 ±0.3 stat ±0.4 syst ) x 10 -11 cm -2 s -1 which is at the level of the Crab flux at these energies, establishing RXJ0852.0-4622 as one of the brightest γ-ray sources in the sky. RXJ0852.0-4622 is the second supernova remnant of which an extended γ-ray morphology could be proved. The observed energy flux in γ-rays between 0.5 and 10 TeV is calculated to be (9 ±1 stat ±2 syst ) x 10 -11 erg cm -2 s -1 . Based on the energy flux in X-rays the expected energy flux due to inverse Compton scattering of relativistic electrons on the cosmic microwave background is estimated. It is found to be several orders of magnitude lower than the observed flux, suggesting that another radiation component significantly contributes to the γ-ray emission of RXJ0852.0-4622. In strong interactions of relativistic protons with the ambient interstellar material neutral pions are produced. The decay of these pions produce γ-rays. The distance to RXJ0852.0-4622 and the density of the ambient interstellar material are open parameters in the interpretation. It is shown for a wide range of these parameters that the transfer of several percent of the kinetic energy of the supernova remnant

Detection of gamma rays from the supernova remnant RX J0852.0-4622 with H.E.S.S.

Energy Technology Data Exchange (ETDEWEB)

Komin, N.R.

2005-10-25

This work reports on the observations of {gamma}-rays from the shell-type supernova remnant RXJ0852.0-4622 carried out with the High Energy Stereoscopic System in February 2004. H.E.S.S., a system of four imaging Cherenkov telescopes, is dedicated to the observation of {gamma}-rays of energies between 100 GeV and several tens of TeV. Emission of -rays from RXJ0852.0-4622 was detected with a significance of 12{sigma} within a live time of 3.2 h. The morphology of the emission region is clearly extended and correlated with the morphology of the X-ray emission. A differential energy spectrum of the photon flux between 0.5 and 10TeV was reconstructed. It is found to follow a power law dN/dE {proportional_to}E{sup -{gamma}} with a spectral index of {gamma}=2.1 {+-}0.1{sub stat} {+-}0.2{sub syst}. The integral photon flux above 1 TeV from the entire remnant is (1.9 {+-}0.3{sub stat} {+-}0.4{sub syst}) x 10{sup -11} cm{sup -2}s{sup -1} which is at the level of the Crab flux at these energies, establishing RXJ0852.0-4622 as one of the brightest {gamma}-ray sources in the sky. RXJ0852.0-4622 is the second supernova remnant of which an extended {gamma}-ray morphology could be proved. The observed energy flux in {gamma}-rays between 0.5 and 10 TeV is calculated to be (9 {+-}1{sub stat} {+-}2{sub syst}) x 10{sup -11} erg cm{sup -2}s{sup -1}. Based on the energy flux in X-rays the expected energy flux due to inverse Compton scattering of relativistic electrons on the cosmic microwave background is estimated. It is found to be several orders of magnitude lower than the observed flux, suggesting that another radiation component significantly contributes to the {gamma}-ray emission of RXJ0852.0-4622. In strong interactions of relativistic protons with the ambient interstellar material neutral pions are produced. The decay of these pions produce {gamma}-rays. The distance to RXJ0852.0-4622 and the density of the ambient interstellar material are open parameters in the

Fermi Observations of the LIGO Event GW170104

Energy Technology Data Exchange (ETDEWEB)

Goldstein, A.; Cleveland, W. H.; Connaughton, V. [Science and Technology Institute, Universities Space Research Association, Huntsville, AL 35805 (United States); Veres, P.; Briggs, M. S.; Hamburg, R.; Jenke, P. A.; Bhat, N. [Center for Space Plasma and Aeronomic Research, University of Alabama in Huntsville, 320 Sparkman Drive, Huntsville, AL 35899 (United States); Burns, E.; Canton, T. Dal [NASA Postdoctoral Program Fellow, Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Blackburn, L. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Christensen, N. [Physics and Astronomy, Carleton College, MN, 55057 (United States); Hui, C. M.; Kocevski, D.; Wilson-Hodge, C. A. [Astrophysics Office, ST12, NASA/Marshall Space Flight Center, Huntsville, AL 35812 (United States); Preece, R. D. [Department of Space Science, University of Alabama in Huntsville, 320 Sparkman Drive, Huntsville, AL 35899 (United States); Siellez, K. [Center for Relativistic Astrophysics and School of Physics, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Veitch, J. [University of Birmingham, Birmingham B15 2TT (United Kingdom); Bissaldi, E. [Istituto Nazionale di Fisica Nucleare, Sezione di Bari, I-70126 Bari (Italy); Gibby, M. H., E-mail: kocevski@slac.stanford.edu, E-mail: melissa.pesce.rollins@pi.infn.it, E-mail: nicola.omodei@stanford.edu, E-mail: giacomov@slac.stanford.edu [Jacobs Technology, Inc., Huntsville, AL (United States); Collaboration: (Fermi-LAT Collaboration); and others

2017-09-01

We present the Fermi Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) observations of the LIGO binary black hole merger (BBH) event GW170104. No candidate electromagnetic counterpart was detected by either GBM or LAT. A detailed analysis of the GBM and LAT data over timescales from seconds to days covering the Laser Interferometer Gravitational-wave Observatory (LIGO) localization region is presented. The resulting flux upper bound from the GBM is (5.2–9.4) × 10{sup −7} erg cm{sup −2} s{sup −1} in the 10–1000 keV range and from the LAT is (0.2–90) × 10{sup −9} erg cm{sup −2} s{sup −1} in the 0.1–1 GeV range. We also describe the improvements to our automated pipelines and analysis techniques for searching for and characterizing the potential electromagnetic counterparts for future gravitational-wave events from Advanced LIGO/Virgo.

Accurate measurements of solar spectral irradiance between 4000-10000 cm-1

Science.gov (United States)

Elsey, J.; Coleman, M. D.; Gardiner, T.; Shine, K. P.

2017-12-01

The near-infrared solar spectral irradiance (SSI) is an important input into simulations of weather and climate; the distribution of energy throughout this region of the spectrum influences atmospheric heating rates and the global hydrological cycle through absorption and scattering by water vapour. Current measurements by a mixture of ground-based and space-based instruments show differences of around 10% in the 4000-7000 cm-1 region, with no resolution to this controversy in sight. This work presents observations of SSI taken using a ground-based Fourier Transform spectrometer between 4000-10000 cm-1 at a field site in Camborne, UK, with particular focus on a rigorously defined uncertainty budget. While there is good agreement between this work and the commonly-used ATLAS3 spectrum between 7000-10000 cm-1, the SSI is systematically lower by 10% than ATLAS3 between 4000-7000 cm-1, with no overlap within the k = 2 measurement uncertainties.

Molecular mechanisms underlying the pilsicainide-induced stabilization of hERG proteins in transfected mammalian cells

Directory of Open Access Journals (Sweden)

Takeshi Onohara, MD

2017-06-01

Conclusions: Pilsicainide penetrates the plasma membrane, stabilizes WT-hERG proteins by acting as a chemical chaperone, and enhances WT-hERG channel currents. This mechanism could also be applicable to modulations of certain mutant-hERG proteins.

2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial

DEFF Research Database (Denmark)

Gillgren, Peter; Drzewiecki, Krzysztof T; Niin, Marianne

2011-01-01

Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin....

Erbium-doped phosphate glass waveguide on silicon with 4.1 dB/cm gain at 1.535 µm

Science.gov (United States)

Yan, Y. C.; Faber, A. J.; de Waal, H.; Kik, P. G.; Polman, A.

1997-11-01

Erbium-doped multicomponent phosphate glass waveguides were deposited by rf sputtering techniques. The Er concentration was 5.3×1020cm-3. By pumping the waveguide at 980 nm with a power of ˜21 mW, a net optical gain of 4.1 dB at 1.535 μm was achieved. This high gain per unit length at low pump power could be achieved because the Er-Er cooperative upconversion interactions in this heavily Er-doped phosphate glass are very weak [the upconversion coefficient is (2.0±0.5)×10-18 cm3/s], presumably due to the homogeneous distribution of Er in the glass and due to the high optical mode confinement in the waveguide which leads to high pump power density at low pump power.

Application of electroretinography (ERG) in early drug development for assessing retinal toxicity in rats

Energy Technology Data Exchange (ETDEWEB)

Huang, Wenhu, E-mail: wenhu.huang@pfizer.com; Collette, Walter; Twamley, Michelle; Aguirre, Shirley A.; Sacaan, Aida

2015-12-15

Retinal ocular toxicity is among the leading causes of drug development attrition in the pharmaceutical industry. Electroretinography (ERG) is a non-invasive functional assay used to assess neuro-retinal physiological integrity by measuring the electrical responses. To directly assess the utility of ERG, a series of studies was conducted following intravitreal and/or iv administration of pan-cyclin-dependent kinase inhibitors: AG-012,986 and AG-024,322 in rats. Both compounds have previously shown to induce retinal toxicity. Retinal injury was evaluated by ERG, histopathology and TUNEL staining. Intravitreal injection of AG-012,986 at ≥ 10 μg/eye resulted in decreases (60%) in ERG b-wave and microscopic changes of mild to moderate retinal degeneration, and at 30 μg/eye led to additional ophthalmic findings. Intravenous administration of AG-012,986 daily at ≥ 5 mg/kg resulted in dose-related decreases (25 to 40%) in b-wave and sporadic to intense positive TUNEL staining. Intravitreal injection of AG-024,322 at 30 μg/eye also resulted in decreases (50 to 60%) in b-wave, mild to marked retinal degeneration and mild vitreous debris. These experiments demonstrate that ERG can be used as a sensitive and reliable functional tool to evaluate retinal toxicity induced by test compounds in rats complementing other classical ocular safety measurements. - Highlights: • There were strong correlations of ERG readouts to in vivo ophthalmic exams, TUNEL assay, and histopathology. • ERG appears to be more sensitive and can detect retinal functional changes at a very early stage of pathogenesis. • ERG can be incorporated into routine exploratory toxicity study to identify compound ocular safety issues. • In drug discovery, ERG is a quick, non-invasive, sensitive and reliable tool in retinal toxicity de-risking.

Application of electroretinography (ERG) in early drug development for assessing retinal toxicity in rats

International Nuclear Information System (INIS)

Huang, Wenhu; Collette, Walter; Twamley, Michelle; Aguirre, Shirley A.; Sacaan, Aida

2015-01-01

Retinal ocular toxicity is among the leading causes of drug development attrition in the pharmaceutical industry. Electroretinography (ERG) is a non-invasive functional assay used to assess neuro-retinal physiological integrity by measuring the electrical responses. To directly assess the utility of ERG, a series of studies was conducted following intravitreal and/or iv administration of pan-cyclin-dependent kinase inhibitors: AG-012,986 and AG-024,322 in rats. Both compounds have previously shown to induce retinal toxicity. Retinal injury was evaluated by ERG, histopathology and TUNEL staining. Intravitreal injection of AG-012,986 at ≥ 10 μg/eye resulted in decreases (60%) in ERG b-wave and microscopic changes of mild to moderate retinal degeneration, and at 30 μg/eye led to additional ophthalmic findings. Intravenous administration of AG-012,986 daily at ≥ 5 mg/kg resulted in dose-related decreases (25 to 40%) in b-wave and sporadic to intense positive TUNEL staining. Intravitreal injection of AG-024,322 at 30 μg/eye also resulted in decreases (50 to 60%) in b-wave, mild to marked retinal degeneration and mild vitreous debris. These experiments demonstrate that ERG can be used as a sensitive and reliable functional tool to evaluate retinal toxicity induced by test compounds in rats complementing other classical ocular safety measurements. - Highlights: • There were strong correlations of ERG readouts to in vivo ophthalmic exams, TUNEL assay, and histopathology. • ERG appears to be more sensitive and can detect retinal functional changes at a very early stage of pathogenesis. • ERG can be incorporated into routine exploratory toxicity study to identify compound ocular safety issues. • In drug discovery, ERG is a quick, non-invasive, sensitive and reliable tool in retinal toxicity de-risking.

Endocytosis of hERG Is Clathrin-Independent and Involves Arf6

Science.gov (United States)

Abuarab, Nada; Smith, Andrew J.; Hardy, Matthew E. L.; Elliott, David J. S.; Sivaprasadarao, Asipu

2013-01-01

The hERG potassium channel is critical for repolarisation of the cardiac action potential. Reduced expression of hERG at the plasma membrane, whether caused by hereditary mutations or drugs, results in long QT syndrome and increases the risk of ventricular arrhythmias. Thus, it is of fundamental importance to understand how the density of this channel at the plasma membrane is regulated. We used antibodies to an extracellular native or engineered epitope, in conjunction with immunofluorescence and ELISA, to investigate the mechanism of hERG endocytosis in recombinant cells and validated the findings in rat neonatal cardiac myocytes. The data reveal that this channel undergoes rapid internalisation, which is inhibited by neither dynasore, an inhibitor of dynamin, nor a dominant negative construct of Rab5a, into endosomes that are largely devoid of the transferrin receptor. These results support a clathrin-independent mechanism of endocytosis and exclude involvement of dynamin-dependent caveolin and RhoA mechanisms. In agreement, internalised hERG displayed marked overlap with glycosylphosphatidylinositol-anchored GFP, a clathrin-independent cargo. Endocytosis was significantly affected by cholesterol extraction with methyl-β-cyclodextrin and inhibition of Arf6 function with dominant negative Arf6-T27N-eGFP. Taken together, we conclude that hERG undergoes clathrin-independent endocytosis via a mechanism involving Arf6. PMID:24392021

Towards a Structural View of Drug Binding to hERG K+ Channels.

Science.gov (United States)

Vandenberg, Jamie I; Perozo, Eduardo; Allen, Toby W

2017-10-01

The human ether-a-go-go-related gene (hERG) K + channel is of great medical and pharmaceutical relevance. Inherited mutations in hERG result in congenital long-QT syndrome which is associated with a markedly increased risk of cardiac arrhythmia and sudden death. hERG K + channels are also remarkably susceptible to block by a wide range of drugs, which in turn can cause drug-induced long-QT syndrome and an increased risk of sudden death. The recent determination of the near-atomic resolution structure of the hERG K + channel, using single-particle cryo-electron microscopy (cryo-EM), provides tremendous insights into how these channels work. It also suggests a way forward in our quest to understand why these channels are so promiscuous with respect to drug binding. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fermi-LAT Observation of Supernova Remnant S147

Energy Technology Data Exchange (ETDEWEB)

Katsuta, J.; Uchiyama, Y.; Tanaka, T.; /SLAC /KIPAC, Menlo Park; Tajima, H.; /SLAC /KIPAC, Menlo Park /Nagoya U., Solar-Terrestrial Environ. Lab.; Bechtol, K.; Funk, S.; Lande, J.; /SLAC /KIPAC, Menlo Park; Ballet, J.; /AIM, Saclay; Hanabata, Y.; /Hiroshima U.; Lemoine-Goumard, M.; /CENBG, Gradignan; Takahashi, T.; /JAXA, Sagamihara

2012-08-17

We present an analysis of gamma-ray data obtained with the Large Area Telescope (LAT) onboard the Fermi Gamma-ray Space Telescope in the region around SNR S147 (G180.0-1.7). A spatially extended gamma-ray source detected in an energy range of 0.2-10 GeV is found to coincide with SNR S147. We confirm its spatial extension at >5{sigma} confidence level. The gamma-ray flux is (3.8 {+-} 0.6) x 10{sup -8} photons cm{sup -2} s{sup -1}, corresponding to a luminosity of 1.3 x 10{sup 34} (d/1.3 kpc){sup 2} erg s{sup -1} in this energy range. The gamma-ray emission exhibits a possible spatial correlation with prominent H{alpha} filaments of S147. There is no indication that the gamma-ray emission comes from the associated pulsar PSR J0538+2817. The gamma-ray spectrum integrated over the remnant is likely dominated by the decay of neutral {pi} mesons produced through the proton-proton collisions in the filaments. Reacceleration of pre-existing CRs and subsequent adiabatic compression in the filaments is sufficient to provide the required energy density of high-energy protons.

Comportamiento Mecánico Estático de los Instrumentos S1, S2, F1 de Protaper Universal® Bajo Torsión y Doblamiento. Análisis por Elementos Finitos

Directory of Open Access Journals (Sweden)

Luisa Fernanda Cartagena

2011-10-01

Full Text Available Propósito: Examinar el comportamiento mecánico estático de los instrumentos ProTaper Universal® S1, S2, F1 bajo torsión y doblamiento teniendo en cuenta las propiedades mecánicas del material, mediante el método de elementos finitos. Metodología: Estudio Observacional descriptivo. Las limas investigadas fueron S1, S2, F1 de ProTaper Universal®, modeladas con el software ANSYS 10 y sometidas a fuerzas de torsión empezando en 0.25N/cm hasta alcanzar el torque máximo recomendado por la casa comercial Maillefer® y doblamiento en un ángulo de 600. Resultados:El máximo esfuerzo ocurre en el núcleo de la sección para todos los instrumentos evaluados;  al incrementar el torque el  esfuerzo  se disipa a la periferia para S1 (D5, D10, D14, S2 (D5, D7, D8, D10, F1 (D2, D3, D5.  La lima S1 al ser sometida a  torsión en D0 y D5 independiente del torque que fuese aplicado el máximo de esfuerzo superaba el límite de deformación plástica en el núcleo de la sección  del instrumento. La lima S2 con torques de  1 ó 1,5 N/cm superó  el límite elástico del material. Lima F1 en D0, D2 con torques de  0.25, 0.5, 1, 1.5, 2 N/cm el esfuerzo máximo no supero el límite de deformación plástica. En la prueba de doblamiento la gran mayoría de la estructura de las limas S1, S2, F1, se encuentra  por debajo del esfuerzo de ruptura (línea neutral es bastante ancha.Conclusion: Las fuerzas de  torsión para todas la limas del estudio mostraron tener mayor riesgo de separación del instrumento en comparación con  las fuerzas de doblamiento. 

First charge collection and position-precision data on the medium-resistivity silicon strip detectors before and after neutron irradiation up to 2x10 sup 1 sup 4 n/cm sup 2

CERN Document Server

Li Zheng; Eremin, V; Li, C J; Verbitskaya, E

1999-01-01

Test strip detectors of 125 mu m, 500 mu m, and 1 mm pitches with about 1 cm sup 2 areas have been made on medium-resistivity silicon wafers (1.3 and 2.7 k OMEGA cm). Detectors of 500 mu m pitch have been tested for charge collection and position precision before and after neutron irradiation (up to 2x10 sup 1 sup 4 n/cm sup 2) using 820 and 1030 nm laser lights with different beam-spot sizes. It has been found that for a bias of 250 V a strip detector made of 1.3 k OMEGA cm (300 mu m thick) can be fully depleted before and after an irradiation of 2x10 sup 1 sup 4 n/cm sup 2. For a 500 mu m pitch strip detector made of 2.7 k OMEGA cm tested with an 1030 nm laser light with 200 mu m spot size, the position reconstruction error is about 14 mu m before irradiation, and 17 mu m after about 1.7x10 sup 1 sup 3 n/cm sup 2 irradiation. We demonstrated in this work that medium resistivity silicon strip detectors can work just as well as the traditional high-resistivity ones, but with higher radiation tolerance. We als...

[ERG diagnosis and differential diagnosis: results of examination over 6 years].

Science.gov (United States)

Stemeyer, G; Stähli, P

1996-05-01

This study reviews the patient material first from the point of view of referral diagnosis. Secondly, we focus on difficulties in selective differential diagnoses. 1501 patients underwent electroretinographic (ERG) testing from 1989 to 1994, amounting to 1815 ERG recordings, including follow-up examinations. The technique applied is full-field, single flash ERG with selective stimulation of the rod- and of the cone-systems. In 3.8% (57 cases) the ERG was performed under general anesthesia in outpatients. Tapetoretinal degenerations, toxic retinal side effects, inflammatory disease and ocular trauma represented, in this order, the major groups of referral diagnoses aside from unclear visual loss. The documentation or the exclusion of tapetoretinal degeneration represented the largest share (57%) of the application of the diagnostic procedure. 171 cases of isolated retinitis pigmentosa (RP) and 33 cases of syndromic RP were identified. Frequent and rare diagnostic entities and their differential diagnoses within this group are discussed. Inevitably, a number of diagnostic decisions remain problematic, in particular at the first examination. These diagnostic difficulties are addressed also and include the differentiation between RP sine pigmento and congenital amaurosis Leber in infants, RP with macular involvement vs. cone-rod degeneration, unilateral RP vs. postinflammatory conditions, and progressive cone dystrophy vs. achromatopsia, cone-rod degeneration or Stargardt's disease. Frequent and meaningful indications for ERG recording and difficult diagnostic decisions arise from this review of a relatively large group of patients. A number of diagnoses can hardly, if not at all be established without ERG testing. These include retinal cause of visual loss in infants, congenital amaurosis Leber, RP sine pigmento, early stages of RP, carrier status in XL RP and in choroideremia, progressive cone dystrophy, toxic retinopathy without fundus changes, retinal involvement

Low-frequency 1/f noise in MoS{sub 2} transistors: Relative contributions of the channel and contacts

Energy Technology Data Exchange (ETDEWEB)

Renteria, J.; Jiang, C. [Nano-Device Laboratory, Department of Electrical Engineering, Bourns College of Engineering, University of California – Riverside, Riverside, California 92521 (United States); Samnakay, R. [Materials Science and Engineering Program, Bourns College of Engineering, University of California – Riverside, Riverside, California 92521 (United States); Rumyantsev, S. L. [Department of Electrical, Computer, and Systems Engineering, Center for Integrated Electronics, Rensselaer Polytechnic Institute, Troy, New York 12180 (United States); Ioffe Physical-Technical Institute, St. Petersburg 194021 (Russian Federation); Goli, P.; Balandin, A. A., E-mail: balandin@ee.ucr.edu [Nano-Device Laboratory, Department of Electrical Engineering, Bourns College of Engineering, University of California – Riverside, Riverside, California 92521 (United States); Materials Science and Engineering Program, Bourns College of Engineering, University of California – Riverside, Riverside, California 92521 (United States); Shur, M. S. [Department of Electrical, Computer, and Systems Engineering, Center for Integrated Electronics, Rensselaer Polytechnic Institute, Troy, New York 12180 (United States)

2014-04-14

We report on the results of the low-frequency (1/f, where f is frequency) noise measurements in MoS{sub 2} field-effect transistors revealing the relative contributions of the MoS{sub 2} channel and Ti/Au contacts to the overall noise level. The investigation of the 1/f noise was performed for both as fabricated and aged transistors. It was established that the McWhorter model of the carrier number fluctuations describes well the 1/f noise in MoS{sub 2} transistors, in contrast to what is observed in graphene devices. The trap densities extracted from the 1/f noise data for MoS{sub 2} transistors, are 2 × 10{sup 19} eV{sup −1}cm{sup −3} and 2.5 × 10{sup 20} eV{sup −1}cm{sup −3} for the as fabricated and aged devices, respectively. It was found that the increase in the noise level of the aged MoS{sub 2} transistors is due to the channel rather than the contact degradation. The obtained results are important for the proposed electronic applications of MoS{sub 2} and other van der Waals materials.

High yield purification of full-length functional hERG K+ channels produced in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Molbaek, Karen; Scharff-Poulsen, Peter; Hélix-Nielsen, Claus

2015-01-01

knowledge this is the first reported high-yield production and purification of full length, tetrameric and functional hERG. This significant breakthrough will be paramount in obtaining hERG crystal structures, and in establishment of new high-throughput hERG drug safety screening assays....

Effects of Tannic Acid, Green Tea and Red Wine on hERG Channels Expressed in HEK293 Cells.

Directory of Open Access Journals (Sweden)

Xi Chu

Full Text Available Tannic acid presents in varying concentrations in plant foods, and in relatively high concentrations in green teas and red wines. Human ether-à-go-go-related gene (hERG channels expressed in multiple tissues (e.g. heart, neurons, smooth muscle and cancer cells, and play important roles in modulating cardiac action potential repolarization and tumor cell biology. The present study investigated the effects of tannic acid, green teas and red wines on hERG currents. The effects of tannic acid, teas and red wines on hERG currents stably transfected in HEK293 cells were studied with a perforated patch clamp technique. In this study, we demonstrated that tannic acid inhibited hERG currents with an IC50 of 3.4 μM and ~100% inhibition at higher concentrations, and significantly shifted the voltage dependent activation to more positive potentials (Δ23.2 mV. Remarkably, a 100-fold dilution of multiple types of tea (green tea, oolong tea and black tea or red wine inhibited hERG currents by ~90%, and significantly shifted the voltage dependent activation to more positive potentials (Δ30.8 mV and Δ26.0 mV, respectively. Green tea Lung Ching and red wine inhibited hERG currents, with IC50 of 0.04% and 0.19%, respectively. The effects of tannic acid, teas and red wine on hERG currents were irreversible. These results suggest tannic acid is a novel hERG channel blocker and consequently provide a new mechanistic evidence for understanding the effects of tannic acid. They also revealed the potential pharmacological basis of tea- and red wine-induced biology activities.

Effects of Tannic Acid, Green Tea and Red Wine on hERG Channels Expressed in HEK293 Cells

Science.gov (United States)

Xu, Bingyuan; Li, Wenya; Lin, Yue; Sun, Xiaorun; Ding, Chunhua; Zhang, Xuan

2015-01-01

Tannic acid presents in varying concentrations in plant foods, and in relatively high concentrations in green teas and red wines. Human ether-à-go-go-related gene (hERG) channels expressed in multiple tissues (e.g. heart, neurons, smooth muscle and cancer cells), and play important roles in modulating cardiac action potential repolarization and tumor cell biology. The present study investigated the effects of tannic acid, green teas and red wines on hERG currents. The effects of tannic acid, teas and red wines on hERG currents stably transfected in HEK293 cells were studied with a perforated patch clamp technique. In this study, we demonstrated that tannic acid inhibited hERG currents with an IC50 of 3.4 μM and ~100% inhibition at higher concentrations, and significantly shifted the voltage dependent activation to more positive potentials (Δ23.2 mV). Remarkably, a 100-fold dilution of multiple types of tea (green tea, oolong tea and black tea) or red wine inhibited hERG currents by ~90%, and significantly shifted the voltage dependent activation to more positive potentials (Δ30.8 mV and Δ26.0 mV, respectively). Green tea Lung Ching and red wine inhibited hERG currents, with IC50 of 0.04% and 0.19%, respectively. The effects of tannic acid, teas and red wine on hERG currents were irreversible. These results suggest tannic acid is a novel hERG channel blocker and consequently provide a new mechanistic evidence for understanding the effects of tannic acid. They also revealed the potential pharmacological basis of tea- and red wine-induced biology activities. PMID:26625122

The 5s25p2 - (5s25p5d + 5s5p3 + 5s25p6s + 5s25p7s) transitions in Sb II and 5s25p - (5s5p2 + 5s2nl) transitions in Sb III

International Nuclear Information System (INIS)

Arcimowicz, B.; Joshi, Y.N.; Kaufman, V.

1989-01-01

The spectrum of antimony was photographed in the 575-2300 A region (1A 10 -10 m) using a hollow cathode and a triggered spark source. The analysis of the 5s 2 5p 2 - (5s 2 5p5d + 5s5p 3 + 5s 2 5p6s + 5s 2 5p7s) transitions in Sb II spectrum was revised and interpreted on the basis of multiconfiguration interaction calculations. Accurate wavelength measurements of Sb III lines lead to a revised ground-state 5s 2 5p 2 P interval value of 6574.5 cm -1 . (author). 15 refs., 9 tabs., 1 fig

Electron mobility in few-layer MoxW1-xS2

International Nuclear Information System (INIS)

Chandrasekar, Hareesh; Nath, Digbijoy N

2015-01-01

Heterostructures of two-dimensional (2D) layered materials are increasingly being explored for electronics in order to potentially extend conventional transistor scaling and to exploit new device designs and architectures. Alloys form a key underpinning of any heterostructure device technology and therefore an understanding of their electronic properties is essential. In this paper, we study the intrinsic electron mobility in few-layer Mo x W 1−x S 2 as limited by various scattering mechanisms. The room temperature, energy-dependent scattering times corresponding to polar longitudinal optical (LO) phonon, alloy and background impurity scattering mechanisms are estimated based on the Born approximation to Fermi’s golden rule. The contribution of individual scattering rates is analyzed as a function of 2D electron density as well as of alloy composition in Mo x W 1−x S 2 . While impurity scattering limits the mobility for low carrier densities (<2–4×10 12 cm −2 ), LO polar phonon scattering is the dominant mechanism for high electron densities. Alloy scattering is found to play a non-negligible role for 0.5 < x < 0.7 in Mo x W 1−x S 2 . The LO phonon-limited and impurity-limited mobilities show opposing trends with respect to alloy mole fractions. The understanding of electron mobility in Mo x W 1−x S 2 presented here is expected to enable the design and realization of heterostructures and devices based on alloys of MoS 2 and WS 2 . (paper)

Operation of low-noise single-gap RPC modules exposed to ionisation rates up to 1 kHz/cm$^2$

CERN Document Server

Cwiok, M; Dominik, Wojciech; Górski, M; Królikowski, J; 10.1016/j.nima.2004.06.123

2004-01-01

Two single gap medium-size RPC modules, made of bakelite plates of very good mechanical quality of the surface and having initial volume resistivity of 1 multiplied by 10**1**0 omegacm, were tested in the Gamma Irradiation Facility at CERN at ionisation rates up to 1 kHz/cm **3. The internal surfaces facing the gas volume of one RPC module were cladded with a thin layer of linseed oil varnish for comparison of oiled and non-oiled RPC operation. The results refer to the gas mixture of C//2H//2F //4/isobutane (97:3) with SF//6 addition below 1%. The single gap modules exhibited full detection efficiency plateau for the high voltage range of about 1 kV at full intensity of gamma rays. Good timing characteristics allowed to reach 95% efficiency at fully opened irradiation source with time window of 20 ns. The intrinsic noise rate for a non-oiled and an oiled RPC gap was, respectively, below 5 and 1 Hz/cm**2 at full efficiency over 1 k V voltage range.

Electron impact excitation-autoionisation of the (2s2)1S, (2p2)1D and (2s2p)1P autoionising states of helium

International Nuclear Information System (INIS)

Samardzic, O.; Hurn, J.A.; Weigold, E.; Brunger, M.J.

1994-01-01

The electron impact excitation of the (2s 2 ) 1 S, (2p 2 ) 1 D and (2s2p) 1 P autoionising states of helium and their subsequent radiationless decay was studied by observation of the ejected electrons. The present work was carried out at an incident energy of 94.6 eV and for ejected electron scattering angles in the range 25-135 deg C. The lineshapes observed in the present ejected electron spectra are analysed using the Shore-Balashov parametrisation. As part of the analysis procedure, numerically rigorous confidence limits were determined for the derived parameters. No previous experimental or theoretical work has been undertaken at the incident energy of the present investigation but, where possible, the resulting parameters are qualitatively compared against the 80 eV results of other experiments and theory. 37 refs., 4 figs

NuSTAR Observations of WISE J1036+0449, A Galaxy at zeta approx 1 Obscured by Hot Dust

Science.gov (United States)

Ricci, C.; Assef, R. J.; Stern, Daniel K.; Nikutta, R.; Alexander, D. M.; Asmus, D.; Ballantyne, D. R.; Bauer, F. E.; Blain, A.W.; Zhang, William W.;

NuSTAR Observations of WISE J1036+0449, A Galaxy at Z Approx. 1 Obscured by Hot Dust

Science.gov (United States)

Ricci, C.; Assef, R. J.; Stern, D.; Nikutta, R.; Alexander, D. M.; Asmus, D.; Ballantyne, D. R.; Bauer, F. E.; Blain, A. W.; Boggs, S.;

Hydrothermal syntheses, structural, Raman, and luminescence studies of Cm[M(CN)2]3.3H2O and Pr[M(CN)2]3.3H2O (M=Ag, Au)

International Nuclear Information System (INIS)

Assefa, Zerihun; Haire, Richard G.; Sykora, Richard E.

2008-01-01

We have prepared Cm[Au(CN) 2 ] 3 .3H 2 O and Cm[Ag(CN) 2 ] 3 .3H 2 O as a part of our continuing investigations into the chemistry of the 5f-elements' dicyanometallates. Single crystals of Cm[Au(CN) 2 ] 3 .3H 2 O were obtained from the reaction of CmCl 3 and KAu(CN) 2 under mild hydrothermal conditions. Due to similarities in size, the related praseodymium compounds were also synthesized and characterized for comparison with the actinide systems. The compounds crystallize in the hexagonal space group P6 3 /mcm, where the curium and the transition metals interconnect through cyanide bridging. Crystallographic data (Mo Kα, λ=0.71073 A): Cm[Au(CN) 2 ] 3 .3H 2 O (1), a=6.6614(5) A, c=18.3135(13) A, V=703.77(9), Z=2; Pr[Au(CN) 2 ] 3 .3H 2 O (3), a=6.6662(8) A, c=18.497(3) A, V=711.83(17), Z=2; Pr[Ag(CN) 2 ] 3 .3H 2 O (4), a=6.7186(8) A, c=18.678(2) A, V=730.18(14), Z=2. The Cm 3+ and/or Pr 3+ ions are coordinated to six N-bound CN - groups resulting in a trigonal prismatic arrangement. Three oxygen atoms of coordinated water molecules tricap the trigonal prismatic arrangement providing a coordination number of nine for the f-elements. The curium ions in both compounds exhibit a strong red emission corresponding to the 6 D 7/2 → 8 S 7/2 transition. This transition is observed at 16,780 cm -1 , with shoulders at 17,080 and 16,840 cm -1 for the Ag complex, while the emission is red shifted by ∼100 cm -1 in the corresponding gold complex. The Pr systems also provide well-resolved emissions upon f-f excitation. - Graphical abstract: Coordination polymeric compounds between a trans-plutonium element, curium and transition metal ions, gold(I) and silver(I), were prepared using the hydrothermal synthetic procedure. The curium ion and the transition metals are interconnected through cyanide bridging. The Cm ion has a tricapped trigonal prismatic coordination environment with coordination number of nine. Detail photoluminescence studies of the complexes are also reported

On- and off-response ERGs elicited by sawtooth stimuli in normal subjects and glaucoma patients.

Science.gov (United States)

Pangeni, Gobinda; Lämmer, Robert; Tornow, Ralf P; Horn, Folkert K; Kremers, Jan

2012-06-01

The aim of this study is to measure the on- and off-responses and their response asymmetries elicited by sawtooth stimuli in normal subjects and glaucoma patients. Furthermore, the correlation between the ERGs and other functional and structural parameters are investigated. Full-field stimuli were produced using a Ganzfeld bowl with Light Emitting Diodes (LEDs) as light sources. On- and off-response ERGs were recorded from 17 healthy subjects, 12 pre-perimetric and 15 perimetric glaucoma patients using 4-Hz luminance rapid-on and rapid-off sawtooth stimuli (white light; mean luminance 55 cd/m(2)) at 100% contrast. The on- and off-responses were added to study response asymmetries. In addition, flash ERGs were elicited by red stimuli (200 cd/m(2)) on a blue background (10 cd/m(2)). The mean deviations (MD) of the visual field defects were obtained by standard automated perimetry. The retinal nerve fibre layer thickness (RNFLT) was measured with Spectral Domain Optical Coherence Tomography (SOCT). We studied the correlation between ERG response amplitudes, visual field mean deviation (MDs) and RNFLT values. The on-responses showed an initial negative (N-on) followed by a positive (P-on), a late positive (LP-on) and a late negative responses (LN-on). The off-responses showed an initial positive (P-off) a late positive (LP-off) and a late negative response (LN-off). The addition of on- and off-responses revealed an initial positive (P-add) and a late negative response (LN-add). The on-response components (N-on, P-on and LN-on) in the glaucoma patients were relatively similar to those of the control subjects. However, the LP-on was significantly elevated (p = 0.03) in perimetric patients. The LP-off was significantly elevated (p < 0.001), and the amplitude of LN-off was significantly reduced in perimetric patients (p = 0.02). The LN-add amplitude was significantly reduced (p < 0.001) and delayed (p = 0.03) in perimetric patients. The amplitudes of the LN-off and LN

X-ray evidence for ultra-fast outflows in AGNs

Science.gov (United States)

Tombesi, Francesco; Sambruna, Rita; Braito, Valentina; Reeves, James; Reynolds, Christopher; Cappi, Massimo

2012-07-01

X-ray evidence for massive, highly ionized, ultra-fast outflows (UFOs) has been recently reported in a number of AGNs through the detection of blue-shifted Fe XXV/XXVI absorption lines. We present the results of a comprehensive spectral analysis of a large sample of 42 local Seyferts and 5 radio galaxies observed with XMM-Newton and Suzaku. We assessed the global detection significance of the absorption lines and performed a detailed photo-ionization modeling. We find that UFOs are common phenomena, being present in >40% of the sources. Their outflow velocity distribution is in the range ˜0.03--0.3c, with mean value of ˜0.14c. The ionization parameter is very high, in the range logξ˜3--6 erg~s^{-1}~cm, and the associated column densities are also large, in the range ˜10^{22}--10^{24} cm^{-2}. Their location is constrained at ˜0.0003--0.03pc (˜10^2--10^4 r_s) from the central black hole, consistent with what is expected for accretion disk winds/outflows. The mass outflow rates are in the interval ˜0.01--1M_{⊙}~yr^{-1} and the associated mechanical power is high, in the range ˜10^{43}--10^{45} erg/s. Therefore, UFOs are capable to provide a significant contribution to the AGN cosmological feedback and their study can provide important clues on the connection between accretion disks, winds and jets.

The TESIS Project: Are Type 2 QSO Hidden in X-Ray Emitting EROs?

Science.gov (United States)

Severgnini, P.; Della Ceca, R.; Braito, V.; Saracco, P.; Longhetti, M.; Bender, R.; Drory, N.; Feulner, G.; Hopp, U.; Mannucci, F.; Maraston, C.

X-ray selected EROs are, on average, the hardest X-ray sources in medium and deep X-ray fields. This coupled with their extremely red colors (R-K > 5) suggest that they represent one of the most promising population where looking for high-luminosity (LX > 1044 erg s-1) and X-ray obscured (NH > 1022 cm-2) type2 AGNs, the so called QSO2 (e.g., [5]; [4]; Mignoli et al. submitted to A&A). These latter are predicted in large density by the synthesis model of the Cosmic X-ray background [9] even if only few observational evidences have been found so far (e.g., [1] and references therein; Caccianiga et al. A&A accepted).

Perpendicular magnetic anisotropy in Ta|Co40Fe40B20|MgAl2O4 structures and perpendicular CoFeB|MgAl2O4|CoFeB magnetic tunnel junction

KAUST Repository

Tao, B. S.

2014-09-08

Magnetic properties of Co40Fe40B20(CoFeB) thin films sandwiched between Ta and MgAl2O4layers have been systematically studied. For as-grown state, Ta/CoFeB/MgAl2O4structures exhibit good perpendicular magnetic anisotropy (PMA) with interface anisotropy Ki=1.22erg/cm2, which further increases to 1.30erg/cm2after annealing, while MgAl2O4/CoFeB/Ta multilayer shows in-plane magnetic anisotropy and must be annealed in order to achieve PMA. For bottom CoFeB layer, the thickness window for PMA is from 0.6 to 1.0nm, while that for top CoFeB layer is between 0.8 and 1.4nm. Perpendicular magnetic tunnel junctions (p-MTJs) with a core structure of CoFeB/MgAl2O4/CoFeB have also been fabricated and tunneling magnetoresistance ratio of about 36% at room temperature and 63% at low temperature have been obtained. The intrinsic excitations in the p-MTJs have been identified by inelastic electron-tunneling spectroscopy.

Perpendicular magnetic anisotropy in Ta|Co40Fe40B20|MgAl2O4 structures and perpendicular CoFeB|MgAl2O4|CoFeB magnetic tunnel junction

KAUST Repository

Tao, B. S.; Li, D. L.; Yuan, Z. H.; Liu, H. F.; Ali, S. S.; Feng, J. F.; Wei, H. X.; Han, X. F.; Liu, Y.; Zhao, Y. G.; Zhang, Q.; Guo, Zaibing; Zhang, Xixiang

2014-01-01

Magnetic properties of Co40Fe40B20(CoFeB) thin films sandwiched between Ta and MgAl2O4layers have been systematically studied. For as-grown state, Ta/CoFeB/MgAl2O4structures exhibit good perpendicular magnetic anisotropy (PMA) with interface anisotropy Ki=1.22erg/cm2, which further increases to 1.30erg/cm2after annealing, while MgAl2O4/CoFeB/Ta multilayer shows in-plane magnetic anisotropy and must be annealed in order to achieve PMA. For bottom CoFeB layer, the thickness window for PMA is from 0.6 to 1.0nm, while that for top CoFeB layer is between 0.8 and 1.4nm. Perpendicular magnetic tunnel junctions (p-MTJs) with a core structure of CoFeB/MgAl2O4/CoFeB have also been fabricated and tunneling magnetoresistance ratio of about 36% at room temperature and 63% at low temperature have been obtained. The intrinsic excitations in the p-MTJs have been identified by inelastic electron-tunneling spectroscopy.

Critical role of alkyl chain branching of organic semiconductors in enabling solution-processed N-channel organic thin-film transistors with mobility of up to 3.50 cm² V(-1) s(-1).

Science.gov (United States)

Zhang, Fengjiao; Hu, Yunbin; Schuettfort, Torben; Di, Chong-an; Gao, Xike; McNeill, Christopher R; Thomsen, Lars; Mannsfeld, Stefan C B; Yuan, Wei; Sirringhaus, Henning; Zhu, Daoben

2013-02-13

Substituted side chains are fundamental units in solution processable organic semiconductors in order to achieve a balance of close intermolecular stacking, high crystallinity, and good compatibility with different wet techniques. Based on four air-stable solution-processed naphthalene diimides fused with 2-(1,3-dithiol-2-ylidene)malononitrile groups (NDI-DTYM2) that bear branched alkyl chains with varied side-chain length and different branching position, we have carried out systematic studies on the relationship between film microstructure and charge transport in their organic thin-film transistors (OTFTs). In particular synchrotron measurements (grazing incidence X-ray diffraction and near-edge X-ray absorption fine structure) are combined with device optimization studies to probe the interplay between molecular structure, molecular packing, and OTFT mobility. It is found that the side-chain length has a moderate influence on thin-film microstructure but leads to only limited changes in OTFT performance. In contrast, the position of branching point results in subtle, yet critical changes in molecular packing and leads to dramatic differences in electron mobility ranging from ~0.001 to >3.0 cm(2) V(-1) s(-1). Incorporating a NDI-DTYM2 core with three-branched N-alkyl substituents of C(11,6) results in a dense in-plane molecular packing with an unit cell area of 127 Å(2), larger domain sizes of up to 1000 × 3000 nm(2), and an electron mobility of up to 3.50 cm(2) V(-1) s(-1), which is an unprecedented value for ambient stable n-channel solution-processed OTFTs reported to date. These results demonstrate that variation of the alkyl chain branching point is a powerful strategy for tuning of molecular packing to enable high charge transport mobilities.

Passive permeability of salicylic acid in renal proximal S2 and S3 tubules

International Nuclear Information System (INIS)

Chatton, J.Y.; Roch-Ramel, F.

1991-01-01

The role of nonionic diffusion in the transport of salicylic acid across rabbit proximal S2 and S3 segments was investigated using the in vitro isolated perfused tubule technique. The [ 14 C] salicylic acid apparent reabsorptive permeability (P'I-b, 10(-5) cm/s) was measured at 19 degrees C with luminal solutions kept at different pH and bath maintained at pH 7.4. In S2 tubules, P'I-b was 25.0 +/- 3.5 when luminal pH was 6.0; P'I-b decreased to 8.1 +/- 1.4 and to 4.4 +/- 1.2 at a luminal pH of 6.5 and 7.0, respectively. In S3 tubules, P'I-b was 17.6 +/- 2.4, 5.3 +/- 1.1 and 3.4 +/- 1.1 at a luminal pH of 6.0, 6.5 and 7.0, respectively. There was a close correlation between P'I-b and the calculated proportion of nonionized salicylic acid present at each pH, indicating that only the nonionized molecule could diffuse in our conditions. We calculated the apparent permeability of nonionic salicylic acid and found 0.248 +/- 0.032 cm/s for S2 and 0.176 +/- 0.022 cm/s for S3 tubules. These calculated permeabilities were independent of pH

Emissions in potassium vapour under 4S1/2-7S1/2 two-photon nsec excitation

International Nuclear Information System (INIS)

Pentaris, D.; Chatzikyriakos, G.; Armyras, A.; Efthimiopoulos, T.

2010-01-01

The two-photon excitation of 4S 1/2 -7S 1/2 transition of potassium atoms is studied. Several coherent emissions and processes are possible, such as parametric four-wave (PFWM), parametric six-wave (PSWM) mixing and competition with the stimulated hyper Raman (SHRS) and the amplified spontaneous emission (ASE). The radiations at the transitions 6P 3/2,1/2 -4S 1/2 , 6S 1/2 -4P 3/2,1/2 and 5P 3/2,1/2 -4S 1/2 are emitted only in the forward direction (indicating a parametric process), while the radiation at the transition 4P 3/2,1/2 -4S 1/2 is emitted in the forward and in the backward direction, indicating an ASE process.

Modeling the emission of the galactic very high energy γ-ray sources G 1.9+0.3, G 330.2+1.0, HESS J1303-631 and PSR B1259-63/LS 2883 observed with H.E.S.S

International Nuclear Information System (INIS)

Sushch, Iurii

2012-01-01

was modeled within a one-zone 1D stationary model yielding a magnetic field of 1.4 ± 0.2 μG and a total energy in electrons above 1 GeV of 2 x 10 48 erg. This estimate of the magnetic field is of the same magnitude as the averaged line-of-sight magnetic field of ∝2 μG provided by the measurement of the pulsar's rotation measure. A magnetic field in a PWN much lower than the averaged ISM magnetic field would be difficult to explain. A low magnetic field is also expected for evolved PWNe for which the magnetic field is believed to have decreased with time. The obtained total energy in electrons yields an estimate for the pulsar birth period between 51 and 75 ms, which is in good agreement with estimations of birth periods for pulsars associated with composite SNRs. Possible extensions of the modeling towards more realistic scenarios which would take into account the time evolution and spatial distribution of the source emission are also discussed. The binary system PSR B1259-63/LS 2883 is the only TeV binary for which the compact companion is unambiguously identified as a pulsar. It consists of a 48 ms pulsar orbiting around a massive Be star. PSR B1259-63/LS 2883 was monitored by H.E.S.S. around the periastron passage on 15th of December 2010. The source was observed by H.E.S.S. in the period from 26 to 32 days after the periastron passage. A firm detection of the source was obtained. The observed flux F(>1 TeV)=(1.61±0.22 stat ±0.32 syst ) x 10 -12 cm -2 s -1 and spectral index Γ=2.82 ±0.25 stat ±0.2 syst are in good agreement with results obtained during previous periastron passages. The observations were performed at similar orbital phases as around the 2004 periastron, for the first time directly confirming the repetitive behavior of the source at VHEs. H.E.S.S. observations were part of a joint multiwavelength (MWL) campaign including also radio, optical, X-ray and, for the first time, high energy (HE; E >100 MeV) observations. Fermi LAT detected a

Sphingosine 1-phosphate (S1P) induces COX-2 expression and PGE2 formation via S1P receptor 2 in renal mesangial cells.

Science.gov (United States)

Völzke, Anja; Koch, Alexander; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

2014-01-01

Understanding the mechanisms of sphingosine 1-phosphate (S1P)-induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) formation in renal mesangial cells may provide potential therapeutic targets to treat inflammatory glomerular diseases. Thus, we evaluated the S1P-dependent signaling mechanisms which are responsible for enhanced COX-2 expression and PGE2 formation in rat mesangial cells under basal conditions. Furthermore, we investigated whether these mechanisms are operative in the presence of angiotensin II (Ang II) and of the pro-inflammatory cytokine interleukin-1β (IL-1β). Treatment of rat and human mesangial cells with S1P led to concentration-dependent enhanced expression of COX-2. Pharmacological and molecular biology approaches revealed that the S1P-dependent increase of COX-2 mRNA and protein expression was mediated via activation of S1P receptor 2 (S1P2). Further, inhibition of Gi and p42/p44 MAPK signaling, both downstream of S1P2, abolished the S1P-induced COX-2 expression. In addition, S1P/S1P2-dependent upregulation of COX-2 led to significantly elevated PGE2 levels, which were further potentiated in the presence of Ang II and IL-1β. A functional consequence downstream of S1P/S1P2 signaling is mesangial cell migration that is stimulated by S1P. Interestingly, inhibition of COX-2 by celecoxib and SC-236 completely abolished the migratory response. Overall, our results demonstrate that extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. Thus, targeting S1P/S1P2 signaling pathways might be a novel strategy to treat renal inflammatory diseases. © 2013.

Advance in ERG Analysis: From Peak Time and Amplitude to Frequency, Power, and Energy

Directory of Open Access Journals (Sweden)

Mathieu Gauvin

2014-01-01

Full Text Available Purpose. To compare time domain (TD: peak time and amplitude analysis of the human photopic electroretinogram (ERG with measures obtained in the frequency domain (Fourier analysis: FA and in the time-frequency domain (continuous (CWT and discrete (DWT wavelet transforms. Methods. Normal ERGs n=40 were analyzed using traditional peak time and amplitude measurements of the a- and b-waves in the TD and descriptors extracted from FA, CWT, and DWT. Selected descriptors were also compared in their ability to monitor the long-term consequences of disease process. Results. Each method extracted relevant information but had distinct limitations (i.e., temporal and frequency resolutions. The DWT offered the best compromise by allowing us to extract more relevant descriptors of the ERG signal at the cost of lesser temporal and frequency resolutions. Follow-ups of disease progression were more prolonged with the DWT (max 29 years compared to 13 with TD. Conclusions. Standardized time domain analysis of retinal function should be complemented with advanced DWT descriptors of the ERG. This method should allow more sensitive/specific quantifications of ERG responses, facilitate follow-up of disease progression, and identify diagnostically significant changes of ERG waveforms that are not resolved when the analysis is only limited to time domain measurements.

Repeated 1-cm Resolution Topographic and 2.5-mm Resolution Photomosiac Surveys of Benthic Communities and Fine Scale Bedforms in Monterey Canyon

Science.gov (United States)

Caress, D. W.; Hobson, B.; Thomas, H. J.; Henthorn, R.; Martin, E. J.; Bird, L.; Risi, M.; Troni, G.; Paull, C. K.; Rock, S.; Padial, J. A.; Hammond, M. M.

2014-12-01

The Monterey Bay Aquarium Research Institute has developed a low altitude, ROV-based seafloor mapping system that combines lidar laser ranging, multibeam sonar, and stereo photographic imagery. When operated at a 3-m altitude, this system maps seafloor topography with a 1-cm lateral resolution and simultaneously collects 2.5-mm resolution color photography. We have twice mapped an 80-m by 80-m area of a chemosynthetic clam community located at 2850-m depth in the Monterey Canyon axis. Both the topography and the photomosaics resolve changes in the clam community over a six-month interval. Many individual animals have moved, and tracks of those animals are visible in the lidar topography. No other changes in the seafloor at this site can be discerned. We have also performed single surveys of bedforms and scours at both 1850-m and 2850-m depths in Monterey Canyon. The highest resolution bathymetry data are collected using a 3DatDepth SL1 lidar laser scanner. This system has a 30° field of view and ranges continuously, achieving a 1 cm sounding spacing at a 3 m altitude and 0.3 m/s speed. Bathymetry data are also collected using a 400-kHz Reson 7125 multibeam sonar. This configuration produces 512 beams across a 135° wide swath; each beam has a 0.5° acrosstrack by 1.0° alongtrack angular width. At a 3-m altitude, the nadir beams have a 2.5 cm acrosstrack and 5 cm alongtrack footprint. Dual Prosilica GX1920 2.4 Mpixel color cameras provide color stereo photography of the seafloor. Illumination is provided by dual xenon strobes. The camera housings have been fitted with corrective optics achieving a 90° field of view with less than 1% distortion. At a 3-m altitude the raw image pixels have a 2.5 mm resolution. Position and attitude data are provided by a Kearfott SeaDevil Inertial Navigation System (INS) integrated with a 300 kHz Teledyne RD Instruments Doppler velocity log (DVL). A separate Paroscientific pressure sensor is mounted adjacent to the INS. The INS

Expressed prostatic secretion biomarkers improve stratification of NCCN active surveillance candidates: performance of secretion capacity and TMPRSS2:ERG models.

Science.gov (United States)

Whelan, Christopher; Kawachi, Mark; Smith, David D; Linehan, Jennifer; Babilonia, Gail; Mejia, Rosa; Wilson, Timothy; Smith, Steven S

2014-01-01

Active surveillance is a viable patient option for prostate cancer provided that a clinical determination of low risk and presumably organ confined disease can be made. To standardize risk stratification schemes the NCCN (National Comprehensive Cancer Network®) provides guidelines for the active surveillance option. We determined the effectiveness of expressed prostatic secretion biomarkers for detecting occult risk factors in NCCN active surveillance candidates. Expressed prostatic secretion specimens were obtained before robot-assisted radical prostatectomy. Secretion capacity biomarkers, including total RNA and expressed prostatic secretion specimen volume, were measured by standard techniques. RNA expression biomarkers, including TXNRD1 mRNA, prostate specific antigen mRNA, TMPRSS2:ERG fusion mRNA and PCA3 mRNA, were measured by quantitative reverse-transcription polymerase chain reaction. Of the 528 patients from whom expressed prostatic secretions were collected 216 were eligible for active surveillance under NCCN guidelines. Variable selection on logistic regression identified 2 models, including one featuring types III and VI TMPRSS2:ERG variants, and one featuring 2 secretion capacity biomarkers. Of the 2 high performing models the secretion capacity model was most effective for detecting cases in this group that were up-staged or up-staged plus upgraded. It decreased the risk of up-staging in patients with a negative test almost eightfold and decreased the risk of up-staging plus upgrading about fivefold while doubling the prevalence of up-staging in the positive test group. Noninvasive expressed prostatic secretion testing may improve patient acceptance of active surveillance by dramatically reducing the presence of occult risk factors among those eligible for active surveillance under NCCN guidelines. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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Indian Academy of Sciences (India)

IAS Admin

two fields feed one another and a wave propagates. In ... falls rapidly like 1/r2, and no energy is carried to infin- ity. In order for .... culation four times), takes a proper time interval,. AT = Zhao L. .... which is about 10-4 erg cm-2 s-1. In other words ...

ERG review of salt constitutive law, salt stress determinations, and salt corrosion and modeling studies

International Nuclear Information System (INIS)

Balon, J.E.

1986-03-01

The Engineering Review Group (ERG) was established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate engineering-related issues in the US Department of Energy's nuclear waste repository program. The August 1983 meeting of the ERG reviewed a RE/SPEC technical report containing a review of eight constitutive laws that have been proposed to model the creep of salt over the ranges of stress and temperature anticipated in a nuclear repository. This report documents the ERG's comments and recommendations on this subject and the ONWI responses to the specific points raised by the ERG

An Investigation on the He−(1s2s2 2S Resonance in Debye Plasmas

Directory of Open Access Journals (Sweden)

Arijit Ghoshal

2017-01-01

Full Text Available The effect of Debye plasma on the 1 s 2 s 2 2 S resonance states in the scattering of electron from helium atom has been investigated within the framework of the stabilization method. The interactions among the charged particles in Debye plasma have been modelled by Debye–Huckel potential. The 1 s 2 s excited state of the helium atom has been treated as consisting of a H e + ionic core plus an electron moving around. The interaction between the core and the electron has then been modelled by a model potential. It has been found that the background plasma environment significantly affects the resonance states. To the best of our knowledge, such an investigation of 1 s 2 s 2 2 S resonance states of the electron–helium system embedded in Debye plasma environment is the first reported in the literature.

Spectroscopic Signatures for Interlayer Coupling in MoS 2 –WSe 2 van der Waals Stacking

KAUST Repository

Chiu, Ming-Hui; Li, Ming-Yang; Zhang, Wengjing; Hsu, Wei-Ting; Chang, Wen-Hao; Terrones, Mauricio; Terrones, Humberto; Li, Lain-Jong

2014-01-01

Stacking of MoS2 and WSe2 monolayers is conducted by transferring triangular MoS2 monolayers on top of WSe2 monolayers, all grown by chemical vapor deposition (CVD). Raman spectroscopy and photoluminescence (PL) studies reveal that these mechanically stacked monolayers are not closely coupled, but after a thermal treatment at 300 degrees C, it is possible to produce van der Waals solids consisting of two interacting transition metal dichalcogenide (TMD) monolayers. The layer-number sensitive Raman out-of-plane mode A(1g)(2) for WSe2 (309 cm(-1)) is found sensitive to the coupling between two TMD monolayers. The presence of interlayer excitonic emissions and the changes in other intrinsic Raman modes such as E '' for MoS2 at 286 cm(-1) and A(1g)(2) for MoS2 at around 463 cm(-1) confirm the enhancement of the interlayer coupling.

Spectroscopic Signatures for Interlayer Coupling in MoS 2 –WSe 2 van der Waals Stacking

KAUST Repository

Chiu, Ming-Hui

2014-09-23

Stacking of MoS2 and WSe2 monolayers is conducted by transferring triangular MoS2 monolayers on top of WSe2 monolayers, all grown by chemical vapor deposition (CVD). Raman spectroscopy and photoluminescence (PL) studies reveal that these mechanically stacked monolayers are not closely coupled, but after a thermal treatment at 300 degrees C, it is possible to produce van der Waals solids consisting of two interacting transition metal dichalcogenide (TMD) monolayers. The layer-number sensitive Raman out-of-plane mode A(1g)(2) for WSe2 (309 cm(-1)) is found sensitive to the coupling between two TMD monolayers. The presence of interlayer excitonic emissions and the changes in other intrinsic Raman modes such as E \\'\\' for MoS2 at 286 cm(-1) and A(1g)(2) for MoS2 at around 463 cm(-1) confirm the enhancement of the interlayer coupling.

Development of superhigh-strength mortars with compressive strength of 3000kgf/cm sup 2 or higher. 3000kgf/cm sup 2 ijo no asshuku kyodo wo motsu mortar no kaihatsu

Energy Technology Data Exchange (ETDEWEB)

Ohama, Y; Izumura, K [Nihon University, Tokyo (Japan). Collete of Engineering; Hayashi, S [Onoda Cement Co. Ltd., Yamaguchi (Japan)

1991-08-01

This paper discusses the preparation factors and curing conditions of superhigh-strength mortar, and explains a method of manufacturing superhigh-strength mortar having still higher strength and its superhigh strength generating mechanism. A recommended cement material for the superhigh-strength mortar is a Portland cement mixed with a high-purity silica at 20% and silica fume at 20%. This was made to a water-cement material ratio of 15% and fine aggregate cement material ratio of 1.06, cured in an autoclave, and further heat-cured at 200{degree}C for one day to obtain a superhigh-strength mortar. The compression and bending strengths reach 2,200 kgf/cm{sup 2} and 180 kgf/cm{sup 2} respectively when used with silica sand, and 3000 kgf/cm{sup 2} and 220 kgf/cm{sup 2} or more when used with stainless steel grits. The heat curing at 200{degree}C for a day increases remarkably the compression strength of the superhigh-strength mortar regardless of the curing conditions before the heat curing. 7 refs., 11 figs., 1 tab.

TeV γ-ray observations of the young synchrotron-dominated SNRs G1.9+0.3 and G330.2+1.0 with H.E.S.S.

Science.gov (United States)

H.E.S.S. Collaboration; Abramowski, A.; Aharonian, F.; Benkhali, F. Ait; Akhperjanian, A. G.; Angüner, E.; Anton, G.; Balenderan, S.; Balzer, A.; Barnacka, A.; Becherini, Y.; Becker Tjus, J.; Bernlöhr, K.; Birsin, E.; Bissaldi, E.; Biteau, J.; Böttcher, M.; Boisson, C.; Bolmont, J.; Bordas, P.; Brucker, J.; Brun, F.; Brun, P.; Bulik, T.; Carrigan, S.; Casanova, S.; Cerruti, M.; Chadwick, P. M.; Chalme-Calvet, R.; Chaves, R. C. G.; Cheesebrough, A.; Chrétien, M.; Colafrancesco, S.; Cologna, G.; Conrad, J.; Couturier, C.; Cui, Y.; Dalton, M.; Daniel, M. K.; Davids, I. D.; Degrange, B.; Deil, C.; deWilt, P.; Dickinson, H. J.; Djannati-Ataï, A.; Domainko, W.; O'C. Drury, L.; Dubus, G.; Dutson, K.; Dyks, J.; Dyrda, M.; Edwards, T.; Egberts, K.; Eger, P.; Espigat, P.; Farnier, C.; Fegan, S.; Feinstein, F.; Fernandes, M. V.; Fernandez, D.; Fiasson, A.; Fontaine, G.; Förster, A.; Füßling, M.; Gajdus, M.; Gallant, Y. A.; Garrigoux, T.; Giavitto, G.; Giebels, B.; Glicenstein, J. F.; Grondin, M.-H.; Grudzińska, M.; Häffner, S.; Hahn, J.; Harris, J.; Heinzelmann, G.; Henri, G.; Hermann, G.; Hervet, O.; Hillert, A.; Hinton, J. A.; Hofmann, W.; Hofverberg, P.; Holler, M.; Horns, D.; Jacholkowska, A.; Jahn, C.; Jamrozy, M.; Janiak, M.; Jankowsky, F.; Jung, I.; Kastendieck, M. A.; Katarzyński, K.; Katz, U.; Kaufmann, S.; Khélifi, B.; Kieffer, M.; Klepser, S.; Klochkov, D.; Kluźniak, W.; Kneiske, T.; Kolitzus, D.; Komin, Nu.; Kosack, K.; Krakau, S.; Krayzel, F.; Krüger, P. P.; Laffon, H.; Lamanna, G.; Lefaucheur, J.; Lemière, A.; Lemoine-Goumard, M.; Lenain, J.-P.; Lennarz, D.; Lohse, T.; Lopatin, A.; Lu, C.-C.; Marandon, V.; Marcowith, A.; Marx, R.; Maurin, G.; Maxted, N.; Mayer, M.; McComb, T. J. L.; Méhault, J.; Meintjes, P. J.; Menzler, U.; Meyer, M.; Moderski, R.; Mohamed, M.; Moulin, E.; Murach, T.; Naumann, C. L.; de Naurois, M.; Niemiec, J.; Nolan, S. J.; Oakes, L.; Ohm, S.; Wilhelmi, E. de Oña; Opitz, B.; Ostrowski, M.; Oya, I.; Panter, M.; Parsons, R. D.; Arribas, M. Paz; Pekeur, N. W.; Pelletier, G.; Perez, J.; Petrucci, P.-O.; Peyaud, B.; Pita, S.; Poon, H.; Pühlhofer, G.; Punch, M.; Quirrenbach, A.; Raab, S.; Raue, M.; Reimer, A.; Reimer, O.; Renaud, M.; Reyes, R. de los; Rieger, F.; Rob, L.; Romoli, C.; Rosier-Lees, S.; Rowell, G.; Rudak, B.; Rulten, C. B.; Sahakian, V.; Sanchez, D. A.; Santangelo, A.; Schlickeiser, R.; Schüssler, F.; Schulz, A.; Schwanke, U.; Schwarzburg, S.; Schwemmer, S.; Sol, H.; Spengler, G.; Spies, F.; Stawarz, Ł.; Steenkamp, R.; Stegmann, C.; Stinzing, F.; Stycz, K.; Sushch, I.; Szostek, A.; Tavernet, J.-P.; Tavernier, T.; Taylor, A. M.; Terrier, R.; Tluczykont, M.; Trichard, C.; Valerius, K.; van Eldik, C.; van Soelen, B.; Vasileiadis, G.; Venter, C.; Viana, A.; Vincent, P.; Völk, H. J.; Volpe, F.; Vorster, M.; Vuillaume, T.; Wagner, S. J.; Wagner, P.; Ward, M.; Weidinger, M.; Weitzel, Q.; White, R.; Wierzcholska, A.; Willmann, P.; Wörnlein, A.; Wouters, D.; Zabalza, V.; Zacharias, M.; Zajczyk, A.; Zdziarski, A. A.; Zech, A.; Zechlin, H.-S.

2014-06-01

The non-thermal nature of the X-ray emission from the shell-type supernova remnants (SNRs) G1.9+0.3 and G330.2+1.0 is an indication of intense particle acceleration in the shock fronts of both objects. This suggests that the SNRs are prime candidates for very-high-energy (VHE; E > 0.1 TeV) γ-ray observations. G1.9+0.3, recently established as the youngest known SNR in the Galaxy, also offers a unique opportunity to study the earliest stages of SNR evolution in the VHE domain. The purpose of this work is to probe the level of VHE γ-ray emission from both SNRs and use this to constrain their physical properties. Observations were conducted with the H.E.S.S. (High Energy Stereoscopic System) Cherenkov Telescope Array over a more than six-year period spanning 2004-2010. The obtained data have effective livetimes of 67 h for G1.9+0.3 and 16 h for G330.2+1.0. The data are analysed in the context of the multiwavelength observations currently available and in the framework of both leptonic and hadronic particle acceleration scenarios. No significant γ-ray signal from G1.9+0.3 or G330.2+1.0 was detected. Upper limits (99 per cent confidence level) to the TeV flux from G1.9+0.3 and G330.2+1.0 for the assumed spectral index Γ = 2.5 were set at 5.6 × 10-13 cm-2 s-1 above 0.26 TeV and 3.2 × 10-12 cm-2 s-1 above 0.38 TeV, respectively. In a one-zone leptonic scenario, these upper limits imply lower limits on the interior magnetic field to BG1.9 ≳ 12 μG for G1.9+0.3 and to BG330 ≳ 8 μG for G330.2+1.0. In a hadronic scenario, the low ambient densities and the large distances to the SNRs result in very low predicted fluxes, for which the H.E.S.S. upper limits are not constraining.

High potency inhibition of hERG potassium channels by the sodium–calcium exchange inhibitor KB-R7943

Science.gov (United States)

Cheng, Hongwei; Zhang, Yihong; Du, Chunyun; Dempsey, Christopher E; Hancox, Jules C

2012-01-01

BACKGROUND AND PURPOSE KB-R7943 is an isothiourea derivative that is used widely as a pharmacological inhibitor of sodium–calcium exchange (NCX) in experiments on cardiac and other tissue types. This study investigated KB-R7943 inhibition of hERG (human ether-à-go-go-related gene) K+ channels that underpin the cardiac rapid delayed rectifier potassium current, IKr. EXPERIMENTAL APPROACH Whole-cell patch-clamp measurements were made of hERG current (IhERG) carried by wild-type or mutant hERG channels and of native rabbit ventricular IKr. Docking simulations utilized a hERG homology model built on a MthK-based template. KEY RESULTS KB-R7943 inhibited both IhERG and native IKr rapidly on membrane depolarization with IC50 values of ∼89 and ∼120 nM, respectively, for current tails at −40 mV following depolarizing voltage commands to +20 mV. Marked IhERG inhibition also occurred under ventricular action potential voltage clamp. IhERG inhibition by KB-R7943 exhibited both time- and voltage-dependence but showed no preference for inactivated over activated channels. Results of alanine mutagenesis and docking simulations indicate that KB-R7943 can bind to a pocket formed of the side chains of aromatic residues Y652 and F656, with the compound's nitrobenzyl group orientated towards the cytoplasmic side of the channel pore. The structurally related NCX inhibitor SN-6 also inhibited IhERG, but with a markedly reduced potency. CONCLUSIONS AND IMPLICATIONS KB-R7943 inhibits IhERG/IKr with a potency that exceeds that reported previously for acute cardiac NCX inhibition. Our results also support the feasibility of benzyloxyphenyl-containing NCX inhibitors with reduced potential, in comparison with KB-R7943, to inhibit hERG. PMID:21950687

FERMI LARGE AREA TELESCOPE OBSERVATION OF SUPERNOVA REMNANT S147

Energy Technology Data Exchange (ETDEWEB)

Katsuta, J.; Uchiyama, Y.; Tanaka, T.; Tajima, H.; Bechtol, K.; Funk, S.; Lande, J. [W. W. Hansen Experimental Physics Laboratory, Kavli Institute for Particle Astrophysics and Cosmology, Department of Physics and SLAC National Accelerator Laboratory, Stanford University, Stanford, CA 94305 (United States); Ballet, J. [Laboratoire AIM, CEA-IRFU/CNRS/Universite Paris Diderot, Service d' Astrophysique, CEA Saclay, 91191 Gif sur Yvette (France); Hanabata, Y. [Department of Physical Sciences, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8526 (Japan); Lemoine-Goumard, M. [Universite Bordeaux 1, CNRS/IN2p3, Centre d' Etudes Nucleaires de Bordeaux Gradignan, 33175 Gradignan (France); Takahashi, T., E-mail: katsuta@slac.stanford.edu, E-mail: uchiyama@slac.stanford.edu [Institute of Space and Astronautical Science, Japanese Aerospace Exploration Agency, 3-1-1 Yoshinodai, Chuo-ku, Sagamihara, Kanagawa 252-5210 (Japan)

2012-06-20

We present an analysis of gamma-ray data obtained with the Large Area Telescope on board the Fermi Gamma-ray Space Telescope in the region around supernova remnant (SNR) S147 (G180.0-1.7). A spatially extended gamma-ray source detected in an energy range of 0.2-10 GeV is found to coincide with SNR S147. We confirm its spatial extension at >5{sigma} confidence level. The gamma-ray flux is (3.8 {+-} 0.6) Multiplication-Sign 10{sup -8} photons cm{sup -2} s{sup -1}, corresponding to a luminosity of 1.3 Multiplication-Sign 10{sup 34} (d/1.3 kpc){sup 2} erg s{sup -1} in this energy range. The gamma-ray emission exhibits a possible spatial correlation with the prominent H{alpha} filaments of SNR S147. There is no indication that the gamma-ray emission comes from the associated pulsar PSR J0538+2817. The gamma-ray spectrum integrated over the remnant is likely dominated by the decay of neutral {pi} mesons produced through the proton-proton collisions in the filaments. The reacceleration of the pre-existing cosmic rays and subsequent adiabatic compression in the filaments is sufficient to provide the energy density required of high-energy protons.

LIF excitation spectra for S 0 → S 1 transition of deuterated anthranilic acid COOD, ND 2 in supersonic-jet expansion

Science.gov (United States)

Kolek, Przemysław; Leśniewski, Sebastian; Andrzejak, Marcin; Góra, Maciej; Cias, Pawel; Weģrzynowicz, Adam; Najbar, Jan

2010-12-01

Laser induced fluorescence (LIF) excitation spectrum for the S 0 → S 1 transition of anthranilic acid molecules deuterated in the substituent groups (COOD, ND 2) was investigated. Analysis of the LIF spectrum allowed for the assignment of the six most prominent fundamental in-plane modes of frequencies up to ca. 850 cm. The experimental results show good correlation with the frequency changes upon deuteration computed with CIS (CI-Singles) and TD-DFT for the S 1 state. Deuteration induced red-shifts of the identified fundamental bands are used for examination of the alternative assignments proposed in earlier studies. Potential energy distributions (PED) and overlaps of the in-plane normal modes with frequencies below 850 cm indicate that the correspondence of the respective vibrations of the deuterated and non-deuterated molecule is very good. A blue-shift of the 00 transition due to the isotopic substitution, is equal to 47 cm. This relatively large value is caused primarily by a significant decrease of the N-H stretching frequency associated with the increase of strength of the intramolecular hydrogen bond upon the electronic excitation. The deuteration shift of the 00 band was interpreted in terms of the differences of the zero point energy (ZPE) between the S 0 and S 1 electronic states, computed with DFT and TD-DFT methods, respectively.

Investigation of 1-cm dose equivalent for photons behind shielding materials

International Nuclear Information System (INIS)

Hirayama, Hideo; Tanaka, Shun-ichi

1991-03-01

The ambient dose equivalent at 1-cm depth, assumed equivalent to the 1-cm dose equivalent in practical dose estimations behind shielding slabs of water, concrete, iron or lead for normally incident photons having various energies was calculated by using conversion factors for a slab phantom. It was compared with the 1-cm depth dose calculated with the Monte Carlo code EGS4. It was concluded from this comparison that the ambient dose equivalent calculated by using the conversion factors for the ICRU sphere could be used for the evaluation of the 1-cm dose equivalent for the sphere phantom within 20% errors. Average and practical conversion factors are defined as the conversion factors from exposure to ambient dose equivalent in a finite slab or an infinite one, respectively. They were calculated with EGS4 and the discrete ordinates code PALLAS. The exposure calculated with simple estimation procedures such as point kernel methods can be easily converted to ambient dose equivalent by using these conversion factors. The maximum value between 1 and 30 mfp can be adopted as the conversion factor which depends only on material and incident photon energy. This gives the ambient dose equivalent on the safe side. 13 refs., 7 figs., 2 tabs

AlGaN/GaN heterostructures with an AlGaN layer grown directly on reactive-ion-etched GaN showing a high electron mobility (>1300 cm2 V-1 s-1)

Science.gov (United States)

Yamamoto, Akio; Makino, Shinya; Kanatani, Keito; Kuzuhara, Masaaki

2018-04-01

In this study, the metal-organic-vapor-phase-epitaxial growth behavior and electrical properties of AlGaN/GaN structures prepared by the growth of an AlGaN layer on a reactive-ion-etched (RIE) GaN surface without regrown GaN layers were investigated. The annealing of RIE-GaN surfaces in NH3 + H2 atmosphere, employed immediately before AlGaN growth, was a key process in obtaining a clean GaN surface for AlGaN growth, that is, in obtaining an electron mobility as high as 1350 cm2 V-1 s-1 in a fabricated AlGaN/RIE-GaN structure. High-electron-mobility transistors (HEMTs) were successfully fabricated with AlGaN/RIE-GaN wafers. With decreasing density of dotlike defects observed on the surfaces of AlGaN/RIE-GaN wafers, both two-dimensional electron gas properties of AlGaN/RIE-GaN structures and DC characteristics of HEMTs were markedly improved. Since dotlike defect density was markedly dependent on RIE lot, rather than on growth lot, surface contaminations of GaN during RIE were believed to be responsible for the formation of dotlike defects and, therefore, for the inferior electrical properties.

Ionization rates and harmonic generation for H interacting with laser pulses of λ = 1064 nm and peak intensities in the range 2 x 1013-2 x 1014 W cm-2

International Nuclear Information System (INIS)

Dionissopoulou, S.; Mercouris, Th.; Nicolaides, C.A.

1996-01-01

We applied the state-specific expansion approach (SSEA) to the solution of the time-dependent Schroedinger equation describing the interaction of H with laser pulses of λ = 1064 nm and peak intensities I 0 = 2 x 10 13 , 6 x 10 13 , 1 x 10 14 and 2 x 10 14 W cm -2 , and computed ionization rates and high-order harmonic spectra. For the first three cases, our results are compared with those of Krause and co-workers (Krause J L, Schafer K J and Kulander K C 1992 Phys. Rev. A45 3998) who employed the grid method. Whereas for I 0 = 1 x 10 14 W cm -2 convergence difficulties were reported for the grid method, no such difficulties were found for the SSEA. Given this fact, we tackled the problem of computing the harmonic spectrum for I 0 = 2 x 10 14 W cm -2 . This spectrum shows a cut-off at the 65th harmonic (3.17 U p + I p ) and an extended plateau containing low-intensity harmonics up to the 181st. The ionization rate is 1.7 x 10 13 s -1 while at the end of the pulse 19.5% of the system is in the 1s ground state and 2.6% in the bound states up to n = 20, l 19. (author)

ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation

DEFF Research Database (Denmark)

Knudsen, Kasper Jermiin; Rehn, Matilda Carolina; Hasemann, Marie Sigurd

2015-01-01

The balance between self-renewal and differentiation is crucial for the maintenance of hematopoietic stem cells (HSCs). Whereas numerous gene regulatory factors have been shown to control HSC self-renewal or drive their differentiation, we have relatively few insights into transcription factors...... and functional HSCs. Molecularly, we could demonstrate that ERG, in addition to promoting the expression of HSC self-renewal genes, also represses a group of MYC targets, thereby explaining why Erg loss closely mimics Myc overexpression. Consistently, the BET domain inhibitor CPI-203, known to repress Myc...... expression, confers a partial phenotypic rescue. In summary, ERG plays a critical role in coordinating the balance between self-renewal and differentiation of HSCs....

Absolute measurements of fluxes from Cassiopeia A, Cygnus A, Taurus A, Virgo A at seven wavelengths in the 1.8-4.2 cm band

International Nuclear Information System (INIS)

Dmitrenko, L.V.; Snegireva, V.V.; Turchin, V.I.; Tsejtlin, N.M.; Voronkov, L.A.; Dmitrenko, D.A.; Kuznetsova, N.A.; Kholodilov, N.N.

1981-01-01

Results of absolute measurements of fluxes from Cassiopeia A, Cygnus A, Taurus A, Virgo A at 1.8-4.17 cm wavelengths are presented. Spectra are built in the wave range of 1.8-100 cm with the use of results obtained earlier. Variability has been detected in radiation of Taurus A as well as ''steps'' in the spectrum of Taurus A with the spectral index α=0 in the region of 2 cm and 3-4 cm [ru

ERG [Engineering Review Group] review of the SRP [Salt Repository Project] salt irradiation effects program: Technical report

International Nuclear Information System (INIS)

Clark, D.E.

1986-11-01

The Engineering Review Group (ERG) was established by the Office of Nuclear Waste Isolation (ONWI) to help evaluate engineering-related issues in the US Department of Energy's nuclear waste repository program. The August 1985 meeting of the ERG reviewed the Salt Repository Project (SRP) salt irradiation effects program. This report documents the ERG's comments and recommendations on these subjects and the ONWI response to the specific points raised by the ERG

Leveraging the NLM map from SNOMED CT to ICD-10-CM to facilitate adoption of ICD-10-CM.

Science.gov (United States)

Cartagena, F Phil; Schaeffer, Molly; Rifai, Dorothy; Doroshenko, Victoria; Goldberg, Howard S

2015-05-01

Develop and test web services to retrieve and identify the most precise ICD-10-CM code(s) for a given clinical encounter. Facilitate creation of user interfaces that 1) provide an initial shortlist of candidate codes, ideally visible on a single screen; and 2) enable code refinement. To satisfy our high-level use cases, the analysis and design process involved reviewing available maps and crosswalks, designing the rule adjudication framework, determining necessary metadata, retrieving related codes, and iteratively improving the code refinement algorithm. The Partners ICD-10-CM Search and Mapping Services (PI-10 Services) are SOAP web services written using Microsoft's.NET 4.0 Framework, Windows Communications Framework, and SQL Server 2012. The services cover 96% of the Partners problem list subset of SNOMED CT codes that map to ICD-10-CM codes and can return up to 76% of the 69,823 billable ICD-10-CM codes prior to creation of custom mapping rules. We consider ways to increase 1) the coverage ratio of the Partners problem list subset of SNOMED CT codes and 2) the upper bound of returnable ICD-10-CM codes by creating custom mapping rules. Future work will investigate the utility of the transitive closure of SNOMED CT codes and other methods to assist in custom rule creation and, ultimately, to provide more complete coverage of ICD-10-CM codes. ICD-10-CM will be easier for clinicians to manage if applications display short lists of candidate codes from which clinicians can subsequently select a code for further refinement. The PI-10 Services support ICD-10 migration by implementing this paradigm and enabling users to consistently and accurately find the best ICD-10-CM code(s) without translation from ICD-9-CM. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Complexation of Cm(III) and Eu(III) with 2,6-bis(5-(2,2-dimethylpropyl)-1H-pyrazol-3-yl)pyridine and 2-bromohexanoic acid studied by time-resolved laser fluorescence spectroscopy

International Nuclear Information System (INIS)

Bremer, A.; Panak, P.J.; Heidelberg Univ.; Geist, A.

2013-01-01

The complexation of Cm(III) and Eu(III) with 2,6-bis(5-(2,2-dimethylpropyl)-1H-pyrazol-3-yl)pyridine (C5-BPP) and 2-bromohexanoic acid as lipophilic anion has been investigated by time-resolved laser fluorescence spectroscopy. Upon increasing ligand concentration three different Cm(III)-C5-BPP species with emission bands at 604.1 nm, 607.9 nm and 611.4 nm, respectively, are found and attributed to complexes with one, two and three C5-BPP molecules in the inner coordination sphere. Comparison with results of TRLFS experiments without 2-bromohexanoic acid shows that the C5-BPP ligand is able to completely displace the lipophilic anion from the inner coordination sphere, forming [Cm(C5-BPP) 3 ] 3+ complexes. This complex is also found in the organic phase of an extraction experiment performed with Cm(III), demonstrating that the lipophilic anion required for the extraction is not directly coordinated to the metal ion in the species formed during extraction. In case of Eu(III) the number of different species formed cannot be determined accurately. Nevertheless, the formation of the complex [EU(C5-BPP) 3 ] 3+ in the presence of 2-bromohexanoic acid is confirmed. (orig.)

The Stacked LYα Emission Profile from the Circum-Galactic Medium of z ˜ 2 Quasars

Science.gov (United States)

Arrigoni Battaia, Fabrizio; Hennawi, Joseph F.; Cantalupo, Sebastiano; Prochaska, J. Xavier

2016-09-01

In the context of the FLASHLIGHT survey, we obtained deep narrowband images of 15 z ˜ 2 quasars with the Gemini Multi-object Spectrograph on Gemini South in an effort to measure Lyα emission from circum- and intergalactic gas on scales of hundreds of kpc from the central quasar. We do not detect bright giant Lyα nebulae (SB ˜ 10-17 erg s-1 cm-2 arcsec-2 at distances >50 kpc) around any of our sources, although we routinely (≃47%) detect smaller-scale Tecnologia e Inovação (Brazil), and Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina).

CM-2 Environmental/Modal Testing of SPACEHAB Racks

Science.gov (United States)

McNelis, Mark E.; Goodnight, Thomas W.

2001-01-01

Combined environmental/modal vibration testing has been implemented at the NASA Glenn Research Center's Structural Dynamics Laboratory. The benefits of combined vibration testing are that it facilitates test article modal characterization and vibration qualification testing. The Combustion Module-2 (CM-2) is a space experiment that will launch on shuttle mission STS-107 in the SPACEHAB Research Double Module. The CM-2 flight hardware is integrated into a SPACEHAB single and double rack. CM-2 rack-level combined vibration testing was recently completed on a shaker table to characterize the structure's modal response and verify the random vibration response. Control accelerometers and limit force gauges, located between the fixture and rack interface, were used to verify the input excitation. Results of the testing were used to verify the loads and environments for flight on the shuttles.

S = -1 and S = -2 few-body hypernuclei

International Nuclear Information System (INIS)

Gibson, B.F.

1997-01-01

The S = -1 and S = -2 few-body bound states are the focus of this discussion. Implications for the understanding of the baryon-baryon interaction are examined. Octet-octet coupling effects not found in conventional, non-strange nuclei are highlighted. TJNAF wave function tests for the S = -1 sector are noted. The need to identify S = -2 hypernuclei to explore the S = -2 strong interaction and to test model predictions is emphasized

Computational analysis of the effects of the hERG channel opener NS1643 in a human ventricular cell model

DEFF Research Database (Denmark)