Efficient coupling of Sec23-Sec24 to Sec13-Sec31 drives COPII-dependent collagen secretion and is essential for normal craniofacial development.

Science.gov (United States)

Townley, Anna K; Feng, Yi; Schmidt, Katy; Carter, Deborah A; Porter, Robert; Verkade, Paul; Stephens, David J

2008-09-15

The COPII coat assembles on endoplasmic reticulum membranes to coordinate the collection of secretory cargo with the formation of transport vesicles. During COPII assembly, Sar1 deforms the membrane and recruits the Sec23-Sec24 complex (Sec23/24), which is the primary cargo-binding adaptor for the system, and Sec13-Sec31 (Sec13/31), which provides a structural outer layer for vesicle formation. Here we show that Sec13 depletion results in concomitant loss of Sec31 and juxtanuclear clustering of pre-budding complexes containing Sec23/24 and cargo. Electron microscopy reveals the presence of curved coated profiles on distended endoplasmic reticulum, indicating that Sec13/31 is not required for the generation or maintenance of the curvature. Surprisingly, export of tsO45-G-YFP, a marker of secretory cargo, is unaffected by Sec13/31 depletion; by contrast, secretion of collagen from primary fibroblasts is strongly inhibited. Suppression of Sec13 expression in zebrafish causes defects in proteoglycan deposition and skeletal abnormalities that are grossly similar to the craniofacial abnormalities of crusher mutant zebrafish and patients with cranio-lenticulo-sutural dysplasia. We conclude that efficient coupling of the inner (Sec23/24) and outer (Sec13/31) layers of the COPII coat is required to drive the export of collagen from the endoplasmic reticulum, and that highly efficient COPII assembly is essential for normal craniofacial development during embryogenesis.

Contrast between the mechanisms for dissociative electron attachment to CH3SCN and CH3NCS

Science.gov (United States)

Miller, Thomas M.; Viggiano, Albert A.; Shuman, Nicholas S.

2018-05-01

The kinetics of thermal electron attachment to methyl thiocyanate (CH3SCN), methyl isothiocyanate (CH3NCS), and ethyl thiocyanate (C2H5SCN) were measured using flowing afterglow-Langmuir probe apparatuses at temperatures between 300 and 1000 K. CH3SCN and C2H5SCN undergo inefficient dissociative attachment to yield primarily SCN- at 300 K (k = 2 × 10-10 cm3 s-1), with increasing efficiency as temperature increases. The increase is well described by activation energies of 0.17 eV (CH3SCN) and 0.14 eV (C2H5SCN). CN- product is formed at product but at a rate at 300 K that is below our detection threshold (k differentiating the two mechanisms. The kinetic modeling reproduces the CH3NCS data only if dissociation through the transient anion is considered.

Atom-transfer radical polymerization of methyl methacrylate (MMA) using CuSCN as the catalyst

NARCIS (Netherlands)

Singha, N.K.; Klumperman, B.

2000-01-01

The effect of CuSCN as a catalyst in atom-transfer radical polymerization (ATRP) was investigated. CuSCN can successfully be used for the ATRP of MMA. Substituted bipyridines as well as imines can be used to stabilize the copper complex in solution. CuSCN induces faster polymerization compared to

VeloUT tracking for the LHCb Upgrade

CERN Document Server

Bowen, E

2014-01-01

This note describes track reconstruction in the LHCb tracking system upstream of the magnet, namely the VELO and UT sub-detectors. The implementation of the VeloUT algorithm and its performance in terms of track reconstruction efficiency, ghost rate and execution time per event are presented. The algorithm has been optimised for use in the Upgrade software trigger of LHCb. The momentum information obtained for the VeloUT tracks (due to a fringe magnetic field between the VELO and UT sub-detectors) can reduce the total execution time per event for the full tracking sequence. The performance of the tracking sequence with and without the use of VeloUT tracks is also presented.

Reduction of the thermal conductivity of the thermoelectric material ScN by Nb alloying

DEFF Research Database (Denmark)

Tureson, Nina; Van Nong, Ngo; Fournier, Daniele

2017-01-01

) orientation. The crystal structure, morphology, thermal conductivity, and thermoelectric and electrical properties were investigated. The ScN reference film exhibited a Seebeck coefficient of −45 μV/K and a power factor of 6 × 10−4 W/m K2 at 750 K. Estimated from room temperature Hall measurements, all...... samples exhibit a high carrier density of the order of 1021 cm−3. Inclusion of heavy transition metals into ScN enables the reduction in thermal conductivity by an increase in phonon scattering. The Nb inserted ScN thin films exhibited a thermal conductivity lower than the value of the ScN reference (10.......5 W m−1 K−1) down to a minimum value of 2.2 Wm−1 K−1. Insertion of Nb into ScN thus resulted in a reduction in thermal conductivity by a factor of ∼5 due to the mass contrast in ScN, which increases the phonon scattering in the material....

Ntal/Lab/Lat2

DEFF Research Database (Denmark)

Iwaki, Shoko; Jensen, Bettina M; Gilfillan, Alasdair M

2007-01-01

T cells. As demonstrated in monocytes and B cells, phosphorylated NTAL/LAB/LAT2 recruits signaling molecules such as Grb2, Gab1 and c-Cbl into receptor-signaling complexes. Although gene knock out and knock down studies have indicated that NTAL/LAB/LAT2 may function as both a positive and negative...

Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death

DEFF Research Database (Denmark)

Bezzina, Connie; Barc, Julien; Mizusawa, Yuka

2013-01-01

Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A mutations in around 20% of cases. Through a genome-wide association study of 312 individuals with Brugada syndrome and 1,115 controls, we detected 2 significant association signals at the SCN10A locus (rs10428132) a...

Investigation of UT procedure for crack depth sizing by phased array UT in Ni-based alloy weld

International Nuclear Information System (INIS)

Hirasawa, Taiji; Fukutomi, Hiroyuki

2013-01-01

Recently, it has been reported that the primary water stress corrosion cracking (PWSCC) has occurred in nickel based alloy weld components such as steam generator safe end weld, reactor vessel safe end weld, and so on, in PWR. Defect detection and sizing are important in order to ensure the reliable operation and life extension of nuclear power plants. In the reactor vessel safe end weld, it was impossible to measure crack depth of PWSCC. The cracks have occurred in the axial direction of the safe end weld. Furthermore, the cracks had some features such as deep, large aspect ratio (ratio of crack depth and length), sharp geometry of crack tip, and so on. Therefore, development and improvement of defect depth sizing capabilities by ultrasonic testing (UT) have been required. Phased array UT technique was applied with regard to defect depth sizing at the inside inspection in Ni-based alloy welds. Phased array UT was examined a standard block specimen with side drilled holes (SDHs). From the experimental results, the performance of linear array probes and dual matrix array probe were investigated. In the basis of the results, UT procedure for defect depth sizing was investigated and proposed. The UT procedure was applied to the defect depth measurement in Ni-based alloy weld specimen with electric discharge machine (EDM) notches. From these results, good accuracy of defect depth sizing by phased array UT for the inside inspection was shown. Therefore, it was clarified the effectiveness of the UT procedure for defect depth sizing in Ni-based alloy weld. (author)

Common and rare variants in SCN10A modulate the risk of atrial fibrillation

DEFF Research Database (Denmark)

Jabbari, Javad; Olesen, Morten S; Yuan, Lei

2015-01-01

BACKGROUND: Genome-wide association studies have shown that the common single nucleotide polymorphism rs6800541 located in SCN10A, encoding the voltage-gated Nav1.8 sodium channel, is associated with PR-interval prolongation and atrial fibrillation (AF). Single nucleotide polymorphism rs6800541...... is in high linkage disequilibrium with the nonsynonymous variant in SCN10A, rs6795970 (V1073A, r(2)=0.933). We therefore sought to determine whether common and rare SCN10A variants are associated with early onset AF. METHODS AND RESULTS: SCN10A was sequenced in 225 AF patients in whom there was no evidence...... of other cardiovascular disease or dysfunction (lone AF). In an association study of the rs6795970 single nucleotide polymorphism variant, we included 515 AF patients and 2 control cohorts of 730 individuals free of AF and 6161 randomly sampled individuals. Functional characterization of SCN10A variants...

Autosomal dominant SCN8A mutation with an unusually mild phenotype.

Science.gov (United States)

Anand, G; Collett-White, F; Orsini, A; Thomas, S; Jayapal, S; Trump, N; Zaiwalla, Z; Jayawant, S

2016-09-01

Mutations in SCN8A, coding for the voltage-gated sodium channel Nav 1.6, have been described in relation to infantile onset epilepsy with developmental delay and cognitive impairment, in particular early onset epileptic encephalopathy (EIEE) type 13. Here we report an infant and his father with early onset focal epileptic seizures but without cognitive or neurological impairment in whom next generation sequence analysis identified a heterozygous mutation (c.5630A > G, p. (Asn1877Ser)) in the SCN8A gene. This mutation, confirmed by Sanger sequence analysis, affects a highly conserved amino acid and in silico tools predicts that it may be pathogenic. The reported infant has a normal developmental profile at 16-month follow-up. His father also had normal development and has no cognitive impairment at 42 years. This is the second known SCN8A mutation associated with a phenotype of benign familial infantile epilepsy. Good seizure control was achieved in our patients with sodium channel blockers. Based on our proband and a recently described group of families with benign familial infantile epilepsy and SCN8A variant we suggest expanding testing to patients with infantile epilepsy and no cognitive impairment. In addition, the same SCN8A variant (c.5630A > G, p. (Asn1877Ser)) is also found in patients with epilepsy and developmental delay highlighting the phenotypic variability and the possible role of other protective genetic factors. Copyright © 2016. Published by Elsevier Ltd.

Facile synthesis of silver/silver thiocyanate (Ag@AgSCN plasmonic nanostructures with enhanced photocatalytic performance

Directory of Open Access Journals (Sweden)

Xinfu Zhao

2017-12-01

Full Text Available A nanostructured plasmonic photocatalyst, silver/silver thiocyanate (Ag@AgSCN, has been prepared by a simple precipitation method followed by UV-light-induced reduction. The ratio of Ag to silver thiocyanate (AgSCN can be controlled by simply adjusting the photo-induced reduction time. The formation mechanism of the product was investigated based on the time-dependent experiments. Further experiments indicated that the prepared Ag@AgSCN nanostructures with an atomic ratio of Ag/AgSCN = 0.0463 exhibited high photocatalytic activity and long-term stability for the degradation of oxytetracycline (84% under visible-light irradiation. In addition to the microstructure and high specific surface area, the enhanced photocatalytic activity was mainly caused by the surface plasmon resonance of Ag nanoparticles, and the high stability of AgSCN resulted in the long-term stability of the photocatalyst product.

The Regulatory Factor ZFHX3 Modifies Circadian Function in SCN via an AT Motif-Driven Axis

Science.gov (United States)

Parsons, Michael J.; Brancaccio, Marco; Sethi, Siddharth; Maywood, Elizabeth S.; Satija, Rahul; Edwards, Jessica K.; Jagannath, Aarti; Couch, Yvonne; Finelli, Mattéa J.; Smyllie, Nicola J.; Esapa, Christopher; Butler, Rachel; Barnard, Alun R.; Chesham, Johanna E.; Saito, Shoko; Joynson, Greg; Wells, Sara; Foster, Russell G.; Oliver, Peter L.; Simon, Michelle M.; Mallon, Ann-Marie; Hastings, Michael H.; Nolan, Patrick M.

2015-01-01

Summary We identified a dominant missense mutation in the SCN transcription factor Zfhx3, termed short circuit (Zfhx3Sci), which accelerates circadian locomotor rhythms in mice. ZFHX3 regulates transcription via direct interaction with predicted AT motifs in target genes. The mutant protein has a decreased ability to activate consensus AT motifs in vitro. Using RNA sequencing, we found minimal effects on core clock genes in Zfhx3Sci/+ SCN, whereas the expression of neuropeptides critical for SCN intercellular signaling was significantly disturbed. Moreover, mutant ZFHX3 had a decreased ability to activate AT motifs in the promoters of these neuropeptide genes. Lentiviral transduction of SCN slices showed that the ZFHX3-mediated activation of AT motifs is circadian, with decreased amplitude and robustness of these oscillations in Zfhx3Sci/+ SCN slices. In conclusion, by cloning Zfhx3Sci, we have uncovered a circadian transcriptional axis that determines the period and robustness of behavioral and SCN molecular rhythms. PMID:26232227

Perovskite solar cells with CuSCN hole extraction layers yield stabilized efficiencies greater than 20%

Science.gov (United States)

Arora, Neha; Dar, M. Ibrahim; Hinderhofer, Alexander; Pellet, Norman; Schreiber, Frank; Zakeeruddin, Shaik Mohammed; Grätzel, Michael

2017-11-01

Perovskite solar cells (PSCs) with efficiencies greater than 20% have been realized only with expensive organic hole-transporting materials. We demonstrate PSCs that achieve stabilized efficiencies exceeding 20% with copper(I) thiocyanate (CuSCN) as the hole extraction layer. A fast solvent removal method enabled the creation of compact, highly conformal CuSCN layers that facilitate rapid carrier extraction and collection. The PSCs showed high thermal stability under long-term heating, although their operational stability was poor. This instability originated from potential-induced degradation of the CuSCN/Au contact. The addition of a conductive reduced graphene oxide spacer layer between CuSCN and gold allowed PSCs to retain >95% of their initial efficiency after aging at a maximum power point for 1000 hours under full solar intensity at 60°C. Under both continuous full-sun illumination and thermal stress, CuSCN-based devices surpassed the stability of spiro-OMeTAD-based PSCs.

Cloning and expression of a zebrafish SCN1B ortholog and identification of a species-specific splice variant

Directory of Open Access Journals (Sweden)

Slat Emily A

2007-07-01

Full Text Available Abstract Background Voltage-gated Na+ channel β1 (Scn1b subunits are multi-functional proteins that play roles in current modulation, channel cell surface expression, cell adhesion, cell migration, and neurite outgrowth. We have shown previously that β1 modulates electrical excitability in vivo using a mouse model. Scn1b null mice exhibit spontaneous seizures and ataxia, slowed action potential conduction, decreased numbers of nodes of Ranvier in myelinated axons, alterations in nodal architecture, and differences in Na+ channel α subunit localization. The early death of these mice at postnatal day 19, however, make them a challenging model system to study. As a first step toward development of an alternative model to investigate the physiological roles of β1 subunits in vivo we cloned two β1-like subunit cDNAs from D. rerio. Results Two β1-like subunit mRNAs from zebrafish, scn1ba_tv1 and scn1ba_tv2, arise from alternative splicing of scn1ba. The deduced amino acid sequences of Scn1ba_tv1 and Scn1ba_tv2 are identical except for their C-terminal domains. The C-terminus of Scn1ba_tv1 contains a tyrosine residue similar to that found to be critical for ankyrin association and Na+ channel modulation in mammalian β1. In contrast, Scn1ba_tv2 contains a unique, species-specific C-terminal domain that does not contain a tyrosine. Immunohistochemical analysis shows that, while the expression patterns of Scn1ba_tv1 and Scn1ba_tv2 overlap in some areas of the brain, retina, spinal cord, and skeletal muscle, only Scn1ba_tv1 is expressed in optic nerve where its staining pattern suggests nodal expression. Both scn1ba splice forms modulate Na+ currents expressed by zebrafish scn8aa, resulting in shifts in channel gating mode, increased current amplitude, negative shifts in the voltage dependence of current activation and inactivation, and increases in the rate of recovery from inactivation, similar to the function of mammalian β1 subunits. In

The large first periplasmic loop of SecD and SecF plays an important role in SecDF functioning

NARCIS (Netherlands)

Nouwen, N; Piwowarek, M; Berrelkamp, G; Driessen, AJM

A remarkable feature of proteins of the SecD and SecF family involved in protein translocation is that they possess a very large first periplasmic domain. Here we report that this large first periplasmic domain is not required for the SecD-SecF interaction but that it is important for catalyzing

Large-scale structural alteration of brain in epileptic children with SCN1A mutation.

Science.gov (United States)

Lee, Yun-Jeong; Yum, Mi-Sun; Kim, Min-Jee; Shim, Woo-Hyun; Yoon, Hee Mang; Yoo, Il Han; Lee, Jiwon; Lim, Byung Chan; Kim, Ki Joong; Ko, Tae-Sung

2017-01-01

Mutations in SCN1A gene encoding the alpha 1 subunit of the voltage gated sodium channel are associated with several epilepsy syndromes including genetic epilepsy with febrile seizures plus (GEFS +) and severe myoclonic epilepsy of infancy (SMEI). However, in most patients with SCN1A mutation, brain imaging has reported normal or non-specific findings including cerebral or cerebellar atrophy. The aim of this study was to investigate differences in brain morphometry in epileptic children with SCN1A mutation compared to healthy control subjects. We obtained cortical morphology (thickness, and surface area) and brain volume (global, subcortical, and regional) measurements using FreeSurfer (version 5.3.0, https://surfer.nmr.mgh.harvard.edu) and compared measurements of children with epilepsy and SCN1A gene mutation ( n  = 21) with those of age and gender matched healthy controls ( n  = 42). Compared to the healthy control group, children with epilepsy and SCN1A gene mutation exhibited smaller total brain, total gray matter and white matter, cerebellar white matter, and subcortical volumes, as well as mean surface area and mean cortical thickness. A regional analysis revealed significantly reduced gray matter volume in the patient group in the bilateral inferior parietal, left lateral orbitofrontal, left precentral, right postcentral, right isthmus cingulate, right middle temporal area with smaller surface area and white matter volume in some of these areas. However, the regional cortical thickness was not significantly different in two groups. This study showed large-scale developmental brain changes in patients with epilepsy and SCN1A gene mutation, which may be associated with the core symptoms of the patients. Further longitudinal MRI studies with larger cohorts are required to confirm the effect of SCN1A gene mutation on structural brain development.

Thienoquinolins exert diuresis by strongly inhibiting UT-A urea transporters

Science.gov (United States)

Ren, Huiwen; Wang, Yanhua; Xing, Yongning; Ran, Jianhua; Liu, Ming; Lei, Tianluo; Zhou, Hong; Li, Runtao; Sands, Jeff M.

2014-01-01

Urea transporters (UT) play an important role in the urine concentration mechanism by mediating intrarenal urea recycling, suggesting that UT inhibitors could have therapeutic use as a novel class of diuretic. Recently, we found a thienoquinolin UT inhibitor, PU-14, that exhibited diuretic activity. The purpose of this study was to identify more potent UT inhibitors that strongly inhibit UT-A isoforms in the inner medullary collecting duct (IMCD). Efficient thienoquinolin UT inhibitors were identified by structure-activity relationship analysis. Urea transport inhibition activity was assayed in perfused rat terminal IMCDs. Diuretic activity of the compound was determined in rats and mice using metabolic cages. The results show that the compound PU-48 exhibited potent UT-A inhibition activity. The inhibition was 69.5% with an IC50 of 0.32 μM. PU-48 significantly inhibited urea transport in perfused rat terminal IMCDs. PU-48 caused significant diuresis in UT-B null mice, which indicates that UT-A is the target of PU-48. The diuresis caused by PU-48 did not change blood Na+, K+, or Cl− levels or nonurea solute excretion in rats and mice. No toxicity was detected in cells or animals treated with PU-48. The results indicate that thienoquinolin UT inhibitors induce a diuresis by inhibiting UT-A in the IMCD. This suggests that they may have the potential to be developed as a novel class of diuretics with fewer side effects than classical diuretics. PMID:25298523

The GLAST Mission, LAT and GRBs

International Nuclear Information System (INIS)

Omodei, Nicola; INFN, Pisa

2006-01-01

The GLAST Large Area Telescope (LAT) is the next generation satellite experiment for high-energy gamma-ray astronomy. It is a pair conversion telescope built with a plastic anticoincidence shield, a segmented CsI electromagnetic calorimeter, and the largest silicon strip tracker ever built. It will cover the energy range from 30 MeV to 300 GeV, shedding light on many issues left open by its predecessor EGRET. One of the most exciting science topics is the detection and observation of gamma-ray bursts (GRBs). In this paper we present the work done so far by the GRB LAT science group in studying the performance of the LAT detector to observe GRBs.We report on the simulation framework developed by the group as well as on the science tools dedicated to GRBs data analysis. We present the LAT sensitivity to GRBs obtained with such simulations, and, finally, the general scheme of GRBs detection that will be adopted on orbit

Tuberculose du col utérin simulant un cancer du col utérin : à propos ...

African Journals Online (AJOL)

Tuberculose du col utérin simulant un cancer du col utérin : à propos d'un cas, au Centre Hospitalier Universitaire Souro Sanou de Bobo-Dioulasso, Burkina Faso. A. Dembélé, V. Konségré, E. Birba, D.A. Somé, H. Zamané, A.S. Ouédraogo, S. Kiemtoré, S. Ouattara, A. Lamien-Sanou, M. Bambara, B. Bonané/Thiéba ...

Mutations in sodium channel {beta}-subunit SCN3B are associated with early-onset lone atrial fibrillation

DEFF Research Database (Denmark)

Olesen, Morten Salling; Jespersen, Thomas; Nielsen, Jonas Bille

2011-01-01

AIMS: Atrial fibrillation (AF) is the most frequent arrhythmia. Screening of SCN5A-the gene encoding the a-subunit of the cardiac sodium channel-has indicated that disturbances of the sodium current may play a central role in the mechanism of lone AF. We tested the hypothesis that lone AF in young...... across species. Electrophysiological studies on the SCN3B mutation were carried out and all three SCN3B mutations caused a functionally reduced sodium channel current. One synonymous variant was found in SCN4B. CONCLUSION: In 192 young lone AF patients, we found three patients with suspected disease...

Electronic structure and physical properties of ScN in pressure: density-functional theory calculations

International Nuclear Information System (INIS)

Guan Pengfei; Wang Chongyu; Yu Tao

2008-01-01

Local density functional is investigated by using the full-potential linearized augmented plane wave (FP-LAPW) method for ScN in the hexagonal structure and the rocksalt structure and for hexagonal structures linking a layered hexagonal phase with wurtzite structure along a homogeneous strain transition path. It is found that the wurtzite ScN is unstable and the layered hexagonal phase, labelled as h o , in which atoms are approximately fivefold coordinated, is metastable, and the rocksalt ScN is stable. The electronic structure, the physical properties of the intermediate structures and the energy band structure along the transition are presented. It is found that the band gaps change from 4.0 to 1.0 eV continuously when c/a value varies from 1.68 to 1.26. It is noticeable that the study of ScN provides an opportunity to apply this kind of material (in wurtzite[h]-derived phase). (condensed matter: electronic structure, electrical, magnetic, and optical properties)

Resonance Raman Spectrum of the Transient (SCN)2 Free Radical Anion

DEFF Research Database (Denmark)

Wilbrandt, Robert Walter; Jensen, N. H.; Pagsberg, Palle Bjørn

1979-01-01

The resonance Raman spectrum of the transient species (λmax = 475 nm, τ½ = 1.6 μs) formed by pulse radiolysis of aqueous solutions of thiocyanate, SCN2−, is reported. The spectrum is discussed in terms of the previous assignment of this transient to the radical anion, (SCN)−2. The observed...... vibrational frequencies of the radical anion are consistent with substantial weakening of the S---S and the Ctriple bond; length as m-dashN bonds are compared with neutral thiocyanogen....

A case of recurrent encephalopathy with SCN2A missense mutation.

Science.gov (United States)

Fukasawa, Tatsuya; Kubota, Tetsuo; Negoro, Tamiko; Saitoh, Makiko; Mizuguchi, Masashi; Ihara, Yukiko; Ishii, Atsushi; Hirose, Shinichi

2015-06-01

Voltage-gated sodium channels regulate neuronal excitability, as well as survival and the patterning of neuronal connectivity during development. Mutations in SCN2A, which encodes the Na(+) channel Nav1.2, cause epilepsy syndromes and predispose children to acute encephalopathy. Here, we report the case of a young male with recurrent acute encephalopathy who carried a novel missense mutation in the SCN2A gene. He was born by normal delivery and developed repetitive apneic episodes at 2days of age. Diffusion-weighted imaging revealed high-intensity areas in diffuse subcortical white matter, bilateral thalami, and basal nuclei. His symptoms improved gradually without any specific treatment, but he exhibited a motor milestone delay after the episode. At the age of 10months, he developed acute cerebellopathy associated with a respiratory syncytial viral infection. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy and seemed to have no obvious sequelae after the episode. He then developed severe diffuse encephalopathy associated with gastroenteritis at the age of 14months. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy but was left with severe neurological sequelae. PCR-based analysis revealed a novel de novo missense mutation, c.4979T>G (p.Leu1660Trp), in the SCN2A gene. This case suggests that SCN2A mutations might predispose children to repetitive encephalopathy with variable clinical and imaging findings. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Large-scale structural alteration of brain in epileptic children with SCN1A mutation

Directory of Open Access Journals (Sweden)

Yun-Jeong Lee

2017-01-01

Significance: This study showed large-scale developmental brain changes in patients with epilepsy and SCN1A gene mutation, which may be associated with the core symptoms of the patients. Further longitudinal MRI studies with larger cohorts are required to confirm the effect of SCN1A gene mutation on structural brain development.

Unified Medical Language System Terminology Services (UTS) API

Data.gov (United States)

U.S. Department of Health & Human Services — The UTS API is intended for application developers to perform Web service calls and retrieve UMLS data within their own applications. The UTS API provides the...

Why do intimate partners live apart? Evidence on LAT relationships across Europe

Directory of Open Access Journals (Sweden)

Aart C. Liefbroer

2015-01-01

Full Text Available Background: Most research asks whether or not cohabitation has come to rival marriage. Little is known about the meaning of living apart together (LAT relationships, and whether LAT is an alternative to marriage and cohabitation or a dating relationship. Objective: We examine across Europe: (1 the prevalence of LAT, (2 the reasons for LAT, and (3 the correlates of (a LAT relationships vis-à-vis being single, married, or cohabiting, and (b different types of LAT union. Methods: Using Generations and Gender Survey data from ten Western and Eastern European countries, we present descriptive statistics about LATs and estimate multinominal logistic regression models to assess the correlates of being in different types of LAT unions. Results: LAT relationships are uncommon, but they are more common in Western than Eastern Europe. Most people in LAT unions intend to live together but are apart for practical reasons. LAT is more common among young people, those enrolled in higher education, people with liberal attitudes, highly educated people, and those who have previously cohabited or been married. Older people and divorced or widowed persons are more likely to choose LAT to maintain independence. Surprisingly, attitudinal and educational differences are more pronounced in Eastern Europe than in Western Europe. Conclusions: A tentative conclusion is that LAT is more often a stage in the union formation process than an alternative to marriage and cohabitation. Yet some groups do view LAT as substituting for marriage and cohabitation, and these groups differ between East and West. In Eastern Europe a cultural, highly educated elite seems to be the first to resist traditional marriage norms and embrace LAT (and cohabitation as alternative living arrangements, whereas this is less the case in Western Europe. In Western Europe, LAT unions are mainly an alternative for persons who have been married before or had children in a prior relationship.

Computerized UT system for stud bolt

International Nuclear Information System (INIS)

Kisanuki, T.; Uchida, K.; Fushimi, T.; Onda, K.

1988-01-01

Cracking of stud bolts used in steam turbine casing, valve and pressure vessel has caused concern regarding the safety and reliability of power plants. In order to detect harmful cracks in early state, the improvement of UT technique is required. As regarding the ultrasonic inspection technique, a longitudinal beam technique and/or an angle beam technique are generally used. The authors report their development of a computerized UT system for bolt inspection and improvement of the angle beam technique

Differential roles of AVP and VIP signaling in the postnatal changes of neural networks for coherent circadian rhythms in the SCN

Science.gov (United States)

Ono, Daisuke; Honma, Sato; Honma, Ken-ichi

2016-01-01

The suprachiasmatic nucleus (SCN) is the site of the master circadian clock in mammals. The SCN neural network plays a critical role in expressing the tissue-level circadian rhythm. Previously, we demonstrated postnatal changes in the SCN network in mice, in which the clock gene products CRYPTOCHROMES (CRYs) are involved. Here, we show that vasoactive intestinal polypeptide (VIP) signaling is essential for the tissue-level circadian PER2::LUC rhythm in the neonatal SCN of CRY double-deficient mice (Cry1,2−/−). VIP and arginine vasopressin (AVP) signaling showed redundancy in expressing the tissue-level circadian rhythm in the SCN. AVP synthesis was significantly attenuated in the Cry1,2−/− SCN, which contributes to aperiodicity in the adult mice together with an attenuation of VIP signaling as a natural process of ontogeny. The SCN network consists of multiple clusters of cellular circadian rhythms that are differentially integrated by AVP and VIP signaling, depending on the postnatal period. PMID:27626074

Oncogenicity of L-type amino-acid transporter 1 (LAT1) revealed by targeted gene disruption in chicken DT40 cells: LAT1 is a promising molecular target for human cancer therapy

Energy Technology Data Exchange (ETDEWEB)

Ohkawa, Mayumi [Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba-ku, Sendai 980-8578 (Japan); Ohno, Yoshiya [Laboratory of Immunobiology, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe-shi, Hyogo 650-8530 (Japan); Masuko, Kazue; Takeuchi, Akiko; Suda, Kentaro; Kubo, Akihiro; Kawahara, Rieko; Okazaki, Shogo [Cell Biology Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, Kinki University, 4-1 Kowakae 3-chome, Higashiosaka-shi, Osaka 577-8502 (Japan); Tanaka, Toshiyuki [Laboratory of Immunobiology, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe-shi, Hyogo 650-8530 (Japan); Saya, Hideyuki [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8502 (Japan); Seki, Masayuki; Enomoto, Takemi [Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba-ku, Sendai 980-8578 (Japan); Yagi, Hideki [Cell Biology Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, Kinki University, 4-1 Kowakae 3-chome, Higashiosaka-shi, Osaka 577-8502 (Japan); Hashimoto, Yoshiyuki [Tohoku University, Sendai (Japan); Masuko, Takashi, E-mail: masuko@phar.kindai.ac.jp [Cell Biology Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, Kinki University, 4-1 Kowakae 3-chome, Higashiosaka-shi, Osaka 577-8502 (Japan)

2011-03-25

Highlights: {yields} We established LAT1 amino-acid transporter-disrupted DT40 cells. {yields} LAT1-disrupted cells showed slow growth and lost the oncogenicity. {yields} siRNA and mAb inhibited human tumor growth in vitro and in vivo. {yields} LAT1 is a promising target molecule for cancer therapy. -- Abstract: L-type amino-acid transporter 1 (LAT1) is the first identified light chain of CD98 molecule, disulfide-linked to a heavy chain of CD98. Following cDNA cloning of chicken full-length LAT1, we have constructed targeting vectors for the disruption of chicken LAT1 gene from genomic DNA of chicken LAT1 consisting of 5.4 kb. We established five homozygous LAT1-disrupted (LAT1{sup -/-}) cell clones, derived from a heterozygous LAT1{sup +/-} clone of DT40 chicken B cell line. Reactivity of anti-chicken CD98hc monoclonal antibody (mAb) with LAT1{sup -/-} DT40 cells was markedly decreased compared with that of wild-type DT40 cells. All LAT1{sup -/-} cells were deficient in L-type amino-acid transporting activity, although alternative-splice variant but not full-length mRNA of LAT1 was detected in these cells. LAT1{sup -/-} DT40 clones showed outstandingly slow growth in liquid culture and decreased colony-formation capacity in soft agar compared with wild-type DT40 cells. Cell-cycle analyses indicated that LAT1{sup -/-} DT40 clones have prolonged cell-cycle phases compared with wild-type or LAT1{sup +/-} DT40 cells. Knockdown of human LAT1 by small interfering RNAs resulted in marked in vitro cell-growth inhibition of human cancer cells, and in vivo tumor growth of HeLa cells in athymic mice was significantly inhibited by anti-human LAT1 mAb. All these results indicate essential roles of LAT1 in the cell proliferation and occurrence of malignant phenotypes and that LAT1 is a promising candidate as a molecular target of human cancer therapy.

Oncogenicity of L-type amino-acid transporter 1 (LAT1) revealed by targeted gene disruption in chicken DT40 cells: LAT1 is a promising molecular target for human cancer therapy

International Nuclear Information System (INIS)

Ohkawa, Mayumi; Ohno, Yoshiya; Masuko, Kazue; Takeuchi, Akiko; Suda, Kentaro; Kubo, Akihiro; Kawahara, Rieko; Okazaki, Shogo; Tanaka, Toshiyuki; Saya, Hideyuki; Seki, Masayuki; Enomoto, Takemi; Yagi, Hideki; Hashimoto, Yoshiyuki; Masuko, Takashi

2011-01-01

Highlights: → We established LAT1 amino-acid transporter-disrupted DT40 cells. → LAT1-disrupted cells showed slow growth and lost the oncogenicity. → siRNA and mAb inhibited human tumor growth in vitro and in vivo. → LAT1 is a promising target molecule for cancer therapy. -- Abstract: L-type amino-acid transporter 1 (LAT1) is the first identified light chain of CD98 molecule, disulfide-linked to a heavy chain of CD98. Following cDNA cloning of chicken full-length LAT1, we have constructed targeting vectors for the disruption of chicken LAT1 gene from genomic DNA of chicken LAT1 consisting of 5.4 kb. We established five homozygous LAT1-disrupted (LAT1 -/- ) cell clones, derived from a heterozygous LAT1 +/- clone of DT40 chicken B cell line. Reactivity of anti-chicken CD98hc monoclonal antibody (mAb) with LAT1 -/- DT40 cells was markedly decreased compared with that of wild-type DT40 cells. All LAT1 -/- cells were deficient in L-type amino-acid transporting activity, although alternative-splice variant but not full-length mRNA of LAT1 was detected in these cells. LAT1 -/- DT40 clones showed outstandingly slow growth in liquid culture and decreased colony-formation capacity in soft agar compared with wild-type DT40 cells. Cell-cycle analyses indicated that LAT1 -/- DT40 clones have prolonged cell-cycle phases compared with wild-type or LAT1 +/- DT40 cells. Knockdown of human LAT1 by small interfering RNAs resulted in marked in vitro cell-growth inhibition of human cancer cells, and in vivo tumor growth of HeLa cells in athymic mice was significantly inhibited by anti-human LAT1 mAb. All these results indicate essential roles of LAT1 in the cell proliferation and occurrence of malignant phenotypes and that LAT1 is a promising candidate as a molecular target of human cancer therapy.

Public List of LAT-Detected Gamma-Ray Pulsars

Data.gov (United States)

National Aeronautics and Space Administration — The following is a compilation of all publicly-announced gamma-ray pulsars detected using the Fermi LAT. Each of the detections has been vetted by the LAT team,...

Development of Field-Controlled Smart Optic Materials (ScN, AlN) with Rare Earth Dopants

Science.gov (United States)

Kim, Hyun-Jung; Park, Yeonjoon; King, Glen C.; Choi, Sang H.

2012-01-01

The purpose of this investigation is to develop the fundamental materials and fabrication technology for field-controlled spectrally active optics that are essential for industry, NASA, and DOD applications such as: membrane optics, filters for LIDARs, windows for sensors, telescopes, spectroscopes, cameras, flat-panel displays, etc. ScN and AlN thin films were fabricated on c-axis Sapphire (0001) or quartz substrate with the RF and DC magnetron sputtering. The crystal structure of AlN in fcc (rocksalt) and hcp (wurtzite) were controlled. Advanced electrical characterizations were performed, including I-V and Hall Effect Measurement. ScN film has a free carrier density of 5.8 x 10(exp 20)/per cubic centimeter and a conductivity of 1.1 x 10(exp 3) per centimeter. The background ntype conductivity of as-grown ScN has enough free electrons that can readily interact with the photons. The high density of free electrons and relatively low mobility indicate that these films contain a high level of shallow donors as well as deep levels. Also, the UV-Vis spectrum of ScN and AlN thin films with rare earth elements (Er or Ho) were measured at room temperature. Their optical band gaps were estimated to be about 2.33eV and 2.24eV, respectively, which are obviously smaller than that of undoped thin film ScN (2.4eV). The red-shifted absorption onset gives direct evidence for the decrease of band gap (Eg) and the energy broadening of valence band states are attributable to the doping. As the doped elements enter the ScN crystal lattices, the localized band edge states form at the doped sites with a reduction of Eg. Using a variable angle spectroscopic ellipsometer, the decrease in refractive index with applied field is observed with a smaller shift in absorption coefficient.

Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome.

Directory of Open Access Journals (Sweden)

Anna Ka-Yee Kwong

Full Text Available BACKGROUND: Dravet syndrome is a severe form of epilepsy. Majority of patients have a mutation in SCN1A gene, which encodes a voltage-gated sodium channel. A recent study has demonstrated that 16% of SCN1A-negative patients have a mutation in PCDH19, the gene encoding protocadherin-19. Mutations in other genes account for only a very small proportion of families. TSPYL4 is a novel candidate gene within the locus 6q16.3-q22.31 identified by linkage study. OBJECTIVE: The present study examined the mutations in epileptic Chinese children with emphasis on Dravet syndrome. METHODS: A hundred children with severe epilepsy were divided into Dravet syndrome and non-Dravet syndrome groups and screened for SCN1A mutations by direct sequencing. SCN1A-negative Dravet syndrome patients and patients with phenotypes resembling Dravet syndrome were checked for PCDH19 and TSPYL4 mutations. RESULTS: Eighteen patients (9 males, 9 females were diagnosed to have Dravet syndrome. Among them, 83% (15/18 had SCN1A mutations including truncating (7, splice site (2 and missense mutations (6. The truncating/splice site mutations were associated with moderate to severe degree of intellectual disability (p<0.05. During the progression of disease, 73% (11/15 had features fitting into the diagnostic criteria of autism spectrum disorder and 53% (8/15 had history of vaccination-induced seizures. A novel PCDH19 p.D377N mutation was identified in one SCN1A-negative female patient with Dravet syndrome and a known PCDH19 p.N340S mutation in a female non-Dravet syndrome patient. The former also inherited a TSPYL4 p.G60R variant. CONCLUSION: A high percentage of SCN1A mutations was identified in our Chinese cohort of Dravet syndrome patients but none in the rest of patients. We demonstrated that truncating/splice site mutations were linked to moderate to severe intellectual disability in these patients. A de novo PCDH19 missense mutation together with an inherited TSPYL4 missense

Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes

DEFF Research Database (Denmark)

Lal, Dennis; Reinthaler, Eva M; Dejanovic, Borislav

2016-01-01

OBJECTIVE: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are...

Fermi-LAT Gamma-ray Bursts and Insight from Swift

Science.gov (United States)

Racusin, Judith L.

2011-01-01

A new revolution in GRB observation and theory has begun over the last 3 years since the launch of the Fermi gamma-ray space telescope. The new window into high energy gamma-rays opened by the Fermi-LAT is providing insight into prompt emission mechanisms and possibly also afterglow physics. The LAT detected GRBs appear to be a new unique subset of extremely energetic and bright bursts. In this talk I will discuss the context and recent discoveries from these LAT GRBs and the large database of broadband observations collected by Swift over the last 7 years and how through comparisons between the Swift, GBM, and LAT GRB samples, we can learn about the unique characteristics and relationships between each population.

THE FIRST FERMI-LAT GAMMA-RAY BURST CATALOG

Energy Technology Data Exchange (ETDEWEB)

Ackermann, M. [Deutsches Elektronen Synchrotron DESY, D-15738 Zeuthen (Germany); Ajello, M. [Space Sciences Laboratory, 7 Gauss Way, University of California, Berkeley, CA 94720-7450 (United States); Asano, K. [Interactive Research Center of Science, Tokyo Institute of Technology, Meguro City, Tokyo 152-8551 (Japan); Axelsson, M. [Department of Astronomy, Stockholm University, SE-106 91 Stockholm (Sweden); Baldini, L. [Università di Pisa and Istituto Nazionale di Fisica Nucleare, Sezione di Pisa I-56127 Pisa (Italy); Ballet, J. [Laboratoire AIM, CEA-IRFU/CNRS/Université Paris Diderot, Service d' Astrophysique, CEA Saclay, 91191 Gif sur Yvette (France); Barbiellini, G. [Istituto Nazionale di Fisica Nucleare, Sezione di Trieste, I-34127 Trieste (Italy); Bastieri, D. [Istituto Nazionale di Fisica Nucleare, Sezione di Padova, I-35131 Padova (Italy); Bechtol, K.; Bloom, E. D. [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); Bellazzini, R.; Bregeon, J. [Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, I-56127 Pisa (Italy); Bhat, P. N. [Center for Space Plasma and Aeronomic Research (CSPAR), University of Alabama in Huntsville, Huntsville, AL 35899 (United States); Bissaldi, E. [Institut für Astro- und Teilchenphysik and Institut für Theoretische Physik, Leopold-Franzens-Universität Innsbruck, A-6020 Innsbruck (Austria); Bonamente, E. [Istituto Nazionale di Fisica Nucleare, Sezione di Perugia, I-06123 Perugia (Italy); Bonnell, J.; Brandt, T. J. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Bouvier, A., E-mail: nicola.omodei@stanford.edu, E-mail: giacomov@slac.stanford.edu [Santa Cruz Institute for Particle Physics, Department of Physics and Department of Astronomy and Astrophysics, University of California at Santa Cruz, Santa Cruz, CA 95064 (United States); and others

2013-11-01

In three years of observations since the beginning of nominal science operations in 2008 August, the Large Area Telescope (LAT) on board the Fermi Gamma-Ray Space Telescope has observed high-energy (∼> 20 MeV) γ-ray emission from 35 gamma-ray bursts (GRBs). Among these, 28 GRBs have been detected above 100 MeV and 7 GRBs above ∼20 MeV. The first Fermi-LAT catalog of GRBs is a compilation of these detections and provides a systematic study of high-energy emission from GRBs for the first time. To generate the catalog, we examined 733 GRBs detected by the Gamma-Ray Burst Monitor (GBM) on Fermi and processed each of them using the same analysis sequence. Details of the methodology followed by the LAT collaboration for the GRB analysis are provided. We summarize the temporal and spectral properties of the LAT-detected GRBs. We also discuss characteristics of LAT-detected emission such as its delayed onset and longer duration compared with emission detected by the GBM, its power-law temporal decay at late times, and the fact that it is dominated by a power-law spectral component that appears in addition to the usual Band model.

The First FERMI-LAT Gamma-Ray Burst Catalog

Science.gov (United States)

Ackermann, M.; Ajello, M.; Asano, K.; Axelsson, M.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bechtol, K.; Bellazzini, R.;

THE FIRST FERMI-LAT GAMMA-RAY BURST CATALOG

International Nuclear Information System (INIS)

Ackermann, M.; Ajello, M.; Asano, K.; Axelsson, M.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bechtol, K.; Bloom, E. D.; Bellazzini, R.; Bregeon, J.; Bhat, P. N.; Bissaldi, E.; Bonamente, E.; Bonnell, J.; Brandt, T. J.; Bouvier, A.

2013-01-01

In three years of observations since the beginning of nominal science operations in 2008 August, the Large Area Telescope (LAT) on board the Fermi Gamma-Ray Space Telescope has observed high-energy (∼> 20 MeV) γ-ray emission from 35 gamma-ray bursts (GRBs). Among these, 28 GRBs have been detected above 100 MeV and 7 GRBs above ∼20 MeV. The first Fermi-LAT catalog of GRBs is a compilation of these detections and provides a systematic study of high-energy emission from GRBs for the first time. To generate the catalog, we examined 733 GRBs detected by the Gamma-Ray Burst Monitor (GBM) on Fermi and processed each of them using the same analysis sequence. Details of the methodology followed by the LAT collaboration for the GRB analysis are provided. We summarize the temporal and spectral properties of the LAT-detected GRBs. We also discuss characteristics of LAT-detected emission such as its delayed onset and longer duration compared with emission detected by the GBM, its power-law temporal decay at late times, and the fact that it is dominated by a power-law spectral component that appears in addition to the usual Band model

Development of 68Ga-SCN-DOTA-Capsaicin as an Imaging Agent Targeting Apoptosis and Cell Cycle Arrest in Breast Cancer.

Science.gov (United States)

Lee, Jun Young; Lee, Sang-Yeun; Kim, Gun Gyun; Hur, Min Goo; Yang, Seung Dae; Park, Jeong-Hoon; Kim, Sang Wook

2017-06-01

68 Ga-labeled capsaicin using a DOTA (1,4,7,10-tetraazocyclododecane-N,N',N″,N'″-tetraacetic acid) derivative [ 68 Ga-SCN-Benzyl(Bn)-DOTA-capsaicin] was studied for the diagnosis of breast cancers, such as MCF-7 and SK-BR-3. The standard compound, 69 Ga-SCN-Bn-DOTA-capsaicin, was also prepared and characterized by spectroscopic analysis. The binding affinity of 68 Ga-SCN-Bn-DOTA-capsaicin was evaluated by using breast cancer cell lines (MCF-7, SK-BR-3) and colon cancer cell (CT-26); the biodistribution was carried out by using MCF-7-bearing nude mice, after which the positron emission tomography (PET) images were obtained at different time intervals (15-120 minutes). 68 Ga-SCN-Bn-DOTA-capsaicin showed a cellular uptake of 0.93% Injected Dose (ID) after 30 minutes of incubation, whereas 68 Ga-SCN-Bn-DOTA showed a lower uptake of 0.25% ID. The tumor-to-blood ID/g% ratios increased and were found to be 0.49, 0.22, and 0.77 for 15, 30, and 60 minutes, respectively. The small-animal PET study showed that the uptake of 68 Ga-SCN-Bn-DOTA-capsaicin was higher in the tumor regions even at 30 minutes after injection. These results suggest that 68 Ga-SCN-Bn-DOTA-capsaicin is a potential targeting agent for PET imaging of MCF-7.

76 FR 13084 - Establishment of Area Navigation (RNAV) Routes; Western United States

Science.gov (United States)

2011-03-10

... Francisco/Oakland, CA, Terminal area by providing additional parallel departure routings and improve arrival....) * * * * * * * Q-128 LIN to MEM [New] LIN VORTAC (Lat. 38[deg]04[min]29[sec] N., long. 121[deg]00[min]14[sec] W...] W.) * * * * * * * Q-130 LIN to PNH [New] LIN VORTAC (Lat. 38[deg]04[min]29[sec] N., long. 121[deg]00...

Formation of scandium nitride (ScN) layer on gallium arsenide (GaAs) substrate using a combined technique of e-beam evaporator and ammonia annealing treatment

Energy Technology Data Exchange (ETDEWEB)

Yong Shee Meng, Alvin [Institute of Nano Optoelectronics Research and Technology (INOR), sains@usm, Persiaran Bukit Jambul, 11900 Bayan Lepas, Penang (Malaysia); Zainal, Norzaini, E-mail: norzaini@usm.my [Nano Optoelectronics Research and Laboratory, Universiti Sains Malaysia, sains@usm, Persiaran Bukit Jambul, 11900, Bayan Lepas, Penang (Malaysia); Hassan, Zainuriah; Ibrahim, Kamarulazizi [Institute of Nano Optoelectronics Research and Technology (INOR), sains@usm, Persiaran Bukit Jambul, 11900 Bayan Lepas, Penang (Malaysia)

2015-12-30

Graphical abstract: - Highlights: • Forming ScN layer using electron e-beam evaporator with successive NH{sub 3} annealing thermal has been successfully demonstrated. • NH{sub 3} annealing played the role in changing the grain structure of the ScN layer. • The existence of Sc−N bonds was confirmed by XPS measurement. • The 900 °C annealed ScN layer showed the best structural and optical characteristics. • ScN layer annealed at 980 °C exhibited poor structural and optical characteristics. - Abstract: A demonstration on a new technique of growing ScN using electron beam (e-beam) evaporator, coupled with successive ammonia (NH{sub 3}) annealing treatment is presented in this paper. The annealing temperature was varied at 750, 800, 850, 900 and 980 °C in order to obtain the best ScN layer. It was found that as the annealing temperature increased, the surface morphology of the ScN layer changed and ScN grains formed abundantly on the surface. The best surface of ScN layer was found in the 900 °C annealed sample. However, the roughness of the ScN increased with temperature. The photoluminescence (PL) peak of the near-to-band-edge (NBE) of ScN was observable in all samples and its intensity was the highest in the 900 °C annealed sample. Note that when the annealing treatment was conducted at 980 °C, the GaN PL peak is observable. Raman peaks of TO(X) of ScN were much evident at the annealing temperature above 900 °C. The formation of Sc−N bonds was confirmed by X-ray spectroscopy (XPS) measurement. In the end of this work, we propose that the formation of ScN using the above techniques was successful, with thermal annealing at the temperature of 900 °C.

Formation of scandium nitride (ScN) layer on gallium arsenide (GaAs) substrate using a combined technique of e-beam evaporator and ammonia annealing treatment

International Nuclear Information System (INIS)

Yong Shee Meng, Alvin; Zainal, Norzaini; Hassan, Zainuriah; Ibrahim, Kamarulazizi

2015-01-01

Graphical abstract: - Highlights: • Forming ScN layer using electron e-beam evaporator with successive NH_3 annealing thermal has been successfully demonstrated. • NH_3 annealing played the role in changing the grain structure of the ScN layer. • The existence of Sc−N bonds was confirmed by XPS measurement. • The 900 °C annealed ScN layer showed the best structural and optical characteristics. • ScN layer annealed at 980 °C exhibited poor structural and optical characteristics. - Abstract: A demonstration on a new technique of growing ScN using electron beam (e-beam) evaporator, coupled with successive ammonia (NH_3) annealing treatment is presented in this paper. The annealing temperature was varied at 750, 800, 850, 900 and 980 °C in order to obtain the best ScN layer. It was found that as the annealing temperature increased, the surface morphology of the ScN layer changed and ScN grains formed abundantly on the surface. The best surface of ScN layer was found in the 900 °C annealed sample. However, the roughness of the ScN increased with temperature. The photoluminescence (PL) peak of the near-to-band-edge (NBE) of ScN was observable in all samples and its intensity was the highest in the 900 °C annealed sample. Note that when the annealing treatment was conducted at 980 °C, the GaN PL peak is observable. Raman peaks of TO(X) of ScN were much evident at the annealing temperature above 900 °C. The formation of Sc−N bonds was confirmed by X-ray spectroscopy (XPS) measurement. In the end of this work, we propose that the formation of ScN using the above techniques was successful, with thermal annealing at the temperature of 900 °C.

Large-scale structural alteration of brain in epileptic children with SCN1A mutation

OpenAIRE

Lee, Yun-Jeong; Yum, Mi-Sun; Kim, Min-Jee; Shim, Woo-Hyun; Yoon, Hee Mang; Yoo, Il Han; Lee, Jiwon; Lim, Byung Chan; Kim, Ki Joong; Ko, Tae-Sung

2017-01-01

Objective: Mutations in SCN1A gene encoding the alpha 1 subunit of the voltage gated sodium channel are associated with several epilepsy syndromes including genetic epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). However, in most patients with SCN1A mutation, brain imaging has reported normal or non-specific findings including cerebral or cerebellar atrophy. The aim of this study was to investigate differences in brain morphometry in epileptic chil...

Development of high-performance phased-array UT system 'DYNARAY' and its application examples

International Nuclear Information System (INIS)

Ehara, Eiji

2011-01-01

This article outlined the history leading to develop high-performance phased-array (PA) UT system called DYNARAY, with up to 256 phased-array active channels and maximum 4096 focal laws, lowering the inspection time. As examples it was applied to in-service inspection of reactor pressure vessel welded joints using module of PA-UT probe or eddy-current probe, inspection of seal welds of dry storage containers using scanner of PA-UT, crack detection of end ring of generators using PA-UT probe and UT inspection of cast austenitic stainless steel using 500 kHz probe. Advanced data acquisition and analysis functions for PA-UT system had been developed. (T. Tanaka)

SCN1A, ABCC2 and UGT2B7 gene polymorphisms in association with individualized oxcarbazepine therapy.

Science.gov (United States)

Ma, Chun-Lai; Wu, Xun-Yi; Jiao, Zheng; Hong, Zhen; Wu, Zhi-Yuan; Zhong, Ming-Kang

2015-01-01

Associations between the effects of SCN1A, SCN2A, ABCC2 and UGT2B7 genetic polymorphisms and oxcarbazepine (OXC) maintenance doses in Han Chinese epileptic patients were investigated. Genetic polymorphisms were detected in 184 epileptic patients receiving OXC monotherapy by high-resolution melting curve and TaqMan method. Carriers of the SCN1A IVS5-91G>A, UGT2B7 c.802T>C and ABCC2 c.1249G>A variant alleles required significantly higher OXC maintenance doses than noncarriers (p GA > AA. SCN1A, UGT2B7 and ABCC2 genetic polymorphisms are associated with OXC maintenance doses and may be useful for the personalization of OXC therapy in epileptic patients. Further studies are needed. Original submitted 6 June 2014; Revision submitted 5 September 2014.

Two alternative binding mechanisms connect the protein translocation Sec71-Sec72 complex with heat shock proteins

Energy Technology Data Exchange (ETDEWEB)

Tripathi, Arati; Mandon, Elisabet C.; Gilmore, Reid; Rapoport, Tom A. (UMASS, MED); (Harvard-Med)

2017-03-12

The biosynthesis of many eukaryotic proteins requires accurate targeting to and translocation across the endoplasmic reticulum membrane. Post-translational protein translocation in yeast requires both the Sec61 translocation channel, and a complex of four additional proteins: Sec63, Sec62, Sec71, and Sec72. The structure and function of these proteins are largely unknown. This pathway also requires the cytosolic Hsp70 protein Ssa1, but whether Ssa1 associates with the translocation machinery to target protein substrates to the membrane is unclear. Here, we use a combined structural and biochemical approach to explore the role of Sec71-Sec72 subcomplex in post-translational protein translocation. To this end, we report a crystal structure of the Sec71-Sec72 complex, which revealed that Sec72 contains a tetratricopeptide repeat (TPR) domain that is anchored to the endoplasmic reticulum membrane by Sec71. We also determined the crystal structure of this TPR domain with a C-terminal peptide derived from Ssa1, which suggests how Sec72 interacts with full-length Ssa1. Surprisingly, Ssb1, a cytoplasmic Hsp70 that binds ribosome-associated nascent polypeptide chains, also binds to the TPR domain of Sec72, even though it lacks the TPR-binding C-terminal residues of Ssa1. We demonstrate that Ssb1 binds through its ATPase domain to the TPR domain, an interaction that leads to inhibition of nucleotide exchange. Taken together, our results suggest that translocation substrates can be recruited to the Sec71-Sec72 complex either post-translationally through Ssa1 or co-translationally through Ssb1.

Measurement and correlation of vapour pressures of pyridine and thiophene with [EMIM][SCN] ionic liquid

International Nuclear Information System (INIS)

Khelassi-Sefaoui, Asma; Mutelet, Fabrice; Mokbel, Ilham; Jose, Jacques; Negadi, Latifa

2014-01-01

Highlights: • VLE of (pyridine + [EMIM][SCN]), or (thiophene + [EMIM][SCN]) binary mixtures were measured. • The investigated temperatures are 273 K to 363 K. • The PC-SAFT equation of state has been used to correlate the vapour pressures of the binary systems. - Abstract: In this work (vapour + liquid) equilibrium (VLE) measurements were performed on binary systems of the ionic liquid 1-ethyl-3-methylimidazolium thiocynate [EMIM][SCN] with thiophene or pyridine at pressures close to the atmospheric pressure using a static device at temperatures between 273 K and 363 K. Experimental data were correlated by the PC-SAFT EoS. The binary interaction parameters k ij were optimised on experimental VLE data. The results obtained for the two binary mixtures studied in this paper indicate that the PC-SAFT EoS can be used to represent systems containing ionic liquids

LAT1 acts as a crucial transporter of amino acids in human thymic carcinoma cells

Directory of Open Access Journals (Sweden)

Keitaro Hayashi

2016-11-01

Full Text Available L-type amino acid transporter 1 (LAT1, SLC7A5 incorporates essential amino acids into cells. Recent studies have shown that LAT1 is a predominant transporter in various human cancers. However, the function of LAT1 in thymic carcinoma remains unknown. Here we demonstrate that LAT1 is a critical transporter for human thymic carcinoma cells. LAT1 was strongly expressed in human thymic carcinoma tissues. LAT1-specific inhibitor significantly suppressed leucine uptake and growth of Ty82 human thymic carcinoma cell lines, suggesting that thymic carcinoma takes advantage of LAT1 as a quality transporter and that LAT1-specific inhibitor might be clinically beneficial in therapy for thymic carcinoma.

Thermoelectric properties of epitaxial ScN films deposited by reactive magnetron sputtering onto MgO(001) substrates

Science.gov (United States)

Burmistrova, Polina V.; Maassen, Jesse; Favaloro, Tela; Saha, Bivas; Salamat, Shuaib; Rui Koh, Yee; Lundstrom, Mark S.; Shakouri, Ali; Sands, Timothy D.

2013-04-01

Epitaxial ScN(001) thin films were grown on MgO(001) substrates by dc reactive magnetron sputtering. The deposition was performed in an Ar/N2 atmosphere at 2 × 10-3 Torr at a substrate temperature of 850 °C in a high vacuum chamber with a base pressure of 10-8 Torr. In spite of oxygen contamination of 1.6 ± 1 at. %, the electrical resistivity, electron mobility, and carrier concentration obtained from a typical film grown under these conditions by room temperature Hall measurements are 0.22 mΩ cm, 106 cm2 V-1 s-1, and 2.5 × 1020 cm-3, respectively. These films exhibit remarkable thermoelectric power factors of 3.3-3.5 × 10-3 W/mK2 in the temperature range of 600 K to 840 K. The cross-plane thermal conductivity is 8.3 W/mK at 800 K yielding an estimated ZT of 0.3. Theoretical modeling of the thermoelectric properties of ScN calculated using a mean-free-path of 23 nm at 300 K is in very good agreement with the experiment. These results also demonstrate that further optimization of the power factor of ScN is possible. First-principles density functional theory combined with the site occupancy disorder technique was used to investigate the effect of oxygen contamination on the electronic structure and thermoelectric properties of ScN. The computational results suggest that oxygen atoms in ScN mix uniformly on the N site forming a homogeneous solid solution alloy. Behaving as an n-type donor, oxygen causes a shift of the Fermi level in ScN into the conduction band without altering the band structure and the density of states.

Hereditary sensory and autonomic neuropathy type IID caused by an SCN9A mutation.

Science.gov (United States)

Yuan, Junhui; Matsuura, Eiji; Higuchi, Yujiro; Hashiguchi, Akihiro; Nakamura, Tomonori; Nozuma, Satoshi; Sakiyama, Yusuke; Yoshimura, Akiko; Izumo, Shuji; Takashima, Hiroshi

2013-04-30

To identify the clinical features of Japanese patients with suspected hereditary sensory and autonomic neuropathy (HSAN) on the basis of genetic diagnoses. On the basis of clinical, in vivo electrophysiologic, and pathologic findings, 9 Japanese patients with sensory and autonomic nervous dysfunctions were selected. Eleven known HSAN disease-causing genes and 5 related genes were screened using a next-generation sequencer. A homozygous mutation, c.3993delGinsTT, was identified in exon 22 of SCN9A from 2 patients/families. The clinical phenotype was characterized by adolescent or congenital onset with loss of pain and temperature sensation, autonomic nervous dysfunctions, hearing loss, and hyposmia. Subsequently, this mutation was discovered in one of patient 1's sisters, who also exhibited sensory and autonomic nervous system dysfunctions, with recurrent fractures being the most predominant feature. Nerve conduction studies revealed definite asymmetric sensory nerve involvement in patient 1. In addition, sural nerve pathologic findings showed loss of large myelinated fibers in patient 1, whereas the younger patient showed normal sural nerve pathology. We identified a novel homozygous mutation in SCN9A from 2 Japanese families with autosomal recessive HSAN. This loss-of-function SCN9A mutation results in disturbances in the sensory, olfactory, and autonomic nervous systems. We propose that SCN9A mutation results in the new entity of HSAN type IID, with additional symptoms including hyposmia, hearing loss, bone dysplasia, and hypogeusia.

In Candida albicans hyphae, Sec2p is physically associated with SEC2 mRNA on secretory vesicles.

Science.gov (United States)

Caballero-Lima, David; Hautbergue, Guillaume M; Wilson, Stuart A; Sudbery, Peter E

2014-11-01

Candida albicans hyphae grow in a highly polarized fashion from their tips. This polarized growth requires the continuous delivery of secretory vesicles to the tip region. Vesicle delivery depends on Sec2p, the Guanine Exchange Factor (GEF) for the Rab GTPase Sec4p. GTP bound Sec4p is required for the transit of secretory vesicles from the trans-Golgi to sites of polarized growth. We previously showed that phosphorylation of Sec2p at residue S584 was necessary for Sec2p to support hyphal, but not yeast growth. Here we show that on secretory vesicles SEC2 mRNA is physically associated with Sec2p. Moreover, we show that the phosphorylation of S584 allows SEC2 mRNA to dissociate from Sec2p and we speculate that this is necessary for Sec2p function and/or translation. During hyphal extension, the growing tip may be separated from the nucleus by up to 15 μm. Transport of SEC2 mRNA on secretory vesicles to the tip localizes SEC2 translation to tip allowing a sufficient accumulation of this key protein at the site of polarized growth. © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

New genetic variants of LATS1 detected in urinary bladder and colon cancer.

Science.gov (United States)

Saadeldin, Mona K; Shawer, Heba; Mostafa, Ahmed; Kassem, Neemat M; Amleh, Asma; Siam, Rania

2014-01-01

LATS1, the large tumor suppressor 1 gene, encodes for a serine/threonine kinase protein and is implicated in cell cycle progression. LATS1 is down-regulated in various human cancers, such as breast cancer, and astrocytoma. Point mutations in LATS1 were reported in human sarcomas. Additionally, loss of heterozygosity of LATS1 chromosomal region predisposes to breast, ovarian, and cervical tumors. In the current study, we investigated LATS1 genetic variations including single nucleotide polymorphisms (SNPs), in 28 Egyptian patients with either urinary bladder or colon cancers. The LATS1 gene was amplified and sequenced and the expression of LATS1 at the RNA level was assessed in 12 urinary bladder cancer samples. We report, the identification of a total of 29 variants including previously identified SNPs within LATS1 coding and non-coding sequences. A total of 18 variants were novel. Majority of the novel variants, 13, were mapped to intronic sequences and un-translated regions of the gene. Four of the five novel variants located in the coding region of the gene, represented missense mutations within the serine/threonine kinase catalytic domain. Interestingly, LATS1 RNA steady state levels was lost in urinary bladder cancerous tissue harboring four specific SNPs (16045 + 41736 + 34614 + 56177) positioned in the 5'UTR, intron 6, and two silent mutations within exon 4 and exon 8, respectively. This study identifies novel single-base-sequence alterations in the LATS1 gene. These newly identified variants could potentially be used as novel diagnostic or prognostic tools in cancer.

A comprehensive approach to identifying repurposed drugs to treat SCN8A epilepsy.

Science.gov (United States)

Atkin, Talia A; Maher, Chani M; Gerlach, Aaron C; Gay, Bryant C; Antonio, Brett M; Santos, Sonia C; Padilla, Karen M; Rader, JulieAnn; Krafte, Douglas S; Fox, Matthew A; Stewart, Gregory R; Petrovski, Slavé; Devinsky, Orrin; Might, Matthew; Petrou, Steven; Goldstein, David B

2018-04-01

Many previous studies of drug repurposing have relied on literature review followed by evaluation of a limited number of candidate compounds. Here, we demonstrate the feasibility of a more comprehensive approach using high-throughput screening to identify inhibitors of a gain-of-function mutation in the SCN8A gene associated with severe pediatric epilepsy. We developed cellular models expressing wild-type or an R1872Q mutation in the Na v 1.6 sodium channel encoded by SCN8A. Voltage clamp experiments in HEK-293 cells expressing the SCN8A R1872Q mutation demonstrated a leftward shift in sodium channel activation as well as delayed inactivation; both changes are consistent with a gain-of-function mutation. We next developed a fluorescence-based, sodium flux assay and used it to assess an extensive library of approved drugs, including a panel of antiepileptic drugs, for inhibitory activity in the mutated cell line. Lead candidates were evaluated in follow-on studies to generate concentration-response curves for inhibiting sodium influx. Select compounds of clinical interest were evaluated by electrophysiology to further characterize drug effects on wild-type and mutant sodium channel functions. The screen identified 90 drugs that significantly inhibited sodium influx in the R1872Q cell line. Four drugs of potential clinical interest-amitriptyline, carvedilol, nilvadipine, and carbamazepine-were further investigated and demonstrated concentration-dependent inhibition of sodium channel currents. A comprehensive drug repurposing screen identified potential new candidates for the treatment of epilepsy caused by the R1872Q mutation in the SCN8A gene. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Two-way communication between SecY and SecA suggests a Brownian ratchet mechanism for protein translocation.

Science.gov (United States)

Allen, William John; Corey, Robin Adam; Oatley, Peter; Sessions, Richard Barry; Baldwin, Steve A; Radford, Sheena E; Tuma, Roman; Collinson, Ian

2016-05-16

The essential process of protein secretion is achieved by the ubiquitous Sec machinery. In prokaryotes, the drive for translocation comes from ATP hydrolysis by the cytosolic motor-protein SecA, in concert with the proton motive force (PMF). However, the mechanism through which ATP hydrolysis by SecA is coupled to directional movement through SecYEG is unclear. Here, we combine all-atom molecular dynamics (MD) simulations with single molecule FRET and biochemical assays. We show that ATP binding by SecA causes opening of the SecY-channel at long range, while substrates at the SecY-channel entrance feed back to regulate nucleotide exchange by SecA. This two-way communication suggests a new, unifying 'Brownian ratchet' mechanism, whereby ATP binding and hydrolysis bias the direction of polypeptide diffusion. The model represents a solution to the problem of transporting inherently variable substrates such as polypeptides, and may underlie mechanisms of other motors that translocate proteins and nucleic acids.

Our Traditional Dessert which is to be Forgotten: UĞUT

Directory of Open Access Journals (Sweden)

Hasan Tangüler

2015-07-01

Full Text Available Uğut (wheatgrass marmalade / dessert is a traditional Turkish food which is almost to be forgotten. It is produced in various regions of Turkey by boiling the mixture of wheatgrass juice, flour and water. The wheatgrass contains amino acids, protein, fiber, vitamins, minerals, and enzyme. It is reported that the wheatgrass has antioxidant, anticancer, anti-aging, laxative, diuretic and antibacterial effects due to its rich composition. Uğut is also a good source of carbohydrate because of its flour contents. In this article, the composition and production methods of Uğut were discussed.

Real-time 3-D SAFT-UT system evaluation and validation

International Nuclear Information System (INIS)

Doctor, S.R.; Schuster, G.J.; Reid, L.D.; Hall, T.E.

1996-09-01

SAFT-UT technology is shown to provide significant enhancements to the inspection of materials used in US nuclear power plants. This report provides guidelines for the implementation of SAFT-UT technology and shows the results from its application. An overview of the development of SAFT-UT is provided so that the reader may become familiar with the technology. Then the basic fundamentals are presented with an extensive list of references. A comprehensive operating procedure, which is used in conjunction with the SAFT-UT field system developed by Pacific Northwest Laboratory (PNL), provides the recipe for both SAFT data acquisition and analysis. The specification for the hardware implementation is provided for the SAFT-UT system along with a description of the subsequent developments and improvements. One development of technical interest is the SAFT real time processor. Performance of the real-time processor is impressive and comparison is made of this dedicated parallel processor to a conventional computer and to the newer high-speed computer architectures designed for image processing. Descriptions of other improvements, including a robotic scanner, are provided. Laboratory parametric and application studies, performed by PNL and not previously reported, are discussed followed by a section on field application work in which SAFT was used during inservice inspections of operating reactors

Real-time 3-D SAFT-UT system evaluation and validation

Energy Technology Data Exchange (ETDEWEB)

Doctor, S.R.; Schuster, G.J.; Reid, L.D.; Hall, T.E. [Pacific Northwest National Lab., Richland, WA (United States)

1996-09-01

SAFT-UT technology is shown to provide significant enhancements to the inspection of materials used in US nuclear power plants. This report provides guidelines for the implementation of SAFT-UT technology and shows the results from its application. An overview of the development of SAFT-UT is provided so that the reader may become familiar with the technology. Then the basic fundamentals are presented with an extensive list of references. A comprehensive operating procedure, which is used in conjunction with the SAFT-UT field system developed by Pacific Northwest Laboratory (PNL), provides the recipe for both SAFT data acquisition and analysis. The specification for the hardware implementation is provided for the SAFT-UT system along with a description of the subsequent developments and improvements. One development of technical interest is the SAFT real time processor. Performance of the real-time processor is impressive and comparison is made of this dedicated parallel processor to a conventional computer and to the newer high-speed computer architectures designed for image processing. Descriptions of other improvements, including a robotic scanner, are provided. Laboratory parametric and application studies, performed by PNL and not previously reported, are discussed followed by a section on field application work in which SAFT was used during inservice inspections of operating reactors.

Functional Na(V)1.8 Channels in Intracardiac Neurons The Link Between SCN10A and Cardiac Electrophysiology

NARCIS (Netherlands)

Verkerk, Arie O.; Remme, Carol Ann; Schumacher, Cees A.; Scicluna, Brendon P.; Wolswinkel, Rianne; de Jonge, Berend; Bezzina, Connie R.; Veldkamp, Marieke W.

2012-01-01

Rationale: The SCN10A gene encodes the neuronal sodium channel isoform Na(V)1.8. Several recent genome-wide association studies have linked SCN10A to PR interval and QRS duration, strongly suggesting an as-yet unknown role for Na(V)1.8 in cardiac electrophysiology. Objective: To demonstrate the

Pitfalls in genetic testing: the story of missed SCN1A mutations

OpenAIRE

Jennings, Lawrence J.; Kirschmann, Dawn

2016-01-01

Investigators from the EuroEPINOMICS rare epilepsy syndromes Dravet working group performed whole-exome sequencing on 31 trios that had been reported negative for SCN1A mutations by Sanger sequencing.

Fermi-LAT Gamma-Ray Bursts and Insights from Swift

Science.gov (United States)

Racusin, Judith L.

2010-01-01

A new revolution in Gamma-ray Burst (GRB) observations and theory has begun over the last two years since the launch of the Fermi Gamma-ray Space Telescope. The new window into high energy gamma-rays opened by the Fermi-Large Area Telescope (LAT) is providing insight into prompt emission mechanisms and possibly also afterglow physics. The LAT detected GRBs appear to be a new unique subset of extremely energetic and bright bursts compared to the large sample detected by Swift over the last 6 years. In this talk, I will discuss the context and recent discoveries from these LAT GRBs and the large database of broadband observations collected by the Swift X-ray Telescope (XRT) and UV/Optical Telescope (UVOT). Through comparisons between the GRBs detected by Swift-BAT, G8M, and LAT, we can learn about the unique characteristics, physical differences, and the relationships between each population. These population characteristics provide insight into the different physical parameters that contribute to the diversity of observational GRB properties.

Decreased expression of LATS1 is correlated with the progression and prognosis of glioma

Directory of Open Access Journals (Sweden)

Ji Tianhai

2012-08-01

Full Text Available Abstract Background LATS1 is a tumor suppressor genes implicated in the pathogenesis of certain types of tumors, but its role is not known in human glioma. Methods Using real-time PCR and immunohistochemistry, we detected the mRNA and protein expression of LATS1 in glioma. The effect of LATS1 on cell growth and invasion were investigated. Results We found that mRNA and protein of LATS1 expression is significantly downregulated in glioma compared with normal control brain tissues. Furthermore, reduced LATS1 expression was markedly negatively correlated with WHO grade and KPS (p Conclusion These results indicate that LATS1 is an important candidate tumor suppressor and its downregulated expression may contribute to glioma progression.

Linkage between increased nociception and olfaction via a SCN9A haplotype.

Directory of Open Access Journals (Sweden)

Dirk Heimann

Full Text Available BACKGROUND AND AIMS: Mutations reducing the function of Nav1.7 sodium channels entail diminished pain perception and olfactory acuity, suggesting a link between nociception and olfaction at ion channel level. We hypothesized that if such link exists, it should work in both directions and gain-of-function Nav1.7 mutations known to be associated with increased pain perception should also increase olfactory acuity. METHODS: SCN9A variants were assessed known to enhance pain perception and found more frequently in the average population. Specifically, carriers of SCN9A variants rs41268673C>A (P610T; n = 14 or rs6746030C>T (R1150W; n = 21 were compared with non-carriers (n = 40. Olfactory function was quantified by assessing odor threshold, odor discrimination and odor identification using an established olfactory test. Nociception was assessed by measuring pain thresholds to experimental nociceptive stimuli (punctate and blunt mechanical pressure, heat and electrical stimuli. RESULTS: The number of carried alleles of the non-mutated SCN9A haplotype rs41268673C/rs6746030C was significantly associated with the comparatively highest olfactory threshold (0 alleles: threshold at phenylethylethanol dilution step 12 of 16 (n = 1, 1 allele: 10.6±2.6 (n = 34, 2 alleles: 9.5±2.1 (n = 40. The same SCN9A haplotype determined the pain threshold to blunt pressure stimuli (0 alleles: 21.1 N/m(2, 1 allele: 29.8±10.4 N/m(2, 2 alleles: 33.5±10.2 N/m(2. CONCLUSIONS: The findings established a working link between nociception and olfaction via Nav1.7 in the gain-of-function direction. Hence, together with the known reduced olfaction and pain in loss-of-function mutations, a bidirectional genetic functional association between nociception and olfaction exists at Nav1.7 level.

Epidural Analgesia with Ropivacaine during Labour in a Patient with a SCN5A Gene Mutation

Directory of Open Access Journals (Sweden)

A. L. M. J. van der Knijff-van Dortmont

2016-01-01

Full Text Available SCN5A gene mutations can lead to ion channel defects which can cause cardiac conduction disturbances. In the presence of specific ECG characteristics, this mutation is called Brugada syndrome. Many drugs are associated with adverse events, making anesthesia in patients with SCN5A gene mutations or Brugada syndrome challenging. In this case report, we describe a pregnant patient with this mutation who received epidural analgesia using low dose ropivacaine and sufentanil during labour.

LAT Daily Lightcurve FITS Files

Data.gov (United States)

National Aeronautics and Space Administration — LAT data between 100 MeV and 10 GeV filtered for solar counts in 1-minute time bins, no energy binning, using light-bucket method. Contains exposure (cm^2 s)...

Effects of Photoperiod Extension on Clock Gene and Neuropeptide RNA Expression in the SCN of the Soay Sheep.

Directory of Open Access Journals (Sweden)

Hugues Dardente

Full Text Available In mammals, changing daylength (photoperiod is the main synchronizer of seasonal functions. The photoperiodic information is transmitted through the retino-hypothalamic tract to the suprachiasmatic nuclei (SCN, site of the master circadian clock. To investigate effects of day length change on the sheep SCN, we used in-situ hybridization to assess the daily temporal organization of expression of circadian clock genes (Per1, Per2, Bmal1 and Fbxl21 and neuropeptides (Vip, Grp and Avp in animals acclimated to a short photoperiod (SP; 8h of light and at 3 or 15 days following transfer to a long photoperiod (LP3, LP15, respectively; 16h of light, achieved by an acute 8-h delay of lights off. We found that waveforms of SCN gene expression conformed to those previously seen in LP acclimated animals within 3 days of transfer to LP. Mean levels of expression for Per1-2 and Fbxl21 were nearly 2-fold higher in the LP15 than in the SP group. The expression of Vip was arrhythmic and unaffected by photoperiod, while, in contrast to rodents, Grp expression was not detectable within the sheep SCN. Expression of the circadian output gene Avp cycled robustly in all photoperiod groups with no detectable change in phasing. Overall these data suggest that synchronizing effects of light on SCN circadian organisation proceed similarly in ungulates and in rodents, despite differences in neuropeptide gene expression.

Solution-processed inorganic copper(I) thiocyanate (CuSCN) hole transporting layers for efficient p–i–n perovskite solar cells

KAUST Repository

Zhao, Kui

2015-08-27

CuSCN is a highly transparent, highly stable, low cost and easy to solution process HTL that is proposed as a low cost replacement to existing organic and inorganic metal oxide hole transporting materials. Here, we demonstrate hybrid organic-inorganic perovskite-based p-i-n planar heterojunction solar cells using a solution-processed copper(I) thiocyanate (CuSCN) bottom hole transporting layer (HTL). CuSCN, with its high workfunction, increases the open circuit voltage (Voc) by 0.23 V to 1.06 V as compared with devices based on the well-known poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) (0.83 V), resulting in a superior power conversion efficiency (PCE) of 10.8% without any notable hysteresis. Photoluminescence measurements suggest a similar efficiency of charge transfer at HTL/perovskite interface as PEDOT:PSS. However, we observe more efficient light harvesting in the presence of CuSCN at shorter wavelengths despite PEDOT:PSS being more transparent. Further investigation of the microstructure and morphology reveals differences in the crystallographic texture of the polycrystalline perovskite film, suggesting somewhat modified perovskite growth on the surface of CuSCN. The successful demonstration of the solution-processed inorganic HTL using simple and low temperature processing routes bodes well for the development of reliable and efficient flexible p-i-n perovskite modules or for integration as a front cell in hybrid tandem solar cells.

(1-Butyl-4-methyl-pyridinium)[Cu(SCN)2]: a coordination polymer and ionic liquid.

Science.gov (United States)

Spielberg, Eike T; Edengeiser, Eugen; Mallick, Bert; Havenith, Martina; Mudring, Anja-Verena

2014-04-25

The compound (C4C1py)[Cu(SCN)2], (C4C1py = 1-Butyl-4-methyl-pyridinium), which can be obtained from CuSCN and the ionic liquid (C4C1py)(SCN), turns out to be a new organic-inorganic hybrid material as it qualifies both, as a coordination polymer and an ionic liquid. It features linked [Cu(SCN)2](-) units, in which the thiocyanates bridge the copper ions in a μ1,3-fashion. The resulting one-dimensional chains run along the a axis, separated by the C4C1py counterions. Powder X-ray diffraction not only confirms the single-crystal X-ray structure solution but proves the reformation of the coordination polymer from an isotropic melt. However, the materials shows a complex thermal behavior often encountered for ionic liquids such as a strong tendency to form a supercooled melt. At a relatively high cooling rate, glass formation is observed. When heating this melt in differential scanning calorimetry (DSC) and temperature-dependent polarizing optical microscopy (POM), investigations reveal the existence of a less thermodynamically stable crystalline polymorph. Raman measurements conducted at 10 and 100 °C point towards the formation of polyanionic chain fragments in the melt. Solid-state UV/Vis spectroscopy shows a broad absorption band around 18,870 cm(-1) (530 nm) and another strong one below 20,000 cm(-1) (<500 nm). The latter is attributed to the d(Cu(I))→π*(SCN)-MLCT (metal-to-ligand charge transfer) transition within the coordination polymer yielding an energy gap of 2.4 eV. At room temperature and upon irradiation with UV light, the material shows a weak fluorescence band at 15,870 cm(-1) (630 nm) with a quantum efficiency of 0.90(2) % and a lifetime of 131(2) ns. Upon lowering the temperature, the luminescence intensity strongly increases. Simultaneously, the band around 450 nm in the excitation spectrum decreases. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Epithelial organization and cyst lumen expansion require efficient Sec13-Sec31-driven secretion.

Science.gov (United States)

Townley, Anna K; Schmidt, Katy; Hodgson, Lorna; Stephens, David J

2012-02-01

Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13-Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture.

Chaperone-Mediated Sec61 Channel Gating during ER Import of Small Precursor Proteins Overcomes Sec61 Inhibitor-Reinforced Energy Barrier

Directory of Open Access Journals (Sweden)

Sarah Haßdenteufel

2018-05-01

Full Text Available Summary: Protein transport into the mammalian endoplasmic reticulum (ER is mediated by the heterotrimeric Sec61 channel. The signal recognition particle (SRP and TRC systems and Sec62 have all been characterized as membrane-targeting components for small presecretory proteins, whereas Sec63 and the lumenal chaperone BiP act as auxiliary translocation components. Here, we report the transport requirements of two natural, small presecretory proteins and engineered variants using semipermeabilized human cells after the depletion of specific ER components. Our results suggest that hSnd2, Sec62, and SRP and TRC receptor each provide alternative targeting pathways for short secretory proteins and define rules of engagement for the actions of Sec63 and BiP during their membrane translocation. We find that the Sec62/Sec63 complex plus BiP can facilitate Sec61 channel opening, thereby allowing precursors that have weak signal peptides or other inhibitory features to translocate. A Sec61 inhibitor can mimic the effect of BiP depletion on Sec61 gating, suggesting that they both act at the same essential membrane translocation step. : Protein transport into the human endoplasmic reticulum (ER is mediated by the heterotrimeric Sec61 channel. Haßdenteufel et al. map the determinants for requirement of different targeting pathways and different auxiliary components of the Sec61 channel in ER import of short presecretory proteins. Different characteristics of precursor polypeptides dictate the engagement of each component. Keywords: endoplasmic reticulum, protein targeting and translocation, Sec61 channel gating, Sec62, Sec63, BiP, CAM741, signal peptide, mature region, cluster of positive charges

Constraints on the pMSSM from LAT Observations of Dwarf Spheroidal Galaxies

Energy Technology Data Exchange (ETDEWEB)

Cotta, R.C.; /SLAC; Drlica-Wagner, A.; Murgia, S.; /SLAC /KIPAC, Menlo Park; Bloom, E.D.; Hewett, J.L.; Rizzo, T.G.; /SLAC

2012-03-15

We examine the ability for the Large Area Telescope (LAT) to constrain Minimal Supersymmetric Standard Model (MSSM) dark matter through a combined analysis of Milky Way dwarf spheroidal galaxies. We examine the Lightest Supersymmetric Particles (LSPs) for a set of {approx}71k experimentally valid supersymmetric models derived from the phenomenological-MSSM (pMSSM). We find that none of these models can be excluded at 95% confidence by the current analysis; nevertheless, many lie within the predicted reach of future LAT analyses. With two years of data, we find that the LAT is currently most sensitive to light LSPs (mLSP < 50 GeV) annihilating into {tau}-pairs and heavier LSPs annihilating into b{bar b}. Additionally, we find that future LAT analyses will be able to probe some LSPs that form a sub-dominant component of dark matter. We directly compare the LAT results to direct detection experiments and show the complementarity of these search methods.

Contrasting oxygen-effects in the inactivation of ribonuclease A by N3, (SCN)-2 and OH radicals

International Nuclear Information System (INIS)

Pruetz, W.A.

1979-01-01

N 3 exhibits higher efficiency than OH in the inactivation of RNase in de-acerated (neutral) aqueous solution. In O 2 -saturated solution the OH-induced inactivation is enhanced, but N 3 and (SCN) - 2 become remarkably inefficient. Our results suggest that semi-oxidized tyrosine, the predominant initial defect induced by N 3 and (SCN) - 2 but not by OH, can be re-reduced upon reaction with O - 2 or cysteine. (orig.) [de

Development and validation of a real-time SAFT-UT system for inservice inspection of LWRs

International Nuclear Information System (INIS)

Doctor, S.R.; Reid, L.D.; Hall, T.E.; Littlefield, R.J.; Gilbert, R.W.; Crawford, S.L.; Baldwin, A.J.; Bowey, R.E.

1985-10-01

A multi-year program is underway at Pacific Northwest Laboratory (PNL) to move the synthetic aperture focusing technique from the Laboratory into the field to inspect light water reactor components. This report is a summary of highlights from the third year's efforts. The work presented here includes: scanner development, SAFT-UT signal processing techniques, SAFT-UT graphics package development, SAFT-UT real-time processor, SAFT-UT field system integration, SAFT-UT evaluation on CCSS, a field trip demonstrating in-field SAFT data processing, and future work. 11 figs

Searching for Dark Matter Signatures in the GLAST LAT Electron Flux

Science.gov (United States)

Moiseev, Alexander; Profumo, Stefano

2008-01-01

We explored several viable scenarios of how LAT might observe DM, when the spectral feature is predicted to be observed in the HE electron flux It has been demonstrated elsewhere that LAT will be capable to detect HE electrons flux in energy range from 20 GeV to - 1 TeV with 520% energy resolution and good statistics If there is a DM-caused feature in the HE electron flux (in the range 20 GeV - 1 TeV), LAT will be the best current instrument to observe it!

LAT 2-year Point Source Catalog

Data.gov (United States)

National Aeronautics and Space Administration — The Fermi Gamma-ray Space Telescope (Fermi) Large Area Telescope (LAT) is a successor to EGRET, with greatly improved sensitivity, resolution, and energy range. This...

Zero lattice mismatch and twin-free single crystalline ScN buffer layers for GaN growth on silicon

Energy Technology Data Exchange (ETDEWEB)

Lupina, L.; Zoellner, M. H.; Dietrich, B.; Capellini, G. [IHP, Im Technologiepark 25, 15236 Frankfurt, Oder (Germany); Niermann, T.; Lehmann, M. [Technische Universität Berlin, Institut für Optik und Atomare Physik, Straße des 17. Juni 135, 10623 Berlin (Germany); Thapa, S. B.; Haeberlen, M.; Storck, P. [SILTRONIC AG, Hanns-Seidel-Platz 4, 81737 München (Germany); Schroeder, T. [IHP, Im Technologiepark 25, 15236 Frankfurt, Oder (Germany); BTU Cottbus, Konrad-Zuse-Str. 1, 03046 Cottbus (Germany)

2015-11-16

We report the growth of thin ScN layers deposited by plasma-assisted molecular beam epitaxy on Sc{sub 2}O{sub 3}/Y{sub 2}O{sub 3}/Si(111) substrates. Using x-ray diffraction, Raman spectroscopy, and transmission electron microscopy, we find that ScN films grown at 600 °C are single crystalline, twin-free with rock-salt crystal structure, and exhibit a direct optical band gap of 2.2 eV. A high degree of crystalline perfection and a very good lattice matching between ScN and GaN (misfit < 0.1%) makes the ScN/Sc{sub 2}O{sub 3}/Y{sub 2}O{sub 3} buffer system a very promising template for the growth of high quality GaN layers on silicon.

Modeling of flux, binding and substitution of urea molecules in the urea transporter dvUT.

Science.gov (United States)

Zhang, Hai-Tian; Wang, Zhe; Yu, Tao; Sang, Jian-Ping; Zou, Xian-Wu; Zou, Xiaoqin

2017-09-01

Urea transporters (UTs) are transmembrane proteins that transport urea molecules across cell membranes and play a crucial role in urea excretion and water balance. Modeling the functional characteristics of UTs helps us understand how their structures accomplish the functions at the atomic level, and facilitates future therapeutic design targeting the UTs. This study was based on the crystal structure of Desulfovibrio vulgaris urea transporter (dvUT). To model the binding behavior of urea molecules in dvUT, we constructed a cooperative binding model. To model the substitution of urea by the urea analogue N,N'-dimethylurea (DMU) in dvUT, we calculated the occupation probability of DMU along the urea pore and the ratio of the occupation probabilities of DMU at the external (S ext ) and internal (S int ) binding sites, and we established the mutual substitution rule for binding and substitution of urea and DMU. Based on these calculations and modelings, together with the use of the Monte Carlo (MC) method, we further modeled the urea flux in dvUT, equilibrium urea binding to dvUT, and the substitution of urea by DMU in the dvUT. Our modeling results are in good agreement with the existing experimental functional data. Furthermore, the modelings have discovered the microscopic process and mechanisms of those functional characteristics. The methods and the results would help our future understanding of the underlying mechanisms of the diseases associated with impaired UT functions and rational drug design for the treatment of these diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Sick sinus syndrome, progressive cardiac conduction disease, atrial flutter and ventricular tachycardia caused by a novel SCN5A mutation

DEFF Research Database (Denmark)

Holst, Anders G; Liang, Bo; Jespersen, Thomas

2010-01-01

father carried the same mutation, but had a milder phenotype, presenting with progressive cardiac conduction later in life. The mutation was found to result in a loss-of-function in the sodium current. In conclusion, the same SCN5A mutation can result in a wide array of clinical phenotypes and perhaps......Mutations in the cardiac sodium channel encoded by the gene SCN5A can result in a wide array of phenotypes. We report a case of a young male with a novel SCN5A mutation (R121W) afflicted by sick sinus syndrome, progressive cardiac conduction disorder, atrial flutter and ventricular tachycardia. His...

External light activates hair follicle stem cells through eyes via an ipRGC-SCN-sympathetic neural pathway.

Science.gov (United States)

Fan, Sabrina Mai-Yi; Chang, Yi-Ting; Chen, Chih-Lung; Wang, Wei-Hung; Pan, Ming-Kai; Chen, Wen-Pin; Huang, Wen-Yen; Xu, Zijian; Huang, Hai-En; Chen, Ting; Plikus, Maksim V; Chen, Shih-Kuo; Lin, Sung-Jan

2018-06-29

Changes in external light patterns can alter cell activities in peripheral tissues through slow entrainment of the central clock in suprachiasmatic nucleus (SCN). It remains unclear whether cells in otherwise photo-insensitive tissues can achieve rapid responses to changes in external light. Here we show that light stimulation of animals' eyes results in rapid activation of hair follicle stem cells with prominent hair regeneration. Mechanistically, light signals are interpreted by M1-type intrinsically photosensitive retinal ganglion cells (ipRGCs), which signal to the SCN via melanopsin. Subsequently, efferent sympathetic nerves are immediately activated. Increased norepinephrine release in skin promotes hedgehog signaling to activate hair follicle stem cells. Thus, external light can directly regulate tissue stem cells via an ipRGC-SCN autonomic nervous system circuit. Since activation of sympathetic nerves is not limited to skin, this circuit can also facilitate rapid adaptive responses to external light in other homeostatic tissues.

The Fermi LAT Very Important Project (VIP) List of Active Galactic Nuclei

Science.gov (United States)

Thompson, David J.; Fermi Large Area Telescope Collaboration

2018-01-01

Using nine years of Fermi Gamma-ray Space Telescope Large Area Telescope (LAT) observations, we have identified 30 projects for Active Galactic Nuclei (AGN) that appear to provide strong prospects for significant scientific advances. This Very Important Project (VIP) AGN list includes AGNs that have good multiwavelength coverage, are regularly detected by the Fermi LAT, and offer scientifically interesting timing or spectral properties. Each project has one or more LAT scientists identified who are actively monitoring the source. They will be regularly updating the LAT results for these VIP AGNs, working together with multiwavelength observers and theorists to maximize the scientific return during the coming years of the Fermi mission. See https://confluence.slac.stanford.edu/display/GLAMCOG/VIP+List+of+AGNs+for+Continued+Study

The Fermi GBM and LAT follow-up of GW150914

Directory of Open Access Journals (Sweden)

Bissaldi E.

2017-01-01

Here we present observations by the Fermi Gamma-Ray BurstMonitor (GBM [1] and by the Large Area Telescope (LAT [2] of the LIGO Gravitational Wave event GW150914, which has been associated to the merger of two stellar-mass BHs. We report the presence of a weak transient event in GBM data, close in time to the LIGO one. We discuss the characteristics of this GBM transient, which are consistent with a weak short GRB arriving at a large angle to the direction in which Fermi was pointing. Furthermore, we report LAT upper limits (ULs for GW150914, and we present the strategy for follow-up observations of GW events with the LAT.

Ab-initio studies of the Sc adsorption and the ScN thin film formation on the GaN(000-1)-(2 × 2) surface

International Nuclear Information System (INIS)

Guerrero-Sánchez, J.; Sánchez-Ochoa, F.; Cocoletzi, Gregorio H.; Rivas-Silva, J.F.; Takeuchi, Noboru

2013-01-01

First principles total energy calculations have been performed to investigate the initial stages of the Sc adsorption and ScN thin film formation on the GaN(000-1)-(2 × 2) surface. Studies are done within the periodic density functional theory as implemented in the PWscf code of the Quantum ESPRESSO package. The Sc adsorption at high symmetry sites results in the bridge site as the most stable structure. When a Sc monolayer is deposited above the surface the T4 site results as the most stable geometry. The Sc migration into the first Ga monolayer induces the Ga displaced ad-atom to be adsorbed at the T4-2 site. A ScN bilayer may be obtained under the Ga monolayer. Finally a ScN bilayer may be formed in the wurtzite phase above the surface. The formation energy plots show that in the moderate Ga-rich conditions we obtain the formation of a ScN bilayer under the gallium monolayer. However at N-rich conditions the formation of ScN bilayer above the surface is the most favorable structure. We report the density of states to explain the electronic structure of the most favorable geometries. - Highlights: • Studies of the initial stages in the formation of Sc and ScN structures on GaN • In the adsorption of Sc on the GaN the Br site is the most favorable geometry. • When a Sc replaces a Ga of the first monolayer the displaced Ga occupies a T4-2 site. • For Ga-rich conditions there is formation of ScN under the Ga monolayer. • In N-rich conditions there is formation of ScN in the wurtzite phase

A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia

Directory of Open Access Journals (Sweden)

Vargas-Alarcon Gilberto

2012-02-01

Full Text Available Abstract Background A consistent line of investigation suggests that autonomic nervous system dysfunction may explain the multi-system features of fibromyalgia (FM; and that FM is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia (DRG are key sympathetic-nociceptive short-circuit sites. Sodium channels located in DRG (particularly Nav1.7 act as molecular gatekeepers for pain detection. Nav1.7 is encoded in gene SCN9A of chromosome 2q24.3 and is predominantly expressed in the DRG pain-sensing neurons and sympathetic ganglia neurons. Several SCN9A sodium channelopathies have been recognized as the cause of rare painful dysautonomic syndromes such as paroxysmal extreme pain disorder and primary erythromelalgia. The aim of this study was to search for an association between fibromyalgia and several SCN9A sodium channels gene polymorphisms. Methods We studied 73 Mexican women suffering from FM and 48 age-matched women who considered themselves healthy. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ. Genomic DNA from whole blood containing EDTA was extracted by standard techniques. The following SCN9A single-nucleotide polymorphisms (SNP were determined by 5' exonuclease TaqMan assays: rs4371369; rs4387806; rs4453709; rs4597545; rs6746030; rs6754031; rs7607967; rs12620053; rs12994338; and rs13017637. Results The frequency of the rs6754031 polymorphism was significantly different in both groups (P = 0.036 mostly due to an absence of the GG genotype in controls. Interestingly; patients with this rs6754031 GG genotype had higher FIQ scores (median = 80; percentile 25/75 = 69/88 than patients with the GT genotype (median = 63; percentile 25/75 = 58/73; P = 0.002 and the TT genotype (median = 71; percentile 25/75 = 64/77; P = 0.001. Conclusion In this ethnic group; a disabling form of FM is associated to a particular SCN9A sodium channel gene variant. These preliminary results raise the possibility that

Hole-transporting transistors and circuits based on the transparent inorganic semiconductor copper(I) thiocyanate (CuSCN) processed from solution at room temperature

KAUST Repository

Pattanasattayavong, Pichaya

2012-12-27

The wide bandgap and highly transparent inorganic compound copper(I) thiocyanate (CuSCN) is used for the first time to fabricate p-type thin-film transistors processed from solution at room temperature. By combining CuSCN with the high-k relaxor ferroelectric polymeric dielectric P(VDF-TrFE-CFE), we demonstrate low-voltage transistors with hole mobilities on the order of 0.1 cm2 V-1 s-1. By integrating two CuSCN transistors, unipolar logic NOT gates are also demonstrated. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

SCN5A mutations and polymorphisms in patients with ventricular fibrillation during acute myocardial infarction.

Science.gov (United States)

Boehringer, Tim; Bugert, Peter; Borggrefe, Martin; Elmas, Elif

2014-10-01

Mutations in the SCN5A gene encoding the Nav1.5 channel α-subunit are known to be risk factors of arrhythmia, including Brugada Syndrome and Long QT syndrome subtype 3. The present study focused on the role of SCN5A variants in the development of ventricular fibrillation (VF) during acute myocardial infarction (AMI). Since VF during AMI is the major cause of sudden death in the Western world, SCN5A mutations represent genetic risk factors for sudden death. By exon re-sequencing, the entire coding region and flanking intron regions were sequenced in 46 AMI/VF+ patients. In total, nine single nucleotide variants were identified of which four represented common single nucleotide polymorphisms (SNPs; 87G>A, 1673A>G, IVS16‑6C>T and 5457T>A). Only five rare variants were identified, each in only one patient. Only two of the rare variants represented missense mutations (3578G>A and 4786T>A). The common SNPs and the missense mutations were also genotyped using polymerase chain reaction methods in 79 AMI/VF‑ patients and 480 healthy controls. The SNPs did not demonstrate significant differences in allele and genotype frequencies between the study groups. The 3578G>A mutation was identified in one out of the 480 controls, whereas the 4786T>A mutation was not present in AMI/VF- patients and controls. In conclusion, the majority of AMI/VF+ patients demonstrated a wild type sequence or common SNPs in SCN5A. Only two out of 46 (4.3%) AMI/VF+ patients revealed mutations that may be involved in Nav1.5 dysfunction and VF. However, this requires further functional validation.

Epithelial organization and cyst lumen expansion require efficient Sec13–Sec31-driven secretion

Science.gov (United States)

Townley, Anna K.; Schmidt, Katy; Hodgson, Lorna; Stephens, David J.

2012-01-01

Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13–Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture. PMID:22331354

Pathophysiological mechanisms of sino-atrial dysfunction and ventricular conduction disease associated with SCN5A deficiency: insights from mouse models

Directory of Open Access Journals (Sweden)

Christopher L-H Huang

2012-07-01

Full Text Available Genetically modified mice provide a number of models for studying cardiac channelopathies related to cardiac Na+ channel (SCN5A abnormalities. We review key pathophysiological features in these murine models that may underlie clinical features observed in sinus node dysfunction and progressive cardiac conduction disease, thereby providing insights into their pathophysiological mechanisms. We describe loss of Na+ channel function and fibrotic changes associated with both loss and gain-of-function Na+ channel mutations. Recent reports further relate the progressive fibrotic changes to upregulation of TGF-β1 production and the transcription factors, Atf3, a stress-inducible gene, and Egr1, to the presence of heterozygous Scn5a inactivation. Both changes are thus directly implicated in the clinically observed disruptions in sino-atrial node pacemaker function, and sino-atrial and ventricular conduction, and their progression with age. Murine systems with genetic modifications in Scn5a thus prove a useful tool to address questions concerning roles of genetic and environmental modifiers on human SCN5A disease phenotypes.

NDE reliability and SAFT-UT final development

International Nuclear Information System (INIS)

Doctor, S.R.; Deffenbaugh, J.D.; Good, M.S.; Green, E.R.; Heasler, P.G.; Reid, L.D.; Simonen, F.A.; Spanner, J.C.; Taylor, T.T.; Vo, T.V.

1990-01-01

The Evaluation and Improvement of NDE Reliability for Inservice Inspection of Light Water Reactors (NDE Reliability) program at the Pacific Northwest Laboratory (PNL) was established by the US Nuclear Regulatory Commission (NRC) to determine the reliability of current inservice inspection (ISI) techniques and to develop recommendations that will ensure a suitably high inspection reliability. This is a progress report covering the programmatic work from October 1987 through September 1988. The program for Validation and Technology Transfer for SAFT-UT is designed to accomplish the final step of moving research results into beneficial application. Accomplishments for FY88 in Synthetic Aperture Focusing of Ultrasonic Test data (SAFT-UT) under this program are discussed in this paper. The information is treated under the copies of Code Activities, Field Validation, and Seminars. (orig.)

Art ist kuku nu ut / Indrek Grigor

Index Scriptorium Estoniae

Grigor, Indrek

2009-01-01

Tartu kunstikuust "Art ist kuku nu ut", mis toimus 9. jaanuarist 29. veebruarini. Peakorraldaja Kaisa Eiche. Programmist, välireklaamist, kunstinäitustest, Bernard Murigneux' valgusskulptuuridest, Lemmit Kaplinski kunstikriitika töötubade sarjast "Kriitikavabrik"

Post-test analysis of semiscale tests S-UT-6 and S-UT-7 using TRAC PF1

International Nuclear Information System (INIS)

Boyack, B.E.

1983-01-01

A posttest study of Semiscale Tests S-UT-6 and S-UT-7 has been completed to assess TRAC-PFl predictions of pressurized water-reactor (PWR) small-break transients. The comparisons of the TRAC calculations and experimental results show that the correct qualitative influence of upper-head injection (UHI) was predicted. The major phenomenological difference predicted was the mode of core voiding. The data show a slow boiloff from the top of the core resulting in a dryout near the top of the core only. TRAC predicted a more extensive voiding with fluid forced from the bottom of the core by a pressure increase in the upper vessel plenum. The pressure increase was the primary consequence of a failure to predict a complete clearance of the seal in the intact-loop pump-suction upflow leg. Further review of the interphasic drag correlations, entrainment correlations, and critical-flow model is recommended. 20 figures

β1-C121W Is Down But Not Out: Epilepsy-Associated Scn1b-C121W Results in a Deleterious Gain-of-Function

Science.gov (United States)

Kruger, Larisa C.; O'Malley, Heather A.; Hull, Jacob M.; Kleeman, Amanda; Patino, Gustavo A.

2016-01-01

Voltage-gated sodium channel (VGSC) β subunits signal through multiple pathways on multiple time scales. In addition to modulating sodium and potassium currents, β subunits play nonconducting roles as cell adhesion molecules, which allow them to function in cell–cell communication, neuronal migration, neurite outgrowth, neuronal pathfinding, and axonal fasciculation. Mutations in SCN1B, encoding VGSC β1 and β1B, are associated with epilepsy. Autosomal-dominant SCN1B-C121W, the first epilepsy-associated VGSC mutation identified, results in genetic epilepsy with febrile seizures plus (GEFS+). This mutation has been shown to disrupt both the sodium-current-modulatory and cell-adhesive functions of β1 subunits expressed in heterologous systems. The goal of this study was to compare mice heterozygous for Scn1b-C121W (Scn1b+/W) with mice heterozygous for the Scn1b-null allele (Scn1b+/−) to determine whether the C121W mutation results in loss-of-function in vivo. We found that Scn1b+/W mice were more susceptible than Scn1b+/− and Scn1b+/+ mice to hyperthermia-induced convulsions, a model of pediatric febrile seizures. β1-C121W subunits are expressed at the neuronal cell surface in vivo. However, despite this, β1-C121W polypeptides are incompletely glycosylated and do not associate with VGSC α subunits in the brain. β1-C121W subcellular localization is restricted to neuronal cell bodies and is not detected at axon initial segments in the cortex or cerebellum or at optic nerve nodes of Ranvier of Scn1bW/W mice. These data, together with our previous results showing that β1-C121W cannot participate in trans-homophilic cell adhesion, lead to the hypothesis that SCN1B-C121W confers a deleterious gain-of-function in human GEFS+ patients. SIGNIFICANCE STATEMENT The mechanisms underlying genetic epilepsy syndromes are poorly understood. Closing this gap in knowledge is essential to the development of new medicines to treat epilepsy. We have used mouse models to

Development of portable phased array UT system for real-time flaw imaging

International Nuclear Information System (INIS)

Goto, M.

1995-01-01

Many functions and features of phased array UT technology must be useful for NDE in the industrial field. Some phased array UT systems have been developed for the inspection of nuclear pressure vessel and turbine components. However, phased array UT is still a special NDE technique and it has not been used widely in the past. The reasons of that are system size, cost, operator performance, equipment design and others. TOSHIBA has newly developed PC controlled portable phased array system to solve those problems. The portable phased array UT system is very compact and light but it is able to drive up to 32-channel linear array probe, to display real-time linear/sector B-scan, to display accumulated B-scan with an encoder and to display profile overlaid B-scan. The first applications were turbine component inspections for precise flaw investigation and flaw image data recording

46 CFR Sec. 13 - Insurance.

Science.gov (United States)

2010-10-01

... REPAIRS UNDER NATIONAL SHIPPING AUTHORITY MASTER LUMP SUM REPAIR CONTRACT-NSA-LUMPSUMREP Sec. 13 Insurance. Article 9 of the NSA-LUMPSUMREP Contract sets forth the Contractor's liabilities and obligations with... 46 Shipping 8 2010-10-01 2010-10-01 false Insurance. Sec. 13 Section 13 Shipping MARITIME...

46 CFR Sec. 15 - Subcontracts.

Science.gov (United States)

2010-10-01

... REPAIRS UNDER NATIONAL SHIPPING AUTHORITY MASTER LUMP SUM REPAIR CONTRACT-NSA-LUMPSUMREP Sec. 15 Subcontracts. Under Article 29 of the NSA-LUMPSUMREP Contract, the Contractor is authorized to subcontract... 46 Shipping 8 2010-10-01 2010-10-01 false Subcontracts. Sec. 15 Section 15 Shipping MARITIME...

Theoretical Interpretation of Pass 8 Fermi-LAT e + + e - Data

Science.gov (United States)

Di Mauro, M.; Manconi, S.; Vittino, A.; Donato, F.; Fornengo, N.; Baldini, L.; Bonino, R.; Di Lalla, N.; Latronico, L.; Maldera, S.; Manfreda, A.; Negro, M.; Pesce-Rollins, M.; Sgrò, C.; Spada, F.

2017-08-01

The flux of positrons and electrons (e + + e -) has been measured by the Fermi Large Area Telescope (LAT) in the energy range between 7 GeV and 2 TeV. We discuss a number of interpretations of Pass 8 Fermi-LAT e + + e - spectrum, combining electron and positron emission from supernova remnants (SNRs) and pulsar wind nebulae (PWNe), or produced by the collision of cosmic rays (CRs) with the interstellar medium. We find that the Fermi-LAT spectrum is compatible with the sum of electrons from a smooth SNR population, positrons from cataloged PWNe, and a secondary component. If we include in our analysis constraints from the AMS-02 positron spectrum, we obtain a slightly worse fit to the e + + e - Fermi-LAT spectrum, depending on the propagation model. As an additional scenario, we replace the smooth SNR component within 0.7 kpc with the individual sources found in Green’s catalog of Galactic SNRs. We find that separate consideration of far and near sources helps to reproduce the e + + e - Fermi-LAT spectrum. However, we show that the fit degrades when the radio constraints on the positron emission from Vela SNR (which is the main contributor at high energies) are taken into account. We find that a break in the power-law injection spectrum at about 100 GeV can also reproduce the measured e + + e - spectrum and, among the CR propagation models that we consider, no reasonable break of the power-law dependence of the diffusion coefficient can modify the electron flux enough to reproduce the observed shape.

Application of immersion phased array UT technique in nickel based alloy weld

International Nuclear Information System (INIS)

Hirasawa, Taiji; Nagai, Satoshi; Murakami, Koji; Yuguchi, Yasuhiro; Ootsubo, Tooru; Naruse, Katsuhiko

2007-01-01

The improvement of defect detection and sizing capabilities for nondestructive inspection technique has been required in order to ensure the reliable operation and life extension of nuclear power plant. Immersion phased array UT technique which is not affected the surface geometry of welds has been developed for inspection of BWR internals such as shroud, shroud support, and so on. Phased array UT technique was applied for shroud support mockup specimen with fatigue crack and partially SCC. From the experimental results, the superior performance of phased array UT for the RPV outside and inside inspection was shown. (author)

Status of advanced UT systems for the nuclear industry

International Nuclear Information System (INIS)

Behravesh, M.; Avioli, M.; Dau, G.; Liu, S.

1987-01-01

An advanced ultrasonic testing (UT) system is a configuration of hardware that includes some type of computer. The computer may be hardwired to perform specific functions or have appropriate software. It may typically be used for data acquisition, signal processing, image generation, pattern recognition and data analysis. Additionally, advanced systems have data storage and are, therefore, different from the standard transducer-pulser/receiver systems that rely on human filtering and written documentation of the filtered data. The number of systems becoming commercially available is growing each year. The NDE managers of utilities, the end users of these systems, are often faced with the decision as to What system is right for my inspection problem? Is an advanced UT system a cost effective way to go? To help this group, the Electric Power Research Institute (EPRI) has initiated a project whose end product will be a Utility NDE Manager's Guide to Advanced UT Systems. A short summary of the available data to date presented here. Tables are used to give an immediate overview of capabilities

Role of common and rare variants in SCN10A

DEFF Research Database (Denmark)

Behr, Elijah R.; Savio-Galimberti, Eleonora; Barc, Julien

2015-01-01

AIMS: Brugada syndrome (BrS) remains genetically heterogeneous and is associated with slowed cardiac conduction. We aimed to identify genetic variation in BrS cases at loci associated with QRS duration. METHODS AND RESULTS: A multi-centre study sequenced seven candidate genes (SCN10A, HAND1, PLN,...

46 CFR Sec. 5 - Accounting.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Accounting. Sec. 5 Section 5 Shipping MARITIME... Sec. 5 Accounting. The General Agent shall record the amounts of compensation paid from the NSA... Accounting Office, at which time the Maritime Administration will take custody of the records. [16 FR 2885...

46 CFR Sec. 12 - Audit.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Audit. Sec. 12 Section 12 Shipping MARITIME... TRANSACTIONS UNDER AGENCY AGREEMENTS Reports and Audit Sec. 12 Audit. (a) The owner will audit as currently as possible subsequent to audit by the agent, all documents relating to the activities, maintenance and...

Red light emission from ZnO:Eu"3"+|CuSCN hetero-junction under cathodic polarization

International Nuclear Information System (INIS)

Sirimanne, P.M.; Minoura, H.

2015-01-01

Eu"3"+ ions were bonded to ZnO ceramic via organic ligand. Surface bonded Eu"3"+ ions were exhibited specific luminescence bands due to electron transitions between f–f intra-configurationally transitions. Further enhancement of luminescence bands was observed by attaching selected oligomers to Eu"3"+ ions. A hetero-junction was prepared by depositing copper-thiocyanate on Eu"3"+ ions bonded ZnO ceramic. Red light emission was observed from surface bonded Eu"3"+ ions in ZnO:Eu"3"+|CuSCN hetero-junction under reverse bias. - Highlights: • Europium doped ZnO ceramic exhibits photo-luminescence. • Semiconductor hetro-junction was prepared. • ZnO:Eu"3"+|CuSCN hetero-junction emits red light under reverse bias.

Autistic-like behaviour in Scn1a+/- mice and rescue by enhanced GABA-mediated neurotransmission.

Science.gov (United States)

Han, Sung; Tai, Chao; Westenbroek, Ruth E; Yu, Frank H; Cheah, Christine S; Potter, Gregory B; Rubenstein, John L; Scheuer, Todd; de la Iglesia, Horacio O; Catterall, William A

2012-09-20

Haploinsufficiency of the SCN1A gene encoding voltage-gated sodium channel Na(V)1.1 causes Dravet's syndrome, a childhood neuropsychiatric disorder including recurrent intractable seizures, cognitive deficit and autism-spectrum behaviours. The neural mechanisms responsible for cognitive deficit and autism-spectrum behaviours in Dravet's syndrome are poorly understood. Here we report that mice with Scn1a haploinsufficiency exhibit hyperactivity, stereotyped behaviours, social interaction deficits and impaired context-dependent spatial memory. Olfactory sensitivity is retained, but novel food odours and social odours are aversive to Scn1a(+/-) mice. GABAergic neurotransmission is specifically impaired by this mutation, and selective deletion of Na(V)1.1 channels in forebrain interneurons is sufficient to cause these behavioural and cognitive impairments. Remarkably, treatment with low-dose clonazepam, a positive allosteric modulator of GABA(A) receptors, completely rescued the abnormal social behaviours and deficits in fear memory in the mouse model of Dravet's syndrome, demonstrating that they are caused by impaired GABAergic neurotransmission and not by neuronal damage from recurrent seizures. These results demonstrate a critical role for Na(V)1.1 channels in neuropsychiatric functions and provide a potential therapeutic strategy for cognitive deficit and autism-spectrum behaviours in Dravet's syndrome.

Electric field-induced hole transport in copper(i) thiocyanate (CuSCN) thin-films processed from solution at room temperature

KAUST Repository

Pattanasattayavong, Pichaya; Ndjawa, Guy Olivier Ngongang; Zhao, Kui; Chou, Kang Wei; Yaacobi-Gross, Nir; O'Regan, Brian C.; Amassian, Aram; Anthopoulos, Thomas D.

2013-01-01

The optical, structural and charge transport properties of solution-processed films of copper(i) thiocyanate (CuSCN) are investigated in this work. As-processed CuSCN films of ∼20 nm in thickness are found to be nano-crystalline, highly transparent and exhibit intrinsic hole transporting characteristics with a maximum field-effect mobility in the range of 0.01-0.1 cm2 V-1 s-1. © 2013 The Royal Society of Chemistry.

Status and Prospects for Combined GPS LOD and VLBI UT1 Measurements

Science.gov (United States)

Senior, K.; Kouba, J.; Ray, J.

2010-01-01

A Kalman filter was developed to combine VLBI estimates of UT1-TAI with biased length of day (LOD) estimates from GPS. The VLBI results are the analyses of the NASA Goddard Space Flight Center group from 24-hr multi-station observing sessions several times per week and the nearly daily 1-hr single-baseline sessions. Daily GPS LOD estimates from the International GNSS Service (IGS) are combined with the VLBI UT1-TAI by modeling the natural excitation of LOD as the integral of a white noise process (i.e., as a random walk) and the UT1 variations as the integration of LOD, similar to the method described by Morabito et al. (1988). To account for GPS technique errors, which express themselves mostly as temporally correlated biases in the LOD measurements, a Gauss-Markov model has been added to assimilate the IGS data, together with a fortnightly sinusoidal term to capture errors in the IGS treatments of tidal effects. Evaluated against independent atmospheric and oceanic axial angular momentum (AAM + OAM) excitations and compared to other UT1/LOD combinations, ours performs best overall in terms of lowest RMS residual and highest correlation with (AAM + OAM) over sliding intervals down to 3 d. The IERS 05C04 and Bulletin A combinations show strong high-frequency smoothing and other problems. Until modified, the JPL SPACE series suffered in the high frequencies from not including any GPS-based LODs. We find, surprisingly, that further improvements are possible in the Kalman filter combination by selective rejection of some VLBI data. The best combined results are obtained by excluding all the 1-hr single-baseline UT1 data as well as those 24-hr UT1 measurements with formal errors greater than 5 μs (about 18% of the multi-baseline sessions). A rescaling of the VLBI formal errors, rather than rejection, was not an effective strategy. These results suggest that the UT1 errors of the 1-hr and weaker 24-hr VLBI sessions are non-Gaussian and more heterogeneous than expected

Upgrade tracking with the UT Hits

CERN Document Server

Gandini, P; Wang, J

2014-01-01

The performance of the LHCb tracking system for the upgrade on long tracks is evaluated in terms of efficiency and ghost rate reduction for several different sets of requirements. We find that the efficiency is quite high and that the ghost rate reduction is substantial. We also describe the current algorithm for adding UT hits to the tracks.

Why do intimate partners live apart? Evidence on LAT relationships across Europe

NARCIS (Netherlands)

Liefbroer, A.C.; Poortman, A.R.; Seltzer, J.A.

2015-01-01

BACKGROUND: Most research asks whether or not cohabitation has come to rival marriage. Little is known about the meaning of living apart together (LAT) relationships, and whether LAT is an alternative to marriage and cohabitation or a dating relationship. OBJECTIVE: We examine across Europe: (1) the

Efficient and stable CH3NH3PbI3-x(SCN)x planar perovskite solar cells fabricated in ambient air with low-temperature process

Science.gov (United States)

Zhang, Zongbao; Zhou, Yang; Cai, Yangyang; Liu, Hui; Qin, Qiqi; Lu, Xubing; Gao, Xingsen; Shui, Lingling; Wu, Sujuan; Liu, Jun-Ming

2018-02-01

Planar perovskite solar cells (PSCs) based on CH3NH3PbI3-x(SCN)x (SCN: thiocyanate) active layer and low-temperature processed TiO2 films are fabricated by a sequential two-step method in ambient air. Here, alkali thiocyanates (NaSCN, KSCN) are added into Pb(SCN)2 precursor to improve the microstructure of CH3NH3PbI3-x(SCN)x perovskite layers and performance of the as-prepared PSCs. At the optimum concentrations of alkali thiocyanates as additives, the as-prepared NaSCN-modified and KSCN-modified PSCs demonstrate the efficiencies of 16.59% and 15.63% respectively, being much higher than 12.73% of the reference PSCs without additives. This improvement is primarily ascribed to the enhanced electron transport, reduced recombination rates and much improved microstructures with large grain size and low defect density at grain boundaries. Importantly, it is revealed that the modified PSCs at the optimized concentrations of alkali thiocyanates additives exhibit remarkably improved stability than the reference PSCs against humid circumstance, and a continuous exposure to humid air without encapsulation over 45 days only records about 5% degradation of the efficiency. These findings provide a facile approach to fabricate efficient and stable PSCs by low processing temperature in ambient air, both of which are highly preferred for future practical applications of PSCs.

Search for Spatially Extended Fermi-LAT Sources Using Two Years of Data

Energy Technology Data Exchange (ETDEWEB)

Lande, Joshua; Ackermann, Markus; Allafort, Alice; Ballet, Jean; Bechtol, Keith; Burnett, Toby; Cohen-Tanugi, Johann; Drlica-Wagner, Alex; Funk, Stefan; Giordano, Francesco; Grondin, Marie-Helene; Kerr, Matthew; Lemoine-Goumard, Marianne

2012-07-13

Spatial extension is an important characteristic for correctly associating {gamma}-ray-emitting sources with their counterparts at other wavelengths and for obtaining an unbiased model of their spectra. We present a new method for quantifying the spatial extension of sources detected by the Large Area Telescope (LAT), the primary science instrument on the Fermi Gamma-ray Space Telescope (Fermi). We perform a series of Monte Carlo simulations to validate this tool and calculate the LAT threshold for detecting the spatial extension of sources. We then test all sources in the second Fermi -LAT catalog (2FGL) for extension. We report the detection of seven new spatially extended sources.

Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders

NARCIS (Netherlands)

Wolff, Markus; Johannesen, Katrine M; Hedrich, Ulrike B S; Masnada, Silvia; Rubboli, Guido; Gardella, Elena; Lesca, Gaetan; Ville, Dorothée; Milh, Mathieu; Villard, Laurent; Afenjar, Alexandra; Chantot-Bastaraud, Sandra; Mignot, Cyril; Lardennois, Caroline; Nava, Caroline; Schwarz, Niklas; Gérard, Marion; Perrin, Laurence; Doummar, Diane; Auvin, Stéphane; Miranda, Maria J; Hempel, Maja; Brilstra, Eva; Knoers, Nine; Verbeek, Nienke; van Kempen, Marjan; Braun, Kees P; Mancini, Grazia; Biskup, Saskia; Hörtnagel, Konstanze; Döcker, Miriam; Bast, Thomas; Loddenkemper, Tobias; Wong-Kisiel, Lily; Baumeister, Friedrich M; Fazeli, Walid; Striano, Pasquale; Dilena, Robertino; Fontana, Elena; Zara, Federico; Kurlemann, Gerhard; Klepper, Joerg; Thoene, Jess G; Arndt, Daniel H; Deconinck, Nicolas; Schmitt-Mechelke, Thomas; Maier, Oliver; Muhle, Hiltrud; Wical, Beverly; Finetti, Claudio; Brückner, Reinhard; Pietz, Joachim; Golla, Günther; Jillella, Dinesh; Linnet, Karen M; Charles, Perrine; Moog, Ute; Õiglane-Shlik, Eve; Mantovani, John F; Park, Kristen; Deprez, Marie; Lederer, Damien; Mary, Sandrine; Scalais, Emmanuel; Selim, Laila; Van Coster, Rudy; Lagae, Lieven; Nikanorova, Marina; Hjalgrim, Helle; Korenke, G Christoph; Trivisano, Marina; Specchio, Nicola; Ceulemans, Berten; Dorn, Thomas; Helbig, Katherine L; Hardies, Katia; Stamberger, Hannah; de Jonghe, Peter; Weckhuysen, Sarah; Lemke, Johannes R; Krägeloh-Mann, Ingeborg; Helbig, Ingo; Kluger, Gerhard; Lerche, Holger; Møller, Rikke S

2017-01-01

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with

Efficient modeling of chiral media using SCN-TLM method

Directory of Open Access Journals (Sweden)

Yaich M.I.

2004-01-01

Full Text Available An efficient approach allowing to include linear bi-isotropic chiral materials in time-domain transmission line matrix (TLM calculations by employing recursive evaluation of the convolution of the electric and magnetic fields and susceptibility functions is presented. The new technique consists to add both voltage and current sources in supplementary stubs of the symmetrical condensed node (SCN of the TLM method. In this article, the details and the complete description of this approach are given. A comparison of the obtained numerical results with those of the literature reflects its validity and efficiency.

Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.

Science.gov (United States)

Lal, Dennis; Reinthaler, Eva M; Dejanovic, Borislav; May, Patrick; Thiele, Holger; Lehesjoki, Anna-Elina; Schwarz, Günter; Riesch, Erik; Ikram, M Arfan; van Duijn, Cornelia M; Uitterlinden, Andre G; Hofman, Albert; Steinböck, Hannelore; Gruber-Sedlmayr, Ursula; Neophytou, Birgit; Zara, Federico; Hahn, Andreas; Gormley, Padhraig; Becker, Felicitas; Weber, Yvonne G; Cilio, Maria Roberta; Kunz, Wolfram S; Krause, Roland; Zimprich, Fritz; Lemke, Johannes R; Nürnberg, Peter; Sander, Thomas; Lerche, Holger; Neubauer, Bernd A

2016-01-01

The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.

Application of ultrasonic inspection technique for crack depth sizing on nickel based alloy weld. Part 3. Establishment of UT procedure for crack depth sizing by phased array UT

International Nuclear Information System (INIS)

Hirasawa, Taiji; Okada, Hisao; Fukutomi, Hiroyuki

2012-01-01

Recently, it is reported that the primary water stress corrosion cracking (PWSCC) was occurred at the nickel based alloy weld components such as steam generator safe end weld, reactor vessel safe end weld, and so on, in PWR. Defect detection and sizing is important in order to ensure the reliable operation and life extension of nuclear power plants. In the reactor vessel safe end weld, it was impossible to measure crack depth of PWSCC. The crack was detected in the axial direction of the safe end weld. Furthermore, the crack had some features such as shallow, large aspect ratio (ratio of crack depth and length), sharp geometry of crack tip, and so on. Therefore, development and improvement of defect detection and sizing capabilities for ultrasonic testing (UT) is required. Phased array technique was applied to nickel based alloy weld specimen with SCC cracks. From the experimental results, good accuracy of crack depth sizing by phased array UT for the inside inspection was shown. From these results, UT procedure for crack depth sizing was verified. Therefore, effectiveness of phased array UT for crack depth sizing in the nickel based alloy welds was shown. (author)

Characterisation of L-Type Amino Acid Transporter 1 (LAT1 Expression in Human Skeletal Muscle by Immunofluorescent Microscopy

Directory of Open Access Journals (Sweden)

Nathan Hodson

2017-12-01

Full Text Available The branch chain amino acid leucine is a potent stimulator of protein synthesis in skeletal muscle. Leucine rapidly enters the cell via the L-Type Amino Acid Transporter 1 (LAT1; however, little is known regarding the localisation and distribution of this transporter in human skeletal muscle. Therefore, we applied immunofluorescence staining approaches to visualise LAT1 in wild type (WT and LAT1 muscle-specific knockout (mKO mice, in addition to basal human skeletal muscle samples. LAT1 positive staining was visually greater in WT muscles compared to mKO muscle. In human skeletal muscle, positive LAT1 staining was noted close to the sarcolemmal membrane (dystrophin positive staining, with a greater staining intensity for LAT1 observed in the sarcoplasmic regions of type II fibres (those not stained positively for myosin heavy-chain 1, Type II—25.07 ± 5.93, Type I—13.71 ± 1.98, p < 0.01, suggesting a greater abundance of this protein in these fibres. Finally, we observed association with LAT1 and endothelial nitric oxide synthase (eNOS, suggesting LAT1 association close to the microvasculature. This is the first study to visualise the distribution and localisation of LAT1 in human skeletal muscle. As such, this approach provides a validated experimental platform to study the role and regulation of LAT1 in human skeletal muscle in response to various physiological and pathophysiological models.

High-Efficiency Fullerene Solar Cells Enabled by a Spontaneously Formed Mesostructured CuSCN-Nanowire Heterointerface

KAUST Repository

Sit, Wai-Yu

2018-02-02

Fullerenes and their derivatives are widely used as electron acceptors in bulk-heterojunction organic solar cells as they combine high electron mobility with good solubility and miscibility with relevant semiconducting polymers. However, studies on the use of fullerenes as the sole photogeneration and charge-carrier material are scarce. Here, a new type of solution-processed small-molecule solar cell based on the two most commonly used methanofullerenes, namely [6,6]-phenyl-C61-butyric acid methyl ester (PC60BM) and [6,6]-phenyl-C71-butyric acid methyl ester (PC70BM), as the light absorbing materials, is reported. First, it is shown that both fullerene derivatives exhibit excellent ambipolar charge transport with balanced hole and electron mobilities. When the two derivatives are spin-coated over the wide bandgap p-type semiconductor copper (I) thiocyanate (CuSCN), cells with power conversion efficiency (PCE) of ≈1%, are obtained. Blending the CuSCN with PC70BM is shown to increase the performance further yielding cells with an open-circuit voltage of ≈0.93 V and a PCE of 5.4%. Microstructural analysis reveals that the key to this success is the spontaneous formation of a unique mesostructured p–n-like heterointerface between CuSCN and PC70BM. The findings pave the way to an exciting new class of single photoactive material based solar cells.

46 CFR Sec. 18 - Group classification.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Group classification. Sec. 18 Section 18 Shipping... Sec. 18 Group classification. In the preparation of specifications, Job Orders, Supplemental Job... inserted thereon: Number Classification 41 Maintenance Repairs (deck, engine and stewards department...

Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders

DEFF Research Database (Denmark)

Wolff, Markus; Johannesen, Katrine M.; Hedrich, Ulrike B. S.

2017-01-01

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infa...

Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

Science.gov (United States)

Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M; Morte, Beatriz; Bernal, Juan

2014-01-01

Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.

Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

Directory of Open Access Journals (Sweden)

Bárbara Núñez

Full Text Available Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2 cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8, in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.

DIRAC framework evaluation for the Fermi-LAT and CTA experiments

International Nuclear Information System (INIS)

Arrabito, L; Cohen-Tanugi, J; Piron, F; Renaud, M; Rolland, V; Diaz, R Graciani; Longo, F; Kuss, M; Sapunov, M; Tsaregorodtsev, A; Zimmer, S

2014-01-01

DIRAC (Distributed Infrastructure with Remote Agent Control) is a general framework for the management of tasks over distributed heterogeneous computing environments. It has been originally developed to support the production activities of the LHCb (Large Hadron Collider Beauty) experiment and today is extensively used by several particle physics and biology communities. Current (Fermi Large Area Telescope – LAT) and planned (Cherenkov Telescope Array – CTA) new generation astrophysical/cosmological experiments, with very large processing and storage needs, are currently investigating the usability of DIRAC in this context. Each of these use cases has some peculiarities: Fermi-LAT will interface DIRAC to its own workflow system to allow the access to the grid resources, while CTA is using DIRAC as workflow management system for Monte Carlo production and analysis on the grid. We describe the prototype effort that we lead toward deploying a DIRAC solution for some aspects of Fermi-LAT and CTA needs.

LAT Onboard Science: Gamma-Ray Burst Identification

International Nuclear Information System (INIS)

Kuehn, Frederick; Hughes, Richard; Smith, Patrick; Winer, Brian; Bonnell, Jerry; Norris, Jay; Ritz, Steven; Russell, James

2007-01-01

The main goal of the Large Area Telescope (LAT) onboard science program is to provide quick identification and localization of Gamma Ray Bursts (GRB) onboard the LAT for follow-up observations by other observatories. The GRB identification and localization algorithm will provide celestial coordinates with an error region that will be distributed via the Gamma ray burst Coordinate Network (GCN). We present results that show our sensitivity to bursts as characterized using Monte Carlo simulations of the GLAST observatory. We describe and characterize the method of onboard track determination and the GRB identification and localization algorithm. Onboard track determination is considerably different than in the on-ground case, resulting in a substantially altered point spread function. The algorithm contains tunable parameters which may be adjusted after launch when real bursts characteristics at very high energies have been identified

A clinical case of epilepsy in a female patient with double mutations in the SCN2A and PCDH19 genes

Directory of Open Access Journals (Sweden)

M. B. Mironov

2017-01-01

Full Text Available The paper describes a 6-year-old female patient with epilepsy caused by mutations in the SCN2A and PCDH19 genes, which clinically appears as epileptic seizures, drug-resistant epilepsy, secondary microcephaly, mental retardation, and autism. It reviews the literature regarding both mutations. World literature lacks publications on a combination of two SCN2A and PCDH19 mutations in one female patient with epileptic encephalopathies.

A Switchable Molecular Dielectric with Two Sequential Reversible Phase Transitions: [(CH3)4P]4[Mn(SCN)6].

Science.gov (United States)

Li, Qiang; Shi, Ping-Ping; Ye, Qiong; Wang, Hui-Ting; Wu, De-Hong; Ye, Heng-Yun; Fu, Da-Wei; Zhang, Yi

2015-11-16

A new organic-inorganic hybrid switchable and tunable dielectric compound, [(CH3)4P]4[Mn(SCN)6] (1), exhibits three distinct dielectric states above room temperature and undergoes two reversible solid-state phase transitions, including a structural phase transition at 330 K and a ferroelastic phase transition with the Aizu notation of mmmF2/m at 352 K. The variable-temperature structural analyses disclose that the origin of the phase transitions and dielectric anomalies can be ascribed to the reorientation or motion of both the [(CH3)4P](+) cations and [Mn(SCN)6](4-) anions in solid-state crystals.

The Novel SCN''- Ion-selective Electrode Based on the 1-Benzyl-3-(4-nitrophenyl) thio-urea Ionophore

Energy Technology Data Exchange (ETDEWEB)

Lee, Kyung Mi; Kang, Dong Hyeon; Choe, Ju Eun; You, Jung Min; Go, Min Jeong; Lee, Jung Seong; Jeon, Seung Won [Chungnam National University, Daejeon (Korea, Republic of)

2014-09-15

A potentiometric sensor based on the 1-benzyl-3-(4-nitrophenyl) thio-urea was synthesized and tested as an ionophore in PVC based membrane sensor towards SCN - ions. This membrane exhibits a linear stable response over a wide concentration range (1.0 × 10''-5 to 1.0 × 10''-2 M) with a slope of -59.2 mV/dec., a detection limit of log[SCN''- ] = -5.05, and a selectivity coefficient for thiocyanate against perchlorate anion of logK{sub s}cn''pot = -0.133. The selectivity series of the membrane is as follows: SCN''- > ClO{sub 4}''- > I''- >NO{sub 3}''- >HSO{sub 3}''- > Cl''-HSO{sub '}'-''4 > F''- > CH{sub 3}COO''- > HCO''-''3 > Br''- > H{sub 2}PO{sub 4}''- > SO{sub 3}''-''2 > SO{sub 4}''-''2 > CO{sub 3}''-''2. The proposed electrode showed good selectivity and a good response for the SCN''- ion over a wide variety of other anions in pH 6.0 buffer solutions and has a fast response time of about < 5s.. The influences of the membrane by pH, ionophore, and plasticizer were studied.

MicroRNA-181b promotes ovarian cancer cell growth and invasion by targeting LATS2

Energy Technology Data Exchange (ETDEWEB)

Xia, Ying; Gao, Yan, E-mail: gaoyanhdhos@126.com

2014-05-09

Highlights: • miR-181b is upregulated in human ovarian cancer tissues. • miR-181b promotes ovarian cancer cell proliferation and invasion. • LATS2 is a direct target of miR-181b. • LATS2 is involved in miR-181b-induced ovarian cancer cell growth and invasion. - Abstract: MicroRNAs (miRNAs) are strongly implicated in tumorigenesis and metastasis. In this study, we showed significant upregulation of miR-181b in ovarian cancer tissues, compared with the normal ovarian counterparts. Forced expression of miR-181b led to remarkably enhanced proliferation and invasion of ovarian cancer cells while its knockdown induced significant suppression of these cellular events. The tumor suppressor gene, LATS2 (large tumor suppressor 2), was further identified as a novel direct target of miR-181b. Specifically, miR-181b bound directly to the 3′-untranslated region (UTR) of LATS2 and suppressed its expression. Restoration of LATS2 expression partially reversed the oncogenic effects of miR-181b. Our results indicate that miR-181b promotes proliferation and invasion by targeting LATS2 in ovarian cancer cells. These findings support the utility of miR-181b as a potential diagnostic and therapeutic target for ovarian cancer.

Copper(I) Thiocyanate (CuSCN) Hole-Transport Layers Processed from Aqueous Precursor Solutions and Their Application in Thin-Film Transistors and Highly Efficient Organic and Organometal Halide Perovskite Solar Cells

KAUST Repository

Wijeyasinghe, Nilushi

2017-07-28

This study reports the development of copper(I) thiocyanate (CuSCN) hole-transport layers (HTLs) processed from aqueous ammonia as a novel alternative to conventional n-alkyl sulfide solvents. Wide bandgap (3.4–3.9 eV) and ultrathin (3–5 nm) layers of CuSCN are formed when the aqueous CuSCN–ammine complex solution is spin-cast in air and annealed at 100 °C. X-ray photoelectron spectroscopy confirms the high compositional purity of the formed CuSCN layers, while the high-resolution valence band spectra agree with first-principles calculations. Study of the hole-transport properties using field-effect transistor measurements reveals that the aqueous-processed CuSCN layers exhibit a fivefold higher hole mobility than films processed from diethyl sulfide solutions with the maximum values approaching 0.1 cm2 V−1 s−1. A further interesting characteristic is the low surface roughness of the resulting CuSCN layers, which in the case of solar cells helps to planarize the indium tin oxide anode. Organic bulk heterojunction and planar organometal halide perovskite solar cells based on aqueous-processed CuSCN HTLs yield power conversion efficiency of 10.7% and 17.5%, respectively. Importantly, aqueous-processed CuSCN-based cells consistently outperform devices based on poly(3,4-ethylenedioxythiophene) polystyrene sulfonate HTLs. This is the first report on CuSCN films and devices processed via an aqueous-based synthetic route that is compatible with high-throughput manufacturing and paves the way for further developments.

Environmental Tests of the Flight GLAST LAT Tracker Towers

Energy Technology Data Exchange (ETDEWEB)

Bagagli, R.; Baldini, L.; Bellazzini, R.; Barbiellini, G.; Belli, F.; Borden, T.; Brez, A.; Brigida, M.; Caliandro, G.A.; Cecchi, C.; Cohen-Tanugi, J.; Angelis, A.De; Drell, P.; Favuzzi, C.; Fusco, P.; Gargano, F.; Germani, S.; Giglietto, N.; Giordano, F.; Goodman, J.; Himel, T.

2008-03-12

The Gamma-ray Large Area Space telescope (GLAST) is a gamma-ray satellite scheduled for launch in 2008. Before the assembly of the Tracker subsystem of the Large Area Telescope (LAT) science instrument of GLAST, every component (tray) and module (tower) has been subjected to extensive ground testing required to ensure successful launch and on-orbit operation. This paper describes the sequence and results of the environmental tests performed on an engineering model and all the flight hardware of the GLAST LAT Tracker. Environmental tests include vibration testing, thermal cycles and thermal-vacuum cycles of every tray and tower as well as the verification of their electrical performance.

75 FR 73983 - Proposed Modification of the Salt Lake City, UT, Class B Airspace Area; Public Meetings

Science.gov (United States)

2010-11-30

... of the Salt Lake City, UT, Class B Airspace Area; Public Meetings AGENCY: Federal Aviation... Class B airspace area at Salt Lake City, UT. The purpose of these meetings is to provide interested... Road, Ogden, UT, 84405. (2) The meeting on Tuesday, February 1, 2011, will be held in the Conference...

Common and rare variants in SCN10A> modulate the risk of atrial fibrillation

DEFF Research Database (Denmark)

Jabbari, Javad; Olesen, Morten S.; Yuan, Lei

2015-01-01

Background: Genome-wide assocn. studies have shown that the common single nucleotide polymorphism rs6800541 located in SCN10A, encoding the voltage-gated Nav1.8 sodium channel, is assocd. with PR-interval prolongation and atrial fibrillation (AF). Single nucleotide polymorphism rs6800541 is in hi...

Reduced Penetrance and Variable Expression of SCN5A Mutations and the Importance of Co-inherited Genetic Variants: Case Report and Review of the Literature

Directory of Open Access Journals (Sweden)

T. Robyns, MD.

2014-05-01

Full Text Available Mutations in the SCN5A gene are responsible for multiple phenotypical presentations including Brugada syndrome, long QT syndrome, progressive familial heart block, sick sinus syndrome, dilated cardiomyopathy, lone atrial fibrillation and multiple overlap syndromes. These different phenotypic expressions of a mutation in a single gene can be explained by variable expression and reduced penetrance. One of the possible explanations of these phenomena is the co-inheritance of genetic variants. We describe a family where the individuals exhibit a compound heterozygosity in the SCN5A gene including a mutation (R1632H and a new variant (M858L. Individuals with both the mutation and new variant present with a more severe phenotype including spontaneous atrial tachyarrhythmia at young age. We give an overview of the different phenotypes of "SCN5A disease" and discuss the importance of co-inherited genetic variants in the expression of SCN5A disease.

Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.

Directory of Open Access Journals (Sweden)

Dennis Lal

Full Text Available The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic.We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients.We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%. Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1 are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test, previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.

Activation of Rab GTPase Sec4 by its GEF Sec2 is required for prospore membrane formation during sporulation in yeast Saccharomyces cerevisiae.

Science.gov (United States)

Suda, Yasuyuki; Tachikawa, Hiroyuki; Inoue, Ichiro; Kurita, Tomokazu; Saito, Chieko; Kurokawa, Kazuo; Nakano, Akihiko; Irie, Kenji

2018-02-01

Sec2 activates Sec4 Rab GTPase as a guanine nucleotide exchange factor for the recruitment of downstream effectors to facilitate tethering and fusion of post-Golgi vesicles at the plasma membrane. During the meiosis and sporulation of budding yeast, post-Golgi vesicles are transported to and fused at the spindle pole body (SPB) to form a de novo membrane, called the prospore membrane. Previous studies have revealed the role of the SPB outer surface called the meiotic outer plaque (MOP) in docking and fusion of post-Golgi vesicles. However, the upstream molecular machinery for post-Golgi vesicular fusion that facilitates prospore membrane formation remains enigmatic. Here, we demonstrate that the GTP exchange factor for Sec4, Sec2, participates in the formation of the prospore membrane. A conditional mutant in which the SEC2 expression is shut off during sporulation showed sporulation defects. Inactivation of Sec2 caused Sec4 targeting defects along the prospore membranes, thereby causing insufficient targeting of downstream effectors and cargo proteins to the prospore membrane. These results suggest that the activation of Sec4 by Sec2 is required for the efficient supply of post-Golgi vesicles to the prospore membrane and thus for prospore membrane formation/extension and subsequent deposition of spore wall materials. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Sodium channel SCN8A (Nav1.6: properties and de novo mutations in epileptic encephalopathy and intellectual disability

Directory of Open Access Journals (Sweden)

Janelle Elizabeth O'Brien

2013-10-01

Full Text Available The sodium channel Nav1.6, encoded by the gene SCN8A, is one of the major voltage-gated channels in human brain. The sequences of sodium channels have been highly conserved during evolution, and minor changes in biophysical properties can have a major impact in vivo. Insight into the role of Nav1.6 has come from analysis of spontaneous and induced mutations of mouse Scn8a during the past 18 years. Only within the past year has the role of SCN8A in human disease become apparent from whole exome and genome sequences of patients with sporadic disease. Unique features of Nav1.6 include its contribution to persistent current, resurgent current, repetitive neuronal firing, and subcellular localization at the axon initial segment and nodes of Ranvier. Loss of Nav1.6 activity results in reduced neuronal excitability, while gain-of-function mutations can increase neuronal excitability. Mouse Scn8a (med mutants exhibit movement disorders including ataxia, tremor and dystonia. Thus far, more than ten human de novo mutations have been identified in patients with two types of disorders, epileptic encephalopathy and intellectual disability. We review these human mutations as well as the unique features of Nav1.6 that contribute to its role in determining neuronal excitability in vivo. A supplemental figure illustrating the positions of amino acid residues within the 4 domains and 24 transmembrane segments of Nav1.6 is provided to facilitate the location of novel mutations within the channel protein.

Bioprospecting the lat gene in soil samples

Indian Academy of Sciences (India)

Unknown

of the work reported here was to discover the presence of the lat gene in ... and the mixture was incubated at 65°C for an hour. On reaching ... 70% ethanol for 4 h at room temperature. Ethanol (70 .... Prolonged exposure of one week confirmed ...

Ut pictura poesis: simbiosis dibujo y haiku

OpenAIRE

RAUSELL LLISO, ALMA

2015-01-01

Invetigación sobre la simbiosis entre dibujo y haikus. La intención no es ilustrar el haiku sino crear una retroalimentación entre ambas disciplinas fomentando la idea de un espectador activo que se involucre en el trabajo. Rausell Lliso, A. (2014). Ut pictura poesis: simbiosis dibujo y haiku. http://hdl.handle.net/10251/47638. Archivo delegado

Pitfalls in genetic testing: the story of missed SCN1A mutations

OpenAIRE

Djémié, T.; Weckhuysen, S.; von Spiczak, S.; Carvill, G. L.; Jaehn, J.; Anttonen, A-K; Brilstra, E.; Caglayan, H. S.; de Kovel, C. G.; Depienne, C.; Gaily, E.; Gennaro, E.; Giraldez, B. G.; Gormley, P.; Guerrero-López, R.

2016-01-01

BACKGROUND: Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated ...

Pitfalls in genetic testing : the story of missed SCN1A mutations

OpenAIRE

Djémié, Tania; Weckhuysen, Sarah; von Spiczak, Sarah; Carvill, Gemma L; Jaehn, Johanna; Anttonen, Anna-Kaisa; Brilstra, Eva; Caglayan, Hande S; de Kovel, Carolien G; Depienne, Christel; Gaily, Eija; Gennaro, Elena; Giraldez, Beatriz G; Gormley, Padhraig; Guerrero-López, Rosa

2016-01-01

BACKGROUND: Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated ...

Imaging the L-type amino acid transporter-1 (LAT1 with Zr-89 immunoPET.

Directory of Open Access Journals (Sweden)

Oluwatayo F Ikotun

Full Text Available The L-type amino acid transporter-1 (LAT1, SLC7A5 is upregulated in a wide range of human cancers, positively correlated with the biological aggressiveness of tumors, and a promising target for both imaging and therapy. Radiolabeled amino acids such as O-(2-[(18F]fluoroethyl-L-tyrosine (FET that are transport substrates for system L amino acid transporters including LAT1 have met limited success for oncologic imaging outside of the brain, and thus new strategies are needed for imaging LAT1 in systemic cancers. Here, we describe the development and biological evaluation of a novel zirconium-89 labeled antibody, [(89Zr]DFO-Ab2, targeting the extracellular domain of LAT1 in a preclinical model of colorectal cancer. This tracer demonstrated specificity for LAT1 in vitro and in vivo with excellent tumor imaging properties in mice with xenograft tumors. PET imaging studies showed high tumor uptake, with optimal tumor-to-non target contrast achieved at 7 days post administration. Biodistribution studies demonstrated tumor uptake of 10.5 ± 1.8 percent injected dose per gram (%ID/g at 7 days with a tumor to muscle ratio of 13 to 1. In contrast, the peak tumor uptake of the radiolabeled amino acid [(18F]FET was 4.4 ± 0.5 %ID/g at 30 min after injection with a tumor to muscle ratio of 1.4 to 1. Blocking studies with unlabeled anti-LAT1 antibody demonstrated a 55% reduction of [(89Zr]DFO-Ab2 accumulation in the tumor at 7 days. These results are the first report of direct PET imaging of LAT1 and demonstrate the potential of immunoPET agents for imaging specific amino acid transporters.

Prevalence of SCN1A-related dravet syndrome among children reported with seizures following vaccination: a population-based ten-year cohort study.

Directory of Open Access Journals (Sweden)

Nienke E Verbeek

Full Text Available OBJECTIVES: To determine the prevalence of Dravet syndrome, an epileptic encephalopathy caused by SCN1A-mutations, often with seizure onset after vaccination, among infants reported with seizures following vaccination. To determine differences in characteristics of reported seizures after vaccination in children with and without SCN1A-related Dravet syndrome. METHODS: Data were reviewed of 1,269 children with seizures following immunization in the first two years of life, reported to the safety surveillance system of the Dutch national immunization program between 1 January 1997 and 31 December 2006. Selective, prospective follow-up was performed of children with clinical characteristics compatible with a diagnosis of Dravet syndrome. RESULTS: In 21.9% (n = 279 of children, a diagnosis of Dravet syndrome could not be excluded based on available clinical data (median age at follow-up 16 months. Additional follow-up data were obtained in 83.9% (n = 234 of these children (median age 8.5 years. 15 (1.2% of 1,269; 95%CI:0.6 to 1.8% children were diagnosed with SCN1A-related Dravet syndrome. Of all reported seizures following vaccinations in the first year of life, 2.5% (95%CI:1.3 to 3.6% were due to SCN1A-related Dravet syndrome, as were 5.9% of reported seizures (95%CI:3.1 to 8.7% after 2(nd or 3(rd DTP-IPV-Hib vaccination. Seizures in children with SCN1A-related Dravet syndrome occurred more often with a body temperature below 38.5°C (57.9% vs. 32.6%, p = 0.020 and reoccurred more often after following vaccinations (26.7% vs. 4.0%, p = 0.003, than in children without a diagnosis of SCN1A-related Dravet Syndrome. CONCLUSIONS: Although Dravet syndrome is a rare genetic epilepsy syndrome, 2.5% of reported seizures following vaccinations in the first year of life in our cohort occurred in children with this disorder. Knowledge on the specific characteristics of vaccination-related seizures in this syndrome might promote early diagnosis

Kinetics of photocurrent generation and an efficient charge separation of a dye-sensitized n-Cu2O/p-CuSCN junction photoelectrode in a solid-state photovoltaic cell

International Nuclear Information System (INIS)

Fernando, C A N; Kumara, N T R N; Gamage, T N

2010-01-01

A Cu/n-Cu 2 O/dye/p-CuSCN junction photoelectrode is fabricated to produce a solid-state dye-sensitized photovoltaic cell. Samples are characterized by XRD, SEM and surface resistivity measurements. Photocurrent generation is found due to light absorption of n-Cu 2 O thin film and dye sensitization between p-CuSCN and the dye. Kinetics of the photocurrent generation of the dye sensitization is studied solving the rate equations by the iteration method obtaining a relationship for the photocurrent quantum efficiency (Φ) depending on the surface concentration (D o ) of the dye and the rate constants of the reactions with connection to the dye sensitization process. The solution obtained in the steady state by iteration is found to be of the form Φ = AD o −BD o 2 (A and B are constants related to the reaction rates of the photocurrent generation process and the concentration of the n-Cu 2 O film). The variation of the n-Cu 2 O concentration with photocurrent is presented. A photocurrent enhancement is observed for the Cu/n-Cu 2 O/dye/p-CuSCN photovoltaic cell compared to that of Cu/n-Cu 2 O, Cu/p-CuSCN/dye and Cu/n-Cu 2 O/p-CuSCN photovoltaic cells. Good rectification characteristics are observed for the Cu/n-Cu 2 O/p-CuSCN photoelectrode compared to that of Cu/n-Cu 2 O and Cu/p-CuSCN photoelectrodes. Photocurrent enhancement is found due to the efficient charge separation process at the n–p junction. Energy band structures of the n–p junction are proposed according to the onset potentials which are used to discuss the mechanism of the efficient charge separation suppressing the recombination process

Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome

DEFF Research Database (Denmark)

Petitprez, Séverine; Jespersen, Thomas; Pruvot, Etienne

2008-01-01

S SCN5A mutation. METHODS AND RESULTS: SCN5A was screened for mutations in a male patient with type-1 BrS pattern ECG. Wild-type (WT) and mutant Na(v)1.5 channels were expressed in HEK293 cells. Sodium currents (I(Na)) were analysed using the whole-cell patch-clamp technique at 37 degrees C......AIMS: Brugada syndrome (BrS) is characterized by arrhythmias leading to sudden cardiac death. BrS is caused, in part, by mutations in the SCN5A gene, which encodes the sodium channel alpha-subunit Na(v)1.5. Here, we aimed to characterize the biophysical properties and consequences of a novel Br....... The electrophysiological effects of the mutation were simulated using the Luo-Rudy model, into which the transient outward current (I(to)) was incorporated. A new mutation (C1850S) was identified in the Na(v)1.5 C-terminal domain. In HEK293 cells, mutant I(Na) density was decreased by 62% at -20 mV. Inactivation of mutant...

The first pseudo-ternary thiocyanate containing two alkali metals. Synthesis and single-crystal structure of LiK{sub 2}[SCN]{sub 3}

Energy Technology Data Exchange (ETDEWEB)

Reckeweg, Olaf; DiSalvo, Francis J. [Cornell Univ., Ithaca, NY (United States). Baker Lab.

2016-04-01

A procedure was empirically developed to prepare the compound LiK{sub 2}[SCN]{sub 3}, which forms colorless, transparent, very fragile, and extremely hygroscopic thin rectangular plates. Its unique crystal structure was determined by single-crystal X-ray diffraction. LiK{sub 2}[SCN]{sub 3} adopts the orthorhombic space group Pna2{sub 1} (no. 33, Z = 4) with the cell parameters a = 1209.32(9), b = 950.85(9), and c = 849.95(6) pm.

46 CFR Sec. 3 - Accounting for revenues.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Accounting for revenues. Sec. 3 Section 3 Shipping... FINANCIAL TRANSACTIONS UNDER AGENCY AGREEMENTS Accounting for Revenues Sec. 3 Accounting for revenues. (a... shipper, consignee, weight or measurement, freight rate and basis (whether the freight rate applies on...

Hvad enhver kordreng skal kunne. Betragtning af motetten Ut Phebi radiis af Josquin Desprez

DEFF Research Database (Denmark)

Christoffersen, Peter Woetmann

2003-01-01

Josquin Desprez, Ut Phebi radiis, motet, prayer mode, hexachord, Ockeghem, Brumel, Isaac, Compère, sound, udtryk......Josquin Desprez, Ut Phebi radiis, motet, prayer mode, hexachord, Ockeghem, Brumel, Isaac, Compère, sound, udtryk...

Association Between IL1B and SCN1A Polymorphism and Febrile Seizures in Children in Siberia

Directory of Open Access Journals (Sweden)

Maria A. Stroganova

2017-06-01

Full Text Available Background: Febrile seizures (FS are a benign, age-dependent, genetically determined state, in which the child’s brain is susceptible to epileptic seizures occurring in response to hyperthermia. We assessed whether polymorphisms of IL1B and SCN1A genes, encoding the proinflammatory cytokine IL1B and SCN1A, respectively, could help to predict FS development and find a new way to treat FS. Methods: We examined 121 children with FS and 30 children with HTS aged from 3 to 36 months. SNPs rs1143634 and rs16944 of IL1B gene, and rs3812718 and rs16851603 of SCN1A gene were determined by quantitative real-time PCR. Results: The analysis for rs1143634 revealed an association between the CC genotype and increased risk of FS development (OR 6.56; P=0.0008 against the background of acute respiratory viral infection. The same result was obtained for rs16944 (OR 3.13; P=0.04 and an association of two homozygous genotypes CC/CC. For rs3812718, the carriage of heterozygous genotype CT demonstrated a direct relationship with FS development (OR 44.95; P=0.000. Conclusion: Children with high FS risk need preventive treatment and joint observation of a pediatrician, pediatric infectionist, and a neurologist-epileptologist.

Stochastic modeling of the Fermi/LAT γ-ray blazar variability

Energy Technology Data Exchange (ETDEWEB)

Sobolewska, M. A.; Siemiginowska, A. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Kelly, B. C. [Department of Physics, Broida Hall, University of California, Santa Barbara, CA 93107 (United States); Nalewajko, K., E-mail: malgosia@camk.edu.pl [JILA, University of Colorado and National Institute of Standards and Technology, 440 UCB, Boulder, CO 80309 (United States)

2014-05-10

We study the γ-ray variability of 13 blazars observed with the Fermi/Large Area Telescope (LAT). These blazars have the most complete light curves collected during the first four years of the Fermi sky survey. We model them with the Ornstein-Uhlenbeck (OU) process or a mixture of the OU processes. The OU process has power spectral density (PSD) proportional to 1/f {sup α} with α changing at a characteristic timescale, τ{sub 0}, from 0 (τ >> τ{sub 0}) to 2 (τ << τ{sub 0}). The PSD of the mixed OU process has two characteristic timescales and an additional intermediate region with 0 < α < 2. We show that the OU model provides a good description of the Fermi/LAT light curves of three blazars in our sample. For the first time, we constrain a characteristic γ-ray timescale of variability in two BL Lac sources, 3C 66A and PKS 2155-304 (τ{sub 0} ≅ 25 days and τ{sub 0} ≅ 43 days, respectively, in the observer's frame), which are longer than the soft X-ray timescales detected in blazars and Seyfert galaxies. We find that the mixed OU process approximates the light curves of the remaining 10 blazars better than the OU process. We derive limits on their long and short characteristic timescales, and infer that their Fermi/LAT PSD resemble power-law functions. We constrain the PSD slopes for all but one source in the sample. We find hints for sub-hour Fermi/LAT variability in four flat spectrum radio quasars. We discuss the implications of our results for theoretical models of blazar variability.

Middle and long-term prediction of UT1-UTC based on combination of Gray Model and Autoregressive Integrated Moving Average

Science.gov (United States)

Jia, Song; Xu, Tian-he; Sun, Zhang-zhen; Li, Jia-jing

2017-02-01

UT1-UTC is an important part of the Earth Orientation Parameters (EOP). The high-precision predictions of UT1-UTC play a key role in practical applications of deep space exploration, spacecraft tracking and satellite navigation and positioning. In this paper, a new prediction method with combination of Gray Model (GM(1, 1)) and Autoregressive Integrated Moving Average (ARIMA) is developed. The main idea is as following. Firstly, the UT1-UTC data are preprocessed by removing the leap second and Earth's zonal harmonic tidal to get UT1R-TAI data. Periodic terms are estimated and removed by the least square to get UT2R-TAI. Then the linear terms of UT2R-TAI data are modeled by the GM(1, 1), and the residual terms are modeled by the ARIMA. Finally, the UT2R-TAI prediction can be performed based on the combined model of GM(1, 1) and ARIMA, and the UT1-UTC predictions are obtained by adding the corresponding periodic terms, leap second correction and the Earth's zonal harmonic tidal correction. The results show that the proposed model can be used to predict UT1-UTC effectively with higher middle and long-term (from 32 to 360 days) accuracy than those of LS + AR, LS + MAR and WLS + MAR.

Main: 1UT7 [RPSD[Archive

Lifescience Database Archive (English)

Full Text Available 1UT7 シロイヌナズナ Arabidopsis Arabidopsis thaliana (L.) Heynh. Nac-Domain Containing Pro... Meristem Protein; Synonym: Nam, Anac, Abscisic Acid Responsive Nac, Dicyanoaurate Derivative; Chain: A, B; ...Fragment: Dna-Binding Nac Domain, Residues 1-168; Engineered: Yes; Other_details:...A.Ernst, A.N.Olsen, K.Skriver, S.Larsen, L.Lo Leggio Structure Of The Conserved Domain Of Anac, A Member Of ... Transcription Factor, Dna Binding, Abscisic Acid Response, Arabidopsis Thaliana, Crystal Structure, Nac Domai

Insights into the Structure, Function, and Ligand Discovery of the Large Neutral Amino Acid Transporter 1, LAT1

Directory of Open Access Journals (Sweden)

Natesh Singh

2018-04-01

Full Text Available The large neutral amino acid transporter 1 (LAT1, or SLC7A5 is a sodium- and pH-independent transporter, which supplies essential amino acids (e.g., leucine, phenylalanine to cells. It plays an important role at the Blood–Brain Barrier (BBB where it facilitates the transport of thyroid hormones, pharmaceuticals (e.g., l-DOPA, gabapentin, and metabolites into the brain. Moreover, its expression is highly upregulated in various types of human cancer that are characterized by an intense demand for amino acids for growth and proliferation. Therefore, LAT1 is believed to be an important drug target for cancer treatment. With the crystallization of the arginine/agmatine antiporter (AdiC from Escherichia Coli, numerous homology models of LAT1 have been built to elucidate the substrate binding site, ligand–transporter interaction, and structure–function relationship. The use of these models in combination with molecular docking and experimental testing has identified novel chemotypes of ligands of LAT1. Here, we highlight the structure, function, transport mechanism, and homology modeling of LAT1. Additionally, results from structure–function studies performed on LAT1 are addressed, which have enhanced our knowledge of the mechanism of substrate binding and translocation. This is followed by a discussion on ligand- and structure-based approaches, with an emphasis on elucidating the molecular basis of LAT1 inhibition. Finally, we provide an exhaustive summary of different LAT1 inhibitors that have been identified so far, including the recently discovered irreversible covalent inhibitors.

Waste Certification Program Plan for UT-Battelle, LLC at Oak Ridge National Laboratory

International Nuclear Information System (INIS)

Beierschmitt, K.J.; Downer, K.M.; Hoke, P.B.

2000-01-01

This document defines the waste certification program (WCP) developed and implemented by UT-Battelle, LLC (UT-Battelle) at Oak Ridge National Laboratory (ORNL). The WCP applies to all UT-Battelle personnel, it's subcontractors, guests, and visitors that do work at ORNL. This program does not include wastes generated by other U.S. Department of Energy (DOE) prime contractors, their employees, or their subcontractors working on this site except by special arrangement. The document describes the program structure, logic, and methodology for certification of UT-Battelle wastes. The purpose of the WCP is to provide assurance that wastes are properly characterized, that adequate information is provided to enable correct U.S. Department of Transportation (DOT) classification, and that the programmatic certification requirements and the Waste Acceptance Criteria (WAC) for receiving organizations/facilities are met. The program meets the waste certification requirements outlined in DO E Order 435.1, ''Radioactive Waste Management,'' in the DOE Performance Objective for Certification of Non-Radioactive Hazardous Waste (DOE, February 1995), and ensures that 40 Code of Federal Regulations (CFR) documentation requirements for waste characterization are met for mixed (both radioactive and hazardous) and hazardous (including polychlorinated biphenyls (PCBs)) waste. Program activities are conducted according to ORNL directives and guidance.

14 CFR Sec. 1-6 - Accounting entities.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Accounting entities. Sec. 1-6 Section 1-6... REGULATIONS UNIFORM SYSTEM OF ACCOUNTS AND REPORTS FOR LARGE CERTIFICATED AIR CARRIERS General Accounting Provisions Sec. 1-6 Accounting entities. (a) Separate accounting records shall be maintained for each air...

Utility guide to advanced UT systems for PSI and ISI

International Nuclear Information System (INIS)

Anon.

1987-01-01

The number of automated UT inspection systems and techniques, currently in the marketplace or being developed, has grown in recent years to the point where a utility engineer reviewing this field is faced with a major task in trying to decide what inspection technique and system will meet his inspection requirements. Recognizing the utility engineer's problem, EPRI initiated this project to produce a utility engineer's guide to advanced, automated UT systems. Of principal concern are those that have been recently introduced, and designed for problem areas such as BWR piping. Older automated scanning systems, used primarily for pressure vessel inspection, are not being ignored, but are not covered here. Costs, benefits and inspection time are addressed for several systems in this report

Constraining decaying dark matter with Fermi LAT gamma-rays

International Nuclear Information System (INIS)

Zhang, Le; Sigl, Günter; Weniger, Christoph; Maccione, Luca; Redondo, Javier

2010-01-01

High energy electrons and positrons from decaying dark matter can produce a significant flux of gamma rays by inverse Compton off low energy photons in the interstellar radiation field. This possibility is inevitably related with the dark matter interpretation of the observed PAMELA and FERMI excesses. The aim of this paper is providing a simple and universal method to constrain dark matter models which produce electrons and positrons in their decay by using the Fermi LAT gamma-ray observations in the energy range between 0.5 GeV and 300 GeV. We provide a set of universal response functions that, once convolved with a specific dark matter model produce the desired constraints. Our response functions contain all the astrophysical inputs such as the electron propagation in the galaxy, the dark matter profile, the gamma-ray fluxes of known origin, and the Fermi LAT data. We study the uncertainties in the determination of the response functions and apply them to place constraints on some specific dark matter decay models that can well fit the positron and electron fluxes observed by PAMELA and Fermi LAT. To this end we also take into account prompt radiation from the dark matter decay. We find that with the available data decaying dark matter cannot be excluded as source of the PAMELA positron excess

14 CFR Sec. 2-4 - Accounting period.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Accounting period. Sec. 2-4 Section 2-4... REGULATIONS UNIFORM SYSTEM OF ACCOUNTS AND REPORTS FOR LARGE CERTIFICATED AIR CARRIERS General Accounting Provisions Sec. 2-4 Accounting period. (a) The accounting year of each air carrier subject to this Uniform...

LatY136F knock-in mouse model for human IgG4-related disease.

Science.gov (United States)

Yamada, Kazunori; Zuka, Masahiko; Ito, Kiyoaki; Mizuguchi, Keishi; Kakuchi, Yasushi; Onoe, Tamehito; Suzuki, Yasunori; Yamagishi, Masakazu; Izui, Shozo; Malissen, Marie; Malissen, Bernard; Kawano, Mitsuhiro

2018-01-01

The adaptor protein Linker for activation of T cell (LAT) is a key signaling hub used by the T cell antigen receptor. Mutant mice expressing loss-of-function mutations affecting LAT and including a mutation in which tyrosine 136 is replaced by a phenylalanine (LatY136F) develop lymphoproliferative disorder involving T helper type 2 effector cells capable of triggering a massive polyclonal B cell activation that leads to hypergammaglobulinemia G1 and E and to non-resolving inflammation and autoimmunity. The purpose of this study was to evaluate whether the phenotypes of LatY136F knock-in mice resemble the immunohistopathological features of immunoglobulin G4-related disease (IgG4-RD). LatY136F knock-in mice were sacrificed at 4-20 weeks of age, and pancreas, kidney, salivary gland and lung were obtained. All organs were stained with hematoxylin-eosin and with Azan for estimation of collagen in fibrosis, and the severity scores of inflammation and fibrosis were evaluated. Immunostainings were performed to analyze the types of infiltrating cells. In addition, the effects of corticosteroid treatment on the development of tissue lesions and serum levels of IgG1 were assessed. Tissue lesions characterized by inflammatory mononuclear cell infiltration and fibrosis were detected in pancreas, kidney, and salivary gland starting from 6 weeks of age. Immunostainings showed pronounced infiltration of plasma cells, CD4-positive T cells, and macrophages. Infiltrating plasma cells predominantly expressed IgG1. The extent of inflammation in pancreas and salivary glands was markedly reduced by corticosteroid treatment. LatY136F knock-in mice displayed increased production of Th2-type IgG1 (a homologue of human IgG4) and developed multiple organ tissue lesions reminiscent of those seen in patients with IgG4-RD. Moreover, the development of these tissue lesions was highly sensitive to corticosteroid treatment like in IgG4-RD. For these reasons we consider the LatY136F knock-in mouse

Fermi-LAT View of Bright Flaring Gamma-Ray Blazars

Science.gov (United States)

Bastieri, D.; Ciprini, S.; Gasparrini, D.

2011-06-01

The Fermi LAT provides a continuous and uniform monitoring of the Universe in the gamma-ray band. During the first year many gamma-ray blazar flares, some unidentified transients and emission by the Sun while in a quiet state were promptly detected. This is mainly due to the design of the mission, featuring a detector, the LAT with a wide field of view, and to the operation of the spacecraft itself, that can cover every region of the sky every 3 hours. Nevertheless, the scientific exploitation of this monitoring is more fruitful when early information about transients reaches a broader community. In this respect, the indefatigable activity of flare advocates, who worked on weekly shifts to validate the results and quickly broadcast information about flares and new detections, was the key to most scientific results.

The incidence of SCN1A-related Dravet syndrome in Denmark is 1:22,000

DEFF Research Database (Denmark)

Bayat, Allan; Hjalgrim, Helle; Møller, Rikke S.

2015-01-01

Dravet syndrome is a severe infantile-onset epileptic encephalopathy associated with mutations in the sodium channel alpha-1 subunit gene SCN1A. We aimed to describe the incidence of Dravet syndrome in the Danish population. Based on a 6-year birth cohort from 2004 to 2009, we propose an incidenc...

Theoretical Interpretation of Pass 8 Fermi -LAT e {sup +} + e {sup −} Data

Energy Technology Data Exchange (ETDEWEB)

Di Mauro, M. [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); Manconi, S.; Donato, F.; Fornengo, N.; Bonino, R.; Negro, M. [Department of Physics, University of Torino, via P. Giuria 1, I-10125 Torino (Italy); Vittino, A. [Physik-Department T30D, Technische Universität München, James-Franck Straße 1, D-85748 Garching (Germany); Baldini, L.; Di Lalla, N.; Manfreda, A. [Università di Pisa and Istituto Nazionale di Fisica Nucleare, Sezione di Pisa I-56127 Pisa (Italy); Latronico, L.; Maldera, S. [Istituto Nazionale di Fisica Nucleare, via P. Giuria 1, I-10125 Torino (Italy); Pesce-Rollins, M.; Sgrò, C.; Spada, F. [Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, I-56127 Pisa (Italy)

2017-08-20

The flux of positrons and electrons ( e {sup +} + e {sup −}) has been measured by the Fermi Large Area Telescope (LAT) in the energy range between 7 GeV and 2 TeV. We discuss a number of interpretations of Pass 8 Fermi -LAT e {sup +} + e {sup −} spectrum, combining electron and positron emission from supernova remnants (SNRs) and pulsar wind nebulae (PWNe), or produced by the collision of cosmic rays (CRs) with the interstellar medium. We find that the Fermi -LAT spectrum is compatible with the sum of electrons from a smooth SNR population, positrons from cataloged PWNe, and a secondary component. If we include in our analysis constraints from the AMS-02 positron spectrum, we obtain a slightly worse fit to the e {sup +} + e {sup −} Fermi -LAT spectrum, depending on the propagation model. As an additional scenario, we replace the smooth SNR component within 0.7 kpc with the individual sources found in Green’s catalog of Galactic SNRs. We find that separate consideration of far and near sources helps to reproduce the e {sup +} + e {sup −} Fermi -LAT spectrum. However, we show that the fit degrades when the radio constraints on the positron emission from Vela SNR (which is the main contributor at high energies) are taken into account. We find that a break in the power-law injection spectrum at about 100 GeV can also reproduce the measured e {sup +} + e {sup −} spectrum and, among the CR propagation models that we consider, no reasonable break of the power-law dependence of the diffusion coefficient can modify the electron flux enough to reproduce the observed shape.

78 FR 58158 - Establishment of Class E Airspace; Wasatch, UT

Science.gov (United States)

2013-09-23

... operations within the National Airspace System. This action also makes a minor adjustment to the geographic... the geographic coordinates of the Wasatch VORTAC needed to be corrected. This action makes the... of IFR operations. The geographic coordinates of the VORTAC are adjusted from (Lat. 40[deg]51'10'' N...

Hydride vapor phase epitaxy growth of GaN, InGaN, ScN, and ScAIN

NARCIS (Netherlands)

Bohnen, T.

2010-01-01

Chemical vapor deposition (CVD); hydride vapor phase epitaxy (HVPE); gallium nitride (GaN); indium gallium nitride (InGaN); scandium nitride (ScN); scandium aluminum nitride (ScAlN); semiconductors; thin films; nanowires; III nitrides; crystal growth - We studied the HVPE growth of different III

BET bromodomain inhibition rescues erythropoietin differentiation of human erythroleukemia cell line UT7

International Nuclear Information System (INIS)

Goupille, Olivier; Penglong, Tipparat; Lefèvre, Carine; Granger, Marine; Kadri, Zahra; Fucharoen, Suthat; Maouche-Chrétien, Leila; Leboulch, Philippe; Chrétien, Stany

2012-01-01

Highlights: ► UT7 erythroleukemia cells are known to be refractory to differentiate. ► Brief JQ1 treatment initiates the first steps of erythroid differentiation program. ► Engaged UT7 cells then maturate in the presence of erythropoietin. ► Sustained JQ1 treatment inhibits both proliferation and erythroid differentiation. -- Abstract: Malignant transformation is a multistep process requiring oncogenic activation, promoting cellular proliferation, frequently coupled to inhibition of terminal differentiation. Consequently, forcing the reengagement of terminal differentiation of transformed cells coupled or not with an inhibition of their proliferation is a putative therapeutic approach to counteracting tumorigenicity. UT7 is a human leukemic cell line able to grow in the presence of IL3, GM-CSF and Epo. This cell line has been widely used to study Epo-R/Epo signaling pathways but is a poor model for erythroid differentiation. We used the BET bromodomain inhibition drug JQ1 to target gene expression, including that of c-Myc. We have shown that only 2 days of JQ1 treatment was required to transitory inhibit Epo-induced UT7 proliferation and to restore terminal erythroid differentiation. This study highlights the importance of a cellular erythroid cycle break mediated by c-Myc inhibition before initiation of the erythropoiesis program and describes a new model for BET bromodomain inhibitor drug application.

BET bromodomain inhibition rescues erythropoietin differentiation of human erythroleukemia cell line UT7

Energy Technology Data Exchange (ETDEWEB)

Goupille, Olivier [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Penglong, Tipparat [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Thalassemia Research Center and Department of Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Thailand); Lefevre, Carine; Granger, Marine; Kadri, Zahra [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Fucharoen, Suthat [Thalassemia Research Center and Department of Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Thailand); Maouche-Chretien, Leila [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Leboulch, Philippe [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Genetics Division, Department of Medicine, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA (United States); Chretien, Stany, E-mail: stany.chretien@cea.fr [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France)

2012-12-07

Highlights: Black-Right-Pointing-Pointer UT7 erythroleukemia cells are known to be refractory to differentiate. Black-Right-Pointing-Pointer Brief JQ1 treatment initiates the first steps of erythroid differentiation program. Black-Right-Pointing-Pointer Engaged UT7 cells then maturate in the presence of erythropoietin. Black-Right-Pointing-Pointer Sustained JQ1 treatment inhibits both proliferation and erythroid differentiation. -- Abstract: Malignant transformation is a multistep process requiring oncogenic activation, promoting cellular proliferation, frequently coupled to inhibition of terminal differentiation. Consequently, forcing the reengagement of terminal differentiation of transformed cells coupled or not with an inhibition of their proliferation is a putative therapeutic approach to counteracting tumorigenicity. UT7 is a human leukemic cell line able to grow in the presence of IL3, GM-CSF and Epo. This cell line has been widely used to study Epo-R/Epo signaling pathways but is a poor model for erythroid differentiation. We used the BET bromodomain inhibition drug JQ1 to target gene expression, including that of c-Myc. We have shown that only 2 days of JQ1 treatment was required to transitory inhibit Epo-induced UT7 proliferation and to restore terminal erythroid differentiation. This study highlights the importance of a cellular erythroid cycle break mediated by c-Myc inhibition before initiation of the erythropoiesis program and describes a new model for BET bromodomain inhibitor drug application.

Analysis of Burst Observations by GLAST's LAT Detector

International Nuclear Information System (INIS)

Band, David L.; Digel, Seth W.

2004-01-01

Analyzing data from GLAST's Large Area Telescope (LAT) will require sophisticated techniques. The PSF and effective area are functions of both photon energy and the position in the field-of-view. During most of the mission the observatory will survey the sky continuously, and thus, the LAT will detect each count from a source at a different detector orientation; each count requires its own response function! The likelihood as a function of celestial position and photon energy will be the foundation of the standard analysis techniques. However, the 20 MeV-300 GeV emission at the time of the ∼ 100 keV burst emission (timescale of ∼ 10 s) can be isolated and analyzed because essentially no non-burst counts are expected within a PSF radius of the burst location during the burst. Both binned and unbinned (in energy) spectral fitting will be possible. Longer timescale afterglow emission will require the likelihood analysis that will be used for persistent sources

Pulsar Timing with the Fermi LAT

Science.gov (United States)

2010-12-01

Pulsar Timing with the Fermi LAT Paul S. Ray∗, Matthew Kerr†, Damien Parent∗∗ and the Fermi PSC‡ ∗Naval Research Laboratory, 4555 Overlook Ave., SW...Laboratory, Washington, DC 20375, USA ‡Fermi Pulsar Search Consortium Abstract. We present an overview of precise pulsar timing using data from the Large...unbinned photon data. In addition to determining the spindown behavior of the pulsars and detecting glitches and timing noise, such timing analyses al

75 FR 57288 - Notice of Inventory Completion: Utah Museum of Natural History, Salt Lake City, UT

Science.gov (United States)

2010-09-20

... Natural History, Salt Lake City, UT AGENCY: National Park Service, Interior. ACTION: Notice. Notice is... possession and control of the Utah Museum of Natural History, Salt Lake City, UT. The human remains and... unworked faunal bone. The associated funerary objects found with the interments indicate that the human...

The Dynamics of SecM-Induced Translational Stalling

Directory of Open Access Journals (Sweden)

Albert Tsai

2014-06-01

Full Text Available SecM is an E. coli secretion monitor capable of stalling translation on the prokaryotic ribosome without cofactors. Biochemical and structural studies have demonstrated that the SecM nascent chain interacts with the 50S subunit exit tunnel to inhibit peptide bond formation. However, the timescales and pathways of stalling on an mRNA remain undefined. To provide a dynamic mechanism for stalling, we directly tracked the dynamics of elongation on ribosomes translating the SecM stall sequence (FSTPVWISQAQGIRAGP using single-molecule fluorescence techniques. Within 1 min, three peptide-ribosome interactions work cooperatively over the last five codons of the SecM sequence, leading to severely impaired elongation rates beginning from the terminal proline and lasting four codons. Our results suggest that stalling is tightly linked to the dynamics of elongation and underscore the roles that the exit tunnel and nascent chain play in controlling fundamental steps in translation.

78 FR 2434 - Notice of Inventory Completion: Natural History Museum of Utah, Salt Lake City, UT

Science.gov (United States)

2013-01-11

... Inventory Completion: Natural History Museum of Utah, Salt Lake City, UT AGENCY: National Park Service..., 2013. ADDRESSES: Duncan Metcalfe, Natural History Museum of Utah, 301 Wakara Way, Salt Lake City, UT... lot of horse tack, a metal punch, 1 piece of worked wood, gunshot, two mirrors, a harness ring, an awl...

Afterglow Population Studies from Swift Follow-Up Observations of Fermi LAT GRBs

Science.gov (United States)

Racusin, Judith L.; Oates, S. R.; McEnery, J.; Vasileiou, V.; Troja, E.; Gehrels, N.

2010-01-01

The small population of Fermi LAT detected GRBs discovered over the last year has been providing interesting and unexpected clues into GRB prompt and afterglow emission mechanisms. Over the last 5 years, it has been Swift that has provided the robust data set of UV/optical and X-ray afterglow observations that opened many windows into other components of GRB emission structure. We explore the new ability to utilize both of these observatories to study the same GRBs over 10 orders of magnitude in energy, although not always concurrently. Almost all LAT GRBs that have been followed-up by Swift within 1-day have been clearly detected and carefully observed. We will present the context of the lower-energy afterglows of this special subset of GRBs that has > 100 MeV emission compared to the hundreds in the Swift database that may or may not have been observed by LAT, and theorize upon the relationship between these properties and the origin of the high energy gamma-ray emission.

The First Fermi-LAT Gamma-Ray Burst Catalog

NARCIS (Netherlands)

Ackermann, M.; et al., [Unknown; van der Horst, A.J.

2013-01-01

In three years of observations since the beginning of nominal science operations in 2008 August, the Large Area Telescope (LAT) on board the Fermi Gamma-Ray Space Telescope has observed high-energy (gsim 20 MeV) γ-ray emission from 35 gamma-ray bursts (GRBs). Among these, 28 GRBs have been detected

Development of phased array UT procedure for crack depth sizing on nickel based alloy weld

International Nuclear Information System (INIS)

Hirasawa, Taiji; Okada, Hisao; Fukutomi, Hiroyuki

2012-01-01

Recently, it is reported that the primary water stress corrosion cracking (PWSCC) has been occurred at the nickel based alloy weld components such as steam generator safe end weld, reactor vessel safe end weld, and so on, in PWR. Defect detection and sizing is important in order to ensure the reliable operation and life extension of nuclear power plants. In the reactor vessel safe end weld, it was impossible to measure crack depth of PWSCC. The crack was detected in the axial direction of the safe end weld. Furthermore, the crack had some features such as shallow, large aspect ratio (ratio of crack depth and length), sharp geometry of crack tip, and so on. Therefore, development and improvement of defect detection and sizing capabilities for ultrasonic inspection technique is required. Phased array UT technique was applied to nickel based alloy weld specimen with SCC cracks. From the experimental results, good accuracy of crack depth sizing by phased array UT for the inside inspection was shown. From these results, UT procedure for crack depth sizing was verified. Therefore, effectiveness of phased array UT for crack depth sizing in the nickel based alloy welds was shown. (author)

Electrophysiological characteristics of a SCN5A voltage sensors mutation R1629Q associated with Brugada syndrome.

Directory of Open Access Journals (Sweden)

Zhipeng Zeng

Full Text Available Brugada syndrome (BrS is an inherited arrhythmogenic syndrome leading to sudden cardiac death, partially associated with autosomal dominant mutations in SCN5A, which encodes the cardiac sodium channel alpha-subunit (Nav1.5. To date some SCN5A mutations related with BrS have been identified in voltage sensor of Nav1.5. Here, we describe a dominant missense mutation (R1629Q localized in the fourth segment of domain IV region (DIV-S4 in a Chinese Han family. The mutation was identified by direct sequencing of SCN5A from the proband's DNA. Co-expression of Wild-type (WT or R1629Q Nav1.5 channel and hβ1 subunit were achieved in human embryonic kidney cells by transient transfection. Sodium currents were recorded using whole cell patch-clamp protocols. No significant changes between WT and R1629Q currents were observed in current density or steady-state activation. However, hyperpolarized shift of steady-state inactivation curve was identified in cells expressing R1629Q channel (WT: V1/2 = -81.1 ± 1.3 mV, n = 13; R1629Q: V1/2 = -101.7 ± 1.2 mV, n = 18. Moreover, R1629Q channel showed enhanced intermediate inactivation and prolonged recovery time from inactivation. In summary, this study reveals that R1629Q mutation causes a distinct loss-of-function of the channel due to alter its electrophysiological characteristics, and facilitates our understanding of biophysical mechanisms of BrS.

78 FR 2430 - Notice of Inventory Completion: Natural History Museum of Utah, Salt Lake City, UT

Science.gov (United States)

2013-01-11

... Inventory Completion: Natural History Museum of Utah, Salt Lake City, UT AGENCY: National Park Service...: Duncan Metcalfe, Natural History Museum of Utah, 301 Wakara Way, Salt Lake City, UT 84108, telephone (801... fragments, 13 pieces of horse tack, 3 saddle fragments, 1 knife sheath, 1 rifle and barrel, 1 lot of bullet...

Search for Dark Matter Satellites Using the FERMI-LAT

Energy Technology Data Exchange (ETDEWEB)

Ackermann, M.; /DESY; Albert, A.; /Ohio State U.; Baldini, L.; /INFN, Pisa; Ballet, J.; /DAPNIA, Saclay; Barbiellini, G.; /INFN, Trieste /Trieste U.; Bastieri, D.; /INFN, Padua /Padua U.; Bechtol, K.; /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept.; Bellazzini, R.; /INFN, Pisa; Blandford, R.D.; /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept.; Bloom, E.D.; /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /SLAC; Bonamente, E.; /INFN, Perugia /Perugia U.; Borgland, A.W.; /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept.; Bottacini, E.; /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept.; Brandt, T.J.; /IRAP, Toulouse /Toulouse III U.; Bregeon, J.; /INFN, Pisa; Brigida, M.; /Bari U. /INFN, Bari; Bruel, P.; /Ecole Polytechnique; Buehler, R.; /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept.; Burnett, T.H.; /Washington U., Seattle; Caliandro, G.A.; /ICE, Bellaterra; Cameron, R.A.; /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /IASF, Milan /IASF, Milan /DAPNIA, Saclay /INFN, Perugia /Perugia U. /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /ASDC, Frascati /Perugia U. /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /Montpellier U. /Stockholm U. /Stockholm U., OKC /ASDC, Frascati /Bari U. /INFN, Bari /Naval Research Lab, Wash., D.C. /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /Montpellier U. /Bari U. /INFN, Bari /Ecole Polytechnique /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /Hiroshima U. /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /Bari U. /INFN, Bari /INFN, Bari /INFN, Perugia /Perugia U. /Bari U. /INFN, Bari /Bari U. /INFN, Bari /Bologna Observ. /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept. /Stanford U., HEPL /KIPAC, Menlo Park /Stanford U., Phys. Dept.; /more authors..

2012-08-16

Numerical simulations based on the {Lambda}CDM model of cosmology predict a large number of as yet unobserved Galactic dark matter satellites. We report the results of a Large Area Telescope (LAT) search for these satellites via the {gamma}-ray emission expected from the annihilation of weakly interacting massive particle (WIMP) dark matter. Some dark matter satellites are expected to have hard {gamma}-ray spectra, finite angular extents, and a lack of counterparts at other wavelengths. We sought to identify LAT sources with these characteristics, focusing on {gamma}-ray spectra consistent with WIMP annihilation through the b{bar b} channel. We found no viable dark matter satellite candidates using one year of data, and we present a framework for interpreting this result in the context of numerical simulations to constrain the velocity-averaged annihilation cross section for a conventional 100 GeV WIMP annihilating through the b{bar b} channel.

Search for Dark Matter Satellites Using the Fermi-Lat

Science.gov (United States)

Ackermann, M.; Albert, A.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bechtol, K.; Bellazzini, R.; Blandford, R. D.; Bloom, E. D.;

Secretome analysis defines the major role of SecDF in Staphylococcus aureus virulence.

Directory of Open Access Journals (Sweden)

Chantal Quiblier

Full Text Available The Sec pathway plays a prominent role in protein export and membrane insertion, including the secretion of major bacterial virulence determinants. The accessory Sec constituent SecDF has been proposed to contribute to protein export. Deletion of Staphylococcus aureus secDF has previously been shown to reduce resistance, to alter cell separation, and to change the expression of certain virulence factors. To analyse the impact of the secDF deletion in S. aureus on protein secretion, a quantitative secretome analysis was performed. Numerous Sec signal containing proteins involved in virulence were found to be decreased in the supernatant of the secDF mutant. However, two Sec-dependent hydrolases were increased in comparison to the wild type, suggesting additional indirect, regulatory effects to occur upon deletion of secDF. Adhesion, invasion, and cytotoxicity of the secDF mutant were reduced in human umbilical vein endothelial cells. Virulence was significantly reduced using a Galleria mellonella insect model. Altogether, SecDF is a promising therapeutic target for controlling S. aureus infections.

A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): A pilot study in a canine model

International Nuclear Information System (INIS)

Fukumoto, Shinya; Hanazono, Kiwamu; Fu, Dah-Renn; Endo, Yoshifumi; Kadosawa, Tsuyoshi; Iwano, Hidetomo; Uchide, Tsuyoshi

2013-01-01

Highlights: •LAT1 is highly expressed in tumors but at low levels in normal tissues. •We examine LAT1 expression and function in malignant melanoma (MM). •LAT1 expression in MM tissues and cell lines is higher than those in normal tissues. •LAT1 selective inhibitors inhibit amino acid uptake and cell growth in MM cells. •New chemotherapeutic protocols including LAT1 inhibitors are effective for treatment. -- Abstract: L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities such as cellular growth, proliferation and maintenance. This amino acid transporter recently has received attention because of its preferential and up-regulated expression in a variety of human tumors in contrast to its limited distribution and low-level expression in normal tissues. In this study, we explored the feasibility of using LAT1 inhibitor as a new therapeutic agent for human malignant melanomas (MM) using canine spontaneous MM as a model for human MM. A comparative study of LAT expression was performed in 48 normal tissues, 25 MM tissues and five cell lines established from MM. The study observed LAT1 mRNA levels from MM tissues and cell lines that were significantly (P 3 H]L-Leucine uptake and cellular growth activities in CMeC-1 were inhibited in a dose-dependent manner by selective LAT1 inhibitors (2-amino-2-norbornane-carboxylic acid, BCH and melphalan, LPM). Inhibitory growth activities of various conventional anti-cancer drugs, including carboplatin, cyclophosphamide, dacarbazine, doxorubicin, mitoxantrone, nimustine, vinblastine and vincristine, were significantly (P < 0.05) enhanced by combination use with BCH or LPM. These findings suggest that LAT1 could be a new therapeutic target for MM

A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): A pilot study in a canine model

Energy Technology Data Exchange (ETDEWEB)

Fukumoto, Shinya; Hanazono, Kiwamu [Veterinary Internal Medicine, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan); Fu, Dah-Renn; Endo, Yoshifumi; Kadosawa, Tsuyoshi [Veterinary Oncology, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan); Iwano, Hidetomo [Veterinary Biochemistry, Department of Basic Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan); Uchide, Tsuyoshi, E-mail: uchide@rakuno.ac.jp [Veterinary Internal Medicine, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan)

2013-09-13

Highlights: •LAT1 is highly expressed in tumors but at low levels in normal tissues. •We examine LAT1 expression and function in malignant melanoma (MM). •LAT1 expression in MM tissues and cell lines is higher than those in normal tissues. •LAT1 selective inhibitors inhibit amino acid uptake and cell growth in MM cells. •New chemotherapeutic protocols including LAT1 inhibitors are effective for treatment. -- Abstract: L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities such as cellular growth, proliferation and maintenance. This amino acid transporter recently has received attention because of its preferential and up-regulated expression in a variety of human tumors in contrast to its limited distribution and low-level expression in normal tissues. In this study, we explored the feasibility of using LAT1 inhibitor as a new therapeutic agent for human malignant melanomas (MM) using canine spontaneous MM as a model for human MM. A comparative study of LAT expression was performed in 48 normal tissues, 25 MM tissues and five cell lines established from MM. The study observed LAT1 mRNA levels from MM tissues and cell lines that were significantly (P < 0.01) higher than in normal tissues. Additionally, MM with distant metastasis showed a higher expression than those without distant metastasis. Functional analysis of LAT1 was performed on one of the five cell lines, CMeC-1. [{sup 3}H]L-Leucine uptake and cellular growth activities in CMeC-1 were inhibited in a dose-dependent manner by selective LAT1 inhibitors (2-amino-2-norbornane-carboxylic acid, BCH and melphalan, LPM). Inhibitory growth activities of various conventional anti-cancer drugs, including carboplatin, cyclophosphamide, dacarbazine, doxorubicin, mitoxantrone, nimustine, vinblastine and vincristine, were significantly (P < 0.05) enhanced by combination use with BCH or LPM

17-AAG suppresses growth and invasion of lung adenocarcinoma cells via regulation of the LATS1/YAP pathway

Science.gov (United States)

Ye, Xiang-Yun; Luo, Qing-Quan; Xu, Yun-Hua; Tang, Nai-Wang; Niu, Xiao-Min; Li, Zi-Ming; Shen, Sheng-Ping; Lu, Shun; Chen, Zhi-Wei

2015-01-01

The large tumour suppressor 1 (LATS1) signalling network has been proved to be an essential regulator within the cell, participating in multiple cellular phenotypes. However, it is unclear concerning the clinical significance of LATS1 and the regulatory mechanisms of 17-Allylamino-17- demethoxygeldanamycin (17-AAG) in lung adenocarcinoma (LAC). The aim of the present study was to investigate the correlation of LATS1 and yes-associated protein (YAP) expression with clinicopathological characteristics in LAC patients, and the effects of 17-AAG on biological behaviours of LAC cells. Subcutaneous LAC tumour models were further established to observe the tumour growth in nude mice. The results showed that the positive expression of LATS1 was significantly lowered (26.7% versus 68.0%, P AAG inhibited proliferation and invasion, and induced cell apoptosis and cycle arrest in LAC cells together with increased expression of E-cadherin and p-LATS1, and decreased expression of YAP and connective tissue growth factor. Tumour volumes and weight were much smaller in 17-AAG-treated groups than those in untreated group (P AAG suppresses growth and invasion of LAC cells via regulation of the LATS1/YAP pathway in vitro and in vivo, suggesting that we may provide a promising therapeutic strategy for the treatment of human LAC. PMID:25712415

Cap and trade schemes on waste management: A case study of the Landfill Allowance Trading Scheme (LATS) in England

International Nuclear Information System (INIS)

Calaf-Forn, Maria; Roca, Jordi; Puig-Ventosa, Ignasi

2014-01-01

Highlights: • LATS has been effective to achieve a reduction of the amount of landfilled waste. • LATS has been one of the few environmental instruments for waste management with a cap and trade methodology. • LATS has achieved to increase recycling of the biodegradable and other waste fractions. - Abstract: The Landfill Allowance Trading Scheme (LATS) is one of the main instruments used in England to enforce the landfill diversion targets established in the Directive 1999/31/EC of the European Parliament and of the Council of 26 April 1999 on the landfill of waste (Landfill Directive). Through the LATS, biodegradable municipal waste (BMW) allowances for landfilling are allocated to each local authority, otherwise known as waste disposal authorities (WDAs). The quantity of landfill allowances received is expected to decrease continuously from 2005/06 to 2019/20 so as to meet the objectives of the Landfill Directive. To achieve their commitments, WDAs can exchange, buy, sell or transfer allowances among each other, or may re-profile their own allocation through banking and/or borrowing. Despite the goals for the first seven years – which included two target years (2005/06 and 2009/10) – being widely achieved (the average allocation of allowances per WDA was 22.9% higher than those finally used), market activity among WDAs was high and prices were not very stable. Results in terms of waste reduction and recycling levels have been satisfactory. The reduction of BMW landfilled (in percentage) was higher during the first seven years of the LATS period (2005/06–2011/12) (around 7% annually) than during the previous period (2001/02–2004/05) (4.2% annually). Since 2008, the significance of the LATS diminished because of an increase in the rate of the UK Landfill Tax. The LATS was suppressed after the 2012/13 target year, before what it was initially scheduled. The purpose of this paper is to describe the particularities of the LATS, analyse its performance as

Cap and trade schemes on waste management: A case study of the Landfill Allowance Trading Scheme (LATS) in England

Energy Technology Data Exchange (ETDEWEB)

Calaf-Forn, Maria, E-mail: mcalaf@ent.cat [Institut de Ciència i Tecnologia Ambientals (ICTA), Universitat Autònoma de Barcelona (UAB), E-08193 Bellaterra, Barcelona (Spain); ENT Environment and Management, Carrer Sant Joan 39, First Floor, E-08800 Vilanova i la Geltrú, Barcelona (Spain); Roca, Jordi [Departament de Teoria Econòmica, Universitat de Barcelona (UB), Diagonal, 696, E-08034 Barcelona (Spain); Puig-Ventosa, Ignasi [ENT Environment and Management, Carrer Sant Joan 39, First Floor, E-08800 Vilanova i la Geltrú, Barcelona (Spain)

2014-05-01

Highlights: • LATS has been effective to achieve a reduction of the amount of landfilled waste. • LATS has been one of the few environmental instruments for waste management with a cap and trade methodology. • LATS has achieved to increase recycling of the biodegradable and other waste fractions. - Abstract: The Landfill Allowance Trading Scheme (LATS) is one of the main instruments used in England to enforce the landfill diversion targets established in the Directive 1999/31/EC of the European Parliament and of the Council of 26 April 1999 on the landfill of waste (Landfill Directive). Through the LATS, biodegradable municipal waste (BMW) allowances for landfilling are allocated to each local authority, otherwise known as waste disposal authorities (WDAs). The quantity of landfill allowances received is expected to decrease continuously from 2005/06 to 2019/20 so as to meet the objectives of the Landfill Directive. To achieve their commitments, WDAs can exchange, buy, sell or transfer allowances among each other, or may re-profile their own allocation through banking and/or borrowing. Despite the goals for the first seven years – which included two target years (2005/06 and 2009/10) – being widely achieved (the average allocation of allowances per WDA was 22.9% higher than those finally used), market activity among WDAs was high and prices were not very stable. Results in terms of waste reduction and recycling levels have been satisfactory. The reduction of BMW landfilled (in percentage) was higher during the first seven years of the LATS period (2005/06–2011/12) (around 7% annually) than during the previous period (2001/02–2004/05) (4.2% annually). Since 2008, the significance of the LATS diminished because of an increase in the rate of the UK Landfill Tax. The LATS was suppressed after the 2012/13 target year, before what it was initially scheduled. The purpose of this paper is to describe the particularities of the LATS, analyse its performance as

Analytical approximations for thermophysical properties of supercritical nitrogen (SCN) to be used in futuristic high temperature superconducting (HTS) cables

Energy Technology Data Exchange (ETDEWEB)

Dondapati, Raja Sekhar, E-mail: drsekhar@ieee.org [School of Mechanical Engineering, Lovely Professional University, Phagwara, Punjab 144401 (India); Ravula, Jeswanth [School of Mechanical Engineering, Lovely Professional University, Phagwara, Punjab 144401 (India); Thadela, S. [Department of Mechanical Engineering, Andhra University, Visakhapatnam, Andhra Pradesh (India); Usurumarti, Preeti Rao [Department of Mechanical Engineering, P.V.K. Institute of Technology, Anantapur, Andhra Pradesh (India)

2015-12-15

Future power transmission applications demand higher efficiency due to the limited resources of energy. In order to meet such demand, a novel method of transmission is being developed using High Temperature Superconducting (HTS) cables. However, these HTS cables need to be cooled below the critical temperature of superconductors used in constructing the cable to retain the superconductivity. With the advent of new superconductors whose critical temperatures having reached up to 134 K (Hg based), a need arises to find a suitable coolant which can accommodate the heating loads on the superconductors. The present work proposes, Supercritical Nitrogen (SCN) to be a feasible coolant to achieve the required cooling. Further, the feasibility of proposed coolant to be used in futuristic HTS cables is investigated by studying the thermophysical properties such as density, viscosity, specific heat and thermal conductivity with respect to temperature (T{sub C} + 10 K) and pressure (P{sub C} + 10 bar). In addition, few temperature dependent analytical functions are developed for thermophysical properties of SCN which are useful in predicting thermohydraulic performance (pressure drop, pumping power and cooling capacity) using numerical or computational techniques. Also, the developed analytical functions are used to calculate the pumping power and the temperature difference between inlet and outlet of HTS cable. These results are compared with those of liquid nitrogen (LN2) and found that the circulating pumping power required to pump SCN is significantly smaller than that to pump LN2. Further, it is found that the temperature difference between the inlet and outlet is smaller as compared to that when LN2 is used, SCN can be preferred to cool long length Hg based HTS cables. - Highlights: • Analytical functions are developed for thermophysical properties of Supercritical Nitrogen. • Error analysis shows extremely low errors in the developed analytical functions. �

Analytical approximations for thermophysical properties of supercritical nitrogen (SCN) to be used in futuristic high temperature superconducting (HTS) cables

International Nuclear Information System (INIS)

Dondapati, Raja Sekhar; Ravula, Jeswanth; Thadela, S.; Usurumarti, Preeti Rao

2015-01-01

Future power transmission applications demand higher efficiency due to the limited resources of energy. In order to meet such demand, a novel method of transmission is being developed using High Temperature Superconducting (HTS) cables. However, these HTS cables need to be cooled below the critical temperature of superconductors used in constructing the cable to retain the superconductivity. With the advent of new superconductors whose critical temperatures having reached up to 134 K (Hg based), a need arises to find a suitable coolant which can accommodate the heating loads on the superconductors. The present work proposes, Supercritical Nitrogen (SCN) to be a feasible coolant to achieve the required cooling. Further, the feasibility of proposed coolant to be used in futuristic HTS cables is investigated by studying the thermophysical properties such as density, viscosity, specific heat and thermal conductivity with respect to temperature (T_C + 10 K) and pressure (P_C + 10 bar). In addition, few temperature dependent analytical functions are developed for thermophysical properties of SCN which are useful in predicting thermohydraulic performance (pressure drop, pumping power and cooling capacity) using numerical or computational techniques. Also, the developed analytical functions are used to calculate the pumping power and the temperature difference between inlet and outlet of HTS cable. These results are compared with those of liquid nitrogen (LN2) and found that the circulating pumping power required to pump SCN is significantly smaller than that to pump LN2. Further, it is found that the temperature difference between the inlet and outlet is smaller as compared to that when LN2 is used, SCN can be preferred to cool long length Hg based HTS cables. - Highlights: • Analytical functions are developed for thermophysical properties of Supercritical Nitrogen. • Error analysis shows extremely low errors in the developed analytical functions. �

N-acetylation and phosphorylation of Sec complex subunits in the ER membrane

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Soromani Christina

2012-12-01

Full Text Available Abstract Background Covalent modifications of proteins provide a mechanism to control protein function. Here, we have investigated modifications of the heptameric Sec complex which is responsible for post-translational protein import into the endoplasmic reticulum (ER. It consists of the Sec61 complex (Sec61p, Sbh1p, Sss1p which on its own mediates cotranslational protein import into the ER and the Sec63 complex (Sec63p, Sec62p, Sec71p, Sec72p. Little is known about the biogenesis and regulation of individual Sec complex subunits. Results We show that Sbh1p when it is part of the Sec61 complex is phosphorylated on T5 which is flanked by proline residues. The phosphorylation site is conserved in mammalian Sec61ß, but only partially in birds, and not in other vertebrates or unicellular eukaryotes, suggesting convergent evolution. Mutation of T5 to A did not affect the ability of mutant Sbh1p to complement the growth defect in a Δsbh1Δsbh2 strain, and did not result in a hypophosphorylated protein which shows that alternate sites can be used by the T5 kinase. A survey of yeast phosphoproteome data shows that Sbh1p can be phosphorylated on multiple sites which are organized in two patches, one at the N-terminus of its cytosolic domain, the other proximal to the transmembrane domain. Surprisingly, although N-acetylation has been shown to interfere with ER targeting, we found that both Sbh1p and Sec62p are cotranslationally N-acetylated by NatA, and N-acetyl-proteome data indicate that Sec61p is modified by the same enzyme. Mutation of the N-acetylation site, however, did not affect Sec62p function in posttranslational protein import into the ER. Disabling NatA resulted in growth retardation, but not in co- or posttranslational translocation defects or instability of Sec62p or Sbh1p. Conclusions We conclude that N-acetylation of transmembrane and tail-anchored proteins does not interfere with their ER-targeting, and that Sbh1p phosphorylation on T5

Prospects for UT1 Measurements from VLBI Intensive Sessions

Science.gov (United States)

Boehm, Johannes; Nilsson, Tobias; Schuh, Harald

2010-01-01

Very Long Baseline Interferometry (VLBI) Intensives are one-hour single baseline sessions to provide Universal Time (UT1) in near real-time up to a delay of three days if a site is not e-transferring the observational data. Due to the importance of UT1 estimates for the prediction of Earth orientation parameters, as well as any kind of navigation on Earth or in space, there is not only the need to improve the timeliness of the results but also their accuracy. We identify the asymmetry of the tropospheric delays as the major error source, and we provide two strategies to improve the results, in particular of those Intensives which include the station Tsukuba in Japan with its large tropospheric variation. We find an improvement when (1) using ray-traced delays from a numerical weather model, and (2) when estimating tropospheric gradients within the analysis of Intensive sessions. The improvement is shown in terms of reduction of rms of length-of-day estimates w.r.t. those derived from Global Positioning System observations

Deep Ultraviolet Copper(I) Thiocyanate (CuSCN) Photodetectors Based on Coplanar Nanogap Electrodes Fabricated via Adhesion Lithography

KAUST Repository

Wyatt-Moon, Gwenhivir

2017-11-28

Adhesion lithography (a-Lith) is a versatile fabrication technique used to produce asymmetric coplanar electrodes separated by a <15 nm nanogap. Here, we use a-Lith to fabricate deep ultraviolet (DUV) photodetectors by combining coplanar asymmetric nanogap electrode architectures (Au/Al) with solution-processable wide-band-gap (3.5–3.9 eV) p-type semiconductor copper(I) thiocyanate (CuSCN). Because of the device’s unique architecture, the detectors exhibit high responsivity (≈79 A W–1) and photosensitivity (≈720) when illuminated with a DUV-range (λpeak = 280 nm) light-emitting diode at 220 μW cm–2. Interestingly, the photosensitivity of the photodetectors remains fairly high (≈7) even at illuminating intensities down to 0.2 μW cm–2. The scalability of the a-Lith process combined with the unique properties of CuSCN paves the way to new forms of inexpensive, yet high-performance, photodetectors that can be manufactured on arbitrary substrate materials including plastic.

Deep Ultraviolet Copper(I) Thiocyanate (CuSCN) Photodetectors Based on Coplanar Nanogap Electrodes Fabricated via Adhesion Lithography

KAUST Repository

Wyatt-Moon, Gwenhivir; Georgiadou, Dimitra G; Semple, James; Anthopoulos, Thomas D.

2017-01-01

Adhesion lithography (a-Lith) is a versatile fabrication technique used to produce asymmetric coplanar electrodes separated by a <15 nm nanogap. Here, we use a-Lith to fabricate deep ultraviolet (DUV) photodetectors by combining coplanar asymmetric nanogap electrode architectures (Au/Al) with solution-processable wide-band-gap (3.5–3.9 eV) p-type semiconductor copper(I) thiocyanate (CuSCN). Because of the device’s unique architecture, the detectors exhibit high responsivity (≈79 A W–1) and photosensitivity (≈720) when illuminated with a DUV-range (λpeak = 280 nm) light-emitting diode at 220 μW cm–2. Interestingly, the photosensitivity of the photodetectors remains fairly high (≈7) even at illuminating intensities down to 0.2 μW cm–2. The scalability of the a-Lith process combined with the unique properties of CuSCN paves the way to new forms of inexpensive, yet high-performance, photodetectors that can be manufactured on arbitrary substrate materials including plastic.

Modeling and simulation of aggregation of membrane protein LAT with molecular variability in the number of binding sites for cytosolic Grb2-SOS1-Grb2.

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Ambarish Nag

Full Text Available The linker for activation of T cells (LAT, the linker for activation of B cells (LAB, and the linker for activation of X cells (LAX form a family of transmembrane adaptor proteins widely expressed in lymphocytes. These scaffolding proteins have multiple binding motifs that, when phosphorylated, bind the SH2 domain of the cytosolic adaptor Grb2. Thus, the valence of LAT, LAB and LAX for Grb2 is variable, depending on the strength of receptor activation that initiates phosphorylation. During signaling, the LAT population will exhibit a time-varying distribution of Grb2 valences from zero to three. In the cytosol, Grb2 forms 1:1 and 2:1 complexes with the guanine nucleotide exchange factor SOS1. The 2:1 complex can bridge two LAT molecules when each Grb2, through their SH2 domains, binds to a phosphorylated site on a separate LAT. In T cells and mast cells, after receptor engagement, receptor phosphoyrlation is rapidly followed by LAT phosphorylation and aggregation. In mast cells, aggregates containing more than one hundred LAT molecules have been detected. Previously we considered a homogeneous population of trivalent LAT molecules and showed that for a range of Grb2, SOS1 and LAT concentrations, an equilibrium theory for LAT aggregation predicts the formation of a gel-like phase comprising a very large aggregate (superaggregate. We now extend this theory to investigate the effects of a distribution of Grb2 valence in the LAT population on the formation of LAT aggregates and superaggregate and use stochastic simulations to calculate the fraction of the total LAT population in the superaggregate.

RUNX1 suppression induces megakaryocytic differentiation of UT-7/GM cells

International Nuclear Information System (INIS)

Nagai, Ryohei; Matsuura, Eri; Hoshika, Yusuke; Nakata, Emi; Nagura, Hironori; Watanabe, Ayako; Komatsu, Norio; Okada, Yoshiaki; Doi, Takefumi

2006-01-01

The transcription factor RUNX1 plays a crucial role in hematopoiesis. RUNX1 regulates both differentiation and proliferation of hematopoietic cells. Several reports have shown that RUNX1 participates in megakaryopoiesis, which is a process that leads to formation of platelets. However, to date, the mechanisms by which this occurs have not been fully elucidated. In the present study, we investigated whether siRNA-mediated depletion of RUNX1 affected megakaryopoiesis of UT-7/GM cells. The depletion of RUNX1 in UT-7/GM cells resulted in up-regulation of the expression of megakaryocytic markers and polyploidization, while cell proliferation was down-regulated. Furthermore, the overexpression of RUNX1 decreased the activity of megakaryocytic gene promoters. These results suggest that RUNX1 down-regulates terminal differentiation of megakaryocytes and promotes proliferation of megakaryocytic progenitors

17-AAG suppresses growth and invasion of lung adenocarcinoma cells via regulation of the LATS1/YAP pathway.

Science.gov (United States)

Ye, Xiang-Yun; Luo, Qing-Quan; Xu, Yun-Hua; Tang, Nai-Wang; Niu, Xiao-Min; Li, Zi-Ming; Shen, Sheng-Ping; Lu, Shun; Chen, Zhi-Wei

2015-03-01

The large tumour suppressor 1 (LATS1) signalling network has been proved to be an essential regulator within the cell, participating in multiple cellular phenotypes. However, it is unclear concerning the clinical significance of LATS1 and the regulatory mechanisms of 17-Allylamino-17- demethoxygeldanamycin (17-AAG) in lung adenocarcinoma (LAC). The aim of the present study was to investigate the correlation of LATS1 and yes-associated protein (YAP) expression with clinicopathological characteristics in LAC patients, and the effects of 17-AAG on biological behaviours of LAC cells. Subcutaneous LAC tumour models were further established to observe the tumour growth in nude mice. The results showed that the positive expression of LATS1 was significantly lowered (26.7% versus 68.0%, P AAG inhibited proliferation and invasion, and induced cell apoptosis and cycle arrest in LAC cells together with increased expression of E-cadherin and p-LATS1, and decreased expression of YAP and connective tissue growth factor. Tumour volumes and weight were much smaller in 17-AAG-treated groups than those in untreated group (P AAG suppresses growth and invasion of LAC cells via regulation of the LATS1/YAP pathway in vitro and in vivo, suggesting that we may provide a promising therapeutic strategy for the treatment of human LAC. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Tests of SEC stability in high flux proton beams

International Nuclear Information System (INIS)

Agoritsas, V.; Witkover, R.L.

1979-01-01

The Secondary Emission Chamber (SEC) is used to measure the beam intensity in slow extracted beam channels of proton synchrotrons around the world. With the improvements in machine intensity, these monitors have been exposed to higher flux conditions than in the past. A change in sensitivity of up to 25% has been observed in the region around the beam spot. Using SEC's of special construction, a series of tests was performed at FNAL, BNL-AGS and CERN-PS. The results of these tests and conclusions about the construction of more stable SEC's are presented

Measurements of the cosmic-ray electron and positron spectrum and anisotropies with the Fermi LAT

Science.gov (United States)

Loparco, F.; Fermi LAT Collaboration

2017-12-01

The Large Area Telescope (LAT) onboard the Fermi satellite is a pair-conversion telescope for high-energy gamma rays of astrophysical origin. Although it was designed to be a high-sensitivity gamma-ray telescope, the LAT has proved to be an excellent electron/positron detector. It has been operating in low Earth orbit since June 2008 and has collected more than 16 million cosmic-ray electron and positron (CRE) events in its first seven years of operation. The huge data sample collected by the LAT enables a precise measurement of the CRE energy spectrum up to the TeV region. A search for anisotropies in the arrival directions of CREs was also performed. The upper limits on the dipole anisotropy probe the presence of nearby young and middle-aged CRE sources.

Adult siblings with homozygous G6PC3 mutations expand our understanding of the severe congenital neutropenia type 4 (SCN4 phenotype

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Fernandez Bridget A

2012-11-01

Full Text Available Abstract Background Severe congenital neutropenia type 4 (SCN4 is an autosomal recessive disorder caused by mutations in the third subunit of the enzyme glucose-6-phosphatase (G6PC3. Its core features are congenital neutropenia and a prominent venous skin pattern, and affected individuals have variable birth defects. Oculocutaneous albinism type 4 (OCA4 is caused by autosomal recessive mutations in SLC45A2. Methods We report a sister and brother from Newfoundland, Canada with complex phenotypes. The sister was previously reported by Cullinane et al., 2011. We performed homozygosity mapping, next generation sequencing and conventional Sanger sequencing to identify mutations that cause the phenotype in this family. We have also summarized clinical data from 49 previously reported SCN4 cases with overlapping phenotypes and interpret the medical histories of these siblings in the context of the literature. Results The siblings’ phenotype is due in part to a homozygous mutation in G6PC3, [c.829C > T, p.Gln277X]. Their ages are 38 and 37 years respectively and they are the oldest SCN4 patients published to date. Both presented with congenital neutropenia and later developed Crohn disease. We suggest that the latter is a previously unrecognized SCN4 manifestation and that not all affected individuals have an intellectual disability. The sister also has a homozygous mutation in SLC45A2, which explains her severe oculocutaneous hypopigmentation. Her brother carried one SLC45A2 mutation and was diagnosed with “partial OCA” in childhood. Conclusions This family highlights that apparently novel syndromes can in fact be caused by two known autosomal recessive disorders.

Fermi-LAT upper limits on gamma-ray emission from colliding wind binaries

International Nuclear Information System (INIS)

Werner, Michael; Reimer, O.; Reimer, A.

2013-01-01

Here, colliding wind binaries (CWBs) are thought to give rise to a plethora of physical processes including acceleration and interaction of relativistic particles. Observation of synchrotron radiation in the radio band confirms there is a relativistic electron population in CWBs. Accordingly, CWBs have been suspected sources of high-energy γ-ray emission since the COS-B era. Theoretical models exist that characterize the underlying physical processes leading to particle acceleration and quantitatively predict the non-thermal energy emission observable at Earth. Furthermore, we strive to find evidence of γ-ray emission from a sample of seven CWB systems: WR 11, WR 70, WR 125, WR 137, WR 140, WR 146, and WR 147. Theoretical modelling identified these systems as the most favourable candidates for emitting γ-rays. We make a comparison with existing γ-ray flux predictions and investigate possible constraints. We used 24 months of data from the Large Area Telescope (LAT) on-board the Fermi Gamma Ray Space Telescope to perform a dedicated likelihood analysis of CWBs in the LAT energy range. As a result, we find no evidence of γ-ray emission from any of the studied CWB systems and determine corresponding flux upper limits. For some CWBs the interplay of orbital and stellar parameters renders the Fermi-LAT data not sensitive enough to constrain the parameter space of the emission models. In the cases of WR140 and WR147, the Fermi-LAT upper limits appear to rule out some model predictions entirely and constrain theoretical models over a significant parameter space. A comparison of our findings to the CWB η Car is made.

75 FR 9476 - Environmental Impact Statement: Salt Lake County, UT

Science.gov (United States)

2010-03-02

... Lake County, UT AGENCY: Federal Highway Administration (FHWA), DOT. ACTION: Notice of intent. SUMMARY... cooperation with UDOT, intends to prepare an EIS on a proposal to analyze and address the regional..., 4700 South, Bangerter Highway and Redwood Road. To provide for local and regional travel demands, the...

Review and discussion of the development of synthetic aperture focusing technique for ultrasonic testing (SAFT-UT)

International Nuclear Information System (INIS)

Busse, L.J.; Collins, H.D.; Doctor, S.R.

1984-03-01

The development and capabilities of synthetic aperture focusing techniques for ultrasonic testing (SAFT-UT) are presented. The purpose of SAFT-UT is to produce high-resolution images of the interior of opaque objects. The goal of this work is to develop and implement methods which can be used to detect and to quantify the extent of defects and cracks in critical components of nuclear reactors (pressure vessels, primary piping systems, and nozzles). This report places particular emphasis upon the practical experimental results that have been obtained using SAFT-UT as well as the theoretical background that underlies synthetic aperture focusing. A discussion regarding high-speed and real-time implementations of two- and three-dimensional synthetic aperture focusing is also presented

The Use of Daily Geodetic UT1 and LOD Data in the Optimal Estimation of UT1 and LOD With the JPL Kalman Earth Orientation Filter

Science.gov (United States)

Freedman, A. P.; Steppe, J. A.

1995-01-01

The Jet Propulsion Laboratory Kalman Earth Orientation Filter (KEOF) uses several of the Earth rotation data sets available to generate optimally interpolated UT1 and LOD series to support spacecraft navigation. This paper compares use of various data sets within KEOF.

LAT Perspectives in Detection of High Energy Cosmic Ray Electrons

International Nuclear Information System (INIS)

Moiseev, Alexander; Ormes, J.F.; Funk, Stefan

2007-01-01

The LAT science objectives and capabilities in the detection of high energy electrons in the energy range from 20 GeV to ∼1.5 TeV are presented. LAT simulations are used to establish the event selections. It is found that maintaining the efficiency of electron detection at the level of 30%, the residual hadron contamination does not exceed 2-3% of the electron flux. It is expected to collect ∼ ten million of electrons with the energy above 20 GeV for one year of observation. Precise spectrum reconstruction with collected electron statistics opens the unique opportunity to investigate several important problems such as models of IC radiation, revealing the signatures of nearby sources such as high energy cutoff in the electron spectrum, testing the propagation model, and search for KKDM particles decay through their contribution to the electron spectrum

The Half-Life of the HSV-1 1.5 kb LAT Intron is similar to the half-Life of the 2.0 kb LAT Intron

Science.gov (United States)

Brinkman, Kerry K.; Mishra, Prakhar; Fraser, Nigel W.

2013-01-01

Herpes Simplex Virus type 1 (HSV-1) establishes a latent infection in the sensory neurons of the peripheral nervous system of humans. Although about 80 genes are expressed during the lytic cycle of the virus infection, essentially only one gene is expressed during the latent cycle. This gene is known as the latency associated transcript (LAT) and it appears to play a role in the latency cycle through an anti-apoptotic function in the 5’ end of the gene and miRNA encoded along the length of the transcript which down regulate some of the viral immediate early (IE) gene products. The LAT gene is about 8.3 kb long and consists of two exons separated by an unusual intron. The intron between the exons consists of two nested introns. This arrangement of introns has been called a twintron. Furthermore, the larger (2 kb) intron has been shown to be very stable. In this study we measure the stability of the shorter 1.5 kb nested intron and find its half-life is similar to the longer intron. This was achieved by deleting the 0.5 kb overlapping intron from a plasmid construct designed to express the LAT transcript from a tet-inducible promoter, and measuring the half-life of the 1.5 kb intron in tissue culture cells. This finding supports the hypothesis that it is the common branch-point region of these nested introns that is responsible for their stability. PMID:23335177

Potencial evocado auditivo de longa latência: diferenças na forma de contagem do estímulo raro

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Rubia Soares Bruno

2016-02-01

Full Text Available RESUMO Objetivo: identificar se existe diferença nos achados do Potencial Evocado Auditivo de Longa Latência em relação à latência e amplitude, em diferentes modos de contagem do estimulo raro, sendo contando mentalmente ou marcando no papel (sem memorizar. Métodos: esse estudo teve caráter prospectivo e transversal. A amostra foi composta por conveniência sendo constituída por 49 indivíduos, sendo 29 do gênero feminino e 20 do gênero masculino. Foram realizados os seguintes procedimentos: Inspeção Visual do Meato Acústico Externo, Audiometria Tonal Liminar, Medidas de Imitância Acústica e Potencial Evocado Auditivo de Longa Latência, o qual foi realizado duas vezes, uma após a outra, com os indivíduos atentando ao estímulo raro, começando sempre contando mentalmente e após marcando em um papel. Resultados: houve diferença estatisticamente significante entre as orelhas para as latências de P1, P2 e amplitude de N1 para o método de marcação no papel, da latência de N1 para o método de contagem mental dos estímulos raros, e da amplitude de P2 em ambos os métodos, porém com todos os valores dentro da faixa de normalidade. Além disso, a diferença estatisticamente significante também foi evidente na comparação entre os gêneros, sendo encontrados valores de latência maiores de P2 e N2 para o gênero masculino em ambos os métodos de contagem dos estímulos raros. A amplitude de P1, P2 e P3 foi menor no gênero masculino nas diferentes formas de contagem, sendo no P2 a diferença apenas no método contando mentalmente. Ao compararmos os métodos, houve diferença estatisticamente significante apenas para a latência de P2, a qual foi maior para o método marcando no papel. Conclusão: não houve diferença para as latências e amplitudes dos potenciais evocados auditivos de longa latência na comparação da contagem do estímulo raro (contando mentalmente e marcando no papel para quase todos os potenciais, com

75 FR 22892 - Environmental Impact Statement: Salt Lake County, UT

Science.gov (United States)

2010-04-30

... Lake County, UT AGENCY: Federal Highway Administration (FHWA), USDOT. ACTION: Notice of Intent. SUMMARY... . SUPPLEMENTARY INFORMATION: The FHWA, in cooperation with UDOT, will prepare an EIS for a proposal to address... (WFRC). Improvements are necessary to meet the projected travel demand in 2030 in the project area and...

Characteristic Assessments of the Phased Array UT System Developed by KHNP

Energy Technology Data Exchange (ETDEWEB)

Cho, Chan-Hee; Jee, Dong-Hyun; Lee, Tae-Hun; Yoo, Hyun-Ju [KHNP CRI, Daejeon (Korea, Republic of)

2016-10-15

The ultrasonic testing (UT) is an important one of the nondestructive examination methods which are used for the in-service inspection in the nuclear power plant. It is mainly used for the inspection of welds in piping and nozzle for many components. Technologies for the ultrasonic testing have been advanced for the reduction of inspection time and the increase of inspection reliability. In the manual ultrasonic testing system, it is not easy to compare the variation of inspection signals over time, because the data cannot be stored during the inspection. For the purpose of inspecting nuclear power components, the KHNP developed a phased array UT system including pulser-receiver, AD converter, beam-former, phased array probe, and scanner with 3-directional degree of freedom. Characteristics of the KHNP PA system and the results of acquired signals are described in detail in this paper.

Characteristic Assessments of the Phased Array UT System Developed by KHNP

International Nuclear Information System (INIS)

Cho, Chan-Hee; Jee, Dong-Hyun; Lee, Tae-Hun; Yoo, Hyun-Ju

2016-01-01

The ultrasonic testing (UT) is an important one of the nondestructive examination methods which are used for the in-service inspection in the nuclear power plant. It is mainly used for the inspection of welds in piping and nozzle for many components. Technologies for the ultrasonic testing have been advanced for the reduction of inspection time and the increase of inspection reliability. In the manual ultrasonic testing system, it is not easy to compare the variation of inspection signals over time, because the data cannot be stored during the inspection. For the purpose of inspecting nuclear power components, the KHNP developed a phased array UT system including pulser-receiver, AD converter, beam-former, phased array probe, and scanner with 3-directional degree of freedom. Characteristics of the KHNP PA system and the results of acquired signals are described in detail in this paper

Leser-Trélat sign presenting in a patient with ovarian cancer: a case report

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Bölke Edwin

2009-07-01

Full Text Available Abstract Introduction Seborrheic keratoses are very common findings in elderly patients. However, a sudden onset and dramatic increase in the number and size of these benign lesions deserves special attention, since this may represent the Leser Trélat sign, a rare paraneoplastic cutaneous syndrome. Case presentation A 92-year-old female presented to our clinic with multiple eruptive seborrheic keratoses, which had dramatically increased in size and number over the past two years. A diagnostic work-up revealed an ovarian carcinoma. Hence, cutaneous findings in our patient were consistent with the diagnosis of the Leser-Trélat sign. Conclusion The Leser-Trélat sign may coincide with the diagnosis of occult cancer or follow or precede it by months or years. Practitioners should take cases of eruptive seborrheic keratoses seriously and perform thorough patient examinations.

75 FR 58433 - Notice of Inventory Completion: Brigham Young University, Museum of Peoples and Cultures, Provo, UT

Science.gov (United States)

2010-09-24

.... Charles Lang and Mr. Platte Lyman donated the human remains to the Deseret Museum, Salt Lake City, UT... Saints in Salt Lake City, UT. The collection became known as the Lang-Lyman Collection, and was acquired... of human hair, 1 mug, 1 leather pouch, 1 piece of buckskin, 1 gourd container, 60 feathers, 1 bone...

Solution-processed inorganic copper(I) thiocyanate (CuSCN) hole transporting layers for efficient p–i–n perovskite solar cells

KAUST Repository

Zhao, Kui; Munir, Rahim; Yan, Buyi; Yang, Yang; Kim, Taesoo; Amassian, Aram

2015-01-01

CuSCN is a highly transparent, highly stable, low cost and easy to solution process HTL that is proposed as a low cost replacement to existing organic and inorganic metal oxide hole transporting materials. Here, we demonstrate hybrid organic

Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: Toward a novel active targeting strategy in breast cancer therapy.

Science.gov (United States)

Li, Lin; Di, Xingsheng; Wu, Mingrui; Sun, Zhisu; Zhong, Lu; Wang, Yongjun; Fu, Qiang; Kan, Qiming; Sun, Jin; He, Zhonggui

2017-04-01

Designing active targeting nanocarriers with increased cellular accumulation of chemotherapeutic agents is a promising strategy in cancer therapy. Herein, we report a novel active targeting strategy based on the large amino acid transporter 1 (LAT1) overexpressed in a variety of cancers. Glutamate was conjugated to polyoxyethylene stearate as a targeting ligand to achieve LAT1-targeting PLGA nanoparticles. The targeting efficiency of nanoparticles was investigated in HeLa and MCF-7 cells. Significant increase in cellular uptake and cytotoxicity was observed in LAT1-targeting nanoparticles compared to the unmodified ones. More interestingly, the internalized LAT1 together with targeting nanoparticles could recycle back to the cell membrane within 3 h, guaranteeing sufficient transporters on cell membrane for continuous cellular uptake. The LAT1 targeting nanoparticles exhibited better tumor accumulation and antitumor effects. These results suggested that the overexpressed LAT1 on cancer cells holds a great potential to be a high-efficiency target for the rational design of active-targeting nanosystems. Copyright © 2016 Elsevier Inc. All rights reserved.

Disruption of the Sec24d gene results in early embryonic lethality in the mouse.

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Andrea C Baines

Full Text Available Transport of newly synthesized proteins from the endoplasmic reticulum (ER to the Golgi is mediated by the coat protein complex COPII. The inner coat of COPII is assembled from heterodimers of SEC23 and SEC24. Though mice with mutations in one of the four Sec24 paralogs, Sec24b, exhibit a neural tube closure defect, deficiency in humans or mice has not yet been described for any of the other Sec24 paralogs. We now report characterization of mice with targeted disruption of Sec24d. Early embryonic lethality is observed in mice completely deficient in SEC24D, while a hypomorphic Sec24d allele permits survival to mid-embryogenesis. Mice haploinsufficient for Sec24d exhibit no phenotypic abnormality. A BAC transgene containing Sec24d rescues the embryonic lethality observed in Sec24d-null mice. These results demonstrate an absolute requirement for SEC24D expression in early mammalian development that is not compensated by the other three Sec24 paralogs. The early embryonic lethality resulting from loss of SEC24D in mice contrasts with the previously reported mild skeletal phenotype of SEC24D deficiency in zebrafish and restricted neural tube phenotype of SEC24B deficiency in mice. Taken together, these observations suggest that the multiple Sec24 paralogs have developed distinct functions over the course of vertebrate evolution.

Cell death by SecTRAPs: thioredoxin reductase as a prooxidant killer of cells.

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Karin Anestål

Full Text Available BACKGROUND: SecTRAPs (selenium compromised thioredoxin reductase-derived apoptotic proteins can be formed from the selenoprotein thioredoxin reductase (TrxR by targeting of its selenocysteine (Sec residue with electrophiles, or by its removal through C-terminal truncation. SecTRAPs are devoid of thioredoxin reductase activity but can induce rapid cell death in cultured cancer cell lines by a gain of function. PRINCIPAL FINDINGS: Both human and rat SecTRAPs killed human A549 and HeLa cells. The cell death displayed both apoptotic and necrotic features. It did not require novel protein synthesis nor did it show extensive nuclear fragmentation, but it was attenuated by use of caspase inhibitors. The redox active disulfide/dithiol motif in the N-terminal domain of TrxR had to be maintained for manifestation of SecTRAP cytotoxicity. Stopped-flow kinetics showed that NADPH can reduce the FAD moiety in SecTRAPs at similar rates as in native TrxR and purified SecTRAPs could maintain NADPH oxidase activity, which was accelerated by low molecular weight substrates such as juglone. In a cellular context, SecTRAPs triggered extensive formation of reactive oxygen species (ROS and consequently antioxidants could protect against the cell killing by SecTRAPs. CONCLUSIONS: We conclude that formation of SecTRAPs could contribute to the cytotoxicity seen upon exposure of cells to electrophilic agents targeting TrxR. SecTRAPs are prooxidant killers of cells, triggering mechanisms beyond those of a mere loss of thioredoxin reductase activity.

"Küsse lat's ..." : [luuletused] / Kauksi Ülle

Index Scriptorium Estoniae

Kauksi Ülle, pseud., 1962-

2002-01-01

Sisu: "Küsse lat's ..." ; "Vanaimä, ma lupa, ku suurõss kasu ..." ; "Mis-ti küsüt, et ..." ; Ussõ pääl üteld ; "Mis' sõs ku olõ 'pihlõ' ma kesk umma mäke ..." "Kos' sa olt? ..." ; "Maarahva miil ..." ; "Havvakirju ragi yts miis ..." ; Hanõ vai luigõ ; Võlg ; Mu viimäne laul sullõ ; "üts korgõ puu pak mullõ paika ...". Eluloolisi andmeid autori kohta lk. 369

14 CFR Sec. 2-5 - Revenue and accounting practices.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Revenue and accounting practices. Sec. 2-5... General Accounting Provisions Sec. 2-5 Revenue and accounting practices. (a) Revenue accounting practices... physically verify the reliability of its passenger revenue accounting practice at least once each accounting...

SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion

Science.gov (United States)

Chen, Xiao-Wei; Wang, He; Bajaj, Kanika; Zhang, Pengcheng; Meng, Zhuo-Xian; Ma, Danjun; Bai, Yongsheng; Liu, Hui-Hui; Adams, Elizabeth; Baines, Andrea; Yu, Genggeng; Sartor, Maureen A; Zhang, Bin; Yi, Zhengping; Lin, Jiandie; Young, Stephen G; Schekman, Randy; Ginsburg, David

2013-01-01

The secretory pathway of eukaryotic cells packages cargo proteins into COPII-coated vesicles for transport from the endoplasmic reticulum (ER) to the Golgi. We now report that complete genetic deficiency for the COPII component SEC24A is compatible with normal survival and development in the mouse, despite the fundamental role of SEC24 in COPII vesicle formation and cargo recruitment. However, these animals exhibit markedly reduced plasma cholesterol, with mutations in Apoe and Ldlr epistatic to Sec24a, suggesting a receptor-mediated lipoprotein clearance mechanism. Consistent with these data, hepatic LDLR levels are up-regulated in SEC24A-deficient cells as a consequence of specific dependence of PCSK9, a negative regulator of LDLR, on SEC24A for efficient exit from the ER. Our findings also identify partial overlap in cargo selectivity between SEC24A and SEC24B, suggesting a previously unappreciated heterogeneity in the recruitment of secretory proteins to the COPII vesicles that extends to soluble as well as trans-membrane cargoes. DOI: http://dx.doi.org/10.7554/eLife.00444.001 PMID:23580231

Efficacy of sodium channel blockers in SCN2A early infantile epileptic encephalopathy.

Science.gov (United States)

Dilena, Robertino; Striano, Pasquale; Gennaro, Elena; Bassi, Laura; Olivotto, Sara; Tadini, Laura; Mosca, Fabio; Barbieri, Sergio; Zara, Federico; Fumagalli, Monica

2017-04-01

Recent clinical evidence supports a targeted therapeutic approach for genetic epileptic encephalopathies based on the molecular dysfunction. A 2-day-old male infant presented with epileptic encephalopathy characterized by burst-suppression EEG background and tonic-clonic migrating partial seizures. The condition was refractory to phenobarbital, pyridoxine, pyridoxal phosphate and levetiracetam, but a dramatic response to an intravenous loading dose of phenytoin was documented by video-EEG monitoring. Over weeks phenytoin was successfully switched to carbamazepine to prevent seizure relapses associated with difficulty in maintaining proper blood levels of phenytoin. Genetic analysis identified a novel de novo heterozygous mutation (c.[4633A>G]p.[Met1545Val]) in SCN2A. At two years and three months of age the patient is still seizure-free on carbamazepine, although a developmental delay is evident. Sodium channel blockers represent the first-line treatment for confirmed or suspected SCN2A-related epileptic encephalopathies. In severe cases with compatible electro-clinical features we propose a treatment algorithm based on a test trial with high dose intravenous phenytoin followed in case of a positive response by carbamazepine, more suitable for long-term maintenance treatment. Because of their rarity, collaborative studies are needed to delineate shared therapeutic protocols for EIEE based on the electro-clinical features and the presumed underlying genetic substrate. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The Role of LAT in Increased CD8+ T Cell Exhaustion in Trigeminal Ganglia of Mice Latently Infected with Herpes Simplex Virus 1▿

Science.gov (United States)

Allen, Sariah J.; Hamrah, Pedram; Gate, David; Mott, Kevin R.; Mantopoulos, Dimosthenis; Zheng, Lixin; Town, Terrence; Jones, Clinton; von Andrian, Ulrich H.; Freeman, Gordon J.; Sharpe, Arlene H.; BenMohamed, Lbachir; Ahmed, Rafi; Wechsler, Steven L.; Ghiasi, Homayon

2011-01-01

Herpes simplex virus (HSV) infection is a classic example of latent viral infection in humans and experimental animal models. The HSV-1 latency-associated transcript (LAT) plays a major role in the HSV-1 latency reactivation cycle and thus in recurrent disease. Whether the presence of LAT leads to generation of dysfunctional T cell responses in the trigeminal ganglia (TG) of latently infected mice is not known. To address this issue, we used LAT-positive [LAT(+)] and LAT-deficient [LAT(−)] viruses to evaluate the effect of LAT on CD8 T cell exhaustion in TG of latently infected mice. The amount of latency as determined by quantitative reverse transcription-PCR (qRT-PCR) of viral DNA in total TG extracts was 3-fold higher with LAT(+) than with LAT(−) virus. LAT expression and increased latency correlated with increased mRNA levels of CD8, PD-1, and Tim-3. PD-1 is both a marker for exhaustion and a primary factor leading to exhaustion, and Tim-3 can also contribute to exhaustion. These results suggested that LAT(+) TG contain both more CD8+ T cells and more CD8+ T cells expressing the exhaustion markers PD-1 and Tim-3. This was confirmed by flow cytometry analyses of expression of CD3/CD8/PD-1/Tim-3, HSV-1, CD8+ T cell pentamer (specific for a peptide derived from residues 498 to 505 of glycoprotein B [gB498–505]), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-α). The functional significance of PD-1 and its ligands in HSV-1 latency was demonstrated by the significantly reduced amount of HSV-1 latency in PD-1- and PD-L1-deficient mice. Together, these results may suggest that both PD-1 and Tim-3 are mediators of CD8+ T cell exhaustion and latency in HSV-1 infection. PMID:21307196

Generación de un modelo knock-out del gen SCN1A en Drosophila melanogaster para el estudio del síndrome de Dravet.

OpenAIRE

PLANELLS CÁRCEL, ANDRÉS

2017-01-01

[ES] El Síndrome de Dravet (SD) es una enfermedad rara infantil que se manifiesta en crisis epilépticas a temprana edad y provoca un deterioro cognitivo y conductual. Esta enfermedad es causada por mutaciones dominantes en el gen SCN1A. Este trabajo se centra en la generación de un modelo knock-out (KO) del gen paralytic en Drosophila melanogaster, homólogo al gen SCN1A en humanos, para su aplicación en el estudio del SD. A la vez se ha estudiado la conducta de cepas sensibles ...

Numerical simulation of sediment transport from Ba Lat Mouth and the process of coastal morphology

International Nuclear Information System (INIS)

Chung, Dang Huu

2008-01-01

This paper presents an application of a 3D numerical model to simulate one vertical layer sediment transport and coastal morphodynamical process for the Hai Hau coastal area located in the north of Vietnam, where a very large amount of suspended sediment is carried into the sea from Ba Lat Mouth every year. Four simulations are based on the real data of waves supplied by the observation station close to Ba Lat Mouth. The conditions of wind and suspended sand concentration at Ba Lat Mouth are basically assumed from practice. The computed results show that the hydrodynamic factors strongly depend on the wind condition and these factors govern the direction and the range of suspended sand transport, especially in the shallow-water region. In the deep-water region this influence is not really clear when the wind force is not strong enough to modify the tidal current. In the area close to Ba Lat Mouth the flow velocity is very large with the maximum flood flow about 2.6 m s −1 and the maximum ebb flow about 1 m s −1 at the mouth, and this is one of the reasons for strong erosion. In the case of tidal flow only, the suspended sand concentration decreases resulting in local deposition. Therefore, the area influenced by suspended transport is small, about 12 km from the mouth. In the condition of wind and waves, the suspended sand transport reaches the end of the computation area within a few days, especially the cases with wind from the north-east-north. Through these simulation results, a common tendency of sediment movement from the north to the south is specified for the Hai Hau coastal area. In addition, the results also show that the coast suffers from strong erosion, especially the region near Ba Lat Mouth. From the simulation results it can be seen that the movement of the Red River sand along the Vietnamese coast is quite possible, which is an answer to a long-standing question. Furthermore, although the suspended sediment concentration is quite large, it is

Mechanisms of Rose Bengal inhibition on SecA ATPase and ion channel activities.

Science.gov (United States)

Hsieh, Ying-Hsin; Huang, Ying-Ju; Jin, Jin-Shan; Yu, Liyan; Yang, Hsiuchin; Jiang, Chun; Wang, Binghe; Tai, Phang C

2014-11-14

SecA is an essential protein possessing ATPase activity in bacterial protein translocation for which Rose Bengal (RB) is the first reported sub-micromolar inhibitor in ATPase activity and protein translocation. Here, we examined the mechanisms of inhibition on various forms of SecA ATPase by conventional enzymatic assays, and by monitoring the SecA-dependent channel activity in the semi-physiological system in cells. We build on the previous observation that SecA with liposomes form active protein-conducting channels in the oocytes. Such ion channel activity is enhanced by purified Escherichia coli SecYEG-SecDF·YajC liposome complexes. Inhibition by RB could be monitored, providing correlation of in vitro activity and intact cell functionality. In this work, we found the intrinsic SecA ATPase is inhibited by RB competitively at low ATP concentration, and non-competitively at high ATP concentrations while the translocation ATPase with precursors and SecYEG is inhibited non-competitively by RB. The Inhibition by RB on SecA channel activity in the oocytes with exogenous ATP-Mg(2+), mimicking translocation ATPase activity, is also non-competitive. The non-competitive inhibition on channel activity has also been observed with SecA from other bacteria which otherwise would be difficult to examine without the cognate precursors and membranes. Copyright © 2014 Elsevier Inc. All rights reserved.

THE FIRST FERMI LAT SUPERNOVA REMNANT CATALOG

Energy Technology Data Exchange (ETDEWEB)

Acero, F.; Ballet, J. [Laboratoire AIM, CEA-IRFU/CNRS/Université Paris Diderot, Service d’Astrophysique, CEA Saclay, F-91191 Gif sur Yvette (France); Ackermann, M.; Buehler, R. [Deutsches Elektronen Synchrotron DESY, D-15738 Zeuthen (Germany); Ajello, M. [Department of Physics and Astronomy, Clemson University, Kinard Lab of Physics, Clemson, SC 29634-0978 (United States); Baldini, L. [Università di Pisa and Istituto Nazionale di Fisica Nucleare, Sezione di Pisa I-56127 Pisa (Italy); Barbiellini, G. [Istituto Nazionale di Fisica Nucleare, Sezione di Trieste, I-34127 Trieste (Italy); Bastieri, D.; Buson, S. [Istituto Nazionale di Fisica Nucleare, Sezione di Padova, I-35131 Padova (Italy); Bellazzini, R. [Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, I-56127 Pisa (Italy); Bissaldi, E. [Istituto Nazionale di Fisica Nucleare, Sezione di Bari, I-70126 Bari (Italy); Blandford, R. D.; Bloom, E. D.; Bottacini, E.; Caliandro, G. A.; Cameron, R. A. [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); Bonino, R. [Istituto Nazionale di Fisica Nucleare, Sezione di Torino, I-10125 Torino (Italy); Brandt, T. J. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Bregeon, J. [Laboratoire Univers et Particules de Montpellier, Université Montpellier, CNRS/IN2P3, Montpellier (France); Bruel, P., E-mail: francesco.depalma@ba.infn.it, E-mail: t.j.brandt@nasa.gov, E-mail: john.w.hewitt@unf.edu [Laboratoire Leprince-Ringuet, École polytechnique, CNRS/IN2P3, Palaiseau (France); and others

2016-05-01

To uniformly determine the properties of supernova remnants (SNRs) at high energies, we have developed the first systematic survey at energies from 1 to 100 GeV using data from the Fermi Large Area Telescope (LAT). Based on the spatial overlap of sources detected at GeV energies with SNRs known from radio surveys, we classify 30 sources as likely GeV SNRs. We also report 14 marginal associations and 245 flux upper limits. A mock catalog in which the positions of known remnants are scrambled in Galactic longitude allows us to determine an upper limit of 22% on the number of GeV candidates falsely identified as SNRs. We have also developed a method to estimate spectral and spatial systematic errors arising from the diffuse interstellar emission model, a key component of all Galactic Fermi LAT analyses. By studying remnants uniformly in aggregate, we measure the GeV properties common to these objects and provide a crucial context for the detailed modeling of individual SNRs. Combining our GeV results with multiwavelength (MW) data, including radio, X-ray, and TeV, we demonstrate the need for improvements to previously sufficient, simple models describing the GeV and radio emission from these objects. We model the GeV and MW emission from SNRs in aggregate to constrain their maximal contribution to observed Galactic cosmic rays.

Commentary on using equivalent latitude in the upper troposphere and lower stratosphere

Directory of Open Access Journals (Sweden)

L. L. Pan

2012-10-01

Full Text Available We discuss the use of potential vorticity (PV based equivalent latitude (EqLat and potential temperature (θ coordinates in the upper troposphere and lower stratosphere (UTLS for chemical transport studies. The main objective is to provide a cautionary note on using EqLat-θ coordinates for aggregating chemical tracers in the UTLS. Several examples are used to show 3-D distributions of EqLat together with chemical constituents for a range of θ. We show that the use of PV-θ coordinates may not be suitable for several reasons when tropospheric processes are an important part of a study. Due to the different static stability structures between the stratosphere and troposphere, the use of θ as a vertical coordinate does not provide equal representations of the UT and LS. Since the θ surfaces in the troposphere often intersect the surface of the Earth, the θ variable does not work well distinguishing the UT from the boundary layer when used globally as a vertical coordinate. We further discuss the duality of PV/EqLat as a tracer versus as a coordinate variable. Using an example, we show that while PV/EqLat serves well as a transport tracer in the UTLS region, it may conceal the chemical structure associated with wave breaking when used as a coordinate to average chemical tracers. Overall, when choosing these coordinates, considerations need to be made not only based on the time scale of PV being a conservative tracer, but also the specific research questions to be addressed.

14 CFR Sec. 1-4 - System of accounts coding.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false System of accounts coding. Sec. 1-4 Section... General Accounting Provisions Sec. 1-4 System of accounts coding. (a) A four digit control number is assigned for each balance sheet and profit and loss account. Each balance sheet account is numbered...

Financial Journalism under Fire: The SEC and Newsroom Ethics.

Science.gov (United States)

Spellman, Robert L.

Although noting that the Securities and Exchange Commission (SEC) has been a valuable ally of journalists, this paper suggests that recent efforts of the SEC in prosecuting the case of R. Foster Winans, Jr., a former writer for the "Wall Street Journal," may be unconstitutional. Following an introduction to the First Amendment issues…

46 CFR Sec. 2 - Description of NSA-WORKSMALREP Contract.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Description of NSA-WORKSMALREP Contract. Sec. 2 Section... REPAIRS-NSA-WORKSMALREP Sec. 2 Description of NSA-WORKSMALREP Contract. This is an individual fixed price contract which may be awarded to any firm not holding an NSA-LUMPSUMREP Contract, as a result of formal...

Constraining decaying dark matter with FERMI-LAT gamma rays

International Nuclear Information System (INIS)

Maccione, L.

2011-01-01

High energy electron sand positrons from decaying dark matter can produce a significant flux of gamma rays by inverse Compton of low energy photons in the interstellar radiation field. This possibility is inevitably related with the dark matter interpretation of the observed PAMELA and FERMI excesses. We will describe a simple and universal method to constrain dark matter models which produce electrons and positrons in their decay by using the FERMI-LAT gamma-ray observations in the energy range between 0.5 GeV and 300 GeV, by exploiting universal response functions that, once convolved with a specific dark matter model, produce the desired constraint. The response functions contain all the astrophysical inputs. Here is discussed the uncertainties in the determination of the response functions and apply them to place constraints on some specific dark matter decay models that can well fit the positron and electron fluxes observed by PAMELA and FERMI LAT, also taking into account prompt radiation from the dark matter decay. With the available data decaying dark matter can not be excluded as source of the PAMELA positron excess.

Voltage-gated Na+ channel SCN5A is a key regulator of a gene transcriptional network that controls colon cancer invasion

Science.gov (United States)

House, Carrie D.; Vaske, Charles J.; Schwartz, Arnold M.; Obias, Vincent; Frank, Bryan; Luu, Truong; Sarvazyan, Narine; Irby, Rosalyn; Strausberg, Robert L.; Hales, Tim G.; Stuart, Joshua M.; Lee, Norman H.

2010-01-01

Voltage-gated Na+ channels (VGSCs) have been implicated in the metastatic potential of human breast, prostate and lung cancer cells. Specifically, the SCN5A gene encoding the VGSC isotype Nav1.5 has been defined as a key driver of human cancer cell invasion. In this study, we examined the expression and function of VGSCs in a panel of colon cancer cell lines by electrophysiological recordings. Na+ channel activity and invasive potential were inhibited pharmacologically by tetrodotoxin or genetically by siRNAs specifically targeting SCN5A. Clinical relevance was established by immunohistochemistry of patient biopsies, where there was strong Nav1.5 protein staining in colon cancer specimens but little to no staining in matched-paired normal colon tissues. We explored the mechanism of VGSC-mediated invasive potential on the basis of reported links between VGSC activity and gene expression in excitable cells. Probabilistic modeling of loss-of-function screens and microarray data established an unequivocal role of VGSC SCN5A as a high level regulator of a colon cancer invasion network, involving genes that encompass Wnt signaling, cell migration, ectoderm development, response to biotic stimulus, steroid metabolic process and cell cycle control. siRNA-mediated knockdown of predicted downstream network components caused a loss of invasive behavior, demonstrating network connectivity and its function in driving colon cancer invasion. PMID:20651255

78 FR 19520 - Notice of Invitation to Participate In Coal Exploration License Application UTU-89492, UT

Science.gov (United States)

2013-04-01

... Friday, excluding Federal holidays (serialized under the number of UTU-89492) in the public room of the... through 7 inclusive, S\\1/2\\NE\\1/4\\, SE\\1/4\\NW\\1/ 4\\, E\\1/2\\SW\\1/4\\, SE\\1/4\\; Sec. 3, lots 1, 2, 5 through 8 inclusive, SW\\1/4\\NE\\1/4\\, NW\\1/ 4\\SE\\1/4\\; Sec. 10, all; Sec. 11, all; Sec. 14, all; Sec. 15, all...

46 CFR Sec. 5 - Measures to protect ship's payrolls.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Measures to protect ship's payrolls. Sec. 5 Section 5... SHIP'S PERSONNEL Sec. 5 Measures to protect ship's payrolls. (a) General Agents are not required to consider the amount of the payroll delivered to the Master at the conclusion of a voyage in determining the...

Characteristics of Schumann Resonance Parameters at Kuju Station

Directory of Open Access Journals (Sweden)

Ikeda Akihiro

2017-01-01

Full Text Available The ground magnetic field variation in the extremely low frequency (ELF range has been measured by an induction magnetometer at Kuju, Japan (KUJ; M.Lat. = 23.4 degrees, M. Lon. = 201.0 degrees since 2003. The first mode of the Schumann resonance (SR around 8 Hz can be seen at KUJ. The SR in H (horizontal northward component shows maximum peaks around 08 UT and 15 UT. In the case of D (horizontal eastward component, the SR shows its maximum peak around 08 UT. These peaks are coincident with the enhancement of lightning activity in Africa and Asia. Thus, we found the influence of the lightning activity on the observed SR at KUJ.

A STACKED ANALYSIS OF 115 PULSARS OBSERVED BY THE FERMI LAT

Energy Technology Data Exchange (ETDEWEB)

McCann, A., E-mail: mccann@kicp.uchicago.edu [Kavli Institute for Cosmological Physics, University of Chicago 933 East 56th Street, Chicago, IL 60637 (United States)

2015-05-10

Due to the low gamma-ray fluxes from pulsars above 50 GeV and the small collecting area of space-based telescopes, the gamma-ray emission discovered by the Fermi Large Area Telescope (LAT) in ∼150 pulsars is largely unexplored at these energies. In this regime, the uncertainties on the spectral data points and/or the constraints from upper limits are not sufficient to provide robust tests of competing emission models in individual pulsars. The discovery of power-law-type emission from the Crab pulsar at energies exceeding 100 GeV provides a compelling justification for exploration of other pulsars at these energies. We applied the method of aperture photometry to measure pulsar emission spectra from Fermi-LAT data and present a stacked analysis of 115 pulsars selected from the Second Fermi-LAT catalog of gamma-ray pulsars. This analysis, which uses an average of ∼4.2 yr of data per pulsar, aggregates low-level emission which cannot be resolved in individual objects but can be detected in an ensemble. We find no significant stacked excess at energies above 50 GeV. An upper limit of 30% of the Crab pulsar level is found for the average flux from 115 pulsars in the 100–177 GeV energy range at the 95% confidence level. Stacked searches exclusive to the young pulsar sample, the millisecond pulsar sample, and several other promising sub-samples also return no significant excesses above 50 GeV.

46 CFR Sec. 10 - Bonds.

Science.gov (United States)

2010-10-01

... REPAIRS UNDER NATIONAL SHIPPING AUTHORITY MASTER LUMP SUM REPAIR CONTRACT-NSA-LUMPSUMREP Sec. 10 Bonds. (a... awarded work and the furnishing of the performance and payment bonds required by Article 14 of the NSA... of the NSA-LUMPSUMREP Contract, the standard form of individual performance bond (Standard Form 25...

75 FR 3955 - Environmental Impact Statement: Davis and Weber Counties, UT

Science.gov (United States)

2010-01-25

... and Weber Counties, UT AGENCY: Federal Highway Administration (FHWA), DOT. ACTION: Notice of Intent... FHWA, in cooperation with UDOT, will prepare an EIS on a proposal to address projected transportation... east of the Great Salt Lake. To provide for local and regional travel demands, the regional...

Domain interactions of the peripheral preprotein translocase subunit SecA

NARCIS (Netherlands)

Blaauwen, T.den; Fekkes, P.; de Wit, J.G.; Kuiper, W.; Driessen, A.J.M.

1996-01-01

The homodimeric SecA protein is the peripheral subunit of the preprotein translocase in bacteria. It binds the preprotein and promotes its translocation across the bacterial cytoplasmic membrane by nucleotide modulated coinsertion and deinsertion into the membrane, SecA has two essential nucleotide

A comparison of LOD and UT1-UTC forecasts by different combined prediction techniques

Science.gov (United States)

Kosek, W.; Kalarus, M.; Johnson, T. J.; Wooden, W. H.; McCarthy, D. D.; Popiński, W.

Stochastic prediction techniques including autocovariance, autoregressive, autoregressive moving average, and neural networks were applied to the UT1-UTC and Length of Day (LOD) International Earth Rotation and Reference Systems Servive (IERS) EOPC04 time series to evaluate the capabilities of each method. All known effects such as leap seconds and solid Earth zonal tides were first removed from the observed values of UT1-UTC and LOD. Two combination procedures were applied to predict the resulting LODR time series: 1) the combination of the least-squares (LS) extrapolation with a stochastic predition method, and 2) the combination of the discrete wavelet transform (DWT) filtering and a stochastic prediction method. The results of the combination of the LS extrapolation with different stochastic prediction techniques were compared with the results of the UT1-UTC prediction method currently used by the IERS Rapid Service/Prediction Centre (RS/PC). It was found that the prediction accuracy depends on the starting prediction epochs, and for the combined forecast methods, the mean prediction errors for 1 to about 70 days in the future are of the same order as those of the method used by the IERS RS/PC.

Protein Export by the Mycobacterial SecA2 System Is Determined by the Preprotein Mature Domain

Science.gov (United States)

Feltcher, Meghan E.; Gibbons, Henry S.; Ligon, Lauren S.

2013-01-01

At the core of the bacterial general secretion (Sec) pathway is the SecA ATPase, which powers translocation of unfolded preproteins containing Sec signal sequences through the SecYEG membrane channel. Mycobacteria have two nonredundant SecA homologs: SecA1 and SecA2. While the essential SecA1 handles “housekeeping” export, the nonessential SecA2 exports a subset of proteins and is required for Mycobacterium tuberculosis virulence. Currently, it is not understood how SecA2 contributes to Sec export in mycobacteria. In this study, we focused on identifying the features of two SecA2 substrates that target them to SecA2 for export, the Ms1704 and Ms1712 lipoproteins of the model organism Mycobacterium smegmatis. We found that the mature domains of Ms1704 and Ms1712, not the N-terminal signal sequences, confer SecA2-dependent export. We also demonstrated that the lipid modification and the extreme N terminus of the mature protein do not impart the requirement for SecA2 in export. We further showed that the Ms1704 mature domain can be efficiently exported by the twin-arginine translocation (Tat) pathway. Because the Tat system exports only folded proteins, this result implies that SecA2 substrates can fold in the cytoplasm and suggests a putative role of SecA2 in enabling export of such proteins. Thus, the mycobacterial SecA2 system may represent another way that bacteria solve the problem of exporting proteins that can fold in the cytoplasm. PMID:23204463

First Fermi-LAT Catalog of Sources above 10 GeV (1FHL)

Data.gov (United States)

National Aeronautics and Space Administration — This catalog of LAT sources above 10 GeV reports the locations, spectra, and variability properties of the 514 sources significantly detected in this range during...

A study of SEC chromatograms on the basis of polymer structure properties

DEFF Research Database (Denmark)

Size Exclusion Chromatography (SEC), widely used in polymer laboratories, provides a convenient method for the determination of full molecular weight distribution (MWD) of polymers. For linear homogeneous polymer samples, the procedure to estimate the true MWD based on the elution curve of SEC has...... already been well established, while for nonlinear polymer samples and mixtures of linear and nonlinear polymers, the measured SEC data are often used just qualitatively. The SEC separation process is rather complicated, and a detailed study using finite element method and/or Brownian Dynamics simulation...... technique is rather difficult without oversimplifying the problem dramatically. However, it has been known for long that SEC separates polymer molecules according to their size in dilute solutions, and experimental studies with well-defined linear and nonlinear polymer samples have shown that a universal...

A Study of SEC Chromatograms on the basis of Polymer Structure Calculations

DEFF Research Database (Denmark)

Hassager, Ole; Wang, Yanwei

2007-01-01

Size Exclusion Chromatography (SEC), widely used in polymer laboratories, provides a convenient method for the determination of full molecular weight distribution (MWD) of polymers. For linear homogeneous polymer samples, the procedure to estimate the true MWD based on the elution curve of SEC has...... already been well established, while for nonlinear polymer samples and mixtures of linear and nonlinear polymers, the measured SEC data are often used just qualitatively. The SEC separation process is rather complicated, and a detailed study using finite element method and/or Brownian Dynamics simulation...... technique is rather difficult without oversimplifying the problem dramatically. However, it has been known for long that SEC separates polymer molecules according to their size in dilute solutions, and experimental studies with well-defined linear and nonlinear polymer samples have shown that a universal...

Directional Solidification of Pure Succinonitrile and a Succinonitrile-Acetone Alloy

Science.gov (United States)

Simpson, James E.; deGroh, Henry C., III; Garimella, Suresh V.

2000-01-01

An experimental study of the horizontal Bridgman growth of pure succinonitrile (SCN) and of a succinonitrile-1.0 mol% acetone alloy (SCN-1.0 mol.% ACE) has been performed. Experiments involving both a stationary thermal field (no-growth case) and a translating thermal field (growth case) were conducted. Growth rates of 2 and 40 micrometers/sec were investigated. For the pure SCN experiments, the velocity field in the melt was estimated using video images of seed particles in the melt. Observations of the seed particles indicate that a primary longitudinal convective cell is formed. The maximum velocity of two different particles which traveled along similar paths was the same and equal to 1.49 +/- 0.01 mm/s. The general accuracy of velocity measurements is estimated to be +/-0.08 mm/s, though the data shows consistency to within +/- 0.02 mm/s. The shape of the solid/liquid interface was also quantitatively determined. The solid/liquid interface was stable (non-dendritic and non-cellular) but not flat: rather it was significantly distorted by the influence of connection in the melt and, for the growth case, by the moving temperature boundary conditions along the ampoule. It was found that the interface shape and position were highly dependent on the alignment of the ampoule in the apparatus. Consequently, the ampoule was carefully aligned for all experiments. The values for front location agree with those determined in previous experiments. For the alloy experiments, the solid/liquid interface was determined to be unstable at growth rates greater than 2.8 micrometers/sec, but stable for the cases of no-growth and growth at 2 micrometers/sec. When compared to the shape of the pure SCN interface, the alloy interface forms closer to the cold zone, indicating that the melting temperature decreased due to the alloying element. Extensive temperature measurements were performed on the outside of the ampoule containing pure SCN. The resulting thermal profiles are presented

Very Bright CV discovered by MASTER-ICATE (Argentina)

Science.gov (United States)

Saffe, C.; Levato, H.; Mallamaci, C.; Lopez, C.; Lipunov, F. Podest V.; Denisenko, D.; Gorbovskoy, E.; Tiurina, N.; Balanutsa, P.; Kornilov, V.; Belinski, A.; Shatskiy, N.; Chazov, V.; Kuznetsov, A.; Yecheistov, V.; Yurkov, V.; Sergienko, Y.; Varda, D.; Sinyakov, E.; Gabovich, A.; Ivanov, K.; Yazev, S.; Budnev, N.; Konstantinov, E.; Chuvalaev, O.; Poleshchuk, V.; Gress, O.; Frolova, A.; Krushinsky, V.; Zalozhnih, I.; Popov, A.; Bourdanov, A.; Parkhomenko, A.; Tlatov, A.; Dormidontov, D.; Senik, V.; Podvorotny, P.; Shumkov, V.; Shurpakov, S.

2013-06-01

MASTER-ICATE very wide-field camera (d=72mm f/1.2 lens + 11 Mpix CCD) located near San Juan, Argentina has discovered OT source at (RA, Dec) = 14h 20m 23.5s -48d 55m 40s on the combined image (exposure 275 sec) taken on 2013-06-08.048 UT. The OT unfiltered magnitude is 12.1m (limit 13.1m). There is no minor planet at this place. The OT is seen in more than 10 images starting from 2013-06-02.967 UT (275 sec exposure) when it was first detected at 12.4m.

Solution-processed p-type copper(I) thiocyanate (CuSCN) for low-voltage flexible thin-film transistors and integrated inverter circuits

KAUST Repository

Petti, Luisa; Pattanasattayavong, Pichaya; Lin, Yen-Hung; Mü nzenrieder, Niko; Cantarella, Giuseppe; Yaacobi-Gross, Nir; Yan, Feng; Trö ster, Gerhard; Anthopoulos, Thomas D.

2017-01-01

, depending on the gate dielectric employed. The promising TFT characteristics enable fabrication of unipolar NOT gates on flexible free-standing plastic substrates with voltage gain of 3.4 at voltages as low as −3.5 V. Importantly, discrete CuSCN transistors

Predictive validity of examinations at the Secondary Education Certificate (SEC) level

OpenAIRE

Farrugia, Josette; Ventura, Frank

2007-01-01

This paper presents the predictive validity of results obtained by 16-year-old Maltese students in the May 2004 Secondary Education Certificate (SEC) examinations in Biology, Chemistry, Physics, Mathematics, Computing, English and Maltese for the Advanced level examinations in these subjects taken by the same students two years later. The study checks whether the SEC level is a good foundation for the higher level, the likelihood of obtaining a high grade at A-level from particular SEC result...

IMPLEMENTASI MANAJEMEN PENGETAHUAN PADA SISTEM PENGELOLAAN IJAZAH DI UPBJJ-UT BOGOR

Directory of Open Access Journals (Sweden)

Ratna Marta Dhewi

2015-04-01

Full Text Available This research aimed to examine the pattern of managing document certification at Bogor regional office for the last decade, furthermore, to design the digital model which offers insights into what is required to strategically align transcript management practice at Bogor regional office. The research was conducted by purposive sampling at Bogor Regional office considering that it represents the complexity of the organization that involves only a few employees with varying computational competencies and various task capabilities. However, they have been able to implement the knowledge management systems in providing services to customers. The data of this research were primary data. Data analysis were conducted based on an ongoing basis, with the following steps: preparation of the theme of data, classification and mapping of data based on a theme that has been set up, compilation, reduction, data cleaning, incorporation into the theme of the final data, triangulation of data, and data interpretation. This research discovered that managing certification documents of graduation at Bogor regional proved to be continuously updated and improved by the management team, and supported by top level management. The finding of this research proposed that the web based digital model of the certification documents management system (from acceptance, storage to distribution is the most suitable model to be implemented at the regional offices. Penelitian ini bertujuan mendeskripsikan pola pengelolaan dokumen sertifikasi di UPBJJ-UT Bogor selama sepuluh tahun terakhir dan menemukan model digital yang paling tepat untuk pengelolaan ijazah/transkrip yang efisien di UPBJJ-UT Bogor. Penelitian ini dilakukan dari bulan Maret sampai November 2011. Pemilihan lokasi penelitian dilakukan dengan cara purposive sampling dengan mempertimbangkan bahwa UPBJJ UT Bogor dapat mewakili kompleksitas organisasi yang melibatkan hanya beberapa pegawai dengan penguasaan komputer yang

Leser–Trélat syndrome in malignant mesothelioma and pulmonary adenocarcinoma

DEFF Research Database (Denmark)

Jepsen, Rikke Karlin; Skov, Anne Guldhammer; Skov, Birgit Guldhammer

2014-01-01

The syndrome of Leser–Trélat (LT) is characterized by the sudden appearance of multiple seborrhoeic keratoses (SKs) in association with internal occult malignancy. Usually, the syndrome has been associated with adenocarcinoma, most frequently of the gastrointestinal tract and breast. The pathogen...

Implications of the cosmic ray electron spectrum and anisotropy measured with Fermi-LAT

Energy Technology Data Exchange (ETDEWEB)

Di Bernardo, Giuseppe [Gothenburg Univ. (Sweden). Dept. of Physics; Evoli, Carmelo [SISSA, Trieste (Italy); Gaggero, Daniele; Grasso, Dario [Pisa Univ. (Italy). Dipt. die Fisica; INFN, Pisa (Italy); Maccione, Luca [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Mazziotta, Mario Nicola [Istituto Nazionale di Fisica Nucleare, Bari (Italy)

2010-11-15

The Fermi Large Area Telescope (LAT) collaboration recently released the updated results of the measurement of the cosmic ray electron (CRE) spectrum and published its first constraints on the CRE anisotropy. With respect to the previous Fermi-LAT results, the CRE spectrum measurement was extended down from 20 to 7 GeV, thus providing a better lever arm to discriminate theoretical models. Here we show that the new data strengthen the evidence for the presence of two distinct electron and positron spectral components. Furthermore, we show that under such hypothesis most relevant CRE and positron data sets are remarkably well reproduced. Consistent fits of cosmic-ray nuclei and antiproton data, which are crucial to validate the adopted propagation setup(s) and to fix the solar modulation potential, are obtained for the Kraichnan and plain-diffusion propagation setups, while the Kolmogorov one is disfavored. We then confirm that nearby pulsars are viable source candidates of the required e{sup {+-}} extra-component. In that case, we show that the predicted CRE anisotropy is compatible with Fermi-LAT constraints and that a positive detection should be at hand of that observatory. Models assuming that only nearby supernova remnants contribute to the high energy tail of the observed CRE spectrum are in contrast with anisotropy limits. (orig.)

46 CFR Sec. 12 - Disposition of removed equipment and scrap.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Disposition of removed equipment and scrap. Sec. 12... CONTRACT-NSA-LUMPSUMREP Sec. 12 Disposition of removed equipment and scrap. (a) Article 8 of the NSA-LUMPSUMREP Contract provides that any ship equipment, fuel, lube oil, supplies, stores, furniture, fixtures...

Fermi -LAT Observations of High-energy Behind-the-limb Solar Flares

Energy Technology Data Exchange (ETDEWEB)

Ackermann, M.; Buehler, R. [Deutsches Elektronen Synchrotron DESY, D-15738 Zeuthen (Germany); Allafort, A.; Bottacini, E.; Cameron, R. A.; Charles, E. [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); Baldini, L. [Università di Pisa and Istituto Nazionale di Fisica Nucleare, Sezione di Pisa I-56127 Pisa (Italy); Barbiellini, G. [Istituto Nazionale di Fisica Nucleare, Sezione di Trieste, I-34127 Trieste (Italy); Bastieri, D. [Istituto Nazionale di Fisica Nucleare, Sezione di Padova, I-35131 Padova (Italy); Bellazzini, R. [Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, I-56127 Pisa (Italy); Bissaldi, E.; Caragiulo, M.; Costanza, F. [Istituto Nazionale di Fisica Nucleare, Sezione di Bari, I-70126 Bari (Italy); Bonino, R. [Istituto Nazionale di Fisica Nucleare, Sezione di Torino, I-10125 Torino (Italy); Bregeon, J. [Laboratoire Univers et Particules de Montpellier, Université Montpellier, CNRS/IN2P3, F-34095 Montpellier (France); Bruel, P. [Laboratoire Leprince-Ringuet, École polytechnique, CNRS/IN2P3, F-91128 Palaiseau (France); Caraveo, P. A. [INAF-Istituto di Astrofisica Spaziale e Fisica Cosmica Milano, via E. Bassini 15, I-20133 Milano (Italy); Cavazzuti, E.; Ciprini, S. [Agenzia Spaziale Italiana (ASI) Science Data Center, I-00133 Roma (Italy); Cecchi, C., E-mail: nicola.omodei@stanford.edu, E-mail: vahep@stanford.edu, E-mail: melissa.pesce.rollins@pi.infn.it [Istituto Nazionale di Fisica Nucleare, Sezione di Perugia, I-06123 Perugia (Italy); and others

2017-02-01

We report on the Fermi -LAT detection of high-energy emission from the behind-the-limb (BTL) solar flares that occurred on 2013 October 11, and 2014 January 6 and September 1. The Fermi -LAT observations are associated with flares from active regions originating behind both the eastern and western limbs, as determined by STEREO . All three flares are associated with very fast coronal mass ejections (CMEs) and strong solar energetic particle events. We present updated localizations of the >100 MeV photon emission, hard X-ray (HXR) and EUV images, and broadband spectra from 10 keV to 10 GeV, as well as microwave spectra. We also provide a comparison of the BTL flares detected by Fermi -LAT with three on-disk flares and present a study of some of the significant quantities of these flares as an attempt to better understand the acceleration mechanisms at work during these occulted flares. We interpret the HXR emission to be due to electron bremsstrahlung from a coronal thin-target loop top with the accelerated electron spectra steepening at semirelativistic energies. The >100 MeV gamma-rays are best described by a pion-decay model resulting from the interaction of protons (and other ions) in a thick-target photospheric source. The protons are believed to have been accelerated (to energies >10 GeV) in the CME environment and precipitate down to the photosphere from the downstream side of the CME shock and landed on the front side of the Sun, away from the original flare site and the HXR emission.

High Prevalence of Long QT Syndrome Associated SCN5A Variants in Patients with Early-Onset Lone Atrial Fibrillation

DEFF Research Database (Denmark)

Olesen, Morten S; Yuan, Lei; Liang, Bo

2012-01-01

a mechanistic overlap between LQTS3 and early-onset lone AF. In 9 of 10 identified mutations and rare variants, we observed compromised biophysical properties affecting the transient peak current. CONCLUSIONS: In a cohort of patients with early-onset lone AF, we identified a high prevalence of SCN5A mutations...

3FHL: The Third Catalog of Hard Fermi -LAT Sources

Energy Technology Data Exchange (ETDEWEB)

Ajello, M. [Department of Physics and Astronomy, Clemson University, Kinard Lab of Physics, Clemson, SC 29634-0978 (United States); Atwood, W. B. [Santa Cruz Institute for Particle Physics, Department of Physics and Department of Astronomy and Astrophysics, University of California at Santa Cruz, Santa Cruz, CA 95064 (United States); Baldini, L. [Università di Pisa and Istituto Nazionale di Fisica Nucleare, Sezione di Pisa I-56127 Pisa (Italy); Ballet, J. [Laboratoire AIM, CEA-IRFU/CNRS/Université Paris Diderot, Service d’Astrophysique, CEA Saclay, F-91191 Gif sur Yvette (France); Barbiellini, G. [Istituto Nazionale di Fisica Nucleare, Sezione di Trieste, I-34127 Trieste (Italy); Bastieri, D. [Istituto Nazionale di Fisica Nucleare, Sezione di Padova, I-35131 Padova (Italy); Bellazzini, R. [Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, I-56127 Pisa (Italy); Bissaldi, E. [Dipartimento di Fisica “M. Merlin” dell’Università e del Politecnico di Bari, I-70126 Bari (Italy); Blandford, R. D.; Bloom, E. D. [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); Bonino, R. [Istituto Nazionale di Fisica Nucleare, Sezione di Torino, I-10125 Torino (Italy); Bregeon, J. [Laboratoire Univers et Particules de Montpellier, Université Montpellier, CNRS/IN2P3, F-34095 Montpellier (France); Britto, R. J. [Department of Physics, University of the Free State, P.O. Box 339, Bloemfontein 9300 (South Africa); Bruel, P., E-mail: majello@slac.stanford.edu [Laboratoire Leprince-Ringuet, École polytechnique, CNRS/IN2P3, F-91128 Palaiseau (France); and others

2017-10-01

We present a catalog of sources detected above 10 GeV by the Fermi Large Area Telescope (LAT) in the first 7 years of data using the Pass 8 event-level analysis. This is the Third Catalog of Hard Fermi -LAT Sources (3FHL), containing 1556 objects characterized in the 10 GeV–2 TeV energy range. The sensitivity and angular resolution are improved by factors of 3 and 2 relative to the previous LAT catalog at the same energies (1FHL). The vast majority of detected sources (79%) are associated with extragalactic counterparts at other wavelengths, including 16 sources located at very high redshift ( z > 2). Of the sources, 8% have Galactic counterparts and 13% are unassociated (or associated with a source of unknown nature). The high-latitude sky and the Galactic plane are observed with a flux sensitivity of 4.4 to 9.5 × 10{sup −11} ph cm{sup −2} s{sup −1}, respectively (this is approximately 0.5% and 1% of the Crab Nebula flux above 10 GeV). The catalog includes 214 new γ -ray sources. The substantial increase in the number of photons (more than 4 times relative to 1FHL and 10 times to 2FHL) also allows us to measure significant spectral curvature for 32 sources and find flux variability for 163 of them. Furthermore, we estimate that for the same flux limit of 10{sup −12} erg cm{sup −2} s{sup −1}, the energy range above 10 GeV has twice as many sources as the range above 50 GeV, highlighting the importance, for future Cherenkov telescopes, of lowering the energy threshold as much as possible.

Moderate expression of SEC16 increases protein secretion by Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Bao, Jichen; Huang, Mingtao; Petranovic, Dina

2017-01-01

in yeast, by moderately overexpressing SEC16, which is involved in protein translocation from the endoplasmic reticulum to the Golgi apparatus. The moderate overexpression of SEC16 increased α-amylase secretion by generating more endoplasmic reticulum exit sites. The production of reactive oxygen species...... were observed. Finally, the moderate overexpression of SEC16 was shown to improve the secretion of two other recombinant proteins, Trichoderma reesei endoglucanase I and Rhizopus oryzae glucan-1,4-α-glucosidase, indicating that this mechanism is of general relevance....

The Variable Stiffness Actuator vsaUT-II: Mechanical Design, Modeling, and Identification

NARCIS (Netherlands)

Groothuis, Stefan; Rusticelli, Giacomo; Zucchelli, Andrea; Stramigioli, Stefano; Carloni, Raffaella

In this paper, the rotational variable stiffness actuator vsaUT-II is presented. This actuation system is characterized by the property that the apparent stiffness at the actuator output can be varied independently from its position. This behavior is realized by implementing a variable transmission

Characterization of Comb-Shaped Copolymers by Multidetection SEC, DLS and SANS

Directory of Open Access Journals (Sweden)

Giulia Gelardi

2017-02-01

Full Text Available PolyCarboxylate ether-based superplasticizers (PCEs are a type of comb-shaped copolymers used as polymeric dispersants in cementitious materials. PCEs have a high degree of dispersity, which limits the suitability of conventional characterization techniques, such as Size Exclusion Chromatography (SEC. Properties of PCEs strongly depend on their molecular structure and a comprehensive characterization is needed to fully understand the structure–property relationships. PCEs with well-defined molecular structures were synthesized to study their solution conformation by SEC and scattering techniques. The combined use of SEC, dynamic light scattering and small-angle neutron scattering allowed us to demonstrate the validity of a scaling law describing the radius of gyration of comb-shaped copolymers as a function of their molecular structure. Moreover, we show that the use of SEC with standard calibration, although widely spread, is not adequate for PCEs.

Solution-processed p-type copper(I) thiocyanate (CuSCN) for low-voltage flexible thin-film transistors and integrated inverter circuits

KAUST Repository

Petti, Luisa

2017-03-17

We report on low operating voltage thin-film transistors (TFTs) and integrated inverters based on copper(I) thiocyanate (CuSCN) layers processed from solution at low temperature on free-standing plastic foils. As-fabricated coplanar bottom-gate and staggered top-gate TFTs exhibit hole-transporting characteristics with average mobility values of 0.0016 cm2 V−1 s−1 and 0.013 cm2 V−1 s−1, respectively, current on/off ratio in the range 102–104, and maximum operating voltages between −3.5 and −10 V, depending on the gate dielectric employed. The promising TFT characteristics enable fabrication of unipolar NOT gates on flexible free-standing plastic substrates with voltage gain of 3.4 at voltages as low as −3.5 V. Importantly, discrete CuSCN transistors and integrated logic inverters remain fully functional even when mechanically bent to a tensile radius of 4 mm, demonstrating the potential of the technology for flexible electronics.

Decreased reactivation of a herpes simplex virus type 1 (HSV-1) latency associated transcript (LAT) mutant using the in vivo mouse UV-B model of induced reactivation

Science.gov (United States)

BenMohamed, Lbachir; Osorio, Nelson; Srivastava, Ruchi; Khan, Arif A.; Simpson, Jennifer L.; Wechsler, Steven L.

2015-01-01

Blinding ocular herpetic disease in humans is due to herpes simplex virus type 1 (HSV-1) reactivations from latency, rather than to primary acute infection. The cellular and molecular mechanisms that control the HSV-1 latency-reactivation cycle remain to be fully elucidated. The aim of this study was to determine if reactivation of the HSV-1 latency associated transcript (LAT) deletion mutant (dLAT2903) was impaired in this model, as it is in the rabbit model of induced and spontaneous reactivation and in the explant TG induced reactivation model in mice. The eyes of mice latently infected with wild type HSV-1 strain McKrae (LAT(+) virus) or dLAT2903 (LAT(−) virus) were irradiated with UV-B and reactivation was determined. We found that compared to LAT(−) virus, LAT(+) virus reactivated at a higher rate as determined by shedding of virus in tears on days 3 to 7 after UV-B treatment. Thus, the UV-B induced reactivation model of HSV-1 appears to be a useful small animal model for studying the mechanisms involved in how LAT enhances the HSV-1 reactivation phenotype. The utility of the model for investigating the immune evasion mechanisms regulating the HSV-1 latency/reactivation cycle and for testing the protective efficacy of candidate therapeutic vaccines and drugs are discussed. PMID:26002839

Fermi-LAT: 4+ Years Out and Just Getting Started!

CERN Multimedia

CERN. Geneva

2012-01-01

The Fermi mission was launched into low Earth orbit in June, 2008. Now in its 5th year of data taking, the primary instrument, the Large Area Telescope (LAT), is now beginning to have a sufficient exposure to probe such fundamental issues as signals from Dark Matter. The achievements of the mission so far will be reviewed and a look towards what the next years could reveal will be presented.

Quest Learning and Assessment, UT Austin

Science.gov (United States)

Lewis, Gerald; McDonald, Patsy; Hostetler, Rhonda

2010-03-01

Quest Learning & Assessment is an innovative web-based tool for instructors and students of math and science. Quest was created at The University of Texas at Austin to address educational challenges at one of the biggest universities in the country. It now serves a primary role in classes taught within UT's College of Natural Sciences. Quest covers subjects ranging from mathematics, chemistry, biology, physics, computer science and statistics. For instructors, Quest offers an easy way to create homework assignments, quizzes and exams with its extensive knowledge base. Since most questions have built-in variations Quest can create custom assignments for each student, which are automatically graded. Once solutions are available, students can read detailed explanations to questions and understand why their answer was correct or incorrect. Quest has graded over 30 million student responses and is now available to all education institutions.

Contribution of SecDF to Staphylococcus aureus resistance and expression of virulence factors

Directory of Open Access Journals (Sweden)

Berger-Bächi Brigitte

2011-04-01

Full Text Available Abstract Background SecDF is an accessory factor of the conserved Sec protein translocation machinery and belongs to the resistance-nodulation-cell division (RND family of multidrug exporters. SecDF has been shown in Escherichia coli and Bacillus subtilis to be involved in the export of proteins. RND proteins can mediate resistance against various substances and might be of relevance in antimicrobial therapy. The role of RND proteins in Staphylococcus aureus has not yet been determined. Results Markerless deletion mutants were constructed to analyze the impact of the so far uncharacterized RND proteins in S. aureus. While the lack of Sa2056 and Sa2339 caused no phenotype regarding growth and resistance, the secDF mutant resulted in a pleiotropic phenotype. The secDF mutant was cold sensitive, but grew normally in rich medium at 37°C. Resistance to beta-lactams, glycopeptides and the RND substrates acriflavine, ethidium bromide and sodium dodecyl sulfate was reduced. The secDF mutant showed an aberrant cell separation and increased spontaneous and Triton X-100 induced autolysis, although the amounts of penicillin-binding proteins in the membrane were unchanged. The impact of secDF deletion on transcription and expression of specific virulence determinants varied: While coagulase transcription and activity were reduced, the opposite was observed for the autolysin Atl. A reduction of the transcription of the cell wall anchored protein A (spa was also found. The accumulation of SpA in the membrane and lowered amounts in the cell wall pointed to an impaired translocation. Conclusions The combination of different effects of secDF deletion on transcription, regulation and translocation lead to impaired cell division, reduced resistance and altered expression of virulence determinants suggesting SecDF to be of major relevance in S. aureus. Thus SecDF could be a potential target for the control and eradication of S. aureus in the future.

The theoretical character of the X1Σ+ and A1Σ+ states of ScN

International Nuclear Information System (INIS)

Feng-Juan, Bai; Chuan-Lu, Yang; Qi, Qian; Ling, Zhang

2009-01-01

This paper calculates the potential energy curves (PECs) of the ground state (X 1 Σ + ) and excited state (A 1 Σ + ) of ScN molecule by multireference configuration interaction method. The correct character of the PECs has been gripped while they had been improperly reported in the literature. Based on the PECs, the spectroscopic parameters and vibrational energy levels are determined, and compared with experimental data and other theoretical works available at the present. (atomic and molecular physics)

Detection of 16 Gamma-Ray Pulsars Through Blind Frequency Searches Using the Fermi LAT

International Nuclear Information System (INIS)

Anderson, B.; Atwood, W.B.; Dormody, M.; Johnson, R.P.; Porter, T.A.; Primack, J.R.; Sadrozinski, H.F.W.; Parkinson, P.M.S.; Ziegler, M.; Abdo, A.A.; Dermer, C.D.; Grove, J.E.; Gwon, C.; Johnson, W.N.; Lovellette, M.N.; Makeev, A.; Ray, P.S.; Strickman, M.S.; Wolff, M.T.; Wood, K.S.; Ackermann, M.; Ajello, M.; Bechtol, K.; Berenji, B.; Blandford, R.D.; Borgland, A.W.; Cameron, R.A.; Chiang, J.; Claus, R.; Digel, S.W.; Silva, E.D.E.; Drell, P.S.; Dubois, R.; Funk, S.; Glanzman, T.; Godfrey, G.; Hayashida, M.; Johannesson, G.; Kamae, T.; Kocian, M.L.; Lande, J.; Madejski, G.M.; Michelson, P.F.; Mitthumsiri, W.; Monzani, M.E.; Moskalenko, I.V.; Murgia, S.; Nolan, P.L.; Paneque, D.; Reimer, A.; Reimer, O.; Rochester, L.S.; Romani, R.W.; Tajima, H.; Tanaka, T.; Thayer, J.G.; Tramacere, A.; Uchiyama, Y.; Usher, T.L.; Van Etten, A.; Waite, A.P.; Wang, P.; Watters, K.; Ackermann, M.; Ajello, M.; Bechtol, K.; Berenji, B.; Bloom, E.D.; Borgland, A.W.; Cameron, R.A.; Chiang, J.; Claus, R.; Digel, S.W.; Silva, E.D.E.; Drell, P.S.; Dubois, R.; Glanzman, T.; Godfrey, G.; Hayashida, M.; Johannesson, G.; Kamae, T.; Kocian, M.L.; Lande, J.; Madejski, G.M.; Michelson, P.F.; Mitthumsiri, W.; Monzani, M.E.; Moskalenko, I.V.; Murgia, S.; Nolan, P.L.; Paneque, D.; Reimer, A.; Reimer, O.; Rochester, L.S.; Romani, R.W.; Tajima, H.; Tanaka, T.; Thayer, J.G.; Tramacere, A.; Uchiyama, Y.; Usher, T.L.; Van Etten, A.; Waite, A.P.; Wang, P.; Watters, K.; Axelsson, M.; Conrad, J.; Meurer, C.; Ryde, F.; Ylinen, T.; Axelsson, M.; Baldini, L.; Bellazzini, R.; Bregeon, J.; Brez, A.; Kuss, M.; Latronico, L.; Omodei, N.; Pesce-Rollins, M.; Razzano, M.; Sgro, C.; Spandre, G.; Ballet, J.; Casandjian, J.M.; Grenier, I.A.; Pierbattista, M.; Starck, J.L.

2009-01-01

Pulsars are rapidly rotating, highly magnetized neutron stars emitting radiation across the electromagnetic spectrum. Although there are more than 1800 known radio pulsars, until recently only seven were observed to pulse in gamma rays, and these were all discovered at other wavelengths. The Fermi Large Area Telescope (LAT) makes it possible to pinpoint neutron stars through their gamma-ray pulsations. We report the detection of 16 gamma-ray pulsars in blind frequency searches using the LAT. Most of these pulsars are coincident with previously unidentified gamma-ray sources, and many are associated with supernova remnants. Direct detection of gamma-ray pulsars enables studies of emission mechanisms, population statistics, and the energetics of pulsar wind nebulae and supernova remnants. (authors)

miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1

Energy Technology Data Exchange (ETDEWEB)

Liu, Shikai; Song, Lili, E-mail: commasll@163.com; Zhang, Liang; Zeng, Saitian; Gao, Fangyuan

2015-04-17

Although multiple miRNAs are found involved in radioresistance development in HR-HPV positive (+) cervical cancer, only limited studies explored the regulative mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in HR-HPV (+) cervical cancer is also significantly associated with radioresistance. However, the detailed regulative network of miR-21 in radioresistance is still not clear. In this study, we confirmed that miR-21 overexpression was associated with higher level of radioresistance in HR-HPV (+) cervical cancer patients and thus decided to further explore its role. Findings of this study found miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells and decrease radiation induced G2/M block and increase S phase accumulation. By using dual luciferase assay, we verified a binding site between miR-21 and 3′-UTR of large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can reverse miR-21 induced higher colony formation rate and also reduced miR-21 induced S phase accumulation and G2/M phase block reduction under radiation treatment. These results suggested that miR-21-LATS1 axis plays an important role in regulating radiosensitivity. - Highlights: • miR-21 is highly expressed in HR-HPV (+) radioresistant cervical cancer patients. • miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells. • miR-21 can decrease radiation induced G2/M block and increase S phase accumulation. • miR-21 modulates radiosensitivity cervical cancer cell by directly targeting LATS1.

miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1

International Nuclear Information System (INIS)

Liu, Shikai; Song, Lili; Zhang, Liang; Zeng, Saitian; Gao, Fangyuan

2015-01-01

Although multiple miRNAs are found involved in radioresistance development in HR-HPV positive (+) cervical cancer, only limited studies explored the regulative mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in HR-HPV (+) cervical cancer is also significantly associated with radioresistance. However, the detailed regulative network of miR-21 in radioresistance is still not clear. In this study, we confirmed that miR-21 overexpression was associated with higher level of radioresistance in HR-HPV (+) cervical cancer patients and thus decided to further explore its role. Findings of this study found miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells and decrease radiation induced G2/M block and increase S phase accumulation. By using dual luciferase assay, we verified a binding site between miR-21 and 3′-UTR of large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can reverse miR-21 induced higher colony formation rate and also reduced miR-21 induced S phase accumulation and G2/M phase block reduction under radiation treatment. These results suggested that miR-21-LATS1 axis plays an important role in regulating radiosensitivity. - Highlights: • miR-21 is highly expressed in HR-HPV (+) radioresistant cervical cancer patients. • miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells. • miR-21 can decrease radiation induced G2/M block and increase S phase accumulation. • miR-21 modulates radiosensitivity cervical cancer cell by directly targeting LATS1

A Critical Analysis of the Role of SNARE Protein SEC22B in Antigen Cross-Presentation

Directory of Open Access Journals (Sweden)

S. Julia Wu

2017-06-01

Full Text Available Cross-presentation initiates immune responses against tumors and viral infections by presenting extracellular antigen on MHC I to activate CD8+ T cell-mediated cytotoxicity. In vitro studies in dendritic cells (DCs established SNARE protein SEC22B as a specific regulator of cross-presentation. However, the in vivo contribution of SEC22B to cross-presentation has not been tested. To address this, we generated DC-specific Sec22b knockout (CD11c-Cre Sec22bfl/fl mice. Contrary to the paradigm, SEC22B-deficient DCs efficiently cross-present both in vivo and in vitro. Although in vitro small hairpin RNA (shRNA-mediated Sec22b silencing in bone-marrow-derived dendritic cells (BMDCs reduced cross-presentation, treatment of SEC22B-deficient BMDCs with the same shRNA produced a similar defect, suggesting the Sec22b shRNA modulates cross-presentation through off-target effects. RNA sequencing of Sec22b shRNA-treated SEC22B-deficient BMDCs demonstrated several changes in the transcriptome. Our data demonstrate that contrary to the accepted model, SEC22B is not necessary for cross-presentation, cautioning against extrapolating phenotypes from knockdown studies alone.

SEC23B is required for pancreatic acinar cell function in adult mice

Science.gov (United States)

Khoriaty, Rami; Vogel, Nancy; Hoenerhoff, Mark J.; Sans, M. Dolors; Zhu, Guojing; Everett, Lesley; Nelson, Bradley; Durairaj, Haritha; McKnight, Brooke; Zhang, Bin; Ernst, Stephen A.; Ginsburg, David; Williams, John A.

2017-01-01

Mice with germline absence of SEC23B die perinatally, exhibiting massive pancreatic degeneration. We generated mice with tamoxifen-inducible, pancreatic acinar cell–specific Sec23b deletion. Inactivation of Sec23b exclusively in the pancreatic acinar cells of adult mice results in decreased overall pancreatic weights from pancreatic cell loss (decreased pancreatic DNA, RNA, and total protein content), as well as degeneration of exocrine cells, decreased zymogen granules, and alterations in the endoplasmic reticulum (ER), ranging from vesicular ER to markedly expanded cisternae with accumulation of moderate-density content or intracisternal granules. Acinar Sec23b deletion results in induction of ER stress and increased apoptosis in the pancreas, potentially explaining the loss of pancreatic cells and decreased pancreatic weight. These findings demonstrate that SEC23B is required for normal function of pancreatic acinar cells in adult mice. PMID:28539403

Prediction of UT1-UTC, LOD and AAM χ3 by combination of least-squares and multivariate stochastic methods

Science.gov (United States)

Niedzielski, Tomasz; Kosek, Wiesław

2008-02-01

This article presents the application of a multivariate prediction technique for predicting universal time (UT1-UTC), length of day (LOD) and the axial component of atmospheric angular momentum (AAM χ 3). The multivariate predictions of LOD and UT1-UTC are generated by means of the combination of (1) least-squares (LS) extrapolation of models for annual, semiannual, 18.6-year, 9.3-year oscillations and for the linear trend, and (2) multivariate autoregressive (MAR) stochastic prediction of LS residuals (LS + MAR). The MAR technique enables the use of the AAM χ 3 time-series as the explanatory variable for the computation of LOD or UT1-UTC predictions. In order to evaluate the performance of this approach, two other prediction schemes are also applied: (1) LS extrapolation, (2) combination of LS extrapolation and univariate autoregressive (AR) prediction of LS residuals (LS + AR). The multivariate predictions of AAM χ 3 data, however, are computed as a combination of the extrapolation of the LS model for annual and semiannual oscillations and the LS + MAR. The AAM χ 3 predictions are also compared with LS extrapolation and LS + AR prediction. It is shown that the predictions of LOD and UT1-UTC based on LS + MAR taking into account the axial component of AAM are more accurate than the predictions of LOD and UT1-UTC based on LS extrapolation or on LS + AR. In particular, the UT1-UTC predictions based on LS + MAR during El Niño/La Niña events exhibit considerably smaller prediction errors than those calculated by means of LS or LS + AR. The AAM χ 3 time-series is predicted using LS + MAR with higher accuracy than applying LS extrapolation itself in the case of medium-term predictions (up to 100 days in the future). However, the predictions of AAM χ 3 reveal the best accuracy for LS + AR.

Competition between Sec- and TAT-dependent protein translocation in Escherichia coli

DEFF Research Database (Denmark)

Cristóbal, S.; de Gier, J.-W.; Nielsen, Henrik

1999-01-01

-routed into the TAT pathway, suggesting that Sec-targeting signals in Lep can override TAT-targeting information in the TorA signal peptide. We also show that the TorA signal peptide can be converted into a Sec-targeting signal peptide by increasing the hydrophobicity of its h-region. Thus, beyond the twin...... the TorA TAT-targeting signal peptide to the Sec-dependent inner membrane protein leader peptidase (Lep). We find that the soluble, periplasmic P2 domain from Lep is re-routed by the TorA signal peptide into the TAT pathway. In contrast, the full-length TorA–Lep fusion protein is not re...

SEC14 is a specific requirement for secretion of phospholipase B1 and pathogenicity of Cryptococcus neoformans

Science.gov (United States)

Chayakulkeeree, Methee; Johnston, Simon Andrew; Oei, Johanes Bijosono; Lev, Sophie; Williamson, Peter Richard; Wilson, Christabel Frewen; Zuo, Xiaoming; Leal, Ana Lusia; Vainstein, Marilene Henning; Meyer, Wieland; Sorrell, Tania Christine; May, Robin Charles; Djordjevic, Julianne Teresa

2011-01-01

Summary Secreted phospholipase B1 (CnPlb1) is essential for dissemination of Cryptococcus neoformans to the central nervous system (CNS) yet essential components of its secretion machinery remain to be elucidated. Using gene deletion analysis we demonstrate that CnPlb1 secretion is dependent on the CnSEC14 product, CnSec14-1p. CnSec14-1p is a homologue of the phosphatidylinositol transfer protein (PITP) ScSec14p, which is essential for secretion and viability in Saccharomyces cerevisiae. In contrast to CnPlb1, neither laccase 1 (Lac1)-induced melanization within the cell wall nor capsule induction were negatively impacted in CnSEC14-1 deletion mutants (CnΔsec14-1 and CnΔsec14-1CnΔsfh5). Similar to the CnPLB1 deletion mutant (CnΔplb1), CnΔsec14-1 was hypo-virulent in mice and did not disseminate to the CNS by day 14 post infection. Furthermore, macrophage expulsion of live CnΔsec14-1 and CnΔplb1 (vomocytosis) was reduced. Individual deletion of CnSEC14-2, a closely-related CnSEC14-1 homologue, and CnSFH5, a distantly-related SEC fourteen-like homologue, did not abrogate CnPlb1 secretion or virulence. However, reconstitution of CnΔsec14-1 with CnSEC14-1 or CnSEC14-2 restored both phenotypes, consistent with functional genetic redundancy. We conclude that CnPlb1 secretion is SEC14-dependent and that C. neoformans preferentially exports virulence determinants to the cell periphery via distinct pathways. We also demonstrate that CnPlb1 secretion is essential for vomocytosis. PMID:21453402

78 FR 53489 - SEC Advisory Committee on Small and Emerging Companies

Science.gov (United States)

2013-08-29

... Web site at www.sec.gov . Persons needing special accommodations to take part because of a disability... Commission will post all statements on the Advisory Committee's Web site ( http://www.sec.gov ./info/smallbus/acsec.shtml ). Statements also will be available for Web site viewing and printing in the Commission's...

78 FR 21432 - SEC Advisory Committee on Small and Emerging Companies

Science.gov (United States)

2013-04-10

... Web site at www.sec.gov . Persons needing special accommodations to take part because of a disability... all statements on the Advisory Committee's Web site ( http://www.sec.gov ./info/smallbus/acsec.shtml). Statements also will be available for Web site viewing and printing in the Commission's Public Reference Room...

Defects and their inspectability by UT in current heavy section steels for nuclear power plant

International Nuclear Information System (INIS)

Onodera, S.; Ohkubo, Y.; Takeya, M.; Wataya, M.

1983-01-01

The ultrasonic examination (UT, hereinafter) techniques and their equipment have been improved in search of the defects in steels and structures for nuclear power plant components, while the acceptance standards of the defects became continually more stringent in a ''sword and armour'' race. Consequently, the steel making technique had to respond in minimizing the possible defects in steels with successful results in the past two decades. The conventional UT procedures cover basically the following categories of function. 1) Detection and location of defects. 2) Sizing of defects. 3) Characterization of defects. 4) Structure and residual stress effects in ultrasonic field. With proper considerations to the configuration of the steels under examination, the inspectability of the possible defects is further to be optimized. However, the final evaluation has often to be left to the discretion of a competent NDE engineer, well experienced in UT and knowledgeable in steel making. It is therefore the intention of the present paper to review the states-of-the-art of the defects found in the current heavy section steels for primary and secondary components of nuclear power plant, manufactured by the authors' plant. Typical defects, detectable size of them and inspectability of them are discussed

Critical role of FcR gamma-chain, LAT, PLCgamma2 and thrombin in arteriolar thrombus formation upon mild, laser-induced endothelial injury in vivo.

Science.gov (United States)

Kalia, Neena; Auger, Jocelyn M; Atkinson, Ben; Watson, Steve P

2008-05-01

The role of collagen receptor complex GPVI-FcR gamma-chain, PLCgamma2 and LAT in laser-induced thrombosis is unclear. Controversy surrounds whether collagen is exposed in this model or whether thrombosis is dependent on thrombin. This study hypothesized that collagen exposure plays a critical role in thrombus formation in this model, which was tested by investigating contributions of FcR gamma-chain, LAT, PLCgamma2 and thrombin. Thrombi were monitored using intravital microscopy in anesthetized wild-type and FcR gamma-chain, LAT and PLCgamma2 knockout mice. Hirudin (thrombin inhibitor) was administered to wild-type and FcR gamma-chain knockout mice. Significantly reduced thrombus formation was observed in FcR gamma-chain and PLCgamma2 knockouts with a greater decrease observed in LAT knockouts. Dramatic reduction was observed in wild-types treated with hirudin, with abolished thrombus formation only observed in FcR gamma-chain knockouts treated with hirudin. GPVI-FcR gamma-chain, LAT and PLCgamma2 are essential for thrombus generation and stability in this laser-induced model of injury. More importantly, a greater role for LAT was identified, which may reflect a role for it downstream of a second matrix protein receptor. However, inhibition of platelet activation by matrix proteins and thrombin generation are both required to maximally prevent thrombus formation.

Anisotropies in the diffuse gamma-ray background from dark matter with Fermi LAT: a closer look

DEFF Research Database (Denmark)

Cuoco, Alessandro; Sellerholm, A.; Conrad, J.

2011-01-01

We perform a detailed study of the sensitivity to the anisotropies related to dark matter (DM) annihilation in the isotropic gamma-ray background (IGRB) as measured by the Fermi Large Area Telescope (Fermi LAT). For the first time, we take into account the effects of the Galactic foregrounds...... of the detector are taken into account by convolving the model maps with the Fermi LAT instrumental response. We then use the angular power spectrum to characterize the anisotropy properties of the simulated data and to study the sensitivity to DM. We consider DM anisotropies of extragalactic origin...

The effect of acetylcholine, LatA and FAA on phloem assimilates translocation of Raphanus sativus L

International Nuclear Information System (INIS)

Yang Chongjun; Zhang Ping

2005-01-01

The petiole phloem of Raphanus sativus L. is treated with the medicaments of acetylcholine (Ach, the expansionist material of protoplasm), latrunculin A (LatA, the dissolubility of microfilament) and FAA (the regularization of phloem). The effects of treatments are measured by the accumulated content of dissoluble sugar and starch in the leaves, and 14 C-labelled assimilates. The regulating role of three medicaments on the translocation of assimilates in the phloem of Raphanus sativus L are investigated. The results indicate that low Ach improves assimilates translocation while LatA and FAA inhibit it in petiole phloem of Raphanus sativus L.. (authors)

An image-based search for pulsars among Fermi unassociated LAT sources

Science.gov (United States)

Frail, D. A.; Ray, P. S.; Mooley, K. P.; Hancock, P.; Burnett, T. H.; Jagannathan, P.; Ferrara, E. C.; Intema, H. T.; de Gasperin, F.; Demorest, P. B.; Stovall, K.; McKinnon, M. M.

2018-03-01

We describe an image-based method that uses two radio criteria, compactness, and spectral index, to identify promising pulsar candidates among Fermi Large Area Telescope (LAT) unassociated sources. These criteria are applied to those radio sources from the Giant Metrewave Radio Telescope all-sky survey at 150 MHz (TGSS ADR1) found within the error ellipses of unassociated sources from the 3FGL catalogue and a preliminary source list based on 7 yr of LAT data. After follow-up interferometric observations to identify extended or variable sources, a list of 16 compact, steep-spectrum candidates is generated. An ongoing search for pulsations in these candidates, in gamma rays and radio, has found 6 ms pulsars and one normal pulsar. A comparison of this method with existing selection criteria based on gamma-ray spectral and variability properties suggests that the pulsar discovery space using Fermi may be larger than previously thought. Radio imaging is a hitherto underutilized source selection method that can be used, as with other multiwavelength techniques, in the search for Fermi pulsars.

Algunas reflexiones acerca de la enseñanza del latín

Directory of Open Access Journals (Sweden)

María Purificación Estebañez

1995-06-01

Full Text Available Las reflexiones y sugerencias que en esta Comunicación desea mosofrecer son, sin duda alguna, el fruto de una larga experiencia en la enseñanza de los Cursos de Latín en la Pontificia UniversidadCatólica del Perú.

Microprocessor-controlled tester for evaluation of the Self-Energized Credential System (SECS)

International Nuclear Information System (INIS)

Corlis, N.E.

1980-03-01

The Self-Energized Credential System (SECS) was developed for use in the Plutonium Protection System (PPS) installed at Hanford, Washington. Evaluation and development of the SECS system was enhanced by the use of a microprocessor-controlled portal tester. This tester used infrared (ir) beam sensors to provide information on the direction of travel of the credential wearer and to detect inoperative credentials. A printed record of the portal number, actual code read, time, and direction of the credential passage provided information essential to an assessment of the operability of the SECS

Hole-transporting transistors and circuits based on the transparent inorganic semiconductor copper(I) thiocyanate (CuSCN) processed from solution at room temperature

KAUST Repository

Pattanasattayavong, Pichaya; Yaacobi-Gross, Nir; Zhao, Kui; Ndjawa, Guy Olivier Ngongang; Li, Jinhua; Yan, Feng; O'Regan, Brian C.; Amassian, Aram; Anthopoulos, Thomas D.

2012-01-01

ferroelectric polymeric dielectric P(VDF-TrFE-CFE), we demonstrate low-voltage transistors with hole mobilities on the order of 0.1 cm2 V-1 s-1. By integrating two CuSCN transistors, unipolar logic NOT gates are also demonstrated. Copyright © 2013 WILEY

Muon-spin rotation studies of the flux lattice in {kappa}-(BEDT-TTF){sub 2}Cu(SCN){sub 2}

Energy Technology Data Exchange (ETDEWEB)

Lee, S.L. [Saint Andrews Univ. (United Kingdom). Sch. of Phys. and Astron.; Blundell, S.J. [Oxford Univ. (United Kingdom). Dept. of Physics; Pratt, F.L. [RIKEN-RAL, Didcot (United Kingdom); Pattenden, P.A. [Oxford Univ. (United Kingdom). Dept. of Physics; Forgan, E.M. [Birmingham Univ. (United Kingdom). School of Physics and Space Research; Sasaki, T. [Tohoku Univ., Sendai (Japan). Inst. for Materials Research; Aegerter, C.M. [Zurich Univ. (Switzerland). Inst. fuer Physik; Hunt, M. [Zurich Univ. (Switzerland). Inst. fuer Physik; Chow, K.H. [Oxford Univ. (United Kingdom). Dept. of Physics; Hayes, W. [Oxford Univ. (United Kingdom). Dept. of Physics; Singleton, J. [Oxford Univ. (United Kingdom). Dept. of Physics; Keller, H. [Zurich Univ. (Switzerland). Inst. fuer Physik; Savic, I.M. [Zurich Univ. (Switzerland). Inst. fuer Physik

1997-02-15

Muon spin rotation ({mu}SR) studies of the vortex lattice in the superconductor {kappa}-(BEDT-TTF){sub 2}Cu(SCN){sub 2} have revealed a crossover from a quasi-2d to a vortex-line lattice structure for fields below a characteristic field B{sub cr}. The {mu}SR-lineshapes measured from the vortex-line lattice have allowed a re-evaluation of the in-plane penetration depth. (orig.)

AICAR Antiproliferative Properties Involve the AMPK-Independent Activation of the Tumor Suppressors LATS 1 and 2.

Science.gov (United States)

Philippe, Chloé; Pinson, Benoît; Dompierre, Jim; Pantesco, Véronique; Viollet, Benoît; Daignan-Fornier, Bertrand; Moenner, Michel

2018-06-01

AICAR (Acadesine) is a pharmacological precursor of purine nucleotide biosynthesis with anti-tumoral properties. Although recognized as an AMP mimetic activator of the protein kinase AMPK, the AICAR monophosphate derivative ZMP was also shown to mediate AMPK-independent effects. In order to unveil these AMPK-independent functions, we performed a transcriptomic analysis in AMPKα1/α2 double knockout murine embryonic cells. Kinetic analysis of the cellular response to AICAR revealed the up-regulation of the large tumor suppressor kinases (Lats) 1 and 2 transcripts, followed by the repression of numerous genes downstream of the transcriptional regulators Yap1 and Taz. This transcriptional signature, together with the observation of increased levels in phosphorylation of Lats1 and Yap1 proteins, suggested that the Hippo signaling pathway was activated by AICAR. This effect was observed in both fibroblasts and epithelial cells. Knockdown of Lats1/2 prevented the cytoplasmic delocalization of Yap1/Taz proteins in response to AICAR and conferred a higher resistance to the drug. These results indicate that activation of the most downstream steps of the Hippo cascade participates to the antiproliferative effects of AICAR. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

75 FR 28667 - Joint CFTC-SEC Advisory Committee on Emerging Regulatory Issues

Science.gov (United States)

2010-05-21

... members, (iii) discussion of Committee agenda and organization; (iv) discussion of the Joint CFTC-SEC... make recommendations related to market structure issues that may have contributed to the volatility, as... ``Joint CFTC-SEC Advisory Committee'' to facilitate the organization and distribution of comments between...

Domain dynamics of the Bacillus subtilis peripheral preprotein translocase subunit SecA

NARCIS (Netherlands)

Driessen, A.J.M.; Ladbury, JE; Chowdhry, BZ

1998-01-01

The homodimeric SecA protein is the peripheral subunit of the preprotein translocase in bacteria. It promotes the preprotein translocation across the cytoplasmic membrane by nucleotide-modulated co-insertion and de-insertion into the integral domain of the translocase. SecA has two essential

46 CFR Sec. 5 - Responsibility for duplicating copies of NSA-WORKSMALREP Contract.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Responsibility for duplicating copies of NSA-WORKSMALREP Contract. Sec. 5 Section 5 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL... INDIVIDUAL CONTRACT FOR MINOR REPAIRS-NSA-WORKSMALREP Sec. 5 Responsibility for duplicating copies of NSA...

Fermi-LAT observation of nonblazar AGNs

Science.gov (United States)

Sahakyan, N.; Baghmanyan, V.; Zargaryan, D.

2018-06-01

Context. Fermi Large Area Telescope (Fermi-LAT) has recently detected γ-ray emission from active galactic nuclei (AGN) that do not show clear evidence for optical blazar characteristics or have jets pointing away from the observer (nonblazar AGNs). These are interesting γ-ray emitters providing an alternative approach to studying high energy emission processes. Aims: This paper investigates the spectral and temporal properties of γ-ray emission from nonblazar AGNs using the recent Fermi-LAT observational data. Methods: The data collected by Fermi-LAT during 2008-2015, from the observations of 26 nonblazar AGNs, including 11 Fanaroff-Riley Type I (FRI) and ten FRII radio galaxies and steep spectrum radio quasars (SSRQs) and five narrow line seyfert 1s (NLSy1s) are analysed using the new PASS 8 event selection and instrument response function. Possible spectral changes above GeV energies are investigated with a detailed spectral analysis. Light curves generated with normal and adaptive time bins are used to study the γ-ray flux variability. Results: Non-blazar AGNs have a γ-ray photon index in the range of 1.84-2.86 and a flux varying from a few times 10-9 photon cm-2 s-1 to 10-7 photon cm-2 s-1. Over long time periods, the power law provides an adequate description of the γ-ray spectra of almost all sources. Significant curvature is observed in the γ-ray spectra of NGC 1275, NGC 6251, SBS 0846 + 513, and PMN J0948 + 0022 and their spectra are better described by log parabola or by the power law with exponential cut-off models. The γ-ray spectra of PKS 0625-25 and 3C 380 show a possible deviation from a simple power-law shape, indicating a spectral cut-off around the observed photon energy of Ecut = 131.2 ± 88.04 GeV and Ecut = 55.57 ± 50.74 GeV, respectively. Our analysis confirms the previous finding of an unusual spectral turnover in the γ-ray spectrum of Cen A: the photon index changes from Γ = 2.75 ± 0.02 to 2.31 ± 0.1 at 2.35 ± 0.08 GeV. In the �

The 12 item Social and Economic Conservatism Scale (SECS).

Science.gov (United States)

Everett, Jim A C

2013-01-01

Recent years have seen a surge in psychological research on the relationship between political ideology (particularly conservatism) and cognition, affect, behaviour, and even biology. Despite this flurry of investigation, however, there is as yet no accepted, validated, and widely used multi-item scale of conservatism that is concise, that is modern in its conceptualisation, and that includes both social and economic conservatism subscales. In this paper the 12-Item Social and Economic Conservatism Scale (SECS) is proposed and validated to help fill this gap. The SECS is suggested to be an important and useful tool for researchers working in political psychology.

Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation

Science.gov (United States)

Lakkaraju, Asvin K. K.; Thankappan, Ratheeshkumar; Mary, Camille; Garrison, Jennifer L.; Taunton, Jack; Strub, Katharina

2012-01-01

Mammalian cells secrete a large number of small proteins, but their mode of translocation into the endoplasmic reticulum is not fully understood. Cotranslational translocation was expected to be inefficient due to the small time window for signal sequence recognition by the signal recognition particle (SRP). Impairing the SRP pathway and reducing cellular levels of the translocon component Sec62 by RNA interference, we found an alternate, Sec62-dependent translocation path in mammalian cells required for the efficient translocation of small proteins with N-terminal signal sequences. The Sec62-dependent translocation occurs posttranslationally via the Sec61 translocon and requires ATP. We classified preproteins into three groups: 1) those that comprise ≤100 amino acids are strongly dependent on Sec62 for efficient translocation; 2) those in the size range of 120–160 amino acids use the SRP pathway, albeit inefficiently, and therefore rely on Sec62 for efficient translocation; and 3) those larger than 160 amino acids depend on the SRP pathway to preserve a transient translocation competence independent of Sec62. Thus, unlike in yeast, the Sec62-dependent translocation pathway in mammalian cells serves mainly as a fail-safe mechanism to ensure efficient secretion of small proteins and provides cells with an opportunity to regulate secretion of small proteins independent of the SRP pathway. PMID:22648169

12,000 l/sec cryopump for hydrogen gas

International Nuclear Information System (INIS)

Shibata, Takemasa; Matsuda, Shinzaburo; Shirakata, Hirofumi; Saito, Masaki; Mizuno, Masayasu.

1978-08-01

In the neutral beam injector of JT-60, cryogenic pumps with pumping rate 10 6 l/sec for hydrogen will be installed in the beam lines. To develop the cryopumps a small-scale pump of 12,000 l/sec was made and its fundamental pumping characteristics were measured. The cryogenic pump consists of liquid helium cooled panel, liquid nitrogen cooled chevron and radiation shields. The cryopanel is cylindrical form and the chevron is arranged concentrically within it. The measured pumping rate agrees with the design one. The pumping rate is not lowered by 30 Torr.l/cm 2 on the cryopanel. Liquid helium consumption rate was also measured and the pressure rise in the vacuum chamber in reactivation of the cryopanel was observed. (auth.)

Lack of association between urotensin-II (UTS2 gene polymorphisms (Thr21Met and Ser89Asn and migraine

Directory of Open Access Journals (Sweden)

Betül Ozan

2017-08-01

Full Text Available Migraine is a common neurovascular brain disorder with heterogeneous clinical presentation, including recurrent headache attacks. The pathophysiology of migraine is complex, and a number of genomic regions have been associated with the development of migraine. In this study, we analyzed the allele and genotype frequencies of the urotensin-II gene (UTS2 polymorphisms, Thr21Met and Ser89Asn, among Turkish patients with migraine. A total of 146 patients with migraine (14 with aura [MA group] and 132 without aura [MO group] were genotyped for Thr21Met and Ser89Asn polymorphisms and compared with 154 age- and sex-matched healthy controls. The UTS2 gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP. No significant differences were observed in allele and genotype frequencies for Thr21Met and Ser89Asn polymorphisms between the patients with migraine and control group. Similarly, we did not observe significant differences in allele and genotype frequencies between MA and MO and control group. Moreover, the haplotype analysis showed no association between UTS2 gene haplotypes (MN, MS, TN, and TS and migraine. In summary, Thr21Met and Ser89Asn polymorphisms of the UTS2 gene are not risk factors for migraine in our sample of Turkish migraine patients.

Main Ionospheric Trough and Equatorial Ionization Anomaly During Substorms With the Different UT Onset Moments

Science.gov (United States)

Klimenko, M. V.; Klimenko, V. V.; Bryukhanov, V. V.

2007-05-01

In the given work the numerical calculation results of ionospheric effects of four modeling substorms which have begun in 00, 06, 12 and 18 UT are presented. Calculations are executed on the basis of Global Self-consistent Model of the Thermosphere, Ionosphere and Protonosphere (GSM TIP), developed in WD IZMIRAN, added by the new block of calculation of electric fields in the ionosphere of the Earth for vernal equinox conditions in the minimum of solar activity. In calculations we considered superposition of magnetospheric convection electric field (at set potential differences through polar caps and field aligned currents of the second zone with taking into account of particle precipitation) and dynamo field generated by thermospheric winds without taking into account the tides. It is shown, that in the given statement of problem the substorms cause strong positive disturbances in F-region of ionosphere in night sector. Negative disturbances are much less and arise, mainly, at night in the middle and low latitudes. During substorms longitudinal extent of main ionospheric trough increases. The substorm beginning in 18 UT, causes negative disturbances in high latitudes except for a southern polar cap. Besides there is "stratification" of the main ionospheric trough. As a result in southern hemisphere the additional high-latitude trough which is absent in quiet conditions is formed. "Stratification" of the main ionospheric trough occurs in northern hemisphere at 6 hours after the beginning of the substorm. These "stratifications" are consequence non-stationary magnetospheric convection. Distinction between these events consists that "stratification" in a southern hemisphere occurs in active phase of substorm, and in northern hemisphere in recovery phase. During a substorm beginning in 00 UT, foF2 increases in all northern polar cap. Positive disturbances of foF2 in the equatorial anomaly region cause all presented substorms, except for a substorm beginning in 18 UT

Dissecting a hidden gene duplication: the Arabidopsis thaliana SEC10 locus.

Directory of Open Access Journals (Sweden)

Nemanja Vukašinović

Full Text Available Repetitive sequences present a challenge for genome sequence assembly, and highly similar segmental duplications may disappear from assembled genome sequences. Having found a surprising lack of observable phenotypic deviations and non-Mendelian segregation in Arabidopsis thaliana mutants in SEC10, a gene encoding a core subunit of the exocyst tethering complex, we examined whether this could be explained by a hidden gene duplication. Re-sequencing and manual assembly of the Arabidopsis thaliana SEC10 (At5g12370 locus revealed that this locus, comprising a single gene in the reference genome assembly, indeed contains two paralogous genes in tandem, SEC10a and SEC10b, and that a sequence segment of 7 kb in length is missing from the reference genome sequence. Differences between the two paralogs are concentrated in non-coding regions, while the predicted protein sequences exhibit 99% identity, differing only by substitution of five amino acid residues and an indel of four residues. Both SEC10 genes are expressed, although varying transcript levels suggest differential regulation. Homozygous T-DNA insertion mutants in either paralog exhibit a wild-type phenotype, consistent with proposed extensive functional redundancy of the two genes. By these observations we demonstrate that recently duplicated genes may remain hidden even in well-characterized genomes, such as that of A. thaliana. Moreover, we show that the use of the existing A. thaliana reference genome sequence as a guide for sequence assembly of new Arabidopsis accessions or related species has at least in some cases led to error propagation.

Shear-wave elastography for breast masses: local shear wave speed (m/sec versus Young modulus (kPa

Directory of Open Access Journals (Sweden)

Ji Hyun Youk

2014-01-01

<sec>

The quantitative elasticity values measured in kPa and m/sec on SWE showed good diagnostic performance. The specificity of the SD and AUC of the wSD measured in kPa were significantly higher than those measured in m/sec.

46 CFR Sec. 2 - Stand-by agreements.

Science.gov (United States)

2010-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION B-CONTROL AND UTILIZATION OF PORTS OPERATING CONTRACT Sec. 2 Stand-by agreements. The Director NSA, Maritime Administration, in advance of an emergency, may negotiate... 1901) under the control of the Maritime Administration and allocated for long term exclusive use by the...

The first fermi-lat catalog of sources above 10 GeV

Energy Technology Data Exchange (ETDEWEB)

Ackermann, M.; Ajello, M.; Allafort, A.; Atwood, W. B.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bechtol, K.; Belfiore, A.; Bellazzini, R.; Bernieri, E.; Bissaldi, E.; Bloom, E. D.; Bonamente, E.; Brandt, T. J.; Bregeon, J.; Brigida, M.; Bruel, P.; Buehler, R.; Burnett, T. H.; Buson, S.; Caliandro, G. A.; Cameron, R. A.; Campana, R.; Caraveo, P. A.; Casandjian, J. M.; Cavazzuti, E.; Cecchi, C.; Charles, E.; Chaves, R. C. G.; Chekhtman, A.; Cheung, C. C.; Chiang, J.; Chiaro, G.; Ciprini, S.; Claus, R.; Cohen-Tanugi, J.; Cominsky, L. R.; Conrad, J.; Cutini, S.; D' Ammando, F.; de Angelis, A.; de Palma, F.; Dermer, C. D.; Desiante, R.; Digel, S. W.; Di Venere, L.; Drell, P. S.; Drlica-Wagner, A.; Favuzzi, C.; Fegan, S. J.; Ferrara, E. C.; Focke, W. B.; Fortin, P.; Franckowiak, A.; Funk, S.; Fusco, P.; Gargano, F.; Gasparrini, D.; Gehrels, N.; Germani, S.; Giglietto, N.; Giommi, P.; Giordano, F.; Giroletti, M.; Godfrey, G.; Gomez-Vargas, G. A.; Grenier, I. A.; Guiriec, S.; Hadasch, D.; Hanabata, Y.; Harding, A. K.; Hayashida, M.; Hays, E.; Hewitt, J.; Hill, A. B.; Horan, D.; Hughes, R. E.; Jogler, T.; Jóhannesson, G.; Johnson, A. S.; Johnson, T. J.; Johnson, W. N.; Kamae, T.; Kataoka, J.; Kawano, T.; Knödlseder, J.; Kuss, M.; Lande, J.; Larsson, S.; Latronico, L.; Lemoine-Goumard, M.; Longo, F.; Loparco, F.; Lott, B.; Lovellette, M. N.; Lubrano, P.; Massaro, E.; Mayer, M.; Mazziotta, M. N.; McEnery, J. E.; Mehault, J.; Michelson, P. F.; Mizuno, T.; Moiseev, A. A.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Murgia, S.; Nemmen, R.; Nuss, E.; Ohsugi, T.; Okumura, A.; Orienti, M.; Ormes, J. F.; Paneque, D.; Perkins, J. S.; Pesce-Rollins, M.; Piron, F.; Pivato, G.; Porter, T. A.; Rainò, S.; Razzano, M.; Reimer, A.; Reimer, O.; Reposeur, T.; Ritz, S.; Romani, R. W.; Roth, M.; Saz Parkinson, P. M.; Schulz, A.; Sgrò, C.; Siskind, E. J.; Smith, D. A.; Spandre, G.; Spinelli, P.; Stawarz, Łukasz; Strong, A. W.; Suson, D. J.; Takahashi, H.; Thayer, J. G.; Thayer, J. B.; Thompson, D. J.; Tibaldo, L.; Tinivella, M.; Torres, D. F.; Tosti, G.; Troja, E.; Uchiyama, Y.; Usher, T. L.; Vandenbroucke, J.; Vasileiou, V.; Vianello, G.; Vitale, V.; Werner, M.; Winer, B. L.; Wood, K. S.; Wood, M.

2013-11-14

We present a catalog of gamma-ray sources at energies above 10 GeV based on data from the Large Area Telescope (LAT) accumulated during the first three years of the Fermi Gamma-ray Space Telescope mission. The first Fermi-LAT catalog of >10GeV sources (1FHL) has 514 sources. For each source we present location, spectrum, a measure of variability, and associations with cataloged sources at other wavelengths. We found that 449 (87%) could be associated with known sources, of which 393 (76% of the 1FHL sources) are active galactic nuclei. Of the 27 sources associated with known pulsars, we find 20 (12) to have significant pulsations in the range >10GeV (>25GeV). In this work we also report that, at energies above 10 GeV, unresolved sources account for 27+/-8 % of the isotropic gamma-ray background, while the unresolved Galactic population contributes only at the few percent level to the Galactic diffuse background. We also highlight the subset of the 1FHL sources that are best candidates for detection at energies above 50-100 GeV with current and future ground-based gamma-ray observatories.

46 CFR Sec. 3 - When the NSA-WORKSMALREP Contract may be used.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false When the NSA-WORKSMALREP Contract may be used. Sec. 3 Section 3 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL SHIPPING AUTHORITY... REPAIRS-NSA-WORKSMALREP Sec. 3 When the NSA-WORKSMALREP Contract may be used. This contract may be used...

Winds of time: Lessons from Utö in the Stockholm Archipelago, 1990–2001

International Nuclear Information System (INIS)

Fjaestad, Maja

2013-01-01

When investigating the success or failure of different wind power projects, it is essential to take into account how they were historically situated. This study focuses on attempts to develop wind power in an archipelago setting, at Utö in Sweden. It has been argued that the development of Swedish wind power slowed during the 1990s; by revisiting the early days of wind power, looking at resistance and support, and connecting success factors, this can be further investigated. Whereas earlier research pointed out institutional conditions and site-specific conditions as crucial for successful wind power development and acceptance, the picture can be made more complete by discussing how wind power projects are affected by time-specific historical conditions. In the case of Utö, these can partly be associated with a newly launched political support program that gave the project political legitimacy and added a “pioneering spirit” to the endeavor. Conversely, when wind power is not seen as “pioneering” or “experimental” any more, but as a mere industrial activity, other incentives may need to be offered to municipalities. -- Highlights: •When evaluating wind power projects, the historical context is important to complement the picture. •The case of Utö is tells important lessons of the Swedish early 1990s. •Success factors in this case: political legitimacy, local support, pioneering spirit, promising technology. •This wind power establishment was not seen as a threat to recreation or landscape. •Lessons for today: how to deal with socio-political acceptance when wind power becomes “industrial”

Anisotropies in the diffuse gamma-ray background from dark matter with Fermi LAT: A closer look

International Nuclear Information System (INIS)

Cuoco, A.; Sellerholm, A.; Conrad, J.; Hannestad, S.

2011-01-01

We perform a detailed study of the sensitivity to the anisotropies related to dark matter (DM) annihilation in the isotropic gamma-ray background (IGRB) as measured by the Fermi Large Area Telescope (Fermi LAT). For the first time, we take into account the effects of the Galactic foregrounds and use a realistic representation of the Fermi LAT. We implement an analysis pipeline which simulates Fermi LAT data sets starting from model maps of the Galactic foregrounds, the Fermi-resolved point sources, the extragalactic diffuse emission and the signal from DM annihilation. The effects of the detector are taken into account by convolving the model maps with the Fermi LAT instrumental response. We then use the angular power spectrum to characterize the anisotropy properties of the simulated data and to study the sensitivity to DM. We consider DM anisotropies of extragalactic origin and of Galactic origin (which can be generated through annihilation in the Milky Way substructures) as opposed to a background of anisotropies generated by sources of astrophysical origin, blazars for example. We find that with statistics from 5 yr of observation, Fermi is sensitive to a DM contribution at the level of 1–10 per cent of the measured IGRB depending on the DM mass m χ and annihilation mode. In terms of the thermally averaged cross-section <σAv>, this corresponds to ~10 –25 cm 3 s –1 , i.e. slightly above the typical expectations for a thermal relic, for low values of the DM mass m χ ≲ 100 GeV. As a result, the anisotropy method for DM searches has a sensitivity comparable to the usual methods based only on the energy spectrum and thus constitutes an independent and complementary piece of information in the DM puzzle.

The 12 item Social and Economic Conservatism Scale (SECS.

Directory of Open Access Journals (Sweden)

Jim A C Everett

Full Text Available Recent years have seen a surge in psychological research on the relationship between political ideology (particularly conservatism and cognition, affect, behaviour, and even biology. Despite this flurry of investigation, however, there is as yet no accepted, validated, and widely used multi-item scale of conservatism that is concise, that is modern in its conceptualisation, and that includes both social and economic conservatism subscales. In this paper the 12-Item Social and Economic Conservatism Scale (SECS is proposed and validated to help fill this gap. The SECS is suggested to be an important and useful tool for researchers working in political psychology.

IRS, FERC let more wells receive Sec. 29 credits

International Nuclear Information System (INIS)

Lewis, F.W.; Grapentine, T.

1993-01-01

Two new ways exist for producers in the U.S. to qualify additional production for federal Sec. 29 nonconventional fuel tax credits. Until now the Federal Energy Regulatory Commission and Internal Revenue Service deadlines had limited eligible production to wells spud or recompleted and filings made under the Natural Gas Policy Act on or before Dec. 31, 1992. Large numbers of producers in many states filed timely NGPA applications seeking federal and state regulatory approval, and currently most producers believe the deadline to apply for Sec. 29 tax credits to have passed. The paper describes several filing exceptions and recommends producer response to the new rules

Fermi-LAT kills dark matter interpretations of AMS-02 data. Or not?

Energy Technology Data Exchange (ETDEWEB)

Belotsky, Konstantin; Budaev, Ruslan; Kirillov, Alexander; Laletin, Maxim, E-mail: k-belotsky@yandex.ru, E-mail: buday48@mail.ru, E-mail: AAKirillov@mephi.ru, E-mail: maxim.laletin@ulg.ac.be [Department of Elementary Particle Physics, National Research Nuclear University MEPhI, 115409 Kashirskoe shosse 31, Moscow (Russian Federation)

2017-01-01

A number of papers attempt to explain the positron anomaly in cosmic rays, observed by PAMELA and AMS-02, in terms of dark matter (DM) decays or annihilations. However, the recent progress in cosmic gamma-ray studies challenges these attempts. Indeed, as we show, any rational DM model explaining the positron anomaly abundantly produces final state radiation and Inverse Compton gamma rays, which inevitably leads to a contradiction with Fermi-LAT isotropic diffuse gamma-ray background measurements. Furthermore, the Fermi-LAT observation of Milky Way dwarf satellites, supposed to be rich in DM, revealed no significant signal in gamma rays. We propose a generic approach in which the major contribution to cosmic rays comes from the dark matter disc and prove that the tension between the DM origin of the positron anomaly and the cosmic gamma-ray observations can be relieved. We consider both a simple model, in which DM decay/annihilate into charged leptons, and a model-independent minimal case of particle production, and we estimate the optimal thickness of DM disk. Possible mechanisms of formation and its properties are briefly discussed.

The bacterial Sec system is required for the organization and function of the MreB cytoskeleton.

Science.gov (United States)

Govindarajan, Sutharsan; Amster-Choder, Orna

2017-09-01

The Sec system is responsible for protein insertion, translocation and secretion across membranes in all cells. The bacterial actin homolog MreB controls various processes, including cell wall synthesis, membrane organization and polarity establishment. Here we show that the two systems genetically interact and that components of the Sec system, especially the SecA motor protein, are essential for spatiotemporal organization of MreB in E. coli, as evidenced by the accumulation of MreB at irregular sites in Sec-impaired cells. MreB mislocalization in SecA-defective cells significantly affects MreB-coordinated processes, such as cell wall synthesis, and induce formation of membrane invaginations enriched in high fluidity domains. Additionally, MreB is not recruited to the FtsZ ring in secA mutant cells, contributing to division arrest and cell filamentation. Our results show that all these faults are due to improper targeting of MreB to the membrane in the absence of SecA. Thus, when we reroute RodZ, MreB membrane-anchor, by fusing it to a SecA-independent integral membrane protein and overproducing it, MreB localization is restored and the defect in cell division is corrected. Notably, the RodZ moiety is not properly inserted into the membrane, strongly suggesting that it only serves as a bait for placing MreB around the cell circumference. Finally, we show that MreB localization depends on SecA also in C. crescentus, suggesting that regulation of MreB by the Sec system is conserved in bacteria. Taken together, our data reveal that the secretion system plays an important role in determining the organization and functioning of the cytoskeletal system in bacteria.

Crystal Growth and Characterization of MT2Si2 Ternary Intermetallics (M = U, RE and T = 3d, 4d, 5d Transition Metals)

NARCIS (Netherlands)

Menovsky, A.A.; Moleman, A.C.; Snel, G.E.; Gortenmulder, T.J.; Palstra, T.T.M.

1986-01-01

Bulk single crystals of the ternary intermetallic compounds UT2Si2 (T = Ni, Pd, Pt and Ru), LaT2Si2 (T = Pd and Rh) and LuPd2Si2 have been grown from the melt with a modified “tri-arc” Czochralski method. The as-grown crystals were characterized by X-ray, microprobe and chemical analyses. The

Roles of the conserved cytoplasmic region and non-conserved carboxy-terminal region of SecE in Escherichia coli protein translocase.

Science.gov (United States)

Kontinen, V P; Yamanaka, M; Nishiyama, K; Tokuda, H

1996-06-01

SecE, an essential membrane component of the Escherichia coli protein translocase, consists of 127 amino acid residues. Only a part of the second putative cytoplasmic region comprising some 13 residues is essential for the SecE function as long as the proper topological arrangement is retained. The Trp84 and Pro85 residues of this region are conserved in all eubacterial SecE homologues. The conservation of positively charged residues corresponding to Arg80 and Lys81 is also substantial. We deleted or replaced these residues to assess their roles in the SecE function. Deletion of the Arg80-Lys81 dipeptide did not abolish the SecE function whereas that of Trp84 or Pro85 caused a loss of the function. Strikingly, however, replacement of Pro85 with either Gly, Ser, or Ala, and that of Trp84 with Lys did not abolish the SecE function. These results indicate that the strong conservation of these residues does not reflect their obligatory requirement for the SecE function. A chimeric SecE possessing the cytoplasmic region of the E. coli SecE and the following region of the Bacillus subtilis SecE was able to form the translocation machinery together with SecA, SecY, and SecG. Although a Leu to Arg mutation at position 108 has been thought to cause a loss of signal recognition fidelity and thereby suppress a signal sequence defect, the same mutation at position 111 caused a complete loss of the function. The levels of SecY and SecG in the secEcsE501 mutant, which expresses SecE at a decreased level and is sensitive to low temperature, increased upon the expression of functional SecE derivatives, irrespective of the site of mutation, suggesting that the levels of SecY and SecG are co-operatively determined by the level of functional, but not non-functional, SecE. Based on these results, the SecE function in the translocase is discussed.

Fermi-LAT and Suzaku observations of the radio galaxy Centaurus B

International Nuclear Information System (INIS)

Katsuta, J.; Tanaka, Y. T.; Stawarz, Ł.; O’Sullivan, S. P.; Cheung, C. C.

2013-01-01

Centaurus B is a nearby radio galaxy positioned in the southern hemisphere close to the Galactic plane. Here, in this work, we present a detailed analysis of about 43 months of accumulated Fermi-LAT data of the γ-ray counterpart of the source initially reported in the 2nd Fermi-LAT catalog, and of newly acquired Suzaku X-ray data. We confirm its detection at GeV photon energies and analyze the extension and variability of the γ-ray source in the LAT dataset, in which it appears as a steady γ-ray emitter. The X-ray core of Centaurus B is detected as a bright source of a continuum radiation. We do not detect, however, any diffuse X-ray emission from the known radio lobes, with the provided upper limit only marginally consistent with the previously claimed ASCA flux. Two scenarios that connect the X-ray and γ-ray properties are considered. In the first one, we assume that the diffuse non-thermal X-ray emission component is not significantly below the derived Suzaku upper limit. In this case, modeling the inverse-Compton emission shows that the observed γ-ray flux of the source may in principle be produced within the lobes. This association would imply that efficient in-situ acceleration of the radiating electrons is occurring and that the lobes are dominated by the pressure from the relativistic particles. In the second scenario, with the diffuse X-ray emission well below the Suzaku upper limits, the lobes in the system are instead dominated by the magnetic pressure. In this case, the observed γ-ray flux is not likely to be produced within the lobes, but instead within the nuclear parts of the jet. In conclusion, by means of synchrotron self-Compton modeling, we show that this possibility could be consistent with the broad-band data collected for the unresolved core of Centaurus B, including the newly derived Suzaku spectrum.

Legal assessment tool (LAT): an interactive tool to address privacy and data protection issues for data sharing.

Science.gov (United States)

Kuchinke, Wolfgang; Krauth, Christian; Bergmann, René; Karakoyun, Töresin; Woollard, Astrid; Schluender, Irene; Braasch, Benjamin; Eckert, Martin; Ohmann, Christian

2016-07-07

In an unprecedented rate data in the life sciences is generated and stored in many different databases. An ever increasing part of this data is human health data and therefore falls under data protected by legal regulations. As part of the BioMedBridges project, which created infrastructures that connect more than 10 ESFRI research infrastructures (RI), the legal and ethical prerequisites of data sharing were examined employing a novel and pragmatic approach. We employed concepts from computer science to create legal requirement clusters that enable legal interoperability between databases for the areas of data protection, data security, Intellectual Property (IP) and security of biosample data. We analysed and extracted access rules and constraints from all data providers (databases) involved in the building of data bridges covering many of Europe's most important databases. These requirement clusters were applied to five usage scenarios representing the data flow in different data bridges: Image bridge, Phenotype data bridge, Personalised medicine data bridge, Structural data bridge, and Biosample data bridge. A matrix was built to relate the important concepts from data protection regulations (e.g. pseudonymisation, identifyability, access control, consent management) with the results of the requirement clusters. An interactive user interface for querying the matrix for requirements necessary for compliant data sharing was created. To guide researchers without the need for legal expert knowledge through legal requirements, an interactive tool, the Legal Assessment Tool (LAT), was developed. LAT provides researchers interactively with a selection process to characterise the involved types of data and databases and provides suitable requirements and recommendations for concrete data access and sharing situations. The results provided by LAT are based on an analysis of the data access and sharing conditions for different kinds of data of major databases in Europe

FERMI-LAT DETECTION OF PULSED GAMMA-RAYS ABOVE 50 GeV FROM THE VELA PULSAR

Energy Technology Data Exchange (ETDEWEB)

Leung, Gene C. K.; Takata, J.; Ng, C. W.; Cheng, K. S. [Department of Physics, The University of Hong Kong, Pokfulam Road (Hong Kong); Kong, A. K. H.; Tam, P. H. T. [Institute of Astronomy and Department of Physics, National Tsing Hua University, Hsinchu, Taiwan (China); Hui, C. Y., E-mail: gene930@connect.hku.hk, E-mail: takata@hku.hk [Department of Astronomy and Space Science, Chungnam National University, Daejeon (Korea, Republic of)

2014-12-20

The first Fermi-Large Area Telescope (LAT) catalog of sources above 10 GeV reported evidence of pulsed emission above 25 GeV from 12 pulsars, including the Vela pulsar, which showed evidence of pulsation at >37 GeV energy bands. Using 62 months of Fermi-LAT data, we analyzed the gamma-ray emission from the Vela pulsar and searched for pulsed emission above 50 GeV. Having confirmed the significance of the pulsation in 30-50 GeV with the H test (p-value ∼10{sup –77}), we extracted its pulse profile using the Bayesian block algorithm and compared it with the distribution of the five observed photons above 50 GeV using the likelihood ratio test. Pulsation was significantly detected for photons above 50 GeV with a p-value of =3 × 10{sup –5} (4.2σ). The detection of pulsation is significant above 4σ at >79 GeV and above 3σ at >90 GeV energy bands, making this the highest energy pulsation significantly detected by the LAT. We explore the non-stationary outer gap scenario of the very high-energy emissions from the Vela pulsar.

SecMAS: Security Enhanced Monitoring and Analysis Systems for Wireless Sensor Networks

Directory of Open Access Journals (Sweden)

Ding Chao

2016-01-01

Full Text Available The monitoring, control, and security guarantee for the communication in the wireless sensor networks (WSNs are currently treated as three independent issues and addressed separately through specialized tools. However, most cases of WSNs applications requires the network administrator change the network configuration in a very short time to response to the change of observed phenomenon with security guarantee. To meet this requirement, we propose a security enhanced monitoring and control platform named SecMAS for WSNs, which provides the real-time visualization about network states and online reconfiguration of the network properties and behaviours in a resource-efficient way. Besides, basic cryptographic primitives and part of the anomaly detection functionalities are implemented in SecMAS to enabling the secure communication in WSNs. Furthermore, we conduct experiments to evaluate the performance of SecMAS in terms of the latency, throughput, communication overhead, and the security capacity. The experimental results demonstrate that the SecMAS system achieves stable, efficient and secure data collection with lightweight quick-response network control.

FLaapLUC: A pipeline for the generation of prompt alerts on transient Fermi-LAT γ-ray sources

Science.gov (United States)

Lenain, J.-P.

2018-01-01

The large majority of high energy sources detected with Fermi-LAT are blazars, which are known to be very variable sources. High cadence long-term monitoring simultaneously at different wavelengths being prohibitive, the study of their transient activities can help shedding light on our understanding of these objects. The early detection of such potentially fast transient events is the key for triggering follow-up observations at other wavelengths. A Python tool, FLaapLUC, built on top of the Science Tools provided by the Fermi Science Support Center and the Fermi-LAT collaboration, has been developed using a simple aperture photometry approach. This tool can effectively detect relative flux variations in a set of predefined sources and alert potential users. Such alerts can then be used to trigger target of opportunity observations with other facilities. It is shown that FLaapLUC is an efficient tool to reveal transient events in Fermi-LAT data, providing quick results which can be used to promptly organise follow-up observations. Results from this simple aperture photometry method are also compared to full likelihood analyses. The FLaapLUC package is made available on GitHub and is open to contributions by the community.

Long-Term Effects of Extreme Trauma on Sleep Quality and the Circadian Rhythm of Sleep and Wakefulness: An Actigraphy Study of Utøya Survivors

OpenAIRE

Ugland, Kaja Skullerud; Landrø, Heidi

2015-01-01

The terror attack at Utøya Island in 2011 was a national tragedy. Most of the survivors were adolescents. The aim of this study was to explore how sleep and circadian rhythm of sleep and wakefulness was affected after the Utøya massacre. In addition we wanted to examine the general sleep pattern among adolescents. Methods: 42 Utøya survivors and 46 control subjects matched on gender, age and socio- demographical variables were studied 18-30 months after the attack. Sleep was assessed by ac...

SecA is required for membrane targeting of the cell division protein DivIVA in vivo

Directory of Open Access Journals (Sweden)

Sven eHalbedel

2014-02-01

Full Text Available The conserved protein DivIVA is involved in different morphogenetic processes in Gram-positive bacteria. In Bacillus subtilis, the protein localises to the cell division site and cell poles, and functions as a scaffold for proteins that regulate division site selection, and for proteins that are required for sporulation. To identify other proteins that bind to DivIVA, we performed an in vivo cross-linking experiment. A possible candidate that emerged was the secretion motor ATPase SecA. SecA mutants have been described that inhibit sporulation, and since DivIVA is necessary for sporulation, we examined the localisation of DivIVA in these mutants. Surprisingly, DivIVA was delocalised, suggesting that SecA is required for DivIVA targeting. To further corroborate this, we performed SecA depletion and inhibition experiments, which provided further indications that DivIVA localisation depends on SecA. Cell fractionation experiments showed that SecA is important for binding of DivIVA to the cell membrane. This was unexpected since DivIVA does not contain a signal sequence, and is able to bind to artificial lipid membranes in vitro without support of other proteins. SecA is required for protein secretion and membrane insertion, and therefore its role in DivIVA localisation is likely indirect. Possible alternative roles of SecA in DivIVA folding and/or targeting are discussed.

46 CFR Sec. 3 - Preparation of invoices.

Science.gov (United States)

2010-10-01

... NSA ORDER NO. 47 Sec. 3 Preparation of invoices. (a) Pursuant to Article 4 of the Service Agreement... under the applicable provisions of NSA Order No. 47. (1) Invoices shall be prepared so as to show... provisions of NSA Order No. 47 due the undersigned General Agent for the month of _____ under Service...

Particle count and black carbon measurements at schools in Las Vegas, NV and in the greater Salt Lake City, UT area.

Science.gov (United States)

Brown, Steven G; Vaughn, David L; Roberts, Paul T

2017-11-01

As part of two separate studies aimed to characterize ambient pollutant concentrations at schools in urban areas, we compare black carbon and particle count measurements at Adcock Elementary in Las Vegas, NV (April-June 2013), and Hunter High School in the West Valley City area of greater Salt Lake City, UT (February 2012). Both schools are in urban environments, but Adcock Elementary is next to the U.S. 95 freeway. Black carbon (BC) concentrations were 13% higher at Adcock compared to Hunter, while particle count concentrations were 60% higher. When wind speeds were low-less than 2 m/sec-both BC and particle count concentrations were significantly higher at Adcock, while concentrations at Hunter did not have as strong a variation with wind speed. When wind speeds were less than 2 m/sec, emissions from the adjacent freeway greatly affected concentrations at Adcock, regardless of wind direction. At both sites, BC and particle count concentrations peaked in the morning during commute hours. At Adcock, particle count also peaked during midday or early afternoon, when BC was low and conditions were conducive to new particle formation. While this midday peak occurred at Adcock on roughly 45% of the measured days, it occurred on only about 25% of the days at Hunter, since conditions for particle formation (higher solar radiation, lower wind speeds, lower relative humidity) were more conducive at Adcock. Thus, children attending these schools are likely to be exposed to pollution peaks during school drop-off in the morning, when BC and particle count concentrations peak, and often again during lunchtime recess when particle count peaks again. Particle count concentrations at two schools were shown to typically be independent of BC or other pollutants. At a school in close proximity to a major freeway, particle count concentrations were high during the midday and when wind speeds were low, regardless of wind direction, showing a large area of effect from roadway emissions

A study on the crack inspection signal characteristics for power plant components by phased array UT

International Nuclear Information System (INIS)

Cho, Yong Sang; Lim, Sang Gyu; Kil, Du Song

2001-01-01

Phased array ultrasonic testing system has become available for practical application in complicated geometry such as turbine blade root, tenon, disc in power industry. This research describes the characteristics of phased array UT signal for various type of blade roots in thermal Power Plant turbines. This application of Phased array ultrasonic testing system has been promoted mainly to save inspection time and labor cost of turbine inspection. The characteristic of phase array UT signal for power plant component is very simple to understand but to difficult for perform the inspection. Since our sophisticated inspection technique and systems are essential for the inspection of steam turbine blade roots that require high reliability, we intend to develop new technology and improve phased array technique based on the wide and much experience for the inspection of turbine components.

Carcinome à cellule vitreuse du col de l'utérus: à propos d'un cas et revue de littérature

Science.gov (United States)

Hakimi, Ihssane; Zazi, Abdelghani; Chahdi, Hafsa; Guelzim, Khalid; Kouach, Jaouad; Babahabib, Myabdellah; Elhassani, Myehdi; Rahali, Driss Moussaoui; Dehayni, Mohammed

2015-01-01

Le carcinome à cellule vitreuse du col de l'utérus est un type de histologique rare de cancer du col de l'utérus qui survient à un âge plus jeune, et s'associe au risque élevé d’échec thérapeutique et le pronostic est plus mauvais en comparaison au type cellulaire squameux. La radiothérapie est associée au risque diminué de récidive. Le but de cette étude est de récapituler à travers d'une observation et une revue de littérature les données sur l'incidence, le comportement clinique et la survie globale de patients avec le carcinome à cellule vitreuse du col de l'utérus. PMID:26664556

Multiple loss-of-function mechanisms contribute to SCN5A-related familial sick sinus syndrome.

Directory of Open Access Journals (Sweden)

Junhong Gui

2010-06-01

Full Text Available To identify molecular mechanisms underlying SCN5A-related sick sinus syndrome (SSS, a rare type of SSS, in parallel experiments we elucidated the electrophysiological properties and the cell surface localization of thirteen human Na(v1.5 (hNa(v1.5 mutant channels previously linked to this disease.Mutant hNa(v1.5 channels expressed by HEK293 cells and Xenopus oocytes were investigated by whole-cell patch clamp and two-microelectrode voltage clamp, respectively. HEK293 cell surface biotinylation experiments quantified the fraction of correctly targeted channel proteins. Our data suggested three distinct mutant channel subtypes: Group 1 mutants (L212P, P1298L, DelF1617, R1632H gave peak current densities and cell surface targeting indistinguishable from wild-type hNa(v1.5. Loss-of-function of these mutants resulted from altered channel kinetics, including a negative shift of steady-state inactivation and a reduced voltage dependency of open-state inactivation. Group 2 mutants (E161K, T220I, D1275N gave significantly reduced whole-cell currents due to impaired cell surface localization (D1275N, altered channel properties at unchanged cell surface localization (T220I, or a combination of both (E161K. Group 3 mutant channels were non-functional, due to an almost complete lack of protein at the plasma membrane (T187I, W1421X, K1578fs/52, R1623X or a probable gating/permeation defect with normal surface localisation (R878C, G1408R.This study indicates that multiple molecular mechanisms, including gating abnormalities, trafficking defects, or a combination of both, are responsible for SCN5A-related familial SSS.

Microscopy analysis of reconstituted COPII coat polymerization and Sec16 dynamics.

Science.gov (United States)

Iwasaki, Hirohiko; Yorimitsu, Tomohiro; Sato, Ken

2017-09-01

The COPII coat and the small GTPase Sar1 mediate protein export from the endoplasmic reticulum (ER) via specialized domains known as the ER exit sites. The peripheral ER protein Sec16 has been proposed to organize ER exit sites. However, it remains unclear how these molecules drive COPII coat polymerization. Here, we characterized the spatiotemporal relationships between the Saccharomyces cerevisiae COPII components during their polymerization by performing fluorescence microscopy of an artificial planar membrane. We demonstrated that Sar1 dissociates from the membrane shortly after the COPII coat recruitment, and Sar1 is then no longer required for the COPII coat to bind to the membrane. Furthermore, we found that Sec16 is incorporated within the COPII-cargo clusters, and that this is dependent on the Sar1 GTPase cycle. These data show how Sar1 drives the polymerization of COPII coat and how Sec16 is spatially distributed during COPII coat polymerization. © 2017. Published by The Company of Biologists Ltd.

Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation

DEFF Research Database (Denmark)

Gardella, Elena; Becker, Felicitas; Møller, Rikke S

2016-01-01

by stretching, motor initiation or by emotional stimuli. In one case, we recorded typical PKD spells by video-EEG-polygraphy, documenting a cortical involvement. INTERPRETATION: Our study establishes SCN8A as a novel gene in which a recurrent mutation causes BFIS/ICCA, expanding the clinical-genetic spectrum...... patient had seizures only at school age. All patients stayed otherwise seizure-free, most without medication. Interictal EEG was normal in all cases but two. Five/16 patients developed additional brief paroxysmal episodes in puberty, either dystonic/dyskinetic or "shivering" attacks, triggered...... identified as the major gene in all three conditions, found to be mutated in 80-90% of familial and 30-35% of sporadic cases. METHODS: We searched for the genetic defect in PRRT2-negative, unrelated families with BFIS or ICCA using whole exome or targeted gene panel sequencing, and performed a detailed...

Revisiting simplified dark matter models in terms of AMS-02 and Fermi-LAT

Science.gov (United States)

Li, Tong

2018-01-01

We perform an analysis of the simplified dark matter models in the light of cosmic ray observables by AMS-02 and Fermi-LAT. We assume fermion, scalar or vector dark matter particle with a leptophobic spin-0 mediator that couples only to Standard Model quarks and dark matter via scalar and/or pseudo-scalar bilinear. The propagation and injection parameters of cosmic rays are determined by the observed fluxes of nuclei from AMS-02. We find that the AMS-02 observations are consistent with the dark matter framework within the uncertainties. The AMS-02 antiproton data prefer 30 (50) GeV - 5 TeV dark matter mass and require an effective annihilation cross section in the region of 4 × 10-27 (7 × 10-27) - 4 × 10-24 cm3/s for the simplified fermion (scalar and vector) dark matter models. The cross sections below 2 × 10-26 cm3/s can evade the constraint from Fermi-LAT dwarf galaxies for about 100 GeV dark matter mass.

Potent inhibitors of human LAT1 (SLC7A5) transporter based on dithiazole and dithiazine compounds for development of anticancer drugs.

Science.gov (United States)

Napolitano, Lara; Scalise, Mariafrancesca; Koyioni, Maria; Koutentis, Panayiotis; Catto, Marco; Eberini, Ivano; Parravicini, Chiara; Palazzolo, Luca; Pisani, Leonardo; Galluccio, Michele; Console, Lara; Carotti, Angelo; Indiveri, Cesare

2017-11-01

The LAT1 transporter is acknowledged as a pharmacological target of tumours since it is strongly overexpressed in many human cancers. The purpose of this work was to find novel compounds exhibiting potent and prolonged inhibition of the transporter. To this aim, compounds based on dithiazole and dithiazine scaffold have been screened in the proteoliposome experimental model. Inhibition was tested on the antiport catalysed by hLAT1 as transport of extraliposomal [ 3 H]histidine in exchange with intraliposomal histidine. Out of 59 compounds tested, 8 compounds, showing an inhibition higher than 90% at 100µM concentration, were subjected to dose-response analysis. Two of them exhibited IC 50 lower than 1µM. Inhibition kinetics, performed on the two best inhibitors, indicated a mixed type of inhibition with respect to the substrate. Furthermore, inhibition of the transporter was still present after removal of the compounds from the reaction mixture, but was reversed on addition of dithioerythritol, a S-S reducing agent, indicating the formation of disulfide(s) between the compounds and the protein. Molecular docking of the two best inhibitors on the hLAT1 homology structural model, highlighted interaction with the substrate binding site and formation of a covalent bond with the residue C407. Indeed, the inhibition was impaired in the hLAT1 mutant C407A confirming the involvement of that Cys residue. Treatment of SiHa cells expressing hLAT1 at relatively high level, with the two most potent inhibitors led to cell death which was not observed after treatment with a compound exhibiting very poor inhibitory effect. Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnostic usefulness of 18F-FAMT PET and L-type amino acid transporter 1 (LAT1) expression in oral squamous cell carcinoma

International Nuclear Information System (INIS)

Nobusawa, Aiko; Kim, Mai; Kaira, Kyoichi; Miyashita, Go; Negishi, Akihide; Yokoo, Satoshi; Oriuchi, Noboru; Higuchi, Tetsuya; Tsushima, Yoshito; Kanai, Yoshikatsu; Oyama, Tetsunari

2013-01-01

l-[3- 18 F]-α-Methyltyrosine ( 18 F-FAMT) was developed as an amino acid tracer for PET imaging to provide better specificity than 2-[ 18 F]fluoro-2-deoxy-d-glucose ( 18 F-FDG) PET for cancer diagnosis. We investigated the diagnostic usefulness of 18 F-FAMT in oral squamous cell carcinoma (OSCC). The correlation between tumour uptake of 18 F-FAMT and L-type amino acid transporter 1 (LAT1) expression was determined. The study group comprised 68 OSCC patients who underwent both 18 F-FAMT and 18 F-FDG PET. Resected tumour sections were stained by immunohistochemistry for LAT1, CD98 and Ki-67, and microvessel density was determined in terms of CD34 and p53 expression. The sensitivity of primary tumour detection by 18 F-FAMT and 18 F-FDG PET was 98 % and 100 %, respectively. The sensitivity, specificity and accuracy of 18 F-FAMT PET for detecting malignant lymph nodes were 68 %, 99 % and 97 %, respectively, and equivalent values for 18 F-FDG PET were 84 %, 94 % and 94 %, respectively. The specificity and accuracy of 18 F-FAMT were significantly higher than those of 18 F-FDG. The uptake of 18 F-FAMT was significantly correlated with LAT1 expression, cell proliferation and advanced stage. The expression of LAT1 in OSCC cells was closely correlated with CD98 levels, cell proliferation and angiogenesis. 18 F-FAMT PET showed higher specificity for detecting malignant lesions than 18 F-FDG PET. The uptake of 18 F-FAMT by OSCC cells can be determined by the presence of LAT1 expression and tumour cell proliferation. (orig.)

Copper diffusion in In2S3 and charge separation at In2S3/CuSCN and TiO2/In2S3 interfaces

International Nuclear Information System (INIS)

Juma, Albert Owino

2013-01-01

The concept of inorganic nanostructured solar cells consists of a very thin absorber layer sandwiched between highly structured electron and hole conductors. When a TiO 2 /In 2 S 3 /CuSCN nanocomposite heterostructure is illuminated with light, photo-generated electrons in In 2 S 3 can be injected into the conduction band of TiO 2 and holes into the valence band of CuSCN. Charge transfer at the interfaces is limited by the deposition parameters, band alignment and diffusion of Cu from CuSCN into In 2 S 3 , which was the focus of this work. TiO 2 nanoparticles were screen printed onto SnO 2 :F (FTO)-coated glass substrates to give a layer of nanoporous (np) TiO 2 . In 2 S 3 layers were deposited by thermal evaporation or ion layer gas reaction (ILGAR) methods producing Cl-free (In(acac) 3 precursor) and Cl-containing (InCl 3 precursor) layers. A spray-spin method was developed for deposition of CuSCN onto In 2 S 3 . Diffusion of Cu into In 2 S 3 layers was investigated by Rutherford backscattering spectrometry (RBS) while charge transport mechanisms were studied with surface photovoltage (SPV) technique in the fixed capacitor configuration. The activation energy (Ea) for Cu diffusion in thermally evaporated and Cl-free ILGAR In 2 S 3 layers was 0.30 and 0.24 eV, respectively but increased to between 0.72 and 0.78 eV for Cl-containing In 2 S 3 with residual Cl concentrations of 7.8 - 13.8 at.%. The diffusion prefactor (D 0 ) was six orders of magnitude higher for Cl-containing compared to Cl-free layers. The relationship between E a and D 0 was described by the Meyer-Neldel rule with a Meyer-Neldel energy of 40 meV. The presence of Cl has no significant influence on the structural properties of In 2 S 3 but resulted in a modified diffusion mechanism for Cu diffusion. The photovoltage of In 2 S 3 /CuSCN samples decreased after annealing for longer than 2 min at 200 C. A defect band was formed near the interface where holes accumulated and electrons tunneled through

50 CFR Table 3 (north) to Part 660... - 2010 Trip Limits for Open Access Gears North of 40°10′ N. Lat.

Science.gov (United States)

2010-10-01

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50 CFR Table 3 (south) to Part 660... - 2010 Trip Limits for Open Access Gears South of 40°10′ N. Lat.

Science.gov (United States)

2010-10-01

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Fermi-LAT View of Bright Flaring Gamma-Ray Blazars D. Bastieri1,2 ...

Indian Academy of Sciences (India)

Sun while in a quiet state were promptly detected. This is mainly due to the design of the mission, featuring a detector, the LAT with a wide field of view, and to ... the energies of all photons falling inside a solid angle, of a proper opening, cen- ... Opportunity (ToO) triggers for multifrequency observations; to start possible ToO.

OMI/Aura Surface Reflectance Climatology Level 3 Global 0.5deg Lat/Lon Grid V003

Data.gov (United States)

National Aeronautics and Space Administration — The OMI Earth Surface Reflectance Climatology product, OMLER (Global 0.5deg Lat/Lon grid) which is based on Version 003 Level-1B top of atmosphere upwelling radiance...

46 CFR Sec. 2 - Submission of repair entries.

Science.gov (United States)

2010-10-01

... MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL SHIPPING AUTHORITY GENERAL AGENT'S RESPONSIBILITY IN CONNECTION WITH FOREIGN REPAIR CUSTOM'S ENTRIES Sec. 2 Submission of repair entries. At the... with the District Director of Customs as defined in 19 CFR 1.1(d) an affidavit on Custom's Form 3417...

Brugada syndrome with a novel missense mutation in SCN5A gene: A case report from Bangladesh

Directory of Open Access Journals (Sweden)

Md. Zahidus Sayeed

2014-01-01

Full Text Available Brugada syndrome is an inherited cardiac arrhythmia that follows autosomal dominant transmission and can cause sudden death. We report a case of Brugada syndrome in a 55-year-old male patient presented with recurrent palpitation, atypical chest pain and presyncope. ECG changes were consistent with type 1 Brugada. Gene analysis revealed a novel missense mutation in SCN5A gene with a genetic variation of D785N and a nucleotide change at 2353G-A. One of his children also had the same mutation. To our knowledge this is the first genetically proved case of Brugada syndrome in Bangladesh.

Amblyomma americanum salivary gland homolog of nSec1 is essential for saliva protein secretion

International Nuclear Information System (INIS)

Karim, Shahid; Ramakrishnan, Vijay G.; Tucker, James S.; Essenberg, Richard C.; Sauer, John R.

2004-01-01

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins assemble in tight core complexes which promote fusion of carrier vesicles with target compartments. Members of this class of proteins are expressed in all eukaryotic cells and distributed in distinct subcellular compartments. All vesicle transport mechanisms known to date have an essential requirement for a member of the Sec1 protein family, including the nSec1 in regulated exocytosis. A homolog of nSec1 was cloned and sequenced from the salivary glands of partially fed female ticks. Double-stranded RNA was used to specifically reduce the amount of nSec1 mRNA and protein in female adult tick salivary glands. This reduction was accompanied by a decrease in anticoagulant protein release by the glands and by abnormalities in feeding by dsRNA treated ticks. We report the efficacy of double-stranded RNA-mediated interference in 'knocking down' nSec1 both in vivo and in vitro in tick salivary glands and the applicability of this technique for studying the mechanism of exocytosis in tick salivary glands

Dark matter implications of Fermi-LAT measurement of anisotropies in the diffuse gamma-ray background

International Nuclear Information System (INIS)

Gómez-Vargas, G.A.; Cuoco, A.; Linden, T.; Sánchez-Conde, M.A.; Siegal-Gaskins, J.M.; Delahaye, T.; Fornasa, M.; Komatsu, E.

2014-01-01

The detailed origin of the diffuse gamma-ray background is still unknown. However, the contribution of unresolved sources is expected to induce small-scale anisotropies in this emission, which may provide a way to identify and constrain the properties of its contributors. Recent studies have predicted the contributions to the angular power spectrum (APS) from extragalactic and galactic dark matter (DM) annihilation or decay. The Fermi-LAT collaboration reported detection of angular power with a significance larger than 3σ in the energy range from 1 GeV to 10 GeV on 22 months of data (Ackermann et al., 2012 [2]). For these preliminary results the already published Fermi-LAT APS measurements (Ackermann et al., 2012 [2]) are compared to the accurate predictions for DM anisotropies from state-of-the-art cosmological simulations as presented in Fornasa et al. (2013) [1] to derive constraints on different DM candidates

Dark matter implications of Fermi-LAT measurement of anisotropies in the diffuse gamma-ray background

Energy Technology Data Exchange (ETDEWEB)

Gómez-Vargas, G.A., E-mail: germanarturo.gomez@uam.es [Departamento de Física Teórica, Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid (Spain); Instituto de Física Teórica IFT-UAM/CSIC, Universidad Autónoma de Madrid, Cantoblanco, E-28049, Madrid (Spain); Istituto Nazionale di Fisica Nucleare, Sez. Roma Tor Vergata, Roma (Italy); Cuoco, A. [The Oskar Klein Centre for Cosmo Particle Physics, AlbaNova, SE-106 91 Stockholm (Sweden); Linden, T. [Department of Physics, University of California, Santa Cruz, CA 95064 (United States); Sánchez-Conde, M.A. [SLAC National Accelerator Laboratory and Kavli Institute for Particle Astrophysics and Cosmology, Menlo Park, CA 94025 (United States); Siegal-Gaskins, J.M. [California Institute of Technology, Pasadena, CA 91125 (United States); Delahaye, T. [LAPTh, Universit e de Savoie, CNRS, 9 chemin de Bellevue, BP110, F-74941 Annecy-le-Vieux Cedex (France); Institut d' Astrophysique de Paris, UMR 7095 – CNRS, Universit e Pierre and Marie Curie, 98 bis boulevard Arago, 75014 Paris (France); Instituto de Física Teórica IFT-UAM/CSIC, Universidad Autónoma de Madrid, Cantoblanco, E-28049, Madrid (Spain); Fornasa, M. [School of Physics and Astronomy, University of Nottingham, NG7 2RD Nottingham (United Kingdom); Komatsu, E. [Max-Planck-Institut fur Astrophysik, Karl-Schwarzschild Str. 1, 85741 Garching (Germany); Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU, WPI), Todai Institutes for Advanced Study, the University of Tokyo, Kashiwa 277-8583 (Japan); Texas Cosmology Center and the Department of Astronomy, The University of Texas at Austin, 1 University Station, C1400, Austin, TX 78712 (United States); and others

2014-04-01

The detailed origin of the diffuse gamma-ray background is still unknown. However, the contribution of unresolved sources is expected to induce small-scale anisotropies in this emission, which may provide a way to identify and constrain the properties of its contributors. Recent studies have predicted the contributions to the angular power spectrum (APS) from extragalactic and galactic dark matter (DM) annihilation or decay. The Fermi-LAT collaboration reported detection of angular power with a significance larger than 3σ in the energy range from 1 GeV to 10 GeV on 22 months of data (Ackermann et al., 2012 [2]). For these preliminary results the already published Fermi-LAT APS measurements (Ackermann et al., 2012 [2]) are compared to the accurate predictions for DM anisotropies from state-of-the-art cosmological simulations as presented in Fornasa et al. (2013) [1] to derive constraints on different DM candidates.

miR-155 Controls Lymphoproliferation in LAT Mutant Mice by Restraining T-Cell Apoptosis via SHIP-1/mTOR and PAK1/FOXO3/BIM Pathways.

Directory of Open Access Journals (Sweden)

Alexandre K Rouquette-Jazdanian

Full Text Available Linker for Activation of T cells (LAT is an adapter protein that is essential for T cell function. Knock-in mice with a LAT mutation impairing calcium flux develop a fatal CD4+ lymphoproliferative disease. miR-155 is a microRNA that is correlated with hyperproliferation in a number of cancers including lymphomas and leukemias and is overexpressed in mutant LAT T cells. To test whether miR-155 was merely indicative of T cell activation or whether it contributes to lymphoproliferative disease in mutant LAT mice, we interbred LAT mutant and miR-155-deficient mice. miR-155 deficiency markedly inhibited lymphoproliferative disease by stimulating BIM-dependent CD4+ T cell apoptosis, even though ERK activation and T cell proliferation were increased in double mutant CD4+ T cells. Bim/Bcl2l11 expression is activated by the forkhead transcription factor FOXO3. Using miR-155-deficient, LAT mutant T cells as a discovery tool, we found two connected pathways that impact the nuclear translocation and activation of FOXO3 in T cells. One pathway is mediated by the inositide phosphatase SHIP-1 and the serine/threonine kinases AKT and PDK1. The other pathway involves PAK1 and JNK kinase activation. We define crosstalk between the two pathways via the kinase mTOR, which stabilizes PAK1. This study establishes a role for PAK1 in T cell apoptosis, which contrasts to its previously identified role in T cell proliferation. Furthermore, miR-155 regulates the delicate balance between PAK1-mediated proliferation and apoptosis in T cells impacting lymphoid organ size and function.

O-acetylation of the serine-rich repeat glycoprotein GspB is coordinated with accessory Sec transport.

Directory of Open Access Journals (Sweden)

Ravin Seepersaud

2017-08-01

Full Text Available The serine-rich repeat (SRR glycoproteins are a family of adhesins found in many Gram-positive bacteria. Expression of the SRR adhesins has been linked to virulence for a variety of infections, including streptococcal endocarditis. The SRR preproteins undergo intracellular glycosylation, followed by export via the accessory Sec (aSec system. This specialized transporter is comprised of SecA2, SecY2 and three to five accessory Sec proteins (Asps that are required for export. Although the post-translational modification and transport of the SRR adhesins have been viewed as distinct processes, we found that Asp2 of Streptococcus gordonii also has an important role in modifying the SRR adhesin GspB. Biochemical analysis and mass spectrometry indicate that Asp2 is an acetyltransferase that modifies N-acetylglucosamine (GlcNAc moieties on the SRR domains of GspB. Targeted mutations of the predicted Asp2 catalytic domain had no effect on transport, but abolished acetylation. Acetylated forms of GspB were only detected when the protein was exported via the aSec system, but not when transport was abolished by secA2 deletion. In addition, GspB variants rerouted to export via the canonical Sec pathway also lacked O-acetylation, demonstrating that this modification is specific to export via the aSec system. Streptococci expressing GspB lacking O-acetylated GlcNAc were significantly reduced in their ability bind to human platelets in vitro, an interaction that has been strongly linked to virulence in the setting of endocarditis. These results demonstrate that Asp2 is a bifunctional protein involved in both the post-translational modification and transport of SRR glycoproteins. In addition, these findings indicate that these processes are coordinated during the biogenesis of SRR glycoproteins, such that the adhesin is optimally modified for binding. This requirement for the coupling of modification and export may explain the co-evolution of the SRR

Flow-injection spectrophotometric determination of captopril in pharmaceutical formulations using a new solid-phase reactor containing AgSCN immobilized in a polyurethane resin

Directory of Open Access Journals (Sweden)

Fernando Campanhã Vicentini

2012-06-01

Full Text Available A simple flow-injection analysis procedure was developed for determining captopril in pharmaceutical formulations employing a novel solid-phase reactor containing silver thiocyanate immobilized in a castor oil derivative polyurethane resin. The method was based on silver mercaptide formation between the captopril and Ag(I in the solid-phase reactor. During such a reaction, the SCN- anion was released and reacted with Fe3+, which generated the FeSCN2+ complex that was continuously monitored at 480 nm. The analytical curve was linear in the captopril concentration range from 3.0 × 10-4 mol L-1 to 1.1 × 10-3 mol L-1 with a detection limit of 8.0 × 10-5 mol L-1. Recoveries between 97.5% and 103% and a relative standard deviation of 2% for a solution containing 6.0 × 10-4 mol L-1 captopril (n = 12 were obtained. The sample throughput was 40 h-1 and the results obtained for captopril in pharmaceutical formulations using this procedure and those obtained using a pharmacopoeia procedure were in agreement at a 95% confidence level.Um procedimento simples de análise por injeção em fluxo foi desenvolvido para a determinação de captopril em formulações farmacêuticas empregando um novo reator em fase sólida contendo tiocianato de prata imobilizado em resina poliuretana obtida a partir de óleo de mamona. O método foi baseado na formação de um mercapto composto de prata, no reator em fase sólida, obtido entre o captopril e Ag (I imobilizada. Durante a reação, íons SCN- eram liberados e reagiam com Fe3+, gerando o complexo FeSCN2+, que foi continuamente monitorado em 480 nm. A curva analítica foi linear no intervalo de concentração de captopril entre 3,0 × 10-4 a 1,1 × 10-3 mol L-1 com um limite de detecção de 8,0 × 10-5 mol L-1. Recuperações entre 97,5-103% e desvio padrão relativo de 2% para uma solução contendo 6,0 × 10-4 mol L-1 de captopril (n = 12 foram obtidos. A frequência de amostragem foi de 40 h-1 e os resultados

The coat protein complex II, COPII, protein Sec13 directly interacts with presenilin-1

International Nuclear Information System (INIS)

Nielsen, Anders Lade

2009-01-01

Mutations in the human gene encoding presenilin-1, PS1, account for most cases of early-onset familial Alzheimer's disease. PS1 has nine transmembrane domains and a large loop orientated towards the cytoplasm. PS1 locates to cellular compartments as endoplasmic reticulum (ER), Golgi apparatus, vesicular structures, and plasma membrane, and is an integral member of γ-secretase, a protein protease complex with specificity for intra-membranous cleavage of substrates such as β-amyloid precursor protein. Here, an interaction between PS1 and the Sec13 protein is described. Sec13 takes part in coat protein complex II, COPII, vesicular trafficking, nuclear pore function, and ER directed protein sequestering and degradation control. The interaction maps to the N-terminal part of the large hydrophilic PS1 loop and the first of the six WD40-repeats present in Sec13. The identified Sec13 interaction to PS1 is a new candidate interaction for linking PS1 to secretory and protein degrading vesicular circuits.

The coat protein complex II, COPII, protein Sec13 directly interacts with presenilin-1

Energy Technology Data Exchange (ETDEWEB)

Nielsen, Anders Lade, E-mail: aln@humgen.au.dk [Department of Human Genetics, The Bartholin Building, University of Aarhus, DK-8000 Aarhus C (Denmark)

2009-10-23

Mutations in the human gene encoding presenilin-1, PS1, account for most cases of early-onset familial Alzheimer's disease. PS1 has nine transmembrane domains and a large loop orientated towards the cytoplasm. PS1 locates to cellular compartments as endoplasmic reticulum (ER), Golgi apparatus, vesicular structures, and plasma membrane, and is an integral member of {gamma}-secretase, a protein protease complex with specificity for intra-membranous cleavage of substrates such as {beta}-amyloid precursor protein. Here, an interaction between PS1 and the Sec13 protein is described. Sec13 takes part in coat protein complex II, COPII, vesicular trafficking, nuclear pore function, and ER directed protein sequestering and degradation control. The interaction maps to the N-terminal part of the large hydrophilic PS1 loop and the first of the six WD40-repeats present in Sec13. The identified Sec13 interaction to PS1 is a new candidate interaction for linking PS1 to secretory and protein degrading vesicular circuits.

Changes in action potentials and intracellular ionic homeostasis in a ventricular cell model related to a persistent sodium current in SCN5A mutations underlying LQT3

Czech Academy of Sciences Publication Activity Database

Christé, G.; Chahine, M.; Chevalier, P.; Pásek, Michal

2008-01-01

Roč. 96, - (2008), s. 281-293 ISSN 0079-6107 Institutional research plan: CEZ:AV0Z20760514 Keywords : cardiac cell * SCN5A mutation * Long QT syndrome * quantitative modelling Subject RIV: BO - Biophysics Impact factor: 6.388, year: 2008

Archive of Geosample Data and Information from the University of Texas at Austin (UT) Institute of Geophysics

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Metadata describing piston cores curated by Institute of Geophysics of the University of Texas at Austin (UT) collected from 1976 to 1978 were coded and contributed...

Issue des accouchements sur utérus cicatriciel dans un hôpital ...

African Journals Online (AJOL)

Certains auteurs ont tendance à privilégier la césarienne comme méthode de prise en charge d'une parturiente porteuse d'un utérus cicatriciel. D'autres auteurs préconisent un accouchement par voie basse quand des paramètres cliniques précis sont observés. Le but de cette étude est d'analyser la prise en charge et ...

46 CFR Sec. 7 - Disbursements at foreign ports.

Science.gov (United States)

2010-10-01

...-agent shall pay invoices from such advances and shall make proper accounting to the agent for all... RULES FOR FINANCIAL TRANSACTIONS UNDER AGENCY AGREEMENTS Disbursements Sec. 7 Disbursements at foreign... or by any other method outlined to and approved by the owner in advance of its use: (a) The agent may...

46 CFR Sec. 4 - Persons authorized to make awards under the NSA-WORKSMALREP Contract.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Persons authorized to make awards under the NSA-WORKSMALREP Contract. Sec. 4 Section 4 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A... INDIVIDUAL CONTRACT FOR MINOR REPAIRS-NSA-WORKSMALREP Sec. 4 Persons authorized to make awards under the NSA...

FERMI/LAT OBSERVATIONS OF SWIFT/BAT SEYFERT GALAXIES: ON THE CONTRIBUTION OF RADIO-QUIET ACTIVE GALACTIC NUCLEI TO THE EXTRAGALACTIC γ-RAY BACKGROUND

International Nuclear Information System (INIS)

Teng, Stacy H.; Mushotzky, Richard F.; Reynolds, Christopher S.; Sambruna, Rita M.; Davis, David S.

2011-01-01

We present the analysis of 2.1 years of Fermi Large Area Telescope (LAT) data on 491 Seyfert galaxies detected by the Swift Burst Alert Telescope (BAT) survey. Only the two nearest objects, NGC 1068 and NGC 4945, which were identified in the Fermi first year catalog, are detected. Using Swift/BAT and radio 20 cm fluxes, we define a new radio-loudness parameter R X,BAT where radio-loud objects have log R X,BAT > –4.7. Based on this parameter, only radio-loud sources are detected by Fermi/LAT. An upper limit to the flux of the undetected sources is derived to be ∼2 × 10 –11 photons cm –2 s –1 , approximately seven times lower than the observed flux of NGC 1068. Assuming a median redshift of 0.031, this implies an upper limit to the γ-ray (1-100 GeV) luminosity of ∼ 41 erg s –1 . In addition, we identified 120 new Fermi/LAT sources near the Swift/BAT Seyfert galaxies with significant Fermi/LAT detections. A majority of these objects do not have Swift/BAT counterparts, but their possible optical counterparts include blazars, flat-spectrum radio quasars, and quasars.

50 CFR Table 5 (south) to Part 660... - 2009-2010 Trip Limits for Open Access Gears South of 40°10′ N. Lat.

Science.gov (United States)

2010-10-01

... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false 2009-2010 Trip Limits for Open Access Gears South of 40°10â² N. Lat. 5 Table 5 (South) to Part 660, Subpart G Wildlife and Fisheries FISHERY... Trip Limits for Open Access Gears South of 40°10′ N. Lat. Link to an amendment published at 75 FR 60995...

50 CFR Table 5 (north) to Part 660... - 2009-2010 Trip Limits for Open Access Gears North of 40°10′ N. Lat.

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2010-10-01

... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false 2009-2010 Trip Limits for Open Access Gears North of 40°10â² N. Lat. 5 Table 5 (North) to Part 660, Subpart G Wildlife and Fisheries FISHERY... Trip Limits for Open Access Gears North of 40°10′ N. Lat. Link to an amendment published at 75 FR 60995...

Phosphotyrosine-mediated LAT assembly on membranes drives kinetic bifurcation in recruitment dynamics of the Ras activator SOS.

Science.gov (United States)

Huang, William Y C; Yan, Qingrong; Lin, Wan-Chen; Chung, Jean K; Hansen, Scott D; Christensen, Sune M; Tu, Hsiung-Lin; Kuriyan, John; Groves, Jay T

2016-07-19

The assembly of cell surface receptors with downstream signaling molecules is a commonly occurring theme in multiple signaling systems. However, little is known about how these assemblies modulate reaction kinetics and the ultimate propagation of signals. Here, we reconstitute phosphotyrosine-mediated assembly of extended linker for the activation of T cells (LAT):growth factor receptor-bound protein 2 (Grb2):Son of Sevenless (SOS) networks, derived from the T-cell receptor signaling system, on supported membranes. Single-molecule dwell time distributions reveal two, well-differentiated kinetic species for both Grb2 and SOS on the LAT assemblies. The majority fraction of membrane-recruited Grb2 and SOS both exhibit fast kinetics and single exponential dwell time distributions, with average dwell times of hundreds of milliseconds. The minor fraction exhibits much slower kinetics, extending the dwell times to tens of seconds. Considering this result in the context of the multistep process by which the Ras GEF (guanine nucleotide exchange factor) activity of SOS is activated indicates that kinetic stabilization from the LAT assembly may be important. This kinetic proofreading effect would additionally serve as a stochastic noise filter by reducing the relative probability of spontaneous SOS activation in the absence of receptor triggering. The generality of receptor-mediated assembly suggests that such effects may play a role in multiple receptor proximal signaling processes.

THE FIRST FERMI-LAT CATALOG OF SOURCES ABOVE 10 GeV

International Nuclear Information System (INIS)

Ackermann, M.; Buehler, R.; Ajello, M.; Allafort, A.; Bechtol, K.; Bloom, E. D.; Atwood, W. B.; Belfiore, A.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bellazzini, R.; Bregeon, J.; Bernieri, E.; Bissaldi, E.; Bonamente, E.; Brandt, T. J.; M. Merlin dell'Università e del Politecnico di Bari, I-70126 Bari (Italy))" data-affiliation=" (Dipartimento di Fisica M. Merlin dell'Università e del Politecnico di Bari, I-70126 Bari (Italy))" >Brigida, M.; Bruel, P.

2013-01-01

We present a catalog of γ-ray sources at energies above 10 GeV based on data from the Large Area Telescope (LAT) accumulated during the first 3 yr of the Fermi Gamma-ray Space Telescope mission. The first Fermi-LAT catalog of >10 GeV sources (1FHL) has 514 sources. For each source we present location, spectrum, a measure of variability, and associations with cataloged sources at other wavelengths. We found that 449 (87%) could be associated with known sources, of which 393 (76% of the 1FHL sources) are active galactic nuclei. Of the 27 sources associated with known pulsars, we find 20 (12) to have significant pulsations in the range >10 GeV (>25 GeV). In this work we also report that, at energies above 10 GeV, unresolved sources account for 27% ± 8% of the isotropic γ-ray background, while the unresolved Galactic population contributes only at the few percent level to the Galactic diffuse background. We also highlight the subset of the 1FHL sources that are best candidates for detection at energies above 50-100 GeV with current and future ground-based γ-ray observatories

Aryl hydrocarbon receptor-dependent up-regulation of the heterodimeric amino acid transporter LAT1 (SLC7A5)/CD98hc (SLC3A2) by diesel exhaust particle extract in human bronchial epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Le Vee, Marc; Jouan, Elodie; Lecureur, Valérie [Institut de Recherches en Santé, Environnement et Travail (IRSET), UMR INSERM U1085, Faculté de Pharmacie, 2 Avenue du Pr Léon Bernard, 35043 Rennes (France); Fardel, Olivier, E-mail: olivier.fardel@univ-rennes1.fr [Institut de Recherches en Santé, Environnement et Travail (IRSET), UMR INSERM U1085, Faculté de Pharmacie, 2 Avenue du Pr Léon Bernard, 35043 Rennes (France); Pôle Biologie, Centre Hospitalier Universitaire, 2 rue Henri Le Guilloux, 35033 Rennes (France)

2016-01-01

The heterodimeric L-type amino acid transporter (LAT) 1/CD98hc is overexpressed in lung cancers with a poor prognosis factor. Factors that contribute to LAT1/CD98hc overexpression in lung cells remain however to be determined, but the implication of atmospheric pollution can be suspected. The present study was therefore designed to analyze the effects of diesel exhaust particle (DEP) extract (DEPe) on LAT1/CD98hc expression in bronchial epithelial BEAS-2B cells. Exposure to DEPe up-regulated LAT1 and CD98hc mRNA levels in a concentration-dependent manner, with DEPe EC{sub 50} values (around 0.2 μg/mL) relevant to environmental situations. DEPe concomitantly induced LAT1/CD98hc protein expression and LAT1-mediated leucine accumulation in BEAS-2B cells. Inhibition of the aryl hydrocarbon receptor (AhR) pathway through the use of a chemical AhR antagonist or the siRNA-mediated silencing of AhR expression was next found to prevent DEPe-mediated induction of LAT1/CD98hc, indicating that this regulation depends on AhR, known to be activated by major chemical DEP components like polycyclic aromatic hydrocarbons. DEPe exposure was finally shown to induce mRNA expression and activity of matrix metalloproteinase (MMP)-2 in BEAS-2B cells, in a CD98hc/focal adhesion kinase (FAK)/extracellular regulated kinase (ERK) manner, thus suggesting that DEPe-mediated induction of CD98hc triggers activation of the integrin/FAK/ERK signaling pathway known to be involved in MMP-2 regulation. Taken together, these data demonstrate that exposure to DEPe induces functional overexpression of the amino acid transporter LAT1/CD98hc in lung cells. Such a regulation may participate to pulmonary carcinogenic effects of DEPs, owing to the well-documented contribution of LAT1 and CD98hc to cancer development. - Highlights: • The amino acid transporter LAT1/CD98hc is up-regulated in DEPe-treated lung cells. • The aryl hydrocarbon receptor is involved in DEPe-triggered induction of LAT1/CD98hc. �

Functional Analysis of Developmentally Regulated Genes chs7 and sec22 in the Ascomycete Sordaria macrospora.

Science.gov (United States)

Traeger, Stefanie; Nowrousian, Minou

2015-04-14

During sexual development, filamentous ascomycetes form complex, three-dimensional fruiting bodies for the generation and dispersal of spores. In previous studies, we identified genes with evolutionary conserved expression patterns during fruiting body formation in several fungal species. Here, we present the functional analysis of two developmentally up-regulated genes, chs7 and sec22, in the ascomycete Sordaria macrospora. The genes encode a class VII (division III) chitin synthase and a soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) protein, respectively. Deletion mutants of chs7 had normal vegetative growth and were fully fertile but showed sensitivity toward cell wall stress. Deletion of sec22 resulted in a reduced number of ascospores and in defects in ascospore pigmentation and germination, whereas vegetative growth was normal in the mutant. A SEC22-EGFP fusion construct under control of the native sec22 promoter and terminator regions was expressed during different stages of sexual development. Expression of several development-related genes was deregulated in the sec22 mutant, including three genes involved in melanin biosynthesis. Our data indicate that chs7 is dispensable for fruiting body formation in S. macrospora, whereas sec22 is required for ascospore maturation and germination and thus involved in late stages of sexual development. Copyright © 2015 Traeger and Nowrousian.

46 CFR Sec. 8 - Extra work and changes.

Science.gov (United States)

2010-10-01

... Contractor may appeal such contract price or revised completion date as provided in Article 27 of the NSA... 46 Shipping 8 2010-10-01 2010-10-01 false Extra work and changes. Sec. 8 Section 8 Shipping... ACCOMPLISHMENT OF VESSEL REPAIRS UNDER NATIONAL SHIPPING AUTHORITY MASTER LUMP SUM REPAIR CONTRACT-NSA-LUMPSUMREP...

Sec16 in conventional and unconventional exocytosis: Working at the interface of membrane traffic and secretory autophagy?

Science.gov (United States)

Tang, Bor Luen

2017-12-01

Sec16 is classically perceived to be a scaffolding protein localized to the transitional endoplasmic reticulum (tER) or the ER exit sites (ERES), and has a conserved function in facilitating coat protein II (COPII) complex-mediated ER exit. Recent findings have, however, pointed toward a role for Sec16 in unconventional exocytosis of certain membrane proteins, such as the Cystic fibrosis transmembrane conductance regulator (CFTR) in mammalian cells, and possibly also α-integrin in certain contexts of Drosophila development. In this regard, Sec16 interacts with components of a recently deciphered pathway of stress-induced unconventional exocytosis, which is dependent on the tether protein Golgi reassembly stacking proteins (GRASPs) and the autophagy pathway. Intriguingly, Sec16 also appears to be post-translationally modified by autophagy-related signaling processes. Sec16 is known to be phosphorylated by the atypical extracellular signal regulated kinase 7 (Erk7) upon serum and amino acid starvation, both represent conditions that trigger autophagy. Recent work has also shown that Sec16 is phosphorylated, and thus regulated by the prominent autophagy-initiating Unc-51-like autophagy activating kinase 1 (Ulk1), as well as another autophagy modulator Leucine-rich repeat kinase 2 (Lrrk2). The picture emerging from Sec16's network of physical and functional interactors allows the speculation that Sec16 is situated (and may in yet undefined ways function) at the interface between COPII-mediated exocytosis of conventional vesicular traffic and the GRASP/autophagy-dependent mode of unconventional exocytosis. © 2017 Wiley Periodicals, Inc.

Institutional investors' reaction to SEC concerns about IFRS and US GAAP reporting

OpenAIRE

Miles, Gietzmann; Helena, Isidro

2013-01-01

For the period of 2006 to 2008, we collect Comment Letters issued by the SEC that question the application of US GAAP by US firms or the application of IFRS by European firms registered with the SEC. We investigate whether institutional investors react to the letters by changing their holdings and whether their responses vary for US registrants and European registrants. We do this via a treatment-effects model in which we test the hypothesis that institutional investors rebalance their portfo...

Apoptosis-linked Gene-2 (ALG-2)/Sec31 Interactions Regulate Endoplasmic Reticulum (ER)-to-Golgi Transport

Science.gov (United States)

Helm, Jared R.; Bentley, Marvin; Thorsen, Kevin D.; Wang, Ting; Foltz, Lauren; Oorschot, Viola; Klumperman, Judith; Hay, Jesse C.

2014-01-01

Luminal calcium released from secretory organelles has been suggested to play a regulatory role in vesicle transport at several steps in the secretory pathway; however, its functional roles and effector pathways have not been elucidated. Here we demonstrate for the first time that specific luminal calcium depletion leads to a significant decrease in endoplasmic reticulum (ER)-to-Golgi transport rates in intact cells. Ultrastructural analysis revealed that luminal calcium depletion is accompanied by increased accumulation of intermediate compartment proteins in COPII buds and clusters of unfused COPII vesicles at ER exit sites. Furthermore, we present several lines of evidence suggesting that luminal calcium affected transport at least in part through calcium-dependent interactions between apoptosis-linked gene-2 (ALG-2) and the Sec31A proline-rich region: 1) targeted disruption of ALG-2/Sec31A interactions caused severe defects in ER-to-Golgi transport in intact cells; 2) effects of luminal calcium and ALG-2/Sec31A interactions on transport mutually required each other; and 3) Sec31A function in transport required luminal calcium. Morphological phenotypes of disrupted ALG-2/Sec31A interactions were characterized. We found that ALG-2/Sec31A interactions were not required for the localization of Sec31A to ER exit sites per se but appeared to acutely regulate the stability and trafficking of the cargo receptor p24 and the distribution of the vesicle tether protein p115. These results represent the first outline of a mechanism that connects luminal calcium to specific protein interactions regulating vesicle trafficking machinery. PMID:25006245

78 FR 66355 - Pleasant Grove City, UT; Notice of Preliminary Determination of a Qualifying Conduit Hydropower...

Science.gov (United States)

2013-11-05

... City, UT; Notice of Preliminary Determination of a Qualifying Conduit Hydropower Facility and... Grove City, Utah (Pleasant Grove) filed a notice of intent to construct a qualifying conduit hydropower facility, pursuant to section 30 of the Federal Power Act, as amended by section 4 of the Hydropower...

Inactivation of protein translocation by cold-sensitive mutations in the yajC-secDF operon

NARCIS (Netherlands)

Nouwen, N; Driessen, AJM

2005-01-01

Most mutations in the yajC-secDF operon identified via genetic screens confer a cold-sensitive growth phenotype. Here we report that two of these mutations confer this cold-sensitive phenotype by inactivating the SecDF-YajC complex in protein translocation.

Kinetic Resolution of sec-Thiols via Enantioselective Oxidation with Rationally Engineered 5-(Hydroxymethyl)furfural Oxidase

NARCIS (Netherlands)

Pickl, Mathias; Swoboda, Alexander; Romero, Elvira; Winkler, Christoph; Binda, Claudia; Mattevi, Andrea; Faber, Kurt; Fraaije, Marco

2018-01-01

Various flavoprotein oxidases were recently shown to oxidize prim-thiols. Here we extend this reactivity towards sec-thiols via structure-guided engineering of 5-(hydroxymethyl)furfural oxidase (HMFO). The variants obtained were employed for the oxidative kinetic resolution of rac-sec-thiols

VizieR Online Data Catalog: Fermi LAT second source catalog (2FGL) (Nolan+, 2012)

Science.gov (United States)

Nolan, P. L.; Abdo, A. A.; Ackermann, M.; Ajello, M.; Allafort, A.; Antolini, E.; Atwood, W. B.; Axelsson, M.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bechtol, K.; Belfiore, A.; Bellazzini, R.; Berenji, B.; Bignami, G. F.; Blandford, R. D.; Bloom, E. D.; Bonamente, E.; Bonnell, J.; Borgland, A. W.; Bottacini, E.; Bouvier, A.; Brandt, T. J.; Bregeon, J.; Brigida, M.; Bruel, P.; Buehler, R.; Burnett, T. H.; Buson, S.; Caliandro, G. A.; Cameron, R. A.; Campana, R.; Canadas, B.; Cannon, A.; Caraveo, P. A.; Casandjian, J. M.; Cavazzuti, E.; Ceccanti, M.; Cecchi, C.; Celik, O.; Charles, E.; Chekhtman, A.; Cheung, C. C.; Chiang, J.; Chipaux, R.; Ciprini, S.; Claus, R.; Cohen-Tanugi, J.; Cominsky, L. R.; Conrad, J.; Corbet, R.; Cutini, S.; D'Ammando, F.; Davis, D. S.; de Angelis, A.; Decesar, M. E.; Deklotz, M.; de Luca A.; den Hartog, P. R.; de Palma, F.; Dermer, C. D.; Digel, S. W.; Do Couto, E. Silva E.; Drell, P. S.; Drlica-Wagner, A.; Dubois, R.; Dumora, D.; Enoto, T.; Escande, L.; Fabiani, D.; Falletti, L.; Favuzzi, C.; Fegan, S. J.; Ferrara, E. C.; Focke, W. B.; Fortin, P.; Frailis, M.; Fukazawa, Y.; Funk, S.; Fusco, P.; Gargano, F.; Gasparrini, D.; Gehrels, N.; Germani, S.; Giebels, B.; Giglietto, N.; Giommi, P.; Giordano, F.; Giroletti, M.; Glanzman, T.; Godfrey, G.; Grenier, I. A.; Grondin, M.-H.; Grove, J. E.; Guillemot, L.; Guiriec, S.; Gustafsson, M.; Hadasch, D.; Hanabata, Y.; Harding, A. K.; Hayashida, M.; Hays, E.; Hill, A. B.; Horan, D.; Hou, X.; Hughes, R. E.; Iafrate, G.; Itoh, R.; Johannesson, G.; Johnson, R. P.; Johnson, T. E.; Johnson, A. S.; Johnson, T. J.; Kamae, T.; Katagiri, H.; Kataoka, J.; Katsuta, J.; Kawai, N.; Kerr, M.; Knodlseder, J.; Kocevski, D.; Kuss, M.; Lande, J.; Landriu, D.; Latronico, L.; Lemoine-Goumard, M.; Lionetto, A. M.; Llena Garde, M.; Longo, F.; Loparco, F.; Lott, B.; Lovellette, M. N.; Lubrano, P.; Madejski, G. M.; Marelli, M.; Massaro, E.; Mazziotta, M. N.; McConville, W.; McEnery, J. E.; Mehault, J.; Michelson, P. F.; Minuti, M.; Mitthumsiri, W.; Mizuno, T.; Moiseev, A. A.; Mongelli, M.; Monte, C.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Murgia, S.; Nakamori, T.; Naumann-God, O. M.; Norris, J. P.; Nuss, E.; Nymark, T.; Ohno, M.; Ohsugi, T.; Okumura, A.; Omodei, N.; Orlando, E.; Ormes, J. F.; Ozaki, M.; Paneque, D.; Panetta, J. H.; Parent, D.; Perkins, J. S.; Pesce-Rollins, M.; Pierbattista, M.; Pinchera, M.; Piron, F.; Pivato, G.; Porter, T. A.; Racusin, J. L.; Raino, S.; Rando, R.; Razzano, M.; Razzaque, S.; Reimer, A.; Reimer, O.; Reposeur, T.; Ritz, S.; Rochester, L. S.; Romani, R. W.; Roth, M.; Rousseau, R.; Ryde, F.; Sadrozinski, H. F.-W.; Salvetti, D.; Sanchez, D. A.; Saz Parkinson, P. M.; Sbarra, C.; Scargle, J. D.; Schalk, T. L.; Sgro, C.; Shaw, M. S.; Shrader, C.; Siskind, E. J.; Smith, D. A.; Spandre, G.; Spinelli, P.; Stephens, T. E.; Strickman, M. S.; Suson, D. J.; Tajima, H.; Takahashi, H.; Takahashi, T.; Tanaka, T.; Thayer, J. G.; Thayer, J. B.; Thompson, D. J.; Tibaldo, L.; Tibolla, O.; Tinebra, F.; Tinivella, M.; Torres, D. F.; Tosti, G.; Troja, E.; Uchiyama, Y.; Vandenbroucke, J.; van Etten, A.; van Klaveren, B.; Vasileiou, V.; Vianello, G.; Vitale, V.; Waite, A. P.; Wallace, E.; Wang, P.; Werner, M.; Winer, B. L.; Wood, D. L.; Wood, K. S.; Wood, M.; Yang, Z.; Zimmer, S.

2012-06-01

This paper presents a catalog of high-energy γ-ray sources detected, in the 100MeV-100GeV energy range, in the first two years of the Fermi Gamma-ray Space Telescope mission by the Large Area Telescope (LAT), during the period 2008 August 4 (15:43 UTC)-2010 August 1 (01:17 UTC). (4 data files).

Phospho-Rasputin Stabilization by Sec16 Is Required for Stress Granule Formation upon Amino Acid Starvation

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Angelica Aguilera-Gomez

2017-07-01

Full Text Available Most cellular stresses induce protein translation inhibition and stress granule formation. Here, using Drosophila S2 cells, we investigate the role of G3BP/Rasputin in this process. In contrast to arsenite treatment, where dephosphorylated Ser142 Rasputin is recruited to stress granules, we find that, upon amino acid starvation, only the phosphorylated Ser142 form is recruited. Furthermore, we identify Sec16, a component of the endoplasmic reticulum exit site, as a Rasputin interactor and stabilizer. Sec16 depletion results in Rasputin degradation and inhibition of stress granule formation. However, in the absence of Sec16, pharmacological stabilization of Rasputin is not enough to rescue the assembly of stress granules. This is because Sec16 specifically interacts with phosphorylated Ser142 Rasputin, the form required for stress granule formation upon amino acid starvation. Taken together, these results demonstrate that stress granule formation is fine-tuned by specific signaling cues that are unique to each stress. These results also expand the role of Sec16 as a stress response protein.

High-Resolution Genetics Identifies the Lipid Transfer Protein Sec14p as Target for Antifungal Ergolines.

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Ireos Filipuzzi

2016-11-01

Full Text Available Invasive infections by fungal pathogens cause more deaths than malaria worldwide. We found the ergoline compound NGx04 in an antifungal screen, with selectivity over mammalian cells. High-resolution chemogenomics identified the lipid transfer protein Sec14p as the target of NGx04 and compound-resistant mutations in Sec14p define compound-target interactions in the substrate binding pocket of the protein. Beyond its essential lipid transfer function in a variety of pathogenic fungi, Sec14p is also involved in secretion of virulence determinants essential for the pathogenicity of fungi such as Cryptococcus neoformans, making Sec14p an attractive antifungal target. Consistent with this dual function, we demonstrate that NGx04 inhibits the growth of two clinical isolates of C. neoformans and that NGx04-related compounds have equal and even higher potency against C. neoformans. Furthermore NGx04 analogues showed fungicidal activity against a fluconazole resistant C. neoformans strain. In summary, we present genetic evidence that NGx04 inhibits fungal Sec14p and initial data supporting NGx04 as a novel antifungal starting point.

Diagnostic usefulness of {sup 18}F-FAMT PET and L-type amino acid transporter 1 (LAT1) expression in oral squamous cell carcinoma

Energy Technology Data Exchange (ETDEWEB)

Nobusawa, Aiko [Gunma University Graduate School of Medicine, Department of Stomatology and Maxillofacial Surgery, Maebashi, Gunma (Japan); Gunma University Graduate School of Medicine, Department of Diagnostic Pathology, Maebashi, Gunma (Japan); Kim, Mai [Gunma University Graduate School of Medicine, Department of Stomatology and Maxillofacial Surgery, Maebashi, Gunma (Japan); Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Kaira, Kyoichi [Gunma University Graduate School of Medicine, Department of Diagnostic Pathology, Maebashi, Gunma (Japan); Gunma University Hospital, Oncology Center, Maebashi, Gunma (Japan); Miyashita, Go; Negishi, Akihide; Yokoo, Satoshi [Gunma University Graduate School of Medicine, Department of Stomatology and Maxillofacial Surgery, Maebashi, Gunma (Japan); Oriuchi, Noboru; Higuchi, Tetsuya; Tsushima, Yoshito [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Kanai, Yoshikatsu [Osaka University, Division of Bio-system Pharmacology, Graduate School of Medicine, Osaka (Japan); Oyama, Tetsunari [Gunma University Graduate School of Medicine, Department of Diagnostic Pathology, Maebashi, Gunma (Japan)

2013-10-15

l-[3-{sup 18}F]-{alpha}-Methyltyrosine ({sup 18}F-FAMT) was developed as an amino acid tracer for PET imaging to provide better specificity than 2-[{sup 18}F]fluoro-2-deoxy-d-glucose ({sup 18}F-FDG) PET for cancer diagnosis. We investigated the diagnostic usefulness of {sup 18}F-FAMT in oral squamous cell carcinoma (OSCC). The correlation between tumour uptake of {sup 18}F-FAMT and L-type amino acid transporter 1 (LAT1) expression was determined. The study group comprised 68 OSCC patients who underwent both {sup 18}F-FAMT and {sup 18}F-FDG PET. Resected tumour sections were stained by immunohistochemistry for LAT1, CD98 and Ki-67, and microvessel density was determined in terms of CD34 and p53 expression. The sensitivity of primary tumour detection by {sup 18}F-FAMT and {sup 18}F-FDG PET was 98 % and 100 %, respectively. The sensitivity, specificity and accuracy of {sup 18}F-FAMT PET for detecting malignant lymph nodes were 68 %, 99 % and 97 %, respectively, and equivalent values for {sup 18}F-FDG PET were 84 %, 94 % and 94 %, respectively. The specificity and accuracy of {sup 18}F-FAMT were significantly higher than those of {sup 18}F-FDG. The uptake of {sup 18}F-FAMT was significantly correlated with LAT1 expression, cell proliferation and advanced stage. The expression of LAT1 in OSCC cells was closely correlated with CD98 levels, cell proliferation and angiogenesis. {sup 18}F-FAMT PET showed higher specificity for detecting malignant lesions than {sup 18}F-FDG PET. The uptake of {sup 18}F-FAMT by OSCC cells can be determined by the presence of LAT1 expression and tumour cell proliferation. (orig.)

Mechanism of conformational coupling in SecA: Key role of hydrogen-bonding networks and water interactions.

Science.gov (United States)

Milenkovic, Stefan; Bondar, Ana-Nicoleta

2016-02-01

SecA uses the energy yielded by the binding and hydrolysis of adenosine triphosphate (ATP) to push secretory pre-proteins across the plasma membrane in bacteria. Hydrolysis of ATP occurs at the nucleotide-binding site, which contains the conserved carboxylate groups of the DEAD-box helicases. Although crystal structures provide valuable snapshots of SecA along its reaction cycle, the mechanism that ensures conformational coupling between the nucleotide-binding site and the other domains of SecA remains unclear. The observation that SecA contains numerous hydrogen-bonding groups raises important questions about the role of hydrogen-bonding networks and hydrogen-bond dynamics in long-distance conformational couplings. To address these questions, we explored the molecular dynamics of SecA from three different organisms, with and without bound nucleotide, in water. By computing two-dimensional hydrogen-bonding maps we identify networks of hydrogen bonds that connect the nucleotide-binding site to remote regions of the protein, and sites in the protein that respond to specific perturbations. We find that the nucleotide-binding site of ADP-bound SecA has a preferred geometry whereby the first two carboxylates of the DEAD motif bridge via hydrogen-bonding water. Simulations of a mutant with perturbed ATP hydrolysis highlight the water-bridged geometry as a key structural element of the reaction path. Copyright © 2015. Published by Elsevier B.V.

CLUES on Fermi-LAT prospects for the extragalactic detection of {mu}{nu}SSM gravitino dark matter

Energy Technology Data Exchange (ETDEWEB)

Gomez-Vargas, G.A., E-mail: germanarturo.gomez@uam.es [Departamento de Fisica Teorica, Universidad Autonoma de Madrid, Cantoblanco, E-28049 Madrid (Spain); Instituto de Fisica Teorica IFT-UAM/CSIC, Universidad Autonoma de Madrid, Cantoblanco, E-28049 Madrid (Spain); Istituto Nazionale di Fisica Nucleare, Sez. Roma Tor Vergata, Roma (Italy)

2012-11-11

The {mu}{nu}SSM is a supersymmetric model that has been proposed to solve the problems generated by other supersymmetric extensions of the standard model of particle physics. Given that R-parity is broken in the {mu}{nu}SSM, the gravitino is a natural candidate for decaying dark matter since its lifetime becomes much longer than the age of the Universe. In this model, gravitino dark matter could be detectable through the emission of a monochromatic gamma ray in a two-body decay. We study the prospects of the Fermi-LAT telescope to detect such monochromatic lines in 5 years of observations of the most massive nearby extragalactic objects. We focus on the Virgo galaxy cluster, since it is associated to a particularly high signal-to-noise ratio and is located at high Galactic latitude. The simulation of both signal and background gamma-ray events is carried out with the Fermi Science Tools, and the dark matter distribution around Virgo is taken from an N-body simulation, with constrained initial conditions provided by the CLUES project. We find that a gravitino with a mass range of 0.6-2 GeV, and with a lifetime range of about 3 Multiplication-Sign 10{sup 27}-2 Multiplication-Sign 10{sup 28}s would be detectable by the Fermi-LAT with a signal-to-noise ratio larger than 3. We also obtain that gravitino masses larger than about 4 GeV are already excluded in the {mu}{nu}SSM by Fermi-LAT data of the galactic halo. These proceedings are based on Ref. [1].

76 FR 28074 - Notice of Inventory Completion: Utah Museum of Natural History, Salt Lake City, UT

Science.gov (United States)

2011-05-13

... of the Utah Museum of Natural History, Salt Lake City, UT. The human remains were removed from Snow.... A detailed assessment of the human remains was made by the Utah Museum of Natural History... with the human remains should contact Duncan Metcalfe, Utah Museum of Natural History, 1390 E...

Evolutionary conservation of dual Sec translocases in the cyanelles of Cyanophora paradoxa

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Löffelhardt Wolfgang

2008-11-01

Full Text Available Abstract Background Cyanelles, the peptidoglycan-armored plastids of glaucocystophytes, occupy a unique bridge position in between free-living cyanobacteria and chloroplasts. In some respects they side with cyanobacteria whereas other features are clearly shared with chloroplasts. The Sec translocase, an example for "conservative sorting" in the course of evolution, is found in the plasma membrane of all prokaryotes, in the thylakoid membrane of chloroplasts and in both these membrane types of cyanobacteria. Results In this paper we present evidence for a dual location of the Sec translocon in the thylakoid as well as inner envelope membranes of the cyanelles from Cyanophora paradoxa, i. e. conservative sorting sensu stricto. The prerequisite was the generation of specific antisera directed against cyanelle SecY that allowed immunodetection of the protein on SDS gels from both membrane types separated by sucrose density gradient floatation centrifugation. Immunoblotting of blue-native gels yielded positive but differential results for both the thylakoid and envelope Sec complexes, respectively. In addition, heterologous antisera directed against components of the Toc/Tic translocons and binding of a labeled precursor protein were used to discriminate between inner and outer envelope membranes. Conclusion The envelope translocase can be envisaged as a prokaryotic feature missing in higher plant chloroplasts but retained in cyanelles, likely for protein transport to the periplasm. Candidate passengers are cytochrome c6 and enzymes of peptidoglycan metabolism. The minimal set of subunits of the Toc/Tic translocase of a primitive plastid is proposed.

14 CFR Sec. 2-1 - Generally accepted accounting principles.

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2010-01-01

...). Persons subject to this part are authorized to implement, as prescribed by the Financial Accounting... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Generally accepted accounting principles... AIR CARRIERS General Accounting Provisions Sec. 2-1 Generally accepted accounting principles. (a) The...

46 CFR Sec. 3 - Application for remission of duties.

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2010-10-01

... Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL SHIPPING AUTHORITY GENERAL AGENT'S RESPONSIBILITY IN CONNECTION WITH FOREIGN REPAIR CUSTOM'S ENTRIES Sec. 3 Application for remission... District Director of Customs as defined in 19 CFR 1.1(d) if the following circumstances prevail: (a) When...

46 CFR Sec. 5 - Procedure for negotiated price awards.

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2010-10-01

... shall be furnished with the information provided for in Article 1(a) of the NSA-LUMPSUMREP Contract. (b... Article 27 of the NSA-LUMPSUMREP Contract. ... 46 Shipping 8 2010-10-01 2010-10-01 false Procedure for negotiated price awards. Sec. 5 Section 5...

Thyrotoxic periodic paralysis associated with a mutation in the sodium channel gene SCN4A.

Science.gov (United States)

Lane, Andrew H; Markarian, Katherine; Braziunene, Ieva

2004-12-01

Thyrotoxic hypokalemic periodic paralysis (THypoKPP) is an uncommon disorder with an unknown etiology. We describe a family in which the proband presented with paralysis and thyrotoxicosis. Because of similarities between familial hypokalemic periodic paralysis (FHypoKPP) and THypoKPP, we sequenced exon 12 of the SCN4A gene, which is known to be mutated in FHypoKPP. We identified an Arg672Ser mutation in the proband and his affected father, as well as the proband's brother. As the brother has paralysis without thyrotoxicosis, our finding suggests that the genetic spectrum of FHypoKPP and THypoKPP overlap. We speculate that thyroid hormone may exert a threshold or permissive effect in hypokalemic periodic paralysis. Non-thyrotoxic family members of individuals with THypoKPP may have an unrecognized risk for paralysis.

Identification and characterization of a novel protective antigen, Sec_205 of Streptococcus equi ssp. Zooepidemicus.

Science.gov (United States)

Liang, Huihuang; Tang, Bin; Zhao, Pengpeng; Deng, Mingyong; Yan, Lili; Zhai, Pan; Wei, Zigong

2018-02-01

Streptococcus equi ssp. zooepidemicus (SEZ) is an important pathogen of swine streptococcal diseases and can infect a wide range of animals as well as human beings. The absence of effective vaccine confounds the control of SEZ infection. Sec_205, a novel protein identified in the previous study, was inducibly over-expressed in Escherichia coli in the present study. The purified recombinant protein could elicit a significant humoral antibody response and provide efficient protection against lethal challenge of SEZ C55138 in mouse model. The protection against SEZ infection was mediated by specific antibodies to Sec_205 to some extent and was identified by the passive protection assay. The Sec_205 was an in vivo-induced antigen confirmed by the real-time PCR and could adhere to the Hep-2 cells by the inhibition assay. These suggest that Sec_205 may play a vital role in pathogenicity and serve as a new vaccine candidate against SEZ infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

Estudo das latências e amplitudes dos potenciais evocados auditivos de média latência em indivíduos audiologicamente normais Middle latency response study of auditory evoked potentials’ amplitudes and lantencies audiologically normal individuals

Directory of Open Access Journals (Sweden)

Ivone Ferreira Neves

2007-02-01

Full Text Available Estudo de coorte contemporânea com corte transversal. O Potencial Evocado Auditivo de Média Latência (PEAML é gerado entre 10 e 80ms e possui múltiplos geradores, com maior contribuição da região tálamo-cortical. O estabelecimento de critérios de normalidade para os valores de latência e amplitude é necessário para uso clínico. OBJETIVOS: Analisar a latência e amplitude do PEAML em indivíduos sem alterações audiológicas, e verificar a confiabilidade da amplitude Pa-Nb. MATERIAL E MÉTODO: Foram coletados os PEAML de 25 indivíduos durante o ano de 2005 e analisados os componentes Na, Pa, Nb para cada orelha testada (A1 e A2, e posicionamento de eletrodo (C3 e C4. RESULTADOS: Observou-se diferença estatisticamente significante entre os valores médios de latência para C3A1 e C4A1 com relação aos componentes Na e Pa, não sendo encontrada esta diferença para o componente Nb e valores médios das amplitudes Na-Pa e Pa-Nb. CONCLUSÃO: Foram estabelecidos os valores das médias e desvios padrão para os parâmetros latência e amplitude dos componentes Na, Pa, Nb, e Na-Pa e Pa-Nb, nas condições C3A1, C4A1, C3A2, C4A2, proporcionando os parâmetros para a análise e interpretação deste potencial.Contemporary cohort cross-sectional study. Introduction: The auditory middle latency response (AMLR is generated between 10 and 80 ms and has multiple generators, with a greater contribution from the thalamus-cortical pathways. The establishment of normality criteria for latency and amplitude values is necessary for clinical use. AIM: to analyze the latency and amplitude of the AMLR in individuals without audiological disorders, and verify the reliability of Pa-Nb amplitude. MATERIALS AND METHODS: The AMLR of 25 individuals was collected during 2005 and the Na, Pa, Nb components were analyzed for each tested ear (A1 and A2, and electrode positioning (C3 and C4. RESULTS: A statistically significant difference was noticed among middle

Shear-wave elastography for breast masses: local shear wave speed (m/sec) versus Young modulus (kPa).

Science.gov (United States)

Youk, Ji Hyun; Son, Eun Ju; Park, Ah Young; Kim, Jeong-Ah

2014-01-01

To evaluate and compare the performance of shear-wave elastography (SWE) for breast masses using the local shear wave speed (m/sec) vs. Young modulus (kPa). A total of 130 breast lesions in 123 women who underwent SWE before ultrasound- guided core needle biopsy or surgical excision were included. With the region-of-interest placed over the stiffest areas of the lesion on SWE, the quantitative mean, maximum, and standard deviation (SD) of the elasticity values were measured in kPa and m/sec for each lesion. The SD was also measured with the region-of-interest including the whole breast lesion (wSD). The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of each elasticity value measured in kPa and m/sec were compared. Of the 130 lesions, 49 (37.7%) were malignant and 81 (62.3%) were benign. The AUCs for the mean, maximum, and SD of the elasticity values using kPa and m/sec did not differ significantly: mean, 0.974 vs. 0.974; maximum, 0.960 vs. 0.976; SD, 0.916 vs. 0.916. However, the AUC for wSD showed a significant difference: 0.964 (kPa) vs. 0.960 (m/sec) (P=0.036). There was no significant difference in the sensitivity and specificity of the mean, maximum, and wSD of the elasticity values. However, the specificity of the SD was significantly different between the two different measurements: 95.1% (kPa) vs. 87.7% (m/sec) (P=0.031). The quantitative elasticity values measured in kPa and m/sec on SWE showed good diagnostic performance. The specificity of the SD and AUC of the wSD measured in kPa were significantly higher than those measured in m/sec.

Shear-wave elastography for breast masses: local shear wave speed (m/sec) versus Young modulus (kPa)

Energy Technology Data Exchange (ETDEWEB)

Youk, Ji Hyun; Son, Eun Ju; Park, Ah Young; Kim, Jeong Ah [Dept. of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2014-03-15

To evaluate and compare the performance of shear-wave elastography (SWE) for breast masses using the local shear wave speed (m/sec) vs. Young modulus (kPa). A total of 130 breast lesions in 123 women who underwent SWE before ultrasound- guided core needle biopsy or surgical excision were included. With the region-of-interest placed over the stiffest areas of the lesion on SWE, the quantitative mean, maximum, and standard deviation (SD) of the elasticity values were measured in kPa and m/sec for each lesion. The SD was also measured with the region-of-interest including the whole breast lesion (wSD). The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of each elasticity value measured in kPa and m/sec were compared. Of the 130 lesions, 49 (37.7%) were malignant and 81 (62.3%) were benign. The AUCs for the mean, maximum, and SD of the elasticity values using kPa and m/sec did not differ significantly: mean, 0.974 vs. 0.974; maximum, 0.960 vs. 0.976; SD, 0.916 vs. 0.916. However, the AUC for wSD showed a significant difference: 0.964 (kPa) vs. 0.960 (m/sec) (P=0.036). There was no significant difference in the sensitivity and specificity of the mean, maximum, and wSD of the elasticity values. However, the specificity of the SD was significantly different between the two different measurements: 95.1% (kPa) vs. 87.7% (m/sec) (P=0.031). The quantitative elasticity values measured in kPa and m/sec on SWE showed good diagnostic performance. The specificity of the SD and AUC of the wSD measured in kPa were significantly higher than those measured in m/sec.

Shear-wave elastography for breast masses: local shear wave speed (m/sec) versus Young modulus (kPa)

International Nuclear Information System (INIS)

Youk, Ji Hyun; Son, Eun Ju; Park, Ah Young; Kim, Jeong Ah

2014-01-01

To evaluate and compare the performance of shear-wave elastography (SWE) for breast masses using the local shear wave speed (m/sec) vs. Young modulus (kPa). A total of 130 breast lesions in 123 women who underwent SWE before ultrasound- guided core needle biopsy or surgical excision were included. With the region-of-interest placed over the stiffest areas of the lesion on SWE, the quantitative mean, maximum, and standard deviation (SD) of the elasticity values were measured in kPa and m/sec for each lesion. The SD was also measured with the region-of-interest including the whole breast lesion (wSD). The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of each elasticity value measured in kPa and m/sec were compared. Of the 130 lesions, 49 (37.7%) were malignant and 81 (62.3%) were benign. The AUCs for the mean, maximum, and SD of the elasticity values using kPa and m/sec did not differ significantly: mean, 0.974 vs. 0.974; maximum, 0.960 vs. 0.976; SD, 0.916 vs. 0.916. However, the AUC for wSD showed a significant difference: 0.964 (kPa) vs. 0.960 (m/sec) (P=0.036). There was no significant difference in the sensitivity and specificity of the mean, maximum, and wSD of the elasticity values. However, the specificity of the SD was significantly different between the two different measurements: 95.1% (kPa) vs. 87.7% (m/sec) (P=0.031). The quantitative elasticity values measured in kPa and m/sec on SWE showed good diagnostic performance. The specificity of the SD and AUC of the wSD measured in kPa were significantly higher than those measured in m/sec.

Identification of SEC62 as a potential marker for 3q amplification and cellular migration in dysplastic cervical lesions

International Nuclear Information System (INIS)

Linxweiler, Maximilian; Bochen, Florian; Schick, Bernhard; Wemmert, Silke; Al Kadah, Basel; Greiner, Markus; Hasenfus, Andrea; Bohle, Rainer-Maria; Juhasz-Böss, Ingolf; Solomayer, Erich-Franz; Takacs, Zoltan Ferenc

2016-01-01

Chromosome 3 amplification affecting the 3q26 region is a common genomic alteration in cervical cancer, typically marking the transition of precancerous intraepithelial lesions to an invasive phenotype. Though potential 3q encoded target genes of this amplification have been identified, a functional correlation of potential oncogenic function is still missing. In this study, we investigated copy number changes and the expression level of SEC62 encoded at 3q26.2 as a new potential 3q oncogene in dysplastic cervical lesions and analyzed its role in cervical cancer cell biology. Expression levels of Sec62 and vimentin were analyzed in liquid based cytology specimens from 107 women with varying grades of cervical dysplasia ranging from normal cases to cancer by immunofluorescence cytology. Additionally, a subset of 20 representative cases was used for FISH analyses targeting SEC62. To further explore the functional role of Sec62 in cervical cancer, HeLa cells were transfected with a SEC62 plasmid or SEC62 siRNA and analyzed for their proliferation and migration potential using real-time monitoring and trans-well systems as well as changes in the expression of EMT markers. FISH analyses of the swabbed cells showed a rising number of SEC62 gains and amplifications correlating to the grade of dysplasia with the highest incidence in high grade squamous intraepithelial lesions and squamous cell carcinomas. When analyzing the expression level of Sec62 and vimentin, we found a gradually increasing expression level of both proteins according to the severity of the dysplasia. In functional analyses, SEC62 silencing inhibited and SEC62 overexpression stimulated the migration of HeLa cells with only marginal effects on cell proliferation, the expression level of EMT markers and the cytoskeleton structure. Our study suggests SEC62 as a target gene of 3q26 amplification and a stimulator of cellular migration in dysplastic cervical lesions. Hence, SEC62 could serve as a potential

Radio Detection of the Fermi-LAT Blind Search Millisecond Pulsar J1311-3430

Science.gov (United States)

Ray, P. S.; Ransom, S. M.; Cheung, C. C.; Giroletti, M.; Cognard, I.; Camilo, F.; Bhattacharyya, B.; Roy, J.; Romani, R. W.; Ferrara, E. C.; Guillemot, L.; Johnston, S.; Keith, M.; Kerr, M.; Kramer, M.; Pletsch, H. J.; Saz Parkinson, P. M.; Wood, K. S.

2013-01-01

We report the detection of radio emission from PSR J1311-3430, the first millisecond pulsar (MSP) discovered in a blind search of Fermi Large Area Telescope (LAT) gamma-ray data. We detected radio pulsations at 2 GHz, visible for delay in the radio pulses as the pulsar appears from eclipse and we speculate on possible mechanisms for the non-detections of the pulse at other orbital phases and observing frequencies.

Copper(I) Thiocyanate (CuSCN) Hole-Transport Layers Processed from Aqueous Precursor Solutions and Their Application in Thin-Film Transistors and Highly Efficient Organic and Organometal Halide Perovskite Solar Cells

KAUST Repository

Wijeyasinghe, Nilushi; Regoutz, Anna; Eisner, Flurin; Du, Tian; Tsetseris, Leonidas; Lin, Yen-Hung; Faber, Hendrik; Pattanasattayavong, Pichaya; Li, Jinhua; Yan, Feng; McLachlan, Martyn A.; Payne, David J.; Heeney, Martin; Anthopoulos, Thomas D.

2017-01-01

spectra agree with first-principles calculations. Study of the hole-transport properties using field-effect transistor measurements reveals that the aqueous-processed CuSCN layers exhibit a fivefold higher hole mobility than films processed from diethyl

Constraints on the Galactic Halo Dark Matter from Fermi-LAT Diffuse Measurements

Science.gov (United States)

Ackermann, M.; Ajello, M.; Atwood, W. B.; Baldini, L.; Barbiellini, G.; Bastieri, D.; Bechtol, K.; Bellazzini, R.; Blandford, R. D.; Bloom, E. D.;

Fission yeast Sec3 and Exo70 are transported on actin cables and localize the exocyst complex to cell poles.

Directory of Open Access Journals (Sweden)

Felipe O Bendezú

Full Text Available The exocyst complex is essential for many exocytic events, by tethering vesicles at the plasma membrane for fusion. In fission yeast, polarized exocytosis for growth relies on the combined action of the exocyst at cell poles and myosin-driven transport along actin cables. We report here the identification of fission yeast Schizosaccharomyces pombe Sec3 protein, which we identified through sequence homology of its PH-like domain. Like other exocyst subunits, sec3 is required for secretion and cell division. Cells deleted for sec3 are only conditionally lethal and can proliferate when osmotically stabilized. Sec3 is redundant with Exo70 for viability and for the localization of other exocyst subunits, suggesting these components act as exocyst tethers at the plasma membrane. Consistently, Sec3 localizes to zones of growth independently of other exocyst subunits but depends on PIP(2 and functional Cdc42. FRAP analysis shows that Sec3, like all other exocyst subunits, localizes to cell poles largely independently of the actin cytoskeleton. However, we show that Sec3, Exo70 and Sec5 are transported by the myosin V Myo52 along actin cables. These data suggest that the exocyst holocomplex, including Sec3 and Exo70, is present on exocytic vesicles, which can reach cell poles by either myosin-driven transport or random walk.

Phospho-Rasputin Stabilization by Sec16 Is Required for Stress Granule Formation upon Amino Acid Starvation.

Science.gov (United States)

Aguilera-Gomez, Angelica; Zacharogianni, Margarita; van Oorschot, Marinke M; Genau, Heide; Grond, Rianne; Veenendaal, Tineke; Sinsimer, Kristina S; Gavis, Elizabeth R; Behrends, Christian; Rabouille, Catherine

2017-07-25

Most cellular stresses induce protein translation inhibition and stress granule formation. Here, using Drosophila S2 cells, we investigate the role of G3BP/Rasputin in this process. In contrast to arsenite treatment, where dephosphorylated Ser142 Rasputin is recruited to stress granules, we find that, upon amino acid starvation, only the phosphorylated Ser142 form is recruited. Furthermore, we identify Sec16, a component of the endoplasmic reticulum exit site, as a Rasputin interactor and stabilizer. Sec16 depletion results in Rasputin degradation and inhibition of stress granule formation. However, in the absence of Sec16, pharmacological stabilization of Rasputin is not enough to rescue the assembly of stress granules. This is because Sec16 specifically interacts with phosphorylated Ser142 Rasputin, the form required for stress granule formation upon amino acid starvation. Taken together, these results demonstrate that stress granule formation is fine-tuned by specific signaling cues that are unique to each stress. These results also expand the role of Sec16 as a stress response protein. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

An adaptive-binning method for generating constant-uncertainty/constant-significance light curves with Fermi-LAT data

International Nuclear Information System (INIS)

Lott, B.; Escande, L.; Larsson, S.; Ballet, J.

2012-01-01

Here, we present a method enabling the creation of constant-uncertainty/constant-significance light curves with the data of the Fermi-Large Area Telescope (LAT). The adaptive-binning method enables more information to be encapsulated within the light curve than with the fixed-binning method. Although primarily developed for blazar studies, it can be applied to any sources. Furthermore, this method allows the starting and ending times of each interval to be calculated in a simple and quick way during a first step. The reported mean flux and spectral index (assuming the spectrum is a power-law distribution) in the interval are calculated via the standard LAT analysis during a second step. In the absence of major caveats associated with this method Monte-Carlo simulations have been established. We present the performance of this method in determining duty cycles as well as power-density spectra relative to the traditional fixed-binning method.

46 CFR Sec. 6 - Disbursements at other domestic ports.

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2010-10-01

... invoices from such advances and make proper accounting to the agent for each advance supported by invoices... RULES FOR FINANCIAL TRANSACTIONS UNDER AGENCY AGREEMENTS Disbursements Sec. 6 Disbursements at other... agent may advance from time to time from the joint bank account the funds necessary to meet the...

Péritonite aigue généralisée par perforation utérine post abortum à ...

African Journals Online (AJOL)

Péritonite aigue généralisée par perforation utérine post abortum à propos d'une observation. Ibrahima Ka, Papa Saloum Diop, Amadou Bocar Niang, Alioucoly Faye, Jean Marck Ndoye, Babacar Fall ...

Radio Detection of the Fermi-LAT Blind Search Millisecond Pulsar J1311-3430

Science.gov (United States)

Ray, P. S.; Ransom, S. M.; Cheung, C. C.; Giroletti, M.; Cognard, I.; Camilo, F.; Bhattacharyya, B.; Roy, J.; Romani, R. W.; Ferrara, E. C.;

EINSTEIN@HOME DISCOVERY OF FOUR YOUNG GAMMA-RAY PULSARS IN FERMI LAT DATA

Energy Technology Data Exchange (ETDEWEB)

Pletsch, H. J.; Allen, B.; Aulbert, C.; Bock, O.; Eggenstein, H. B.; Fehrmann, H.; Machenschalk, B.; Papa, M. A. [Max-Planck-Institut für Gravitationsphysik (Albert-Einstein-Institut), D-30167 Hannover (Germany); Guillemot, L.; Champion, D. J.; Karuppusamy, R.; Kramer, M.; Ng, C. [Max-Planck-Institut für Radioastronomie, Auf dem Hügel 69, D-53121 Bonn (Germany); Anderson, D. [Space Sciences Laboratory, University of California, Berkeley, CA 94720 (United States); Hammer, D.; Siemens, X. [Department of Physics, University of Wisconsin-Milwaukee, Milwaukee, WI 53201 (United States); Keith, M. [CSIRO Astronomy and Space Science, Australia Telescope National Facility (Australia); Ray, P. S., E-mail: holger.pletsch@aei.mpg.de, E-mail: lucas.guillemot@cnrs-orleans.fr [Space Science Division, Naval Research Laboratory, Washington, DC 20375-5352 (United States)

2013-12-10

We report the discovery of four gamma-ray pulsars, detected in computing-intensive blind searches of data from the Fermi Large Area Telescope (LAT). The pulsars were found using a novel search approach, combining volunteer distributed computing via Einstein@Home and methods originally developed in gravitational-wave astronomy. The pulsars PSRs J0554+3107, J1422–6138, J1522–5735, and J1932+1916 are young and energetic, with characteristic ages between 35 and 56 kyr and spin-down powers in the range 6 × 10{sup 34}—10{sup 36} erg s{sup –1}. They are located in the Galactic plane and have rotation rates of less than 10 Hz, among which the 2.1 Hz spin frequency of PSR J0554+3107 is the slowest of any known gamma-ray pulsar. For two of the new pulsars, we find supernova remnants coincident on the sky and discuss the plausibility of such associations. Deep radio follow-up observations found no pulsations, suggesting that all four pulsars are radio-quiet as viewed from Earth. These discoveries, the first gamma-ray pulsars found by volunteer computing, motivate continued blind pulsar searches of the many other unidentified LAT gamma-ray sources.

Study of the boxlike dark matter signals from dwarf spheroidal galaxies with Fermi-LAT data

Science.gov (United States)

Li, Shang; Liang, Yun-Feng; Xia, Zi-Qing; Zu, Lei; Duan, Kai-Kai; Shen, Zhao-Qiang; Feng, Lei; Yuan, Qiang; Fan, Yi-Zhong

2018-04-01

The observation of a special spectral feature in the gamma-ray data would be one of the best ways to identify dark matter (DM). The box-shaped gamma-ray spectra could be generated by the decay of intermediate particles produced by DM annihilation or decay. It provides another kind of signal that can be relatively easily distinguished from astrophysical backgrounds besides the linelike signals. Dwarf spheroidal galaxies are expected to be dominated by DM and may be one of the most promising targets for indirect DM searches. In this paper, we study the box-shaped DM signals with Fermi-LAT observations of dwarf spheroidal galaxies. We analyze 106 months of Fermi-LAT data to derive the upper limits on the annihilation cross section or the decay timescale of DM. In addition, we compare the results for different sample selections and DM density distributions. We expect that more dwarf spheroidal galaxies will be found and the sensitivity of box-shaped gamma-ray signal searches will be significantly improved in the future.

Search for Large Extra Dimensions Based on Observations of Neutron Stars with the Fermi-LAT

Energy Technology Data Exchange (ETDEWEB)

Berenji, Bijan [Stanford Univ., CA (United States)

2012-09-19

Large extra dimensions (LED) have been proposed to account for the apparent weakness of gravitation. These theories also indicate that the postulated massive Kaluza-Klein (KK) gravitons may be produced by nucleon-nucleon bremsstrahlung in the course of core collapse of supernovae. Hannestad and Raffelt have predicted energy spectra of gamma ray emission from the decay of KK gravitons trapped by the gravity of the remnant neutron stars (NS). These and other authors have used EGRET data on NS to obtain stringent limits on LED. Fermi-LAT is observing radio pulsar positions obtained from radio and x-ray catalogs. NS with certain characteristics are unlikely emitter of gamma rays, and emit in radio and perhaps x-rays. This talk will focus on the blind analysis we plan to perform, which has been developed using the 1st 2 months of all sky data and Monte Carlo simulations, to obtain limits on LED based on about 1 year of Fermi-LAT data. Preliminary limits from this analysis using these first 2 months of data will be also be discussed.

CLUES on Fermi-LAT prospects for the extragalactic detection of μνSSM gravitino dark matter

Energy Technology Data Exchange (ETDEWEB)

Gómez-Vargas, G.A.; Muñoz, C.; Yepes, G. [Departamento de Física Teórica, Universidad Autónoma de Madrid, Cantoblanco, E-28049, Madrid (Spain); Fornasa, M.; Zandanel, F.; Prada, F. [Instituto de Astrofísica de Andalucía (CSIC), E-18008, Granada (Spain); Cuesta, A.J., E-mail: germanarturo.gomez@uam.es, E-mail: mattia@iaa.es, E-mail: fabio@iaa.es, E-mail: antonio.cuesta@yale.edu, E-mail: carlos.munnoz@uam.es, E-mail: fprada@iaa.es, E-mail: gustavo.yepes@uam.es [Yale Center for Astronomy and Astrophysics, Yale University, CT 06511, New Haven (United States)

2012-02-01

The μνSSM is a supersymmetric model that has been proposed to solve the problems generated by other supersymmetric extensions of the standard model of particle physics. Given that R-parity is broken in the μνSSM, the gravitino is a natural candidate for decaying dark matter since its lifetime becomes much longer than the age of the Universe. In this model, gravitino dark matter could be detectable through the emission of a monochromatic gamma ray in a two-body decay. We study the prospects of the Fermi-LAT telescope to detect such monochromatic lines in 5 years of observations of the most massive nearby extragalactic objects. The dark matter halo around the Virgo galaxy cluster is selected as a reference case, since it is associated to a particularly high signal-to-noise ratio and is located in a region scarcely affected by the astrophysical diffuse emission from the galactic plane. The simulation of both signal and background gamma-ray events is carried out with the Fermi Science Tools, and the dark matter distribution around Virgo is taken from a N-body simulation of the nearby extragalactic Universe, with constrained initial conditions provided by the CLUES project. We find that a gravitino with a mass range of 0.6–2 GeV, and with a lifetime range of about 3 × 10{sup 27}–2 × 10{sup 28} s would be detectable by the Fermi-LAT with a signal-to-noise ratio larger than 3. We also obtain that gravitino masses larger than about 4 GeV are already excluded in the μνSSM by Fermi-LAT data of the galactic halo.

Fermi/LAT observations of dwarf galaxies highly constrain a dark matter interpretation of excess positrons seen in AMS-02, HEAT, and PAMELA

Energy Technology Data Exchange (ETDEWEB)

López, Alejandro [Michigan Center for Theoretical Physics, University of Michigan – Ann Arbor, 450 Church St., Ann Arbor (United States); Savage, Christopher [Nordita (Nordic Institute for Theoretical Physics), KTH Royal Institute of Technology and Stockholm University, Roslagstullsbacken 23, Stockholm (Sweden); Spolyar, Douglas; Adams, Douglas Q., E-mail: aolopez@umich.edu, E-mail: chris@savage.name, E-mail: dspolyar@gmail.com, E-mail: doug.q.adams@gmail.com [Oskar Klein Centre for Cosmoparticle Physics, Stockholm University, Roslagstullsbacken 23, Roslagstullsbacken 21, Stockholm (Sweden)

2016-03-01

It is shown that a Weakly Interacting Massive dark matter Particle (WIMP) interpretation for the positron excess observed in a variety of experiments, HEAT, PAMELA, and AMS-02, is highly constrained by the Fermi/LAT observations of dwarf galaxies. In particular, this paper examines the annihilation channels that best fit the current AMS-02 data (Boudaud et al., 2014), specifically focusing on channels and parameter space not previously explored by the Fermi/LAT collaboration. The Fermi satellite has surveyed the γ-ray sky, and its observations of dwarf satellites are used to place strong bounds on the annihilation of WIMPs into a variety of channels. For the single channel case, we find that dark matter annihilation into (b b-bar ,e{sup +}e{sup -}, μ{sup +}μ{sup -}, τ{sup +}τ{sup -},4-e or 4-τ ) is ruled out as an explanation of the AMS positron excess (here b quarks are a proxy for all quarks, gauge and Higgs bosons). In addition, we find that the Fermi/LAT 2σ upper limits, assuming the best-fit AMS-02 branching ratios, exclude multichannel combinations into b b-bar and leptons. The tension between the results might relax if the branching ratios are allowed to deviate from their best-fit values, though a substantial change would be required. Of all the channels we considered, the only viable channel that survives the Fermi/LAT constraint and produces a good fit to the AMS-02 data is annihilation (via a mediator) to 4-μ, or mainly to 4-μ in the case of multichannel combinations.

A Rainha do Ignoto (1899, de Emília Freitas, uma obra utópica

Directory of Open Access Journals (Sweden)

Elenara Walter Quinhones

2015-06-01

Full Text Available A obra Utopia (1516, de Thomas More, inaugurou, no ocidente, o gênero literário utópico. Essa obra serviu de protótipo para diversos autores criarem ficcionalmente suas sociedades perfeitas. A partir dos anos 1970, as escritoras Joanna Russ, Marge Piercy, Margaret Atwood e Octavia E. Butler descobriram que desde os momentos iniciais da literatura de utopia, ela já vinha sendo utilizada como instrumento de crítica social por parte de diversas autoras. No Brasil, a autoria feminina do século XIX e início do século XX manteve-se em um processo de invisibilidade. Após o resgate historiográfico nacional encontrou-se a obra A Rainha do Ignoto (1899, de Emília Freitas, que é delineada sob a proposição de um mundo novo. Esta pesquisa tem como objetivo discutir a obra de Freitas, tendo como ponto de partida que ela se insere na literatura utópica do romance ocidental, e analisar os imbricamentos políticos e históricos na obra, à luz dos conceitos de interdisciplinaridade e intertextualidade.

A characteristics of the small crack evaluation technique by triangle method with phased array UT

International Nuclear Information System (INIS)

Cho, Yong Sang

2005-01-01

Ultrasonic testing is a kind of nondestructive test to detect a crack or discontinuity in material or material surface by sending ultrasound to it. This conventional ultrasonic test has some difficulties to detect crack or inspect material specially in the case of complex-shaped power plant components such as Turbine blade root. Phased array UT system and its application methods for complex shaped power plant components will be a good alternative method which overcome present UT weakness. This study was aimed at developing a new method for finding the crack on material or material structures, and especially for determining the crack length without moving transducer. Especially ultrasonic phased array with electronic scan technique was used in carrying out both sizing and detect ability of crack as its depth and length changes. The response of ultrasonic phased array was analyzed to obtain the special method of determining crack length without moving the transducer and detect-ability of crack minimal length and depth from the material. The result showed a newly developed method for crack length determining is very real method which has its accuracy and verify the effectiveness of method compared to a conventional crack length determining method

Development of Wall Thinning Distinction Method using the Multi-inspecting UT Data of Carbon Steel Piping

Energy Technology Data Exchange (ETDEWEB)

Hwang, Kyeong Mo; Yun, Hun; Lee, Chan Kyoo [KEPCO E and C, Yongin (Korea, Republic of)

2012-05-15

To manage the wall thinning of carbon steel piping in nuclear power plants, the utility of Korea has performed thickness inspection for some quantity of pipe components during refueling outages and determined whether repair or replacement after evaluating UT (Ultrasonic Test) data. When the existing UT data evaluation methods, such as Band, Blanket, PTP (Point to Point) Methods, are applied to a certain pipe component, unnecessary re-inspecting situations may be generated even though the component does not thinned. In those cases, economical loss caused by repeated inspection and problems of maintaining the pipe integrity followed by decreasing of newly inspected components may be generated. EPRI (Electric Power Research Institute) in USA has suggested several statistical methods, TPM (Total Point Method), LSS (Least Square Slope) Method, etc. to distinguish whether multiple inspecting components have thinned or not. This paper presents the analysis results for multiple inspecting components over three times based on both NAM (Near Area of Minimum) Method developed by KEPCO-E and C and the other methods suggested by EPRI.

17 CFR 200.80b - Appendix B-SEC releases.

Science.gov (United States)

2010-04-01

...; CONDUCT AND ETHICS; AND INFORMATION AND REQUESTS Information and Requests § 200.80b Appendix B—SEC... purchased through the Superintendent of Documents as described in § 200.80c of this part. The Statistical... purchase through the Superintendent of Documents. [40 FR 1009, Jan. 6, 1975, as amended at 49 FR 12686, Mar...

Geology of Crownpoint Sec. 29 uranium deposit, McKinley County

International Nuclear Information System (INIS)

Wentworth, D.W.; Porter, D.A.; Jensen, H.N.

1980-01-01

The Crownpoint Sec. 29 deposit, located in the west-central part of the Grants mineral belt, represents a relatively recent uranium discovery in the Westwater Canyon Member (Jurassic) of the Morrison Formation. This deposit, estimated as containing up to 10 million pounds of uranium oxide, occurs in four vertically separate sandstone units. The average depth of the ore mineralization is approximately 2,000 ft (610 m) below the ground surface. Present-day structure of the Crownpoint Sec. 29 area is relatively simple and consists of gentle north-northeast-dipping strata with no known faulting. This deposit is located in an east-southeast-trending Westwater Canyon depocenter, whose course is believed to have been influenced by subtle Jurassic structure, which was penecontemporaneous with sedimentation. The deposit has been delineated by drilling on 200-ft (60-m) centers, involving approximately 348 holes and is awaiting shaft sinking and mine development

Anisotropies in the diffuse gamma-ray background measured by the Fermi-LAT

Energy Technology Data Exchange (ETDEWEB)

Cuoco, A. [Stockholm University-Oskar Klein Center AlbaNova University Center, Fysikum, SE-10691 Stockholm (Sweden); Linden, T. [Department of Physics, University of California, Santa Cruz, 1156 High Street, Santa Cruz, CA 95064 (United States); Mazziotta, M.N. [Istituto Nazionale di Fisica Nucleare, Sezione di Bari, 70126 Bari (Italy); Siegal-Gaskins, J.M. [Einstein Postdoctoral Fellow, California Institute of Technology 1200 E. California Blvd., Pasadena, CA 91125 (United States); Vitale, Vincenzo, E-mail: vincenzo.vitale@roma2.infn.it [Istituto Nazionale di Fisica Nucleare, Sezione di Tor Vergata, 00133 Roma (Italy); Komatsu, E. [Texas Cosmology Center and Department of Astronomy, University of Texas, Austin, Dept. of Astronomy, 2511 Speedway, Austin, TX 78712 (United States)

2012-11-11

The small angular scale fluctuations of the (on large scale) isotropic gamma-ray background (IGRB) carry information about the presence of unresolved source classes. A guaranteed contribution to the IGRB is expected from the unresolved gamma-ray AGN while other extragalactic sources, Galactic gamma-ray source populations and dark matter Galactic and extragalactic structures (and sub-structures) are candidate contributors. The IGRB was measured with unprecedented precision by the Large Area Telescope (LAT) on-board of the Fermi gamma-ray observatory, and these data were used for measuring the IGRB angular power spectrum (APS). Detailed Monte Carlo simulations of Fermi-LAT all-sky observations were performed to provide a reference against which to compare the results obtained for the real data set. The Monte Carlo simulations are also a method for performing those detailed studies of the APS contributions of single source populations, which are required in order to identify the actual IGRB contributors. We present preliminary results of an anisotropy search in the IGRB. At angular scales <2 Degree-Sign (e.g., above multipole 155), angular power above the photon noise level is detected, at energies between 1 and 10 GeV in each energy bin, with statistical significance between 7.2 and 4.1{sigma}. The obtained energy dependences point to the presence of one or more unclustered source populations with the components having an average photon index {Gamma}=2.40{+-}0.07.

Fermi/LAT Observations of Swift/BAT Seyfert Galaxies: On the Contribution of Radio-Quiet Active Galactic Nuclei to the Extragalactic gamma-Ray Background

Science.gov (United States)

Teng, Stacy H.; Mushotzky, Richard F.; Sambruna, Rita M.; Davis, David S.; Reynolds, Christopher S.

2011-01-01

We present the analysis of 2.1 years of Fermi Large Area Telescope (LAT) data on 491 Seyfert galaxies detected by the Swift Burst Alert Telescope (BAT) survey. Only the two nearest objects, NGC 1068 and NGC 4945, which were identified in the Fermi first year catalog, are detected. Using Swift/BAT and radio 20 cm fluxes, we define a new radio-loudness parameter R(sub X,BAT) where radio-loud objects have logR(sub X,BAT) > -4.7. Based on this parameter, only radio-loud sources are detected by Fermi/LAT. An upper limit to the flux of the undetected sources is derived to be approx.2x10(exp -11) photons/sq cm/s, approximately seven times lower than the observed flux of NGC 1068. Assuming a median redshift of 0.031, this implies an upper limit to the gamma-ray (1-100 GeV) luminosity of BAT Seyfert galaxies with significant Fermi/LAT detections. A majority of these objects do not have Swift/BAT counterparts, but their possible optical counterparts include blazars, flat-spectrum radio quasars, and quasars.

Da Lat Nuclear Research Reactor. Role and perspective in the development of radioisotope and nuclear technique application in Vietnam

International Nuclear Information System (INIS)

Tran Ha Anh; Tran Khac An; Ngo Phu Khang; Nguyen Mong Sinh

1995-01-01

The Da Lat Nuclear Research Reactor is playing a central role in the development of both the Nuclear Research Institute and nuclear application in our country. Thanks to this main scientific tool, the Nuclear Research Institute nearly 10 years after the completion of its renovation from the previous American-made TRIGA MARK 2 reactor is being able to implement numerous scientific and technological research projects and to develop significant applications of radioisotopes and various nuclear techniques. A general overview of the research and development activities of the Institute based on the Da Lat Nuclear Research Reactor is given as well as those aiming at ensuring its safe, reliable and efficient operation and at enlarging the perspectives of its utilisation in the future. (authors). 5 refs., 1 fig., 1 tab

Fracture unicondylienne latérale sagittale du fémur associée à une ...

African Journals Online (AJOL)

Un patient de 24 ans a subit un traumatisme du genou droit suite à un accident de la voie publique occasionnant une fracture simultanée uni condylienne latérale et patellaire verticale. Cette association est exceptionnelle et aucun cas n'as été retrouvé dans la littérature .Un diagnostic précis clinique et radiologique suivi ...

Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system

NARCIS (Netherlands)

Bezzina, Connie R.; Rook, Martin B.; Groenewegen, W. Antoinette; Herfst, Lucas J.; van der Wal, Allard C.; Lam, Jan; Jongsma, Habo J.; Wilde, Arthur A. M.; Mannens, Marcel M. A. M.

2003-01-01

Cardiac conduction defects associate with mutations in SCN5A, the gene encoding the cardiac Na+ channel. In the present study, we characterized a family in which the proband was born in severe distress with irregular wide complex tachycardia. His older sister died at 1 year of age from severe

Evaluation on ultrasonic examination methods applied to Ni-base alloy weld including cracks due to stress corrosion cracking found in BWR reactor internal

International Nuclear Information System (INIS)

Aoki, Takayuki; Kobayashi, Hiroyuki; Higuchi, Shinichi; Shimizu, Sadato

2005-01-01

A Ni-base alloy weld, including cracks due to stress corrosion cracking found in the reactor internal of the oldest BWR in Japan, Tsuruga unit 1, in 1999, was examined by three (3) types of UT method. After this examination, a depth of each crack was confirmed by carrying out a little excavation with a grinder and PT examination by turns until each crack disappeared. Then, the depth measured by the former method was compared with the one measured by the latter method. In this fashion, performances of the UT methods were verified. As a result, a combination of the three types of UT method was found to meet the acceptance criteria given by ASME Sec.XI Appendix VIII, Performance Demonstration for Ultrasonic Examination Systems-Supplement 6. In this paper, the results of the UT examination described above and their evaluation are discussed. (author)

Detergent-induced stabilization and improved 3D map of the human heteromeric amino acid transporter 4F2hc-LAT2.

Science.gov (United States)

Meury, Marcel; Costa, Meritxell; Harder, Daniel; Stauffer, Mirko; Jeckelmann, Jean-Marc; Brühlmann, Béla; Rosell, Albert; Ilgü, Hüseyin; Kovar, Karin; Palacín, Manuel; Fotiadis, Dimitrios

2014-01-01

Human heteromeric amino acid transporters (HATs) are membrane protein complexes that facilitate the transport of specific amino acids across cell membranes. Loss of function or overexpression of these transporters is implicated in several human diseases such as renal aminoacidurias and cancer. HATs are composed of two subunits, a heavy and a light subunit, that are covalently connected by a disulphide bridge. Light subunits catalyse amino acid transport and consist of twelve transmembrane α-helix domains. Heavy subunits are type II membrane N-glycoproteins with a large extracellular domain and are involved in the trafficking of the complex to the plasma membrane. Structural information on HATs is scarce because of the difficulty in heterologous overexpression. Recently, we had a major breakthrough with the overexpression of a recombinant HAT, 4F2hc-LAT2, in the methylotrophic yeast Pichia pastoris. Microgram amounts of purified protein made possible the reconstruction of the first 3D map of a human HAT by negative-stain transmission electron microscopy. Here we report the important stabilization of purified human 4F2hc-LAT2 using a combination of two detergents, i.e., n-dodecyl-β-D-maltopyranoside and lauryl maltose neopentyl glycol, and cholesteryl hemisuccinate. The superior quality and stability of purified 4F2hc-LAT2 allowed the measurement of substrate binding by scintillation proximity assay. In addition, an improved 3D map of this HAT could be obtained. The detergent-induced stabilization of the purified human 4F2hc-LAT2 complex presented here paves the way towards its crystallization and structure determination at high-resolution, and thus the elucidation of the working mechanism of this important protein complex at the molecular level.

Detergent-induced stabilization and improved 3D map of the human heteromeric amino acid transporter 4F2hc-LAT2.

Directory of Open Access Journals (Sweden)

Marcel Meury

Full Text Available Human heteromeric amino acid transporters (HATs are membrane protein complexes that facilitate the transport of specific amino acids across cell membranes. Loss of function or overexpression of these transporters is implicated in several human diseases such as renal aminoacidurias and cancer. HATs are composed of two subunits, a heavy and a light subunit, that are covalently connected by a disulphide bridge. Light subunits catalyse amino acid transport and consist of twelve transmembrane α-helix domains. Heavy subunits are type II membrane N-glycoproteins with a large extracellular domain and are involved in the trafficking of the complex to the plasma membrane. Structural information on HATs is scarce because of the difficulty in heterologous overexpression. Recently, we had a major breakthrough with the overexpression of a recombinant HAT, 4F2hc-LAT2, in the methylotrophic yeast Pichia pastoris. Microgram amounts of purified protein made possible the reconstruction of the first 3D map of a human HAT by negative-stain transmission electron microscopy. Here we report the important stabilization of purified human 4F2hc-LAT2 using a combination of two detergents, i.e., n-dodecyl-β-D-maltopyranoside and lauryl maltose neopentyl glycol, and cholesteryl hemisuccinate. The superior quality and stability of purified 4F2hc-LAT2 allowed the measurement of substrate binding by scintillation proximity assay. In addition, an improved 3D map of this HAT could be obtained. The detergent-induced stabilization of the purified human 4F2hc-LAT2 complex presented here paves the way towards its crystallization and structure determination at high-resolution, and thus the elucidation of the working mechanism of this important protein complex at the molecular level.

Altered hippocampal replay is associated with memory impairment in mice heterozygous for the Scn2a gene.

Science.gov (United States)

Middleton, Steven J; Kneller, Emily M; Chen, Shuo; Ogiwara, Ikuo; Montal, Mauricio; Yamakawa, Kazuhiro; McHugh, Thomas J

2018-06-04

An accumulating body of experimental evidence has implicated hippocampal replay occurring within sharp wave ripples (SPW-Rs) as crucial for learning and memory in healthy subjects. This raises speculation that neurological disorders impairing memory disrupt either SPW-Rs or their underlying neuronal activity. We report that mice heterozygous for the gene Scn2a, a site of frequent de novo mutations in humans with intellectual disability, displayed impaired spatial memory. While we observed no changes during encoding, to either single place cells or cell assemblies, we identified abnormalities restricted to SPW-R episodes that manifest as decreased cell assembly reactivation strengths and truncated hippocampal replay sequences. Our results suggest that alterations to hippocampal replay content may underlie disease-associated memory deficits.

Gamma-Ray Flaring Activity from the Gravitationally Lensed Blazar PKS 1830-211 Observed by Fermi LAT

Energy Technology Data Exchange (ETDEWEB)

Abdo, A. A.; et al.

2015-01-23

The Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope routinely detects the MeV-peaked flat-spectrum radio quasar PKS 1830–211 (z = 2.507). Its apparent isotropic γ-ray luminosity (E > 100 MeV), averaged over ~3 years of observations and peaking on 2010 October 14/15 at 2.9 × 10(50) erg s(–)(1), makes it among the brightest high-redshift Fermi blazars. No published model with a single lens can account for all of the observed characteristics of this complex system. Based on radio observations, one expects time-delayed variability to follow about 25 days after a primary flare, with flux about a factor of 1.5 less. Two large γ-ray flares of PKS 1830–211 have been detected by the LAT in the considered period, and no substantial evidence for such a delayed activity was found. This allows us to place a lower limit of about 6 on the γ-ray flux ratio between the two lensed images. Swift XRT observations from a dedicated Target of Opportunity program indicate a hard spectrum with no significant correlation of X-ray flux with the γ-ray variability. The spectral energy distribution can be modeled with inverse Compton scattering of thermal photons from the dusty torus. The implications of the LAT data in terms of variability, the lack of evident delayed flare events, and different radio and γ-ray flux ratios are discussed. Microlensing effects, absorption, size and location of the emitting regions, the complex mass distribution of the system, an energy-dependent inner structure of the source, and flux suppression by the lens galaxy for one image path may be considered as hypotheses for understanding our results.

Experiments of 10 Gbit/sec quantum stream cipher applicable to optical Ethernet and optical satellite link

Science.gov (United States)

Hirota, Osamu; Ohhata, Kenichi; Honda, Makoto; Akutsu, Shigeto; Doi, Yoshifumi; Harasawa, Katsuyoshi; Yamashita, Kiichi

2009-08-01

The security issue for the next generation optical network which realizes Cloud Computing System Service with data center" is urgent problem. In such a network, the encryption by physical layer which provide super security and small delay should be employed. It must provide, however, very high speed encryption because the basic link is operated at 2.5 Gbit/sec or 10 Gbit/sec. The quantum stream cipher by Yuen-2000 protocol (Y-00) is a completely new type random cipher so called Gauss-Yuen random cipher, which can break the Shannon limit for the symmetric key cipher. We develop such a cipher which has good balance of the security, speed and cost performance. In SPIE conference on quantum communication and quantum imaging V, we reported a demonstration of 2.5 Gbit/sec system for the commercial link and proposed how to improve it to 10 Gbit/sec. This paper reports a demonstration of the Y-00 cipher system which works at 10 Gbit/sec. A transmission test in a laboratory is tried to get the basic data on what parameters are important to operate in the real commercial networks. In addition, we give some theoretical results on the security. It is clarified that the necessary condition to break the Shannon limit requires indeed the quantum phenomenon, and that the full information theoretically secure system is available in the satellite link application.

Development of ultrasonic instrument 'UT1000 Series'

International Nuclear Information System (INIS)

Ogura, Yukio; Ikeda, Toshimichi

1984-01-01

The ultrasonic flaw detectors with 'A-scope indication' have been frequently used as the means for confirming the soundness of structures and equipments, but there are problems in their operational, quantifying and recording capabilities. Recently, the digital ultrasonic measuring instrument of touch panel type ''UT 1000 Series'' has been developed, which resolves these problems by a single effort. This measuring instrument is that of portable type, which gives the digital output of measured results in real time only by lightly touching the peak point of an echo on the Brown tube. This instrument contains the rich software for measurement, and can measure the positions and dimensions of defects and the pressure on contact surfaces with high accuracy. 'A-scope indication' is the indication with an oscilloscope taking the intensity of echo and the propagation time of ultrasonic waves on the ordinate and abscissa, respectively. There are three types of the instrument, that is, for detecting defects, for measuring contact surface pressure and for both purposes. The size of the instrument is 240 mm width, 350 mm length and 175 mm height, and the weight is 8.5 kgf. The specification, function and features of the ultrasonic flaw detector, touch panel, gain setter, key board, microcomputer and others are reported. (Kako, I.)

Boolean and advanced searching for EDGAR data on www.sec.gov

Data.gov (United States)

Securities and Exchange Commission — This search allows users to enter complex boolean queries to access all but the most recent day's EDGAR filings on www.sec.gov. Filings are from 1994 to present.

New stage in high-energy gamma-ray studies with GAMMA-400 after Fermi-LAT

Directory of Open Access Journals (Sweden)

Topchiev N.P.

2017-01-01

Full Text Available Fermi-LAT has made a significant contribution to the study of high-energy gamma-ray diffuse emission and the observations of 3000 discrete sources. However, one third of all gamma-ray sources (both galactic and extragalactic are unidentified, the data on the diffuse gamma-ray emission should be clarified, and signatures of dark matter particles in the high-energy gamma-ray range are not observed up to now. GAMMA-400, the currently developing gamma-ray telescope, will have angular (∼0.01∘ at 100 GeV and energy (∼1% at 100 GeV resolutions in the energy range of 10–1000 GeV which are better than Fermi-LAT (as well as ground gamma-ray telescopes by a factor of 5–10. It will observe some regions of the Universe (such as the Galactic Center, Fermi Bubbles, Crab, Cygnus, etc. in a highly elliptic orbit (without shading the telescope by the Earth continuously for a long time. It will allow us to identify many discrete sources, to clarify the structure of extended sources, to specify the data on the diffuse emission, and to resolve gamma rays from dark matter particles.

Fermi-LAT γ-ray anisotropy and intensity explained by unresolved radio-loud active galactic nuclei

International Nuclear Information System (INIS)

Mauro, Mattia Di; Cuoco, Alessandro; Donato, Fiorenza; Siegal-Gaskins, Jennifer M.

2014-01-01

Radio-loud active galactic nuclei (AGN) are expected to contribute substantially to both the intensity and anisotropy of the isotropic γ-ray background (IGRB). In turn, the measured properties of the IGRB can be used to constrain the characteristics of proposed contributing source classes. We consider individual subclasses of radio-loud AGN, including low-, intermediate-, and high-synchrotron-peaked BL Lacertae objects, flat-spectrum radio quasars, and misaligned AGN. Using updated models of the γ-ray luminosity functions of these populations, we evaluate the energy-dependent contribution of each source class to the intensity and anisotropy of the IGRB. We find that collectively radio-loud AGN can account for the entirety of the IGRB intensity and anisotropy as measured by the Fermi Large Area Telescope (LAT). Misaligned AGN provide the bulk of the measured intensity but a negligible contribution to the anisotropy, while high-synchrotron-peaked BL Lacertae objects provide the dominant contribution to the anisotropy. In anticipation of upcoming measurements with the Fermi-LAT and the forthcoming Cherenkov Telescope Array, we predict the anisotropy in the broader energy range that will be accessible to future observations

Fermi-LAT γ-ray anisotropy and intensity explained by unresolved radio-loud active galactic nuclei

Energy Technology Data Exchange (ETDEWEB)

Mauro, Mattia Di; Cuoco, Alessandro; Donato, Fiorenza [Dipartimento di Fisica, Università di Torino, via P. Giuria 1, Torino, 10125 Italy (Italy); Siegal-Gaskins, Jennifer M., E-mail: mattia.dimauro@to.infn.it, E-mail: alessandro.cuoco@to.infn.it, E-mail: donato@to.infn.it, E-mail: jsg@tapir.caltech.edu [California Institute of Technology, 1200 E. California Blvd., Pasadena, CA, 91125 (United States)

2014-11-01

Radio-loud active galactic nuclei (AGN) are expected to contribute substantially to both the intensity and anisotropy of the isotropic γ-ray background (IGRB). In turn, the measured properties of the IGRB can be used to constrain the characteristics of proposed contributing source classes. We consider individual subclasses of radio-loud AGN, including low-, intermediate-, and high-synchrotron-peaked BL Lacertae objects, flat-spectrum radio quasars, and misaligned AGN. Using updated models of the γ-ray luminosity functions of these populations, we evaluate the energy-dependent contribution of each source class to the intensity and anisotropy of the IGRB. We find that collectively radio-loud AGN can account for the entirety of the IGRB intensity and anisotropy as measured by the Fermi Large Area Telescope (LAT). Misaligned AGN provide the bulk of the measured intensity but a negligible contribution to the anisotropy, while high-synchrotron-peaked BL Lacertae objects provide the dominant contribution to the anisotropy. In anticipation of upcoming measurements with the Fermi-LAT and the forthcoming Cherenkov Telescope Array, we predict the anisotropy in the broader energy range that will be accessible to future observations.

SEC16 in COPII coat dynamics at ER exit sites

NARCIS (Netherlands)

Sprangers, Joep; Rabouille, Catherine

Protein export from the endoplasmic reticulum (ER), the first step in protein transport through the secretory pathway, is mediated by coatomer protein II (COPII)-coated vesicles at ER exit sites. COPII coat assembly on the ER is well understood and the conserved large hydrophilic protein Sec16

Kinetic Resolution of sec-Thiols by Enantioselective Oxidation with Rationally Engineered 5-(Hydroxymethyl)furfural Oxidase.

Science.gov (United States)

Pickl, Mathias; Swoboda, Alexander; Romero, Elvira; Winkler, Christoph K; Binda, Claudia; Mattevi, Andrea; Faber, Kurt; Fraaije, Marco W

2018-03-05

Various flavoprotein oxidases were recently shown to oxidize primary thiols. Herein, this reactivity is extended to sec-thiols by using structure-guided engineering of 5-(hydroxymethyl)furfural oxidase (HMFO). The variants obtained were employed for the oxidative kinetic resolution of racemic sec-thiols, thus yielding the corresponding thioketones and nonreacted R-configured thiols with excellent enantioselectivities (E≥200). The engineering strategy applied went beyond the classic approach of replacing bulky amino acid residues with smaller ones, as the active site was additionally enlarged by a newly introduced Thr residue. This residue established a hydrogen-bonding interaction with the substrates, as verified in the crystal structure of the variant. These strategies unlocked HMFO variants for the enantioselective oxidation of a range of sec-thiols. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The SAFT-UT (synthetic aperture focusing technique for ultrasonic testing) real-time inspection system: Operational principles and implementation

Energy Technology Data Exchange (ETDEWEB)

Hall, T. E.; Reid, L. D.; Doctor, S. R.

1988-06-01

This document provides a technical description of the real-time imaging system developed for rapid flaw detection and characterization utilizing the synthetic aperture focusing technique for ultrasonic testing (SAFT-UT). The complete fieldable system has been designed to perform inservice inspection of light-water reactor components. Software was written on a DEC LSI 11/23 computer system to control data collection. The unprocessed data is transferred to a VAX 11/730 host computer to perform data processing and image display tasks. A parallel architecture peripheral to the host computer, referred to as the Real-Time SAFT Processor, rapidly performs the SAFT processing function. From the host's point of view, this device operates on the SAFT data in such a way that one may consider it to be a specialized or SAFT array processor. A guide to SAFT-UT theory and conventions is included, along with a detailed description of the operation of the software, how to install the software, and a detailed hardware description.

Fermi-LAT and Suzaku Observations of the Radio Galaxy Centaurus B

International Nuclear Information System (INIS)

Katsuta, Junichiro

2012-01-01

CentaurusB is a nearby radio galaxy positioned in the Southern hemisphere close to the Galactic plane. Here we present a detailed analysis of about 43 months accumulation of Fermi-LAT data and of newly acquired Suzaku X-ray data for Centaurus B. The source is detected at GeV photon energies, although we cannot completely exclude the possibility that it is an artifact due to incorrect modeling of the bright Galactic diffuse emission in the region. The LAT image provides a weak hint of a spatial extension of the γ rays along the radio lobes, which is consistent with the lack of source variability in the GeV range. We note that the extension cannot be established statistically due to the low number of the photons. Surprisingly, we do not detect any diffuse emission of the lobes at X-ray frequencies, with the provided upper limit only marginally consistent with the previously claimed ASCA flux. The broad-band modeling shows that the observed γ-ray flux of the source may be produced within the lobes, if the diffuse non-thermal X-ray emission component is not significantly below the derived Suzaku upper limit. This association would imply that efficient in-situ acceleration of the ultrarelativistic particles is occurring and that the lobes are dominated by the pressure from the relativistic particles. However, if the diffuse X-ray emission is much below the Suzaku upper limits, the observed γ-ray flux is not likely to be produced within the lobes, but instead within the unresolved core of Centaurus B. In this case, the extended lobes could be dominated by the pressure of the magnetic field.

Fermi-LAT and Suzaku Observations of the Radio Galaxy Centaurus B

Energy Technology Data Exchange (ETDEWEB)

Katsuta, Junichiro; /Stanford U., HEPL /KIPAC, Menlo Park; Tanaka, Y.T.; /Hiroshima U.; Stawarz, L.; /JAXA, Sagamihara /Jagiellonian U., Astron. Observ.; O' Sullivan, S.P.; /Australia, CSIRO, Epping; Cheung, C.C.; /NAS, Washington, D.C.; Kataoka, J.; /Waseda U., RISE; Funk, S.; /Stanford U., HEPL /KIPAC, Menlo Park; Yuasa, T.; Odaka, H.; Takahashi, T.; /JAXA, Sagamihara; Svoboda, J.; /European Space Agency

2012-08-17

CentaurusB is a nearby radio galaxy positioned in the Southern hemisphere close to the Galactic plane. Here we present a detailed analysis of about 43 months accumulation of Fermi-LAT data and of newly acquired Suzaku X-ray data for Centaurus B. The source is detected at GeV photon energies, although we cannot completely exclude the possibility that it is an artifact due to incorrect modeling of the bright Galactic diffuse emission in the region. The LAT image provides a weak hint of a spatial extension of the {gamma} rays along the radio lobes, which is consistent with the lack of source variability in the GeV range. We note that the extension cannot be established statistically due to the low number of the photons. Surprisingly, we do not detect any diffuse emission of the lobes at X-ray frequencies, with the provided upper limit only marginally consistent with the previously claimed ASCA flux. The broad-band modeling shows that the observed {gamma}-ray flux of the source may be produced within the lobes, if the diffuse non-thermal X-ray emission component is not significantly below the derived Suzaku upper limit. This association would imply that efficient in-situ acceleration of the ultrarelativistic particles is occurring and that the lobes are dominated by the pressure from the relativistic particles. However, if the diffuse X-ray emission is much below the Suzaku upper limits, the observed {gamma}-ray flux is not likely to be produced within the lobes, but instead within the unresolved core of Centaurus B. In this case, the extended lobes could be dominated by the pressure of the magnetic field.

The thermal degradation of poly(iso-butyl methacrylate and poly(sec-butyl methacrylate

Directory of Open Access Journals (Sweden)

IVANKA G. POPOVIC

2000-12-01

Full Text Available The non-oxidative thermal degradation of poly(iso-butyl methacrylate and poly(sec-butyl methacrylate was investigated by studying changes in the polymer residue. Due to the different number of b-hydrogens in their ester substituents, these two polymeric isomers behave differently when subjected to elevated temperatures. Poly(iso-butyl methacrylate degrades quantitatively by depolymerisation with zip lengths of the same order of magnitude as those of poly(methyl methacrylate. Poly(sec-butyl methacrylate degrades by a combined degradation mechanism of depolymerisation and de-esterification. De-esterification becomes a significant thermolysis route at temperatures higher than 240°C.

Impact of Convection and Long Range Transport on Short-Lived Trace Gases in the UT/LS

Science.gov (United States)

Atlas, E. L.; Schauffler, S.; Navarro, M. A.; Lueb, R.; Hendershot, R.; Ueyama, R.

2017-12-01

Chemical composition of the air in the upper troposphere/lower stratosphere is controlled by a balance of transport, photochemistry, and physical processes, such as interactions with clouds, ice, and aerosol. The chemistry of the air masses that reach the upper troposphere can potentially have profound impacts on the chemistry in the near tropopause region. For example, the transport of reactive organic halogens and their transformation to inorganic halogen species, e.g., Br, BrO, etc., can have a significant impact on ozone budgets in this region and even deeper the stratosphere. Trace gas measurements in the region near the tropopause can also indicate potential sources of surface emissions that are transported to high altitudes. Measurement of trace gases, including such compounds as non-methane hydrocarbons, hydrochlorofluorocarbons, halogenated solvents, methyl halides, etc., can be used to characterize source emissions from industrial, urban, biomass burning, or marine origins. Recent airborne research campaigns have been conducted to better characterize the chemical composition and variations in the UT/LS region. This presentation will discuss these measurements, with a special emphasis on the role of convection and transport in modifying the chemical composition of the UT/LS.

Characterization of proton conducting blend polymer electrolyte using PVA-PAN doped with NH{sub 4}SCN

Energy Technology Data Exchange (ETDEWEB)

Premalatha, M. [PG & Research Department of Physics, N.M.S.S.Vellaichamy Nadar College, Madurai-625 019 (India); Materials Research Center, Coimbatore-641 045 (India); Mathavan, T., E-mail: tjmathavan@gmail.com, E-mail: kingslin.genova20@gmail.com [PG & Research Department of Physics, N.M.S.S.Vellaichamy Nadar College, Madurai-625 019 (India); Selvasekarapandian, S. [Materials Research Center, Coimbatore-641 045 (India); Genova, F. Kingslin Mary, E-mail: tjmathavan@gmail.com, E-mail: kingslin.genova20@gmail.com; Umamaheswari, R. [Department of physics, S.F.R College for Women, Sivakasi-626 128 (India)

2016-05-23

Polymer electrolytes with proton conductivity based on blend polymer using polyvinyl alcohol (PVA) and poly acrylo nitrile (PAN) doped with ammonium thiocyanate have been prepared by solution casting method using DMF as solvent. The complex formation between the blend polymer and the salt has been confirmed by FTIR Spectroscopy. The amorphous nature of the blend polymer electrolytes have been confirmed by XRD analysis. The highest conductivity at 303 K has been found to be 3.25 × 10{sup −3} S cm{sup −1} for 20 mol % NH{sub 4}SCN doped 92.5PVA:7.5PAN system. The increase in conductivity of the doped blend polymer electrolytes with increasing temperature suggests the Arrhenius type thermally activated process. The activation energy is found to be low (0.066 eV) for the highest conductivity sample.

TOMS/Earth Probe UV Reflectivity Daily L3 Global 1x1.25 deg Lat/Lon Grid V008

Data.gov (United States)

National Aeronautics and Space Administration — This data product contains TOMS/Earth Probe UV Reflectivity Daily L3 Global 1x1.25 deg Lat/Lon Grid Version 8 data in ASCII format. (The shortname for this Level-3...

Methyl chloride in the UT/LS observed by CARIBIC: global distribution, Asian summer monsoon outflow, and use as a tracer for tropical air

Science.gov (United States)

Baker, A. K.; Umezawa, T.; Oram, D.; Sauvage, C.; Rauthe-Schoech, A.; Montzka, S. A.; Zahn, A.; Brenninkmeijer, C. A. M.

2014-12-01

We present spatiotemporal variations of methyl chloride (CH3Cl) in the UT/LS observed mainly by the CARIBIC passenger aircraft for the years 2005-2011. The CH3Cl mixing ratio in the UT over Europe was higher than that observed at a European surface baseline station year-round, indicative of a persistent positive vertical gradient at NH mid latitudes. A series of flights over Africa and South Asia show that CH3Cl mixing ratios increase toward tropical latitudes, and the observed UT CH3Cl level over these two regions and the Atlantic was higher than that measured at remote surface sites. Strong emissions of CH3Cl in the tropics combined with meridional transport through the UT may explain such vertical and latitudinal gradients. Comparisons with CO data indicate that non-combustion sources in the tropics dominantly contribute to forming the latitudinal gradient of CH3Cl in the UT. We also observed elevated CH3Cl and CO in air influenced by biomass burning in South America and Africa, and the enhancement ratios derived for CH3Cl to CO in those regions agree with previous observations. In contrast, correlations indicate a high CH3Cl to CO ratio of 2.9±0.5 ppt ppb-1 in the Asian summer monsoon anticyclone and domestic biofuel emissions in South Asia are inferred to be responsible. We estimated CH3Cl emissions from South Asia to be 134±23 Gg Cl yr-1, which is higher than a previous estimate due to the higher CH3Cl to CO ratio observed in this study. We also examine the use of CH3Cl as a tracer of tropical tropospheric air in the LMS, where we identified air masses with elevated CH3Cl that were however stratospheric in terms of N2O. Back trajectories suggest recent low-latitude origins of such air masses in early summer. In this season, high CH3Cl LMS air shows a clear branch connecting stratospheric and tropical tropospheric air on N2O-CH3Cl scatterplots. This distinct feature vanishes in late summer when the LMS is ventilated by tropospheric air.

Surgical management of diabetic foot and role of UT (University of Texas) classification

International Nuclear Information System (INIS)

Mishwani, A.H.; Kiyani, K.A.

2011-01-01

To evaluate the role of University of Texas Classification in the management of Diabetic foot. Design: Descriptive study Place and Duration of Study: Surgical unit II Combined Military Hospital Rawalpindi (2003 to 2008) and Department of Surgery Combined Military Hospital Peshawar (July 2008 to Jan 2010). Patients and Method: A total of 300 patients who reported to Surgical Department with a foot ulcer or infection and diagnosed to have Diabetes Mellitus were studied. Patients of both gender and age >12 years were included. Patients of end stage renal disease, compromised immunity or on steroid therapy were excluded. Detailed history and clinical examination were recorded. Routine investigations including complete blood examination, urine routine examination, renal function tests, x-ray foot, chest x-ray, ECG and pus for culture and sensitivity were recorded. Lesions were classified according to University of Texas classification and treated accordingly. Results: Majority of the patients were of 50 to 70 years age group. Male to female ratio was 4:1. Big toe was the commonest site followed by fore foot and heel. Patients were classified according to UT classification. Patients were managed with antibiotics, dressings, incision and drainage, debridement, vacuum assisted closure (VAC) with or without skin grafting and amputations of different types. Staphylococcus aureus was the commonest isolate. Conclusion: Our study has shown that UT classification is an effective system of assessing the severity of Diabetic foot at the time of presentation and planning its management. Amputation rates, time of healing and morbidity increases with increasing stage and grade. (author)

{sup 18}F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with {sup 18}F-FDG and {sup 11}C-Methionine PET

Energy Technology Data Exchange (ETDEWEB)

Watabe, Tadashi [Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics, Osaka (Japan); Osaka University Graduate School of Medicine, PET Molecular Imaging Center, Osaka (Japan); Ikeda, Hayato; Aoki, Masanao [Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics, Osaka (Japan); Nagamori, Shushi; Wiriyasermkul, Pattama; Tanaka, Yoko; Hagiwara, Kohei; Kanai, Yoshikatsu [Osaka University Graduate School of Medicine, Department of Bio-system Pharmacology, Osaka (Japan); Naka, Sadahiro [Osaka University, Osaka University Graduate School of Medicine, Osaka University Hospital, Osaka (Japan); Kanai, Yasukazu [Osaka University Graduate School of Medicine, PET Molecular Imaging Center, Osaka (Japan); Osaka University Graduate School of Medicine, Department of Molecular Imaging in Medicine, Osaka (Japan); Shimosegawa, Eku [Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics, Osaka (Japan); Osaka University Graduate School of Medicine, PET Molecular Imaging Center, Osaka (Japan); Osaka University, Osaka University Graduate School of Medicine, Osaka University Hospital, Osaka (Japan); Hatazawa, Jun [Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics, Osaka (Japan); Osaka University Graduate School of Medicine, PET Molecular Imaging Center, Osaka (Japan); Osaka University, Immunology Frontier Research Center, Osaka (Japan)

2017-02-15

The purpose of this study was to evaluate the usefulness of L-4-borono-2-{sup 18}F-fluoro-phenylalanine ({sup 18}F-FBPA) as a tumor-specific probe, in comparison to {sup 18}F-FDG and {sup 11}C-methionine (Met), focusing on its transport selectivity by L-type amino acid transporter 1 (LAT1), which is highly upregulated in cancers. Cellular analyses of FBPA were performed to evaluate the transportability and K{sub m} value. PET studies were performed in rat xenograft models of C6 glioma (n = 12) and in rat models of turpentine oil-induced subcutaneous inflammation (n = 9). The kinetic parameters and uptake values on static PET images were compared using the one-tissue compartment model (K{sub 1}, k{sub 2}) and maximum standardized uptake value (SUVmax). The cellular analyses showed that FBPA had a lower affinity to a normal cell-type transporter LAT2 and induced less efflux through LAT2 among FBPA, Met, and BPA, while the efflux through LAT1 induced by FBPA was similar among the three compounds. The K{sub m} value of {sup 18}F-FBPA for LAT1 (196.8 ± 11.4 μM) was dramatically lower than that for LAT2 (2813.8 ± 574.5 μM), suggesting the higher selectivity of {sup 18}F-FBPA for LAT1. K{sub 1} and k{sub 2} values were significantly smaller in {sup 18}F-FBPA PET (K{sub 1} = 0.04 ± 0.01 ml/ccm/min and k{sub 2} = 0.07 ± 0.01 /min) as compared to {sup 11}C-Met PET (0.22 ± 0.09 and 0.52 ± 0.10, respectively) in inflammatory lesions. Static PET analysis based on the SUVmax showed significantly higher accumulation of {sup 18}F-FDG in the tumor and inflammatory lesions (7.2 ± 2.1 and 4.6 ± 0.63, respectively) as compared to both {sup 18}F-FBPA (3.2 ± 0.40 and 1.9 ± 0.19) and {sup 11}C-Met (3.4 ± 0.43 and 1.6 ± 0.11). No significant difference was observed between {sup 18}F-FBPA and {sup 11}C-Met in the static PET images. This study shows the utility of {sup 18}F-FBPA as a tumor-specific probe of LAT1 with low accumulation in the inflammatory lesions. (orig.)

"1"8F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with "1"8F-FDG and "1"1C-Methionine PET

International Nuclear Information System (INIS)

Watabe, Tadashi; Ikeda, Hayato; Aoki, Masanao; Nagamori, Shushi; Wiriyasermkul, Pattama; Tanaka, Yoko; Hagiwara, Kohei; Kanai, Yoshikatsu; Naka, Sadahiro; Kanai, Yasukazu; Shimosegawa, Eku; Hatazawa, Jun

2017-01-01

The purpose of this study was to evaluate the usefulness of L-4-borono-2-"1"8F-fluoro-phenylalanine ("1"8F-FBPA) as a tumor-specific probe, in comparison to "1"8F-FDG and "1"1C-methionine (Met), focusing on its transport selectivity by L-type amino acid transporter 1 (LAT1), which is highly upregulated in cancers. Cellular analyses of FBPA were performed to evaluate the transportability and K_m value. PET studies were performed in rat xenograft models of C6 glioma (n = 12) and in rat models of turpentine oil-induced subcutaneous inflammation (n = 9). The kinetic parameters and uptake values on static PET images were compared using the one-tissue compartment model (K_1, k_2) and maximum standardized uptake value (SUVmax). The cellular analyses showed that FBPA had a lower affinity to a normal cell-type transporter LAT2 and induced less efflux through LAT2 among FBPA, Met, and BPA, while the efflux through LAT1 induced by FBPA was similar among the three compounds. The K_m value of "1"8F-FBPA for LAT1 (196.8 ± 11.4 μM) was dramatically lower than that for LAT2 (2813.8 ± 574.5 μM), suggesting the higher selectivity of "1"8F-FBPA for LAT1. K_1 and k_2 values were significantly smaller in "1"8F-FBPA PET (K_1 = 0.04 ± 0.01 ml/ccm/min and k_2 = 0.07 ± 0.01 /min) as compared to "1"1C-Met PET (0.22 ± 0.09 and 0.52 ± 0.10, respectively) in inflammatory lesions. Static PET analysis based on the SUVmax showed significantly higher accumulation of "1"8F-FDG in the tumor and inflammatory lesions (7.2 ± 2.1 and 4.6 ± 0.63, respectively) as compared to both "1"8F-FBPA (3.2 ± 0.40 and 1.9 ± 0.19) and "1"1C-Met (3.4 ± 0.43 and 1.6 ± 0.11). No significant difference was observed between "1"8F-FBPA and "1"1C-Met in the static PET images. This study shows the utility of "1"8F-FBPA as a tumor-specific probe of LAT1 with low accumulation in the inflammatory lesions. (orig.)

Three Millisecond Pulsars in Fermi LAT Unassociated Bright Sources

Science.gov (United States)

Ransom, S. M.; Ray, P. S.; Camilo, F.; Roberts, M. S. E.; Celik, O.; Wolff, M. T.; Cheung, C. C.; Kerr, M.; Pennucci, T.; DeCesar, M. E.;

New Theoretical Estimates of the Contribution of Unresolved Star-Forming Galaxies to the Extragalactic Gamma-Ray Background (EGB) as Measured by EGRET and the Fermi-LAT

Science.gov (United States)

Venters, Tonia M.

2011-01-01

We present new theoretical estimates of the contribution of unresolved star-forming galaxies to the extragalactic gamma-ray background (EGB) as measured by EGRET and the Fermi-LAT. We employ several methods for determining the star-forming galaxy contribution the the EGB, including a method positing a correlation between the gamma-ray luminosity of a galaxy and its rate of star formation as calculated from the total infrared luminosity, and a method that makes use of a model of the evolution of the galaxy gas mass with cosmic time. We find that depending on the model, unresolved star-forming galaxies could contribute significantly to the EGB as measured by the Fermi-LAT at energies between approx. 300 MeV and approx. few GeV. However, the overall spectrum of unresolved star-forming galaxies can explain neither the EGRET EGB spectrum at energies between 50 and 200 MeV nor the Fermi-LAT EGB spectrum at energies above approx. few GeV.

Direct demonstration of ATP-dependent release of SecA from a translocating preprotein by surface plasmon resonance

NARCIS (Netherlands)

de Keyzer, J; van der Does, C; Kloosterman, TG; Driessen, AJM

2003-01-01

Translocase mediates the transport of preproteins across the inner membrane of Escherichia coli. SecA binds with high affinity to the membrane-embedded protein-conducting SecYEG complex and serves as both a receptor for secretory proteins and as an ATP-driven molecular motor. Cycles of ATP binding

Single and combined deletions of the NTAL/LAB and LAT adaptors minimally affect B-cell development and function

Czech Academy of Sciences Publication Activity Database

Wang, Y.; Horváth, Ondřej; Hamm-Baarke, A.; Richelme, M.; Grégoire, C.; Guinamard, R.; Hořejší, Václav; Angelisová, Pavla; Špička, Jiří; Schraven, B.; Malissen, B.; Malissen, M.

2005-01-01

Roč. 25, č. 11 (2005), s. 4455-4465 ISSN 0270-7306 R&D Projects: GA MŠk(CZ) 1M0506 Institutional research plan: CEZ:AV0Z50520514 Keywords : NTAL * LAT * B-cell Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.093, year: 2005

Superconductivity in U-T alloys (T = Mo, Pt, Pd, Nb, Zr stabilized in the cubic γ-U structure by splat-cooling technique

Directory of Open Access Journals (Sweden)

N.-T.H. Kim-Ngan

2016-06-01

Full Text Available We succeed to retain the high-temperature (cubic γ-U phase down to low temperatures in U-T alloys with less required T alloying concentration (T = Mo, Pt, Pd, Nb, Zr by means of splat-cooling technique with a cooling rate better than 106 K/s. All splat-cooled U-T alloys become superconducting with the critical temperature Tc in the range of 0.61 K–2.11 K. U-15 at.% Mo splat consisting of the γ-U phase with an ideal bcc A2 structure is a BCS superconductor having the highest critical temperature (2.11 K.

Internationality meets locality - ART IST KUKU NU UT festival in Tartu / Tanel Rander

Index Scriptorium Estoniae

Rander, Tanel, 1980-

2012-01-01

Kunstifestivalist ART IST KUKU NU UT. Näitusest "Möh? Fui! Öäk! Ossa! Vau! Eesti kaasaegse kunsti klassika" (06.09.-18.11.2012) Tartu Kunstimuuseumis. Festivali projektijuht Kaisa Eiche, kunstiline juht ja näituse kuraator Rael Artel. Näitusel osalesid Jaan Toomik, Raul Meel, Kai Kaljo, Johnson & Johnson, Anna-Stina Treumund ja Flo Kasearu. Chris Fitzpatrick'u kureeritud näitusest "Sõida tasa üle silla" (07.-30.09.2012) galeriis Noorus. Kuku Nunnu stipendiaadi Eike Epliku isikunäitusest "Tüdruk, kes kõike arnastas" (07.09.-28.10.2012) Y-galeriis

Presença do pensamento utópico nos romances de Lima Barreto

OpenAIRE

Alice Atsuko Matsuda

2009-01-01

A presente tese teve como objetivo verificar como se configurou o pensamento utópico nos romances de Lima Barreto. Os romances analisados foram: Recordações do escrivão Isaías Caminha (1909), Triste fim de Policarpo Quaresma (1911 em folhetim e 1916 em livro), Numa e a ninfa (1915 em folhetim e 1917 em livro), Vida e morte de M. J. Gonzaga de Sá (1919), Clara dos Anjos (1948 – publicação póstuma). Partiu-se do pressuposto de que o romancista tinha uma postura de um romantismo revolucionário o...

Limiar e latência do reflexo acústico sob efeito de estimulação contralateral Threshold and latency of acoustic reflex under effect of contralateral noise

Directory of Open Access Journals (Sweden)

Isabella Elias Burjato Raposo do Amaral

2008-03-01

Full Text Available OBJETIVO: Investigar o efeito inibitório da via eferente auditiva na variação do limiar e da latência do reflexo acústico ipsilateral com estimulação contralateral. MÉTODOS: Foram avaliados 17 pacientes entre 18 e 30 anos, com audição dentro dos padrões de normalidade submetidos à pesquisa de limiar e de latência do reflexo acústico, com e sem estimulação contralateral. RESULTADOS: Foram observadas médias de latência sem ruído contralateral para as freqüências de 500, 1000 e 2000 Hz respectivamente em 234,48, 214,96 e 236,71 milissegundos. Os valores de latência com ruído nas mesmas freqüências foram 230,74, 214,00 e 232,15 milissegundos. CONCLUSÃO: Houve diminuição da latência e aumento dos limiares do reflexo acústico quando apresentado estímulo supressor na orelha contralateral.PURPOSE: To investigate the inhibitory effect of the efferent auditory path in the variation of the threshold and the latency of ipsilateral acoustic reflex with contralateral stimulation. METHODS: Seventeen male and female patients, with ages between 18 and 30 years and with average normal hearing, were evaluated. After verification of inclusion criteria, the subjects were submitted to acoustic reflex threshold and latency testings, with and without contralateral masking. RESULTS: The latency average rates without contralateral noise at the frequencies 500 Hz, 1000 Hz and 2000 Hz were, respectively, 234,48, 214,96 and 236,71 milliseconds. The latency rates with noise at the same frequencies were 230,74, 214,00 and 232,15 milliseconds. CONCLUSION: The results showed latency decrease and increase on the acoustic reflex thresholds with contralateral white noise suppressor stimulus.

Luminescence studies of Sm(III) and Cm(III) complexes in NaSCN/DHDECMP extraction systems

CERN Document Server

Chung, D Y; Kimura, T

1999-01-01

Laser-induced fluorescence (LIF) studies of Sm(III) and Cm(III) complexes in the NaSCN/DHDECMP solvent extraction system were carried out. Luminescence lifetimes were measured to determine the number of water molecules coordinated to Sm(III), Tb(III), Dy(III), and Cm(III) in the sodium thiocyanate solution and in the DHDECMP phase. The hydration number of Sm(III), Tb(III), Dy(III), and Cm(III) in the sodium thiocyanate solution decreased linearly with increasing sodium thiocyanate concentration. The hydration numbers of Sm(III), Dy(III), and Cm(III) in the DHDECMP phase decreased with increasing sodium thiocyanate concentration. The water molecules in the inner coordination sphere of Sm(III) and Dy(III) extracted into the DHDECMP were not completely removed at low sodium thiocyanate concentration but decreased with increasing sodium thiocyanate concentration. However, in the case of Cm(III) extracted into the DHDECMP phase from the sodium thiocyanate solution, there was no water in the inner coordination sphe...

The DTU15 MSS (Mean Sea Surface) and DTU15LAT (Lowest Astronomical Tide) reference surface

DEFF Research Database (Denmark)

Andersen, Ole Baltazar; Stenseng, Lars; Piccioni, Gaia

in the Arctic Ocean for DTU10MSS and DTU13MSS.A new reference surface for off-shore vertical referencing is introduced. This is called the DTU15LAT.The surface is derived from the DTU15MSS and the DTU10 Global ocean tide to give a 19 year Lowest Astronomical Tide referenced to either the Mean sea surface...

78 FR 42526 - Compliance Policy Guide Sec. 690.800 Salmonella

Science.gov (United States)

2013-07-16

... food for animals. It does not create or confer any rights for or on any person and does not operate to...] Compliance Policy Guide Sec. 690.800 Salmonella in Food for Animals; Availability AGENCY: Food and Drug... Animals'' (the CPG). The CPG provides guidance to FDA staff on Salmonella-contaminated food for animals...

EIGHT γ-RAY PULSARS DISCOVERED IN BLIND FREQUENCY SEARCHES OF FERMI LAT DATA

International Nuclear Information System (INIS)

Saz Parkinson, P. M.; Dormody, M.; Ziegler, M.; Belfiore, A.; Johnson, R. P.; Ray, P. S.; Abdo, A. A.; Grove, J. E.; Gwon, C.; Ballet, J.; Baring, M. G.; Burnett, T. H.; Caliandro, G. A.; Camilo, F.; Caraveo, P. A.; De Luca, A.; Ferrara, E. C.; Harding, A. K.; Johnson, T. J.; Freire, P. C. C.

2010-01-01

We report the discovery of eight γ-ray pulsars in blind frequency searches of ∼650 source positions using the Large Area Telescope (LAT), on board the Fermi Gamma-ray Space Telescope. We present the timing models, light curves, and detailed spectral parameters of the new pulsars. PSRs J1023-5746, J1044-5737, J1413-5205, J1429-5911, and J1954+2836 are young (τ c 10 36 erg s -1 ), and located within the Galactic plane (|b| 0 ). The remaining three pulsars, PSRs J1846+0919, J1957+5033, and J2055+25, are less energetic, and located off the plane. Five pulsars are associated with sources included in the Fermi-LAT bright γ-ray source list, but only one, PSR J1413-6205, is clearly associated with an EGRET source. PSR J1023-5746 has the smallest characteristic age (τ c = 4.6 kyr) and is the most energetic ( E-dot = 1.1x10 37 erg s -1 ) of all γ-ray pulsars discovered so far in blind searches. By analyzing >100 ks of publicly available archival Chandra X-ray data, we have identified the likely counterpart of PSR J1023-5746 as a faint, highly absorbed source, CXOU J102302.8-574606. The large X-ray absorption indicates that this could be among the most distant γ-ray pulsars detected so far. PSR J1023-5746 is positionally coincident with the TeV source HESS J1023-575, located near the young stellar cluster Westerlund 2, while PSR J1954+2836 is coincident with a 4.3σ excess reported by Milagro at a median energy of 35 TeV. PSRs J1957+5033 and J2055+25 have the largest characteristic ages (τ c ∼ 1 Myr) and are the least energetic ( E-dot ∼5x10 33 erg s -1 ) of the newly discovered pulsars. We used recent XMM observations to identify the counterpart of PSR J2055+25 as XMMU J205549.4+253959. Deep radio follow-up observations of the eight pulsars resulted in no detections of pulsations and upper limits comparable to the faintest known radio pulsars, indicating that these pulsars can be included among the growing population of radio-quiet pulsars in our Galaxy being

Uniform and pitting corrosion events induced by SCN- anions on Al alloys surfaces and the effect of UV light

International Nuclear Information System (INIS)

Amin, Mohammed A.

2011-01-01

The influence of the alloying elements on the uniform and pitting corrosion processes of Al-6061, Al-4.5%Cu, Al-7.5%Cu, Al-6%Si and Al-12%Si alloys was studied in 0.50 M KSCN solution at 25 o C. Open-circuit potential, Tafel polarization, linear polarization resistance (LPR) and ICP-AES measurements were used to study the uniform corrosion process on the surfaces of the tested alloys. Cyclic polarization, potentiostatic current-time transients and impedance techniques were employed for pitting corrosion studies. Obtained results were compared with pure Al. Passivation kinetics of the tested Al samples were also studied as a function of applied potential, [SCN - ] and sample composition by means of potentiostatic current transients. The induction time, after which the growth of stable pits occurs, decreased with increasing applied potential and [SCN - ]. Regarding to uniform corrosion, alloyed Cu was found to enhance the corrosion rate, while alloyed Si suppressed it. Alloying elements of the tested samples diminished pitting attack to an extent depending on the percentage of the alloying element in the sample. Among the investigated materials, Al-Si alloys exhibited the highest corrosion resistance towards uniform and pitting corrosion processes in KSCN solutions. The passive and dissolution behaviour of Al was also studied under the conditions of continuous illumination (300-450 nm) based on cyclic polarization and potentiostatic techniques. The incident photons had a little influence on pit initiation and a marked effect on pit growth. These explained in terms of a photo-induced modification of the passive film formed on the anode surface, which render it more resistant to pitting. The effects of UV photons energy and period of illumination on the morphology of the pitted surfaces were also studied.

OMI/Aura Surface UVB Irradiance and Erythemal Dose Daily L2 Global 0.25 deg Lat/Lon Grid V003

Data.gov (United States)

National Aeronautics and Space Administration — The Version 003 of Aura-OMI Spectral Surface UVB Irradiance and Erythemal Dose Level-2G data product (Daily level-2 data binned into global 0.25 deg Lat/Lon grids)...

Aerosols in the tropical and subtropical UT/LS: in-situ measurements of submicron particle abundance and volatility

Directory of Open Access Journals (Sweden)

S. Borrmann

2010-06-01

Full Text Available Processes occurring in the tropical upper troposphere (UT, the Tropical Transition Layer (TTL, and the lower stratosphere (LS are of importance for the global climate, for stratospheric dynamics and air chemistry, and for their influence on the global distribution of water vapour, trace gases and aerosols. In this contribution we present aerosol and trace gas (in-situ measurements from the tropical UT/LS over Southern Brazil, Northern Australia, and West Africa. The instruments were operated on board of the Russian high altitude research aircraft M-55 "Geophysica" and the DLR Falcon-20 during the campaigns TROCCINOX (Araçatuba, Brazil, February 2005, SCOUT-O3 (Darwin, Australia, December 2005, and SCOUT-AMMA (Ouagadougou, Burkina Faso, August 2006. The data cover submicron particle number densities and volatility from the COndensation PArticle counting System (COPAS, as well as relevant trace gases like N₂O, ozone, and CO. We use these trace gas measurements to place the aerosol data into a broader atmospheric context. Also a juxtaposition of the submicron particle data with previous measurements over Costa Rica and other tropical locations between 1999 and 2007 (NASA DC-8 and NASA WB-57F is provided. The submicron particle number densities, as a function of altitude, were found to be remarkably constant in the tropical UT/LS altitude band for the two decades after 1987. Thus, a parameterisation suitable for models can be extracted from these measurements. Compared to the average levels in the period between 1987 and 2007 a slight increase of particle abundances was found for 2005/2006 at altitudes with potential temperatures, Θ, above 430 K. The origins of this increase are unknown except for increases measured during SCOUT-AMMA. Here the eruption of the Soufrière Hills volcano in the Caribbean caused elevated particle mixing ratios. The vertical profiles from Northern hemispheric mid-latitudes between 1999 and 2006 also are

Modulation of biosynthesis and regulatory action of 24(S),25-epoxycholesterol (S-EC) in cultured cells by progesterone (PG)

International Nuclear Information System (INIS)

Panini, S.R.; Gupta, A.K.; Sexton, R.C.; Parish, E.J.; Rudney, H.

1987-01-01

Treatment of IEC-6 cells with PG caused a strong inhibition of cholesterol biosynthesis at the level of desmosterol reductase. In addition, two new products were observed in PG-treated cells. The first compound was designated as cholesta-5,7,24-trien-3β-ol based on its HPLC chromatographic properties. The second compound was identified as S-EC based on (1) a comparison of its chromatographic properties with those of authentic EC and (2) by its conversion to 25-hydroxycholesterol (HC) upon reduction with LiAlH 4 . In spite of cellular accumulation of S-EC in the presence of PG, the activity of HMG-CoA reductase (HMGR) which is known to be sensitive to oxysterols, was elevated rather than suppressed. On the other hand, when PG-treated cells were refed fresh medium without PG, HMGR activity was suppressed. Exogenous S-EC was a potent suppressor of HMGR in untreated IEC-6 cells. Suppression of HMGR by S-EC but not by HC could be prevented by progesterone. Exogenous [ 3 H]S-EC was not metabolized by IEC-6 cells. These results support the hypothesis that S-EC plays a normal regulatory role in sterol biosynthesis and indicate that enhanced S-EC synthesis observed in the presence of PG may be due to interference with this regulatory action

Experimental determination of the high-temperature rate constant for the reaction of OH with sec-butanol.

Science.gov (United States)

Pang, Genny A; Hanson, Ronald K; Golden, David M; Bowman, Craig T

2012-10-04

The overall rate constant for the reaction of OH with sec-butanol [CH(3)CH(OH)CH(2)CH(3)] was determined from measurements of the near-first-order OH decay in shock-heated mixtures of tert-butylhydroperoxide (as a fast source of OH) with sec-butanol in excess. Three kinetic mechanisms from the literature describing sec-butanol combustion were used to examine the sensitivity of the rate constant determination to secondary kinetics. The overall rate constant determined can be described by the Arrhenius expression 6.97 × 10(-11) exp(-1550/T[K]) cm(3) molecule(-1) s(-1), valid over the temperature range of 888-1178 K. Uncertainty bounds of ±30% were found to adequately account for the uncertainty in secondary kinetics. To our knowledge, the current data represent the first efforts toward an experimentally determined rate constant for the overall reaction of OH with sec-butanol at combustion-relevant temperatures. A rate constant predicted using a structure-activity relationship from the literature was compared to the current data and previous rate constant measurements for the title reaction at atmospheric-relevant temperatures. The structure-activity relationship was found to be unable to correctly predict the measured rate constant at all temperatures where experimental data exist. We found that the three-parameter fit of 4.95 × 10(-20)T(2.66) exp(+1123/T[K]) cm(3) molecule(-1) s(-1) better describes the overall rate constant for the reaction of OH with sec-butanol from 263 to 1178 K.

Dark matter and pulsar model constraints from Galactic center Fermi/LAT γ-ray observations

Science.gov (United States)

Gordon, Chris; Macias, Oscar

2014-05-01

Employing Fermi/LAT γ-ray observations, several independent groups have found excess extended γ-ray emission at the Galactic center (GC). Both, annihilating dark matter (DM) or a population of ~ 103 unresolved millisecond pulsars (MSPs) are regarded as well motivated possible explanations. However, there is significant uncertainties in the diffuse Galactic background at the GC. We have performed a revaluation of these two models for the extended γ-ray source at the GC by accounting for the systematic uncertainties of the Galactic diffuse emission model. We also marginalize over point source and diffuse background parameters in the region of interest. We show that the excess emission is significantly more extended than a point source. We find that the DM (or pulsar population) signal is larger than the systematic errors and therefore proceed to determine the sectors of parameter space that provide an acceptable fit to the data. We found that a population of several thousand MSPs with parameters consistent with the average spectral shape of Fermi/LAT measured MSPs was able to fit the GC excess emission. For DM, we found that a pure τ+τ- annihilation channel is not a good fit to the data. But a mixture of τ+τ- and bb with a of order the thermal relic value and a DM mass of around 20 to 60 GeV provides an adequate fit.

The translocon protein Sec61 mediates antigen transport from endosomes in the cytosol for cross-presentation to CD8(+) T cells.

Science.gov (United States)

Zehner, Matthias; Marschall, Andrea L; Bos, Erik; Schloetel, Jan-Gero; Kreer, Christoph; Fehrenschild, Dagmar; Limmer, Andreas; Ossendorp, Ferry; Lang, Thorsten; Koster, Abraham J; Dübel, Stefan; Burgdorf, Sven

2015-05-19

The molecular mechanisms regulating antigen translocation into the cytosol for cross-presentation are under controversial debate, mainly because direct data is lacking. Here, we have provided direct evidence that the activity of the endoplasmic reticulum (ER) translocon protein Sec61 is essential for endosome-to-cytosol translocation. We generated a Sec61-specific intrabody, a crucial tool that trapped Sec61 in the ER and prevented its recruitment into endosomes without influencing Sec61 activity and antigen presentation in the ER. Expression of this ER intrabody inhibited antigen translocation and cross-presentation, demonstrating that endosomal Sec61 indeed mediates antigen transport across endosomal membranes. Moreover, we showed that the recruitment of Sec61 toward endosomes, and hence antigen translocation and cross-presentation, is dependent on dendritic cell activation by Toll-like receptor (TLR) ligands. These data shed light on a long-lasting question regarding antigen cross-presentation and point out a role of the ER-associated degradation machinery in compartments distinct from the ER. Copyright © 2015 Elsevier Inc. All rights reserved.

TOMS/Earth Probe UV Aerosol Index Monthly L3 Global 1x1.25 deg Lat/Lon Grid V008

Data.gov (United States)

National Aeronautics and Space Administration — This data product contains TOMS/Earth Probe UV Aerosol Index Monthly L3 Global 1x1.25 deg Lat/Lon Grid Version 8 data in ASCII format. (The shortname for this...

TOMS/Nimbus-7 UV Aerosol Index Monthly L3 Global 1x1.25 deg Lat/Lon Grid V008

Data.gov (United States)

National Aeronautics and Space Administration — This data product contains TOMS/Nimbus-7 UV Aerosol Index Monthly L3 Global 1x1.25 deg Lat/Lon Grid Version 8 data in ASCII format. The Total Ozone Mapping...

TOMS/Earth Probe Total Column Ozone Daily L3 Global 1x1.25 deg Lat/Lon Grid V008

Data.gov (United States)

National Aeronautics and Space Administration — This data product contains TOMS/Earth Probe Total Column Ozone Daily L3 Global 1x1.25 deg Lat/Lon Grid Version 8 data in ASCII format. (The shortname for this...

TOMS/Nimbus-7 Total Column Ozone Monthly L3 Global 1x1.25 deg Lat/Lon Grid V008

Data.gov (United States)

National Aeronautics and Space Administration — This data product contains TOMS/Nimbus-7 Total Column Ozone Monthly L3 Global 1x1.25 deg Lat/Lon Grid Version 8 data in ASCII format. The Total Ozone Mapping...

TOMS/Nimbus-7 UV Aerosol Index Daily L3 Global 1x1.25 deg Lat/Lon Grid V008

Data.gov (United States)

National Aeronautics and Space Administration — This data product contains TOMS/Nimbus-7 UV Aerosol Index Daily L3 Global 1x1.25 deg Lat/Lon Grid Version 8 data in ASCII format. The Total Ozone Mapping...

TOMS/Nimbus-7 Total Column Ozone Daily L3 Global 1x1.25 deg Lat/Lon Grid V008

Data.gov (United States)

National Aeronautics and Space Administration — This data product contains TOMS/Nimbus-7 Total Column Ozone Daily L3 Global 1x1.25 deg Lat/Lon Grid Version 8 data in ASCII format. The Total Ozone Mapping...

Sclérose latérale amyotrophique et traumatisme

Directory of Open Access Journals (Sweden)

M. Schachter

1959-09-01

Full Text Available À propos d'une deuxième observation personnelle de sclérose latérale amyotrophique d'origine traumatique, nous passons en revue les connaissances actuelles sur le chapitre de neuro-traumatologie. Dans l'observation présente le traumatisme cranien n'avait pas entrainé de perte de la connaissance; l'intervalle entre traumatisme et installation des premiers signes (à caractère bulbaire surtout fut de pratiquement un mois; mais on connaît des cas où cet intervalle a été de l'ordre de plusieurs années, comme dans notre première observation (15 ans. La relation entre traumatisme et maladie de Charcot est encore discutée, mais il est indubitable que ce facteur peut déclencher, à lui seul, cette maladie, sans que l'on doive faire intervenir d'autres facteurs pré-dispo-sants.

Système de prévention du risque de renversement latéral pour des véhicules évoluant en milieu naturel

OpenAIRE

Richier , M.; Lenain , R.; Thuilot , Benoît; Debain , C.

2012-01-01

International audience; Un algorithme dédié aux Véhicules Légers Tout-Terrain (VLTT) permettant l'estimation et l'anticipation du renversement est présenté dans ce papier. Il repose sur une estimation temps réel du Transfert de Charge Latéral (TCL), représentatif des instabilités dynamiques latérales. Le TCL est calculé grâce à un modèle dynamique divisé en deux projections 2D. A partir de ce modèle et d'un système de perception bas prix, un observateur est proposé. Il permet d'estimer en tem...

Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders.

Science.gov (United States)

Wolff, Markus; Johannesen, Katrine M; Hedrich, Ulrike B S; Masnada, Silvia; Rubboli, Guido; Gardella, Elena; Lesca, Gaetan; Ville, Dorothée; Milh, Mathieu; Villard, Laurent; Afenjar, Alexandra; Chantot-Bastaraud, Sandra; Mignot, Cyril; Lardennois, Caroline; Nava, Caroline; Schwarz, Niklas; Gérard, Marion; Perrin, Laurence; Doummar, Diane; Auvin, Stéphane; Miranda, Maria J; Hempel, Maja; Brilstra, Eva; Knoers, Nine; Verbeek, Nienke; van Kempen, Marjan; Braun, Kees P; Mancini, Grazia; Biskup, Saskia; Hörtnagel, Konstanze; Döcker, Miriam; Bast, Thomas; Loddenkemper, Tobias; Wong-Kisiel, Lily; Baumeister, Friedrich M; Fazeli, Walid; Striano, Pasquale; Dilena, Robertino; Fontana, Elena; Zara, Federico; Kurlemann, Gerhard; Klepper, Joerg; Thoene, Jess G; Arndt, Daniel H; Deconinck, Nicolas; Schmitt-Mechelke, Thomas; Maier, Oliver; Muhle, Hiltrud; Wical, Beverly; Finetti, Claudio; Brückner, Reinhard; Pietz, Joachim; Golla, Günther; Jillella, Dinesh; Linnet, Karen M; Charles, Perrine; Moog, Ute; Õiglane-Shlik, Eve; Mantovani, John F; Park, Kristen; Deprez, Marie; Lederer, Damien; Mary, Sandrine; Scalais, Emmanuel; Selim, Laila; Van Coster, Rudy; Lagae, Lieven; Nikanorova, Marina; Hjalgrim, Helle; Korenke, G Christoph; Trivisano, Marina; Specchio, Nicola; Ceulemans, Berten; Dorn, Thomas; Helbig, Katherine L; Hardies, Katia; Stamberger, Hannah; de Jonghe, Peter; Weckhuysen, Sarah; Lemke, Johannes R; Krägeloh-Mann, Ingeborg; Helbig, Ingo; Kluger, Gerhard; Lerche, Holger; Møller, Rikke S

2017-05-01

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infantile/childhood onset epilepsies (≥3 months of age) occur almost as often as those with an early infantile onset (<3 months), and are thus more frequent than previously reported; (ii) distinct phenotypes can be seen within the late onset group, including myoclonic-atonic epilepsy (two patients), Lennox-Gastaut not emerging from West syndrome (two patients), and focal epilepsies with an electrical status epilepticus during slow sleep-like EEG pattern (six patients); and (iii) West syndrome constitutes a common phenotype with a major recurring mutation (p.Arg853Gln: two new and four previously reported children). Other known phenotypes include Ohtahara syndrome, epilepsy of infancy with migrating focal seizures, and intellectual disability or autism without epilepsy. To assess the response to antiepileptic therapy, we retrospectively reviewed the treatment regimen and the course of the epilepsy in 66 patients for which well-documented medical information was available. We find that the use of sodium channel blockers was often associated with clinically relevant seizure reduction or seizure freedom in children with early infantile epilepsies (<3 months), whereas other antiepileptic drugs were less effective. In contrast, sodium channel blockers were rarely effective in epilepsies with later onset (≥3 months) and sometimes induced seizure worsening. Regarding the genetic findings, truncating mutations were exclusively seen in patients with late onset epilepsies and lack of response to sodium channel blockers. Functional characterization of four selected missense mutations using whole cell patch-clamping in tsA201 cells-together with data from the literature-suggest that

14 CFR Sec. 19-5 - Air transport traffic and capacity elements.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Air transport traffic and capacity elements... AIR CARRIERS Operating Statistics Classifications Sec. 19-5 Air transport traffic and capacity... reported as applicable to specified air transport traffic and capacity elements. (b) These reported items...

Route Generation for a Synthetic Character (BOT) Using a Partial or Incomplete Knowledge Route Generation Algorithm in UT2004 Virtual Environment

Science.gov (United States)

Hanold, Gregg T.; Hanold, David T.

2010-01-01

This paper presents a new Route Generation Algorithm that accurately and realistically represents human route planning and navigation for Military Operations in Urban Terrain (MOUT). The accuracy of this algorithm in representing human behavior is measured using the Unreal Tournament(Trademark) 2004 (UT2004) Game Engine to provide the simulation environment in which the differences between the routes taken by the human player and those of a Synthetic Agent (BOT) executing the A-star algorithm and the new Route Generation Algorithm can be compared. The new Route Generation Algorithm computes the BOT route based on partial or incomplete knowledge received from the UT2004 game engine during game play. To allow BOT navigation to occur continuously throughout the game play with incomplete knowledge of the terrain, a spatial network model of the UT2004 MOUT terrain is captured and stored in an Oracle 11 9 Spatial Data Object (SOO). The SOO allows a partial data query to be executed to generate continuous route updates based on the terrain knowledge, and stored dynamic BOT, Player and environmental parameters returned by the query. The partial data query permits the dynamic adjustment of the planned routes by the Route Generation Algorithm based on the current state of the environment during a simulation. The dynamic nature of this algorithm more accurately allows the BOT to mimic the routes taken by the human executing under the same conditions thereby improving the realism of the BOT in a MOUT simulation environment.

Decaying dark matter in light of the PAMELA and Fermi LAT data

International Nuclear Information System (INIS)

Ibarra, Alejandro; Tran, David

2009-06-01

A series of experiments measuring high-energy cosmic rays have recently reported strong indications for the existence of an exotic source of high-energy electrons and positrons. If interpreted in terms of the decay of dark matter particles, the PAMELA measurements of the positron fraction and the Fermi LAT measurements of the total electron plus positron flux restrict the possible decaying dark matter scenarios to a few cases. Pursuing a model-independent approach, we identify some promising scenarios of dark matter decay and calculate the predictions for the diffuse extragalactic gamma-ray flux, including the contributions from inverse Compton scattering with the interstellar radiation field. (orig.)

Informação empresarial: dos sistemas transacionais à latência zero

Directory of Open Access Journals (Sweden)

Orandi Mina Falsarella

Full Text Available De cunho teórico e conceitual, o texto discorre sobre o uso das Tecnologias de Informação nas empresas em geral. Apresenta os conceitos básicos atribuídos à informação nesse ambiente e discorre sobre os diversos tipos de sistemas computadorizados de informações, disponíveis atualmente para as empresas. Discute o conceito de Latência Zero que, por meio de indicadores, contribui para o monitoramento do ambiente nas organizações, permitindo melhorar o tempo entre a ocorrência de um determinado evento e a tomada de decisão.

Experimental results from CEM-UTS single shot 9 mj railgun

International Nuclear Information System (INIS)

Hayes, R.J.; Zowarka, R.C.

1991-01-01

The Center for Electromechanics at the University of Texas at Austin (CEM-UT) has designed and fabricated a 10-m long 90 mm bore railgun. During the test program, a number of solid armatures and projectile packages have been tested in a 50 m deep vertical test range. The experiments are powered by six homopolar generator (HPG) charged inductive stores, sequentially staged to provide the desired acceleration profile. Prior to testing, computer simulations are run to determine the preferred current profile and predict system performance. During projectile flight, high speed films, x-rays, muzzle volts, and velocity/acceleration profiles are recorded along with power supply operating parameters. Postshot diagnostics include bore wear analysis and armature and target recovery. Comparisons of predicted and recorded shot performance are also made. On selected tests, an energy balance is performed to determine efficiencies of the various system components. In this paper, a summary of all 90 mm gun shots is presented along with critical data collected from selected tests

Targeting cell migration and the endoplasmic reticulum stress response with calmodulin antagonists: a clinically tested small molecule phenocopy of SEC62 gene silencing in human tumor cells

International Nuclear Information System (INIS)

Linxweiler, Maximilian; Greiner, Markus; Schorr, Stefan; Schäuble, Nico; Jung, Martin; Linxweiler, Johannes; Langer, Frank; Schäfers, Hans-Joachim; Cavalié, Adolfo; Zimmermann, Richard

2013-01-01

Tumor cells benefit from their ability to avoid apoptosis and invade other tissues. The endoplasmic reticulum (ER) membrane protein Sec62 is a key player in these processes. Sec62 is essential for cell migration and protects tumor cells against thapsigargin-induced ER stress, which are both linked to cytosolic Ca 2+ . SEC62 silencing leads to elevated cytosolic Ca 2+ and increased ER Ca 2+ leakage after thapsigargin treatment. Sec62 protein levels are significantly increased in different tumors, including prostate, lung and thyroid cancer. In lung cancer, the influence of Sec62 protein levels on patient survival was analyzed using the Kaplan-Meier method and log-rank test. To elucidate the underlying pathophysiological functions of Sec62, Ca 2+ imaging techniques, real-time cell analysis and cell migration assays were performed. The effects of treatment with the calmodulin antagonists, trifluoperazine (TFP) and ophiobolin A, on cellular Ca 2+ homeostasis, cell growth and cell migration were compared with the effects of siRNA-mediated Sec62 depletion or the expression of a mutated SEC62 variant in vitro. Using Biacore analysis we examined the Ca 2+ -sensitive interaction of Sec62 with the Sec61 complex. Sec62 overproduction significantly correlated with reduced patient survival. Therefore, Sec62 is not only a predictive marker for this type of tumor, but also an interesting therapeutic target. The present study suggests a regulatory function for Sec62 in the major Ca 2+ leakage channel in the ER, Sec61, by a direct and Ca 2+ -sensitive interaction. A Ca 2+ -binding motif in Sec62 is essential for its molecular function. Treatment of cells with calmodulin antagonists mimicked Sec62 depletion by inhibiting cell migration and rendering the cells sensitive to thapsigargin treatment. Targeting tumors that overproduce Sec62 with calmodulin antagonists in combination with targeted thapsigargin analogues may offer novel personalized therapeutic options

75 FR 66769 - Draft Compliance Policy Guide Sec. 690.800 Salmonella

Science.gov (United States)

2010-10-29

...] Draft Compliance Policy Guide Sec. 690.800 Salmonella in Animal Feed; Availability; Extension of Comment... that are adulterated due to the presence of Salmonella. The Agency is taking this action in response to... action against animal feed or feed ingredients that are adulterated due to the presence of Salmonella...

Water Resources Data, Colorado, Water Year 1999. Volume 1. Missouri River Basin, Arkansas River Basin, and Rio Grande Basin

Science.gov (United States)

2000-04-01

because they are subject to change. Current prices can be obtained by writing to the above address. When ordering or inquiring about prices for any...CO WATER-QUALITY RECORDS LOCATIOI -Lat 38=16󈧖», long 104°43󈧇", in SEV4 NEV4 sec.36, T.20 S. ielt bank 200 ft downstream from northeast comer of

Generation of the SCN1A epilepsy mutation in hiPS cells using the TALEN technique

Science.gov (United States)

Chen, Wanjuan; Liu, Jingxin; Zhang, Longmei; Xu, Huijuan; Guo, Xiaogang; Deng, Sihao; Liu, Lipeng; Yu, Daiguan; Chen, Yonglong; Li, Zhiyuan

2014-06-01

Human induced pluripotent stem cells (iPSC) can be used to understand the pathological mechanisms of human disease. These cells are a promising source for cell-replacement therapy. However, such studies require genetically defined conditions. Such genetic manipulations can be performed using the novel Transcription Activator-Like Effector Nucleases (TALENs), which generate site-specific double-strand DNA breaks (DSBs) with high efficiency and precision. Combining the TALEN and iPSC methods, we developed two iPS cell lines by generating the point mutation A5768G in the SCN1A gene, which encodes the voltage-gated sodium channel Nav1.1 α subunit. The engineered iPSC maintained pluripotency and successfully differentiated into neurons with normal functional characteristics. The two cell lines differ exclusively at the epilepsy-susceptibility variant. The ability to robustly introduce disease-causing point mutations in normal hiPS cell lines can be used to generate a human cell model for studying epileptic mechanisms and for drug screening.

Development and validation of real-time SAFT-UT system for inservice inspection of LWRs

International Nuclear Information System (INIS)

Doctor, S.R.; Hall, T.E.; Reid, L.D.; Mart, G.A.

1988-01-01

The Pacific Northwest Laboratory is working to design, fabricate, and evaluate a real-time flaw detection and characterization system based on the synthetic aperture focusing technique for ultrasonic testing (SAFT-UT). The system is designed to perform inservice inspection of light-water reactor components. Included objectives of this program for the Nuclear Regulatory Commission are to develop procedures for system calibration and field operation, to validate the system through laboratory and field inspections, and to generate an engineering database to support ASME Code acceptance of the technology. This progress report covers the programmatic work from October 1986 through September 1987. (author)

The Solar Neighborhood. XXV. Discovery of New Proper Motion Stars with 0.40 sec/yr > mu > or = 0.18 sec/yr Between Declinations -47 deg and 00 deg

Science.gov (United States)

Boyd, Mark R.; Winters, Jennifer G.; Henry, Todd J.; Jao, Wei-Chun; Finch, Charlie T.; Subasavage, John P.; Hambly, Nigel C.

2011-01-01

We present 2817 new southern proper motion systems with 0.40 sec/yr > mu > or = 0.18 sec/yr and declination between 47 deg and 00 deg. This is a continuation of the SuperCOSMOS-RECONS (SCR) proper motion searches of the southern sky. We use the same photometric relations as previous searches to provide distance estimates based on the assumption that the objects are single main-sequence stars. We find 79 new red dwarf systems predicted to be within 25 pc, including a few new components of previously known systems. Two systems--SCR 1731-2452 at 9.5 pc and SCR 1746-3214 at 9.9 pc--are anticipated to be within 10 pc. We also find 23 new white dwarf (WD) candidates with distance estimates of 15-66 pc, as well as 360 new red subdwarf candidates. With this search, we complete the SCR sweep of the southern sky for stars with mu > or = 0.18 sec/yr and R(sub 59F) < or = 16.5, resulting in a total of 5042 objects in 4724 previously unreported proper motion systems. Here we provide selected comprehensive lists from our SCR proper motion search to date, including 152 red dwarf systems estimated to be within 25 pc (9 within 10 pc), 46 WDs (10 within 25 pc), and 598 subdwarf candidates. The results of this search suggest that there are more nearby systems to be found at fainter magnitudes and lower proper motion limits than those probed so far.

O plantão noturno em anestesia reduz a latência ao sono

OpenAIRE

Mathias, Lígia Andrade da Silva Telles; Coelho, Christina Morotomi Funatsu; Vilela, Elizabeth Pricoli; Vieira, Joaquim Edson; Pagnocca, Marcelo Lacava

2004-01-01

JUSTIFICATIVA E OBJETIVOS: Os médicos em geral, os anestesiologistas em particular, têm jornadas de trabalho prolongadas. Os residentes de Anestesiologia podem apresentar fadiga e estresse significativos. O objetivo deste trabalho foi verificar, em residentes de primeiro e segundo anos a latência do sono em períodos após plantão. MÉTODO: Foram avaliados 11 residentes em situações distintas: às 7 horas da manhã, após noite de sono normal (> 7h), sem plantão nos 3 dias anteriores (M1); às 7 hor...

Generating randomised virtualised scenarios for ethical hacking and computer security education: SecGen implementation and deployment

OpenAIRE

Schreuders, ZC; Ardern, L

2015-01-01

Computer security students benefit from having hands-on experience with hacking tools and with access to vulnerable systems that they can attack and defend. However, vulnerable VMs are static; once they have been exploited by a student there is no repeatable challenge as the vulnerable boxes never change. A new novel solution, SecGen, has been created and deployed. SecGen solves the issue by creating vulnerable machines with randomised vulnerabilities and services, with constraints that ensur...

Dark matter and pulsar model constraints from Galactic Center Fermi-LAT gamma-ray observations

Science.gov (United States)

Gordon, Chris; Macías, Oscar

2013-10-01

Employing Fermi-LAT gamma-ray observations, several independent groups have found excess extended gamma-ray emission at the Galactic Center (GC). Both annihilating dark matter (DM) or a population of ˜103 unresolved millisecond pulsars (MSPs) are regarded as well-motivated possible explanations. However, there are significant uncertainties in the diffuse galactic background at the GC. We have performed a revaluation of these two models for the extended gamma-ray source at the GC by accounting for the systematic uncertainties of the Galactic diffuse emission model. We also marginalize over point-source and diffuse background parameters in the region of interest. We show that the excess emission is significantly more extended than a point source. We find that the DM (or pulsar-population) signal is larger than the systematic errors and therefore proceed to determine the sectors of parameter space that provide an acceptable fit to the data. We find that a population of 1000-2000 MSPs with parameters consistent with the average spectral shape of Fermi-LAT measured MSPs is able to fit the GC excess emission. For DM, we find that a pure τ+τ- annihilation channel is not a good fit to the data. But a mixture of τ+τ- and bb¯ with a ⟨σv⟩ of order the thermal relic value and a DM mass of around 20 to 60 GeV provides an adequate fit.

Evaluation of the Monotonic Lagrangian Grid and Lat-Long Grid for Air Traffic Management

Science.gov (United States)

Kaplan, Carolyn; Dahm, Johann; Oran, Elaine; Alexandrov, Natalia; Boris, Jay

2011-01-01

The Air Traffic Monotonic Lagrangian Grid (ATMLG) is used to simulate a 24 hour period of air traffic flow in the National Airspace System (NAS). During this time period, there are 41,594 flights over the United States, and the flight plan information (departure and arrival airports and times, and waypoints along the way) are obtained from an Federal Aviation Administration (FAA) Enhanced Traffic Management System (ETMS) dataset. Two simulation procedures are tested and compared: one based on the Monotonic Lagrangian Grid (MLG), and the other based on the stationary Latitude-Longitude (Lat- Long) grid. Simulating one full day of air traffic over the United States required the following amounts of CPU time on a single processor of an SGI Altix: 88 s for the MLG method, and 163 s for the Lat-Long grid method. We present a discussion of the amount of CPU time required for each of the simulation processes (updating aircraft trajectories, sorting, conflict detection and resolution, etc.), and show that the main advantage of the MLG method is that it is a general sorting algorithm that can sort on multiple properties. We discuss how many MLG neighbors must be considered in the separation assurance procedure in order to ensure a five-mile separation buffer between aircraft, and we investigate the effect of removing waypoints from aircraft trajectories. When aircraft choose their own trajectory, there are more flights with shorter duration times and fewer CD&R maneuvers, resulting in significant fuel savings.

NEW FERMI-LAT EVENT RECONSTRUCTION REVEALS MORE HIGH-ENERGY GAMMA RAYS FROM GAMMA-RAY BURSTS

Energy Technology Data Exchange (ETDEWEB)

Atwood, W. B. [Santa Cruz Institute for Particle Physics, Department of Physics and Department of Astronomy and Astrophysics, University of California at Santa Cruz, Santa Cruz, CA 95064 (United States); Baldini, L. [Universita di Pisa and Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, I-56127 Pisa (Italy); Bregeon, J.; Pesce-Rollins, M.; Sgro, C.; Tinivella, M. [Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, I-56127 Pisa (Italy); Bruel, P. [Laboratoire Leprince-Ringuet, Ecole polytechnique, CNRS/IN2P3, Palaiseau (France); Chekhtman, A. [Center for Earth Observing and Space Research, College of Science, George Mason University, Fairfax, VA 22030 (United States); Cohen-Tanugi, J. [Laboratoire Univers et Particules de Montpellier, Universite Montpellier 2, CNRS/IN2P3, F-34095 Montpellier (France); Drlica-Wagner, A.; Omodei, N.; Rochester, L. S.; Usher, T. L. [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); Granot, J. [Department of Natural Sciences, The Open University of Israel, 1 University Road, P.O. Box 808, Ra' anana 43537 (Israel); Longo, F. [Istituto Nazionale di Fisica Nucleare, Sezione di Trieste, I-34127 Trieste (Italy); Razzaque, S. [Department of Physics, University of Johannesburg, Auckland Park 2006 (South Africa); Zimmer, S., E-mail: melissa.pesce.rollins@pi.infn.it, E-mail: nicola.omodei@stanford.edu, E-mail: granot@openu.ac.il [Department of Physics, Stockholm University, AlbaNova, SE-106 91 Stockholm (Sweden)

2013-09-01

Based on the experience gained during the four and a half years of the mission, the Fermi-LAT Collaboration has undertaken a comprehensive revision of the event-level analysis going under the name of Pass 8. Although it is not yet finalized, we can test the improvements in the new event reconstruction with the special case of the prompt phase of bright gamma-ray bursts (GRBs), where the signal-to-noise ratio is large enough that loose selection cuts are sufficient to identify gamma rays associated with the source. Using the new event reconstruction, we have re-analyzed 10 GRBs previously detected by the Large Area Telescope (LAT) for which an X-ray/optical follow-up was possible and found four new gamma rays with energies greater than 10 GeV in addition to the seven previously known. Among these four is a 27.4 GeV gamma ray from GRB 080916C, which has a redshift of 4.35, thus making it the gamma ray with the highest intrinsic energy ({approx}147 GeV) detected from a GRB. We present here the salient aspects of the new event reconstruction and discuss the scientific implications of these new high-energy gamma rays, such as constraining extragalactic background light models, Lorentz invariance violation tests, the prompt emission mechanism, and the bulk Lorentz factor of the emitting region.

The SecA2 pathway of Mycobacterium tuberculosis exports effectors that work in concert to arrest phagosome and autophagosome maturation.

Science.gov (United States)

Zulauf, Katelyn E; Sullivan, Jonathan Tabb; Braunstein, Miriam

2018-04-30

To subvert host defenses, Mycobacterium tuberculosis (Mtb) avoids being delivered to degradative phagolysosomes in macrophages by arresting the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. The SecA2 dependent protein export system is required for phagosome maturation arrest and consequently growth of Mtb in macrophages. To better understand the role of the SecA2 pathway in phagosome maturation arrest, we identified two effectors exported by SecA2 that contribute to this process: the phosphatase SapM and the kinase PknG. Then, utilizing the secA2 mutant of Mtb as a platform to study effector functions, we identified specific steps in phagosome maturation inhibited by SapM and/or PknG. By identifying a histidine residue that is essential for SapM phosphatase activity, we confirmed for the first time that the phosphatase activity of SapM is required for its effects on phagosome maturation in macrophages. We further demonstrated that SecA2 export of SapM and PknG contributes to the ability of Mtb to replicate in macrophages. Finally, we extended our understanding of the SecA2 pathway, SapM, and PknG by revealing that their contribution goes beyond preventing Mtb delivery to mature phagolysosomes and includes inhibiting Mtb delivery to autophagolysosomes. Together, our results revealed SapM and PknG to be two effectors exported by the SecA2 pathway of Mtb with distinct as well as cumulative effects on phagosome and autophagosome maturation. Our results further reveal that Mtb must have additional mechanisms of limiting acidification of the phagosome, beyond inhibiting recruitment of the V-ATPase proton pump to the phagosome, and they indicate differences between effects of Mtb on phagosome and autophagosome maturation.

Recent activity of the Rapid Burster (MXB 1730-335)

DEFF Research Database (Denmark)

Kuulkers, E.; Brandt, Søren Kristian; Markwardt, C.

2008-01-01

Observations taken as part of the INTEGRAL Galactic bulge monitoring program (see ATel #1385) on 2008, February 23 13:32-17:13 (UT) showed bursting activity from the X-ray transient, the Rapid Burster (MXB 1730-335). During one of the 1800-sec pointings when the source was in the field- of-view o...

Welfare Effects of Tax and Price Changes and the CES-UT Utility Function

DEFF Research Database (Denmark)

Munk, Knud Jørgen

Dixit's 1975 paper "Welfare Effects of Tax and Price Changes" constitutes a seminal contribution to the theory of tax reform within a second-best general equilibrium framework. The present paper clarifies ambiguities with respect to normalisation which has led to misinterpretation of some of Dixit......'s analytical results. It proves that a marginal tax reform starting from a proportional tax system will improve social welfare if it increases the supply of labour, whatever the rule of normalisation adopted. In models which impose additive separability between consumption and leisure in household preferences...... elasticities can be derived from the parameters of the CES-UT and how it may be used for applied tax reform analysis...

Hydrogen Production From Water By Thermo-Chemical Methods (UT-3): Evaluation of Side Reactions By Simulation Process

International Nuclear Information System (INIS)

Rusli, A.

1997-01-01

Hydogen fuel with its advantages will be able to replace all the positions of fossil fuels post o il and gas or migas . Among the advantages of hydrogen fuel are pollution free, abundant of raw material in the form of water molecule, flexible in application, able to stroge and transport as well as fossil energy sources (oil and gas). Hydogen could be produced from water by means of thermochemical, thermolysis, photolysis and electrolysis. Nuclear heat (HTGR), solar heat or waste heat from steel industry can be used as energy source for these processes. In case of thermochemical method, some problems realated to production process should be studied and evaluated. Simulation is considered can be applied to study the effects of side reactions and also to resolve its problems in hydrogen production process. In this paper is reported the evalution results of hydrogen production process by thermochemical (UT-3) through both of the experimental and computer simulation. It has been proposed a new flow chart of hydrogen production to achieve the hydrogen production continuously. A simulator has been developed based on experimental data and related mathematical equations. This simulator can be used to scle-up the UT-3 thermochemical cycle for hydrogen production process

The radio and optical counterpart of the new Fermi LAT flaring source J0109+6134

Science.gov (United States)

Paredes, J. M.; Martí, J.; Peracaula, M.

2010-02-01

Following the recent ATELs #2414, #2416 and #2420 concerning the Fermi-LAT, AGILE and Swift/XRT consistent detections of the new gamma-ray flaring source J0109+6134, we wish to remind that the proposed radio counterpart (VCS2 J0109+6133/GT 0106+613) was extensively observed nearly two decades ago by different authors in the context of the GT catalogue of Galactic Plane radio sources (Taylor and Gregory 1983, AJ, 88, 1784; Gregory and Taylor 1986, AJ 92, 371).

Development and implementation of UT procedures for nuclear and other applications using TRL phased array probes

International Nuclear Information System (INIS)

Chardome, V.; Delaide, M.; Cermak, J.; Cruysweegs, E.; Plateau, M.

2006-01-01

In the past, Vincotte developed, qualified and applied various UT procedures for the automated in-service inspection of austenitic and dissimilar metal welds, using conventional ultrasonic probes. In a process of continuous improvement, Vincotte is upgrading these existing procedures by applying low frequency TRL phased array probes. This presentation situates this recent innovation within the phased array history of Vincotte. Particular attention will be paid to these newest phased array developments, in terms of probe development, angled beam generation and scanning patterns. (orig.)

Further X-ray observations of Nova Del 2013 with Swift

Science.gov (United States)

Nelson, T.; Mukai, K.; Chomiuk, L.; Sokoloski, J.; Weston, J.; Zheng, Y.; Rupen, M.; Mioduszewski, A.; Linford, J.; Finzell, T.

2013-08-01

We observed Nova Del 2013 (see CBET #3628) with the Swift satellite on 2013-08-18, four days after discovery (see also ATEL #5283). The exposures were carried out between 0.0 and 15.7 UT, and are therefore coincident with the first appearance of gamma-ray emission from this nova as seen with the Fermi-LAT (ATEL #5302). The XRT instrument was operated in Window Timing (WT) in order to mitigate the impact of optical loading on the CCD, and the total exposure time was 4522s.

HESS J1640–465 AND HESS J1641–463: TWO INTRIGUING TeV SOURCES IN LIGHT OF NEW FERMI-LAT OBSERVATIONS

Energy Technology Data Exchange (ETDEWEB)

Lemoine-Goumard, M.; Grondin, M.-H.; Laffon, H.; Reposeur, T. [Centre d' Études Nucléaires de Bordeaux Gradignan, IN2P3/CNRS, Université Bordeaux 1, BP120, F-33175 Gradignan Cedex (France); Acero, F.; Ballet, J., E-mail: lemoine@cenbg.in2p3.fr, E-mail: grondin@cenbg.in2p3.fr [Laboratoire AIM, CEA-IRFU/CNRS/Université Paris Diderot, Service d' Astrophysique, CEA Saclay, F-91191 Gif sur Yvette (France)

2014-10-10

We report on γ-ray analysis of the region containing the bright TeV source HESS J1640–465 and the close-by TeV source HESS J1641–463 using 64 months of observations with the Fermi Large Area Telescope (LAT). Previously only one GeV source was reported in this region and was associated with HESS J1640–465. With an increased data set and the improved sensitivity afforded by the reprocessed data (P7REP) of the LAT, we now report the detection, morphological study, and spectral analysis of two distinct sources above 100 MeV. The softest emission in this region comes from the TeV source HESS J1641–463 which is well fitted with a power law of index Γ = 2.47 ± 0.05 ± 0.06 and presents no significant γ-ray signal above 10 GeV, which contrasts with its hard spectrum at TeV energies. The Fermi-LAT spectrum of the second TeV source, HESS J1640–465 is well described by a power-law shape of index Γ = 1.99 ± 0.04 ± 0.07 that links up naturally with the spectral data points obtained by the High Energy Stereoscopic System (H.E.S.S.). These new results provide new constraints concerning the identification of these two puzzling γ-ray sources.

HESS J1640–465 AND HESS J1641–463: TWO INTRIGUING TeV SOURCES IN LIGHT OF NEW FERMI-LAT OBSERVATIONS

International Nuclear Information System (INIS)

Lemoine-Goumard, M.; Grondin, M.-H.; Laffon, H.; Reposeur, T.; Acero, F.; Ballet, J.

2014-01-01

We report on γ-ray analysis of the region containing the bright TeV source HESS J1640–465 and the close-by TeV source HESS J1641–463 using 64 months of observations with the Fermi Large Area Telescope (LAT). Previously only one GeV source was reported in this region and was associated with HESS J1640–465. With an increased data set and the improved sensitivity afforded by the reprocessed data (P7REP) of the LAT, we now report the detection, morphological study, and spectral analysis of two distinct sources above 100 MeV. The softest emission in this region comes from the TeV source HESS J1641–463 which is well fitted with a power law of index Γ = 2.47 ± 0.05 ± 0.06 and presents no significant γ-ray signal above 10 GeV, which contrasts with its hard spectrum at TeV energies. The Fermi-LAT spectrum of the second TeV source, HESS J1640–465 is well described by a power-law shape of index Γ = 1.99 ± 0.04 ± 0.07 that links up naturally with the spectral data points obtained by the High Energy Stereoscopic System (H.E.S.S.). These new results provide new constraints concerning the identification of these two puzzling γ-ray sources

Cloning, purification, crystallization and preliminary crystallographic analysis of SecA from Enterococcus faecalis

International Nuclear Information System (INIS)

Meining, Winfried; Scheuring, Johannes; Fischer, Markus; Weinkauf, Sevil

2006-01-01

SecA ATPase from E. faecalis has been cloned, overexpressed, purified and crystallized. Crystals belong to space group C2 and diffract to 2.4 Å resolution. The gene coding for SecA from Enterococcus faecalis was cloned and overexpressed in Escherichia coli. In this protein, the lysine at position 6 was replaced by an asparagine in order to reduce sensitivity towards proteases. The modified protein was purified and crystallized. Crystals diffracting to 2.4 Å resolution were obtained using the vapour-diffusion technique. The crystals belong to the monoclinic space group C2, with unit-cell parameters a = 203.4, b = 49.8, c = 100.8 Å, α = γ = 90.0, β = 119.1°. A selenomethionine derivative was prepared and is currently being tested in crystallization trials

75 FR 27028 - Joint CFTC-SEC Advisory Committee on Emerging Regulatory Issues

Science.gov (United States)

2010-05-13

... regulatory issues and their potential impact on investors and the securities markets. The Committee will lend... SECURITIES AND EXCHANGE COMMISSION [Release No. 33-9123; File No. 265-26] COMMODITY FUTURES TRADING COMMISSION Joint CFTC-SEC Advisory Committee on Emerging Regulatory Issues AGENCY: Securities and...

La mujer en el radiador en Cabeza borradora (Eraserhead, 1972-1976) de David Lynch: disección utópica del ojo

OpenAIRE

Villaplana Ruiz, Virginia

1998-01-01

Villaplana, V. (1998). La mujer en el radiador en Cabeza borradora (Eraserhead, 1972-1976) de David Lynch: disección utópica del ojo. Banda aparte. (11):29-31. http://hdl.handle.net/10251/43165. 29 31 11

Relação entre potenciais evocados auditivos de média latência e distúrbio de processamento auditivo: estudo de casos

Directory of Open Access Journals (Sweden)

Ana Carla Leite Romero

2013-04-01

Full Text Available O Potencial Evocado Auditivo de Média Latência é um teste objetivo promissor na audiologia na pesquisa neuro-diagnóstica das disfunções do sistema auditivo. Tem como vantagens a precisão e objetividade na avaliação e por isso é útil em crianças. O presente estudo teve como objetivo analisar os potenciais evocados auditivos de média latência em dois pacientes com distúrbio de processamento auditivo e relacionar as medidas objetivas e comportamentais. Para tanto foi realizado estudo de caso de dois pacientes (P1= feminino, 12 anos; P2= masculino, 17 anos, ambos com ausência de alterações sensoriais, distúrbios neurológicos, neuropsiquiátricos. Ambos foram submetidos à anamnese, inspeção do meato acústico externo, avaliação audiológica e avaliação do exame de potencial evocado auditivo de média latência. Houve associação significante entre os resultados dos exames comportamentais e objetivos. Na anamnese, houve queixas referentes à dificuldade de escuta em ambiente ruidoso, localização sonora, desatenção, além de trocas fonológicas na escrita e na fala. Foram observadas alterações no processo de decodificação auditiva à direita em ambos os casos na avaliação comportamental do processamento auditivo e no exame de potencial evocado auditivo de média latência a resposta da via contralateral direita foi deficitária, confirmando as dificuldades dos pacientes estudados na atribuição de significado às informações acústicas em condição de competição sonora à direita nos dois casos. Para os casos estudados comprovou-se à associação entre os resultados, porém há necessidade de novos estudos com maior amostra para confirmação dos dados.

Flecainide provocation reveals concealed brugada syndrome in a long QT syndrome family with a novel L1786Q mutation in SCN5A

DEFF Research Database (Denmark)

Kanters, Jørgen K.; Yuan, Lei; Hedley, Paula L

2014-01-01

BACKGROUND: Mutations in SCN5A can result in both long QT type 3 (LQT3) and Brugada syndrome (BrS), and a few mutations have been found to have an overlapping phenotype. Long QT syndrome is characterized by prolonged QT interval, and a prerequisite for a BrS diagnosis is ST elevation in the right...... interval. The proband presented with an aborted cardiac arrest, and his mother died suddenly and unexpectedly at the age of 65. Flecainide treatment revealed coved ST elevation in all mutation carriers. Electrophysiological investigations of the mutant in HEK293 cells indicated a reduced peak current...

Knowledge Management in Scientific and Technical Support Organizations for Regulatory Bodies: SEC NRS Experience

International Nuclear Information System (INIS)

Saulskaya, N.

2016-01-01

Full text: Nuclear industry, similar to other high-tech industries, is based on knowledge and to a great extent depends on personnel qualification, their skills and abilities. Knowledge management processes were recognized of the utmost importance for the IAEA. The IAEA GA adopted a number of resolutions on nuclear knowledge. In this context, knowledge management is considered as an integrated, systematic approach to the process of assessment, obtaining, development, distribution, use, transfer and maintenance of knowledge related to achievement of strategic targets of organization development. KM makes it possible to learn lessons from its own experience. The report presents a long-term experience of SEC NRS in knowledge management and capacity building, which is critically important for SEC NRS as scientific and technical support organization for Rostechnadzor. KM in SEC NRS is performed through the HRM, primarily through HRD, assessment, motivation of the labor activity, and regulation of social-psychological processes. The practice of implementation of NKM through the functions of human resources management is of particular interest for embarking countries. The best practices will be reflected in the IAEA Safety Report “Knowledge Management for Regulatory Bodies and TSO”, which is currently being developed by a team of the IAEA experts. (author

Experimental determination of the isothermal (vapour + liquid) equilibria of binary aqueous solutions of sec-butylamine and cyclohexylamine at several temperatures

Energy Technology Data Exchange (ETDEWEB)

Chiali-Baba Ahmed, Nouria [LATA2M, Laboratoire de Thermodynamique Appliquee et Modelisation Moleculaire, University AbouBekr Belkaid of Tlemcen, Post Office Box 119, Tlemcen 13000 (Algeria); Negadi, Latifa, E-mail: latifanegadi@yahoo.fr [LATA2M, Laboratoire de Thermodynamique Appliquee et Modelisation Moleculaire, University AbouBekr Belkaid of Tlemcen, Post Office Box 119, Tlemcen 13000 (Algeria); Mokbel, Ilham [LSA, Laboratoire des Sciences Analytiques, CNRS-UMR 5280, Universite Claude Bernard - Lyon I, 43, Bd du 11 Novembre 1918, Villeurbanne Cedex 69622 (France); Kaci, Ahmed Ait [Laboratoire de Thermodynamique et Modelisation Moleculaire, Universite des Sciences et de la Technologie Houari Boumediene, Post Office Box 32, El Alia 16111, Bab Ezzouar (Algeria); Jose, Jacques [LSA, Laboratoire des Sciences Analytiques, CNRS-UMR 5280, Universite Claude Bernard - Lyon I, 43, Bd du 11 Novembre 1918, Villeurbanne Cedex 69622 (France)

2012-01-15

Highlights: > Vapour pressures of sec-butylamine or cyclohexylamine and their aqueous solutions. > The investigated temperatures are 273 K and 363 K. > The (cyclohexylamine + water) mixture shows positive azeotropic behaviour. > The (sec-butylamine + water) or (cyclohexylamine + water) exhibit positive G{sup E}. - Abstract: The vapour pressures of (sec-butylamine + water), (cyclohexylamine + water) binary mixtures, and of pure sec-butylamine and cyclohexylamine components were measured by means of two static devices at temperatures between 293 (or 273) K and 363 K. The data were correlated with the Antoine equation. From these data, excess Gibbs functions (G{sup E}) were calculated for several constant temperatures and fitted to a fourth-order Redlich-Kister equation using the Barker's method. The (cyclohexylamine + water) system shows positive azeotropic behaviour for all investigated temperatures. The two binary mixtures exhibit positive deviations in G{sup E} for all investigated temperatures over the whole composition range.

Geophysical excitation of LOD/UT1 estimated from the output of the global circulation models of the atmosphere - ERA-40 reanalysis and of the ocean - OMCT

Science.gov (United States)

Korbacz, A.; Brzeziński, A.; Thomas, M.

2008-04-01

We use new estimates of the global atmospheric and oceanic angular momenta (AAM, OAM) to study the influence on LOD/UT1. The AAM series was calculated from the output fields of the atmospheric general circulation model ERA-40 reanalysis. The OAM series is an outcome of global ocean model OMCT simulation driven by global fields of the atmospheric parameters from the ERA- 40 reanalysis. The excitation data cover the period between 1963 and 2001. Our calculations concern atmospheric and oceanic effects in LOD/UT1 over the periods between 20 days and decades. Results are compared to those derived from the alternative AAM/OAM data sets.

Fermi LAT detection of renewed strong GeV activity from the FSRQ 3C 279

Science.gov (United States)

Ojha, Roopesh; van Zyl, Pfesesani; Fermi Large Area Telescope Collaboration

2018-04-01

The Large Area Telescope (LAT), one of two instruments on the Fermi Gamma-ray Space Telescope, has observed an intense and hard gamma-ray flare from a source positionally consistent with the flat spectrum radio quasar 3C 279, also known as 3FGL J1256.1-0547 (Acero et al. 2015, ApJS, 218, 23), with radio coordinates R.A.: 12h56m11.1665s, Dec: -05d47m21.523s (J2000.0; Johnston et al. 1995, AJ, 110, 880).

Influence of Herpes Simplex Virus Latency-Associated Transcript (LAT) on the Distribution of Latently Infected Neurons

Science.gov (United States)

2007-03-20

the Qiagen AllPrep DNA/RNA Minikit ( Valencia , CA) after homogenization with an Omni rotor-stator homogenizer with disposable tips (Omni...VP19, VP23, and VP26. VP5 makes pentons ( orange ) and hexons (red), connected by triplexes of VP19 and VP23 (green). Hexons are decorated at the...A. Mallakin, D. C. Bloom , and J. M. Hill. 2003. Overlapping subdeletions within a 348-bp in the 5’ exon of the LAT region that facilitates

Differential effects of common variants in SCN2A on general cognitive ability, brain physiology, and messenger RNA expression in schizophrenia cases and control individuals.

Science.gov (United States)

Dickinson, Dwight; Straub, Richard E; Trampush, Joey W; Gao, Yuan; Feng, Ningping; Xie, Bin; Shin, Joo Heon; Lim, Hun Ki; Ursini, Gianluca; Bigos, Kristin L; Kolachana, Bhaskar; Hashimoto, Ryota; Takeda, Masatoshi; Baum, Graham L; Rujescu, Dan; Callicott, Joseph H; Hyde, Thomas M; Berman, Karen F; Kleinman, Joel E; Weinberger, Daniel R

2014-06-01

One approach to understanding the genetic complexity of schizophrenia is to study associated behavioral and biological phenotypes that may be more directly linked to genetic variation. To identify single-nucleotide polymorphisms associated with general cognitive ability (g) in people with schizophrenia and control individuals. Genomewide association study, followed by analyses in unaffected siblings and independent schizophrenia samples, functional magnetic resonance imaging studies of brain physiology in vivo, and RNA sequencing in postmortem brain samples. The discovery cohort and unaffected siblings were participants in the National Institute of Mental Health Clinical Brain Disorders Branch schizophrenia genetics studies. Additional schizophrenia cohorts were from psychiatric treatment settings in the United States, Japan, and Germany. The discovery cohort comprised 339 with schizophrenia and 363 community control participants. Follow-up analyses studied 147 unaffected siblings of the schizophrenia cases and independent schizophrenia samples including a total of an additional 668 participants. Imaging analyses included 87 schizophrenia cases and 397 control individuals. Brain tissue samples were available for 64 cases and 61 control individuals. We studied genomewide association with g, by group, in the discovery cohort. We used selected genotypes to test specific associations in unaffected siblings and independent schizophrenia samples. Imaging analyses focused on activation in the prefrontal cortex during working memory. Brain tissue studies yielded messenger RNA expression levels for RefSeq transcripts. The schizophrenia discovery cohort showed genomewide-significant association of g with polymorphisms in sodium channel gene SCN2A, accounting for 10.4% of g variance (rs10174400, P = 9.27 × 10(-10)). Control individuals showed a trend for g/genotype association with reversed allelic directionality. The genotype-by-group interaction was also genomewide

Crystal structure, NMR study, dc-conductivity and dielectric relaxation studies of a new compound [C2H10N2]Cd(SCN2Cl2

Directory of Open Access Journals (Sweden)

Gargouri M.

2012-06-01

Full Text Available The crystal structure, the solid NMR spectroscopy and the complex impedance study have been carried out on [C2H10N2]CdCl2(SCN2. Characterization by single crystal X-ray crystallography shows that the cadmium atoms have à 2N2S2Cl hexa-coordination sphere, exhibiting pseudo-octahedral geometry. The cadmium atoms are bridged by two thiocyanate ions generating 1-D polymeric-chains. These chains are themselves interconnected by means of N-H…Cl(NCS hydrogen bonds originating from the organic cation [(NH32(CH22]2+. 111Cd isotropic chemical shifts span a range of 268ppm. The cadmium atom exhibits multiplets that result from 111Cd-14N spin-spin coupling. Examination of 111Cd and 13C MAS line shapes shows direct measurement of the indirect spin-spin coupling constant 2J(111Cd, 14N = 105Hz and the dipolar coupling constant of 1381Hz . Impedance spectroscopy measurements of [C2H10N2]CdCl2(SCN2 have been studied from 209Hz to 5 MHz over the temperature range 300-370 K. The Cole-Cole (Z” versus Z’ plots are fitted to two equivalent circuits models. The formalism of complex permittivity and impedance were employed to analyze the experimental data. The dc conductivity follows the Arrhenius relation with an activation energy Ea = 0.54 (3 eV.

Application of Piezocomposite Twin, Side by Side, Phased Array UT Probes for the Inspection of Stainless Steel

International Nuclear Information System (INIS)

Delaide, M.; Dumas, Ph

2005-01-01

UT probes to be used for the examination of coarse-grain structure must allow to detect and size cracks, with a high reliability level. The combination of TRL probes, with phased array and piezocomposite technologies allows to improve probes performances and inspection speed. Single element crystals are replaced by matrix arrays, allowing to deflect and skew the beams, to change the inspection depth. This paper describes the designing, the manufacturing and the characterisation of several probes

14 CFR Sec. 2-3 - Distribution of revenues and expenses within entities.

Science.gov (United States)

2010-01-01

... CERTIFICATED AIR CARRIERS General Accounting Provisions Sec. 2-3 Distribution of revenues and expenses within.... (c) Expense items contributing to more than one function shall be charged to the general overhead functions to which applicable except that where only incidental contribution is made to more than a single...

Neofunctionalization of the Sec1 α1,2fucosyltransferase paralogue in leporids contributes to glycan polymorphism and resistance to rabbit hemorrhagic disease virus.

Directory of Open Access Journals (Sweden)

Kristina Nyström

2015-04-01

Full Text Available RHDV (rabbit hemorrhagic disease virus, a virulent calicivirus, causes high mortalities in European rabbit populations (Oryctolagus cuniculus. It uses α1,2fucosylated glycans, histo-blood group antigens (HBGAs, as attachment factors, with their absence or low expression generating resistance to the disease. Synthesis of these glycans requires an α1,2fucosyltransferase. In mammals, there are three closely located α1,2fucosyltransferase genes rSec1, rFut2 and rFut1 that arose through two rounds of duplications. In most mammalian species, Sec1 has clearly become a pseudogene. Yet, in leporids, it does not suffer gross alterations, although we previously observed that rabbit Sec1 variants present either low or no activity. Still, a low activity rSec1 allele correlated with survival to an RHDV outbreak. We now confirm the association between the α1,2fucosyltransferase loci and survival. In addition, we show that rabbits express homogenous rFut1 and rFut2 levels in the small intestine. Comparison of rFut1 and rFut2 activity showed that type 2 A, B and H antigens recognized by RHDV strains were mainly synthesized by rFut1, and all rFut1 variants detected in wild animals were equally active. Interestingly, rSec1 RNA levels were highly variable between individuals and high expression was associated with low binding of RHDV strains to the mucosa. Co-transfection of rFut1 and rSec1 caused a decrease in rFut1-generated RHDV binding sites, indicating that in rabbits, the catalytically inactive rSec1 protein acts as a dominant-negative of rFut1. Consistent with neofunctionalization of Sec1 in leporids, gene conversion analysis showed extensive homogenization between Sec1 and Fut2 in leporids, at variance with its limited degree in other mammals. Gene conversion additionally involving Fut1 was also observed at the C-terminus. Thus, in leporids, unlike in most other mammals where it became extinct, Sec1 evolved a new function with a dominant-negative effect