115 research outputs found

    Use of a krypton isotope for rapid ion changeover at the Lawrence Berkeley Laboratory 88-inch cyclotron

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    An isotope of krypton, Kr86, has been combined with a mix of Ar, Ne, and N ions at the electron cyclotron resonance (ECR) source, at the Lawrence Berkeley Laboratory cyclotron, to provide rapid ion changeover in Single Event Phenomena (SEP) testing. The new technique has been proved out successfully by a recent Jet Propulsion Laboratory (JPL) test in which it was found that there was no measurable contamination from other isotopes

    Pengaruh Experiential Marketing Terhadap Kepuasan Konsumen (Studi Kasus: Cinema Xxi Imax Gandaria City, Jakarta)

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    The objective of this study is to examine the effect of experiential marketing on customer satisfaction, taking the case study of Cinema XXI IMAX Gandaria City, Jakarta. The concepts of experiential marketing (i.e. strategic experiential modules and experience providers) and customer satisfaction were taken from various resources. Both primary and secondary data were employed. Secondary data were taken from journals, books, and articles. Primary data were collected using self-administered questionnaire which were distributed to the respondents through online and offline method. Respondents were those who had watched at Cinema XXI IMAX Gandaria City, Jakarta for at least two times in the last six months. Using purposive sampling technique, a total sample of 100 respondents was obtained. Validity and reliability tests were employed to examine the research instruments. The statistical data were analyzed by SPSS software version 17.0. The multiple linier regression analysis was employed to verify the hypotheses. The result shows that strategic experiential modules and experience providers partially and simultaneously, had significant influence on customer satisfaction

    The time course of auditory and language-specific mechanisms in compensation for sibilant assimilation

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    Models of spoken-word recognition differ on whether compensation for assimilation is language-specific or depends on general auditory processing. English and French participants were taught words that began or ended with the sibilants /s/ and /∍/. Both languages exhibit some assimilation in sibilant sequences (e.g., /s/ becomes like [∍] in dress shop and classe chargÊe), but they differ in the strength and predominance of anticipatory versus carryover assimilation. After training, participants were presented with novel words embedded in sentences, some of which contained an assimilatory context either preceding or following. A continuum of target sounds ranging from [s] to [∍] was spliced into the novel words, representing a range of possible assimilation strengths. Listeners' perceptions were examined using a visual-world eyetracking paradigm in which the listener clicked on pictures matching the novel words. We found two distinct language-general context effects: a contrastive effect when the assimilating context preceded the target, and flattening of the sibilant categorization function (increased ambiguity) when the assimilating context followed. Furthermore, we found that English but not French listeners were able to resolve the ambiguity created by the following assimilatory context, consistent with their greater experience with assimilation in this context. The combination of these mechanisms allows listeners to deal flexibly with variability in speech forms

    De Novo Unbalanced Translocations in Prader-Willi and Angelman Syndrome Might Be the Reciprocal Product of inv dup(15)s

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    The 15q11-q13 region is characterized by high instability, caused by the presence of several paralogous segmental duplications. Although most mechanisms dealing with cryptic deletions and amplifications have been at least partly characterized, little is known about the rare translocations involving this region. We characterized at the molecular level five unbalanced translocations, including a jumping one, having most of 15q transposed to the end of another chromosome, whereas the der(15)(pter->q11-q13) was missing. Imbalances were associated either with Prader-Willi or Angelman syndrome. Array-CGH demonstrated the absence of any copy number changes in the recipient chromosome in three cases, while one carried a cryptic terminal deletion and another a large terminal deletion, already diagnosed by classical cytogenetics. We cloned the breakpoint junctions in two cases, whereas cloning was impaired by complex regional genomic architecture and mosaicism in the others. Our results strongly indicate that some of our translocations originated through a prezygotic/postzygotic two-hit mechanism starting with the formation of an acentric 15qter->q1::q1->qter representing the reciprocal product of the inv dup(15) supernumerary marker chromosome. An embryo with such an acentric chromosome plus a normal chromosome 15 inherited from the other parent could survive only if partial trisomy 15 rescue would occur through elimination of part of the acentric chromosome, stabilization of the remaining portion with telomere capture, and formation of a derivative chromosome. All these events likely do not happen concurrently in a single cell but are rather the result of successive stabilization attempts occurring in different cells of which only the fittest will finally survive. Accordingly, jumping translocations might represent successful rescue attempts in different cells rather than transfer of the same 15q portion to different chromosomes. We also hypothesize that neocentromerization of the original acentric chromosome during early embryogenesis may be required to avoid its loss before cell survival is finally assured

    Water Contamination Reduces the Tolerance of Coral Larvae to Thermal Stress

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    Coral reefs are highly susceptible to climate change, with elevated sea surface temperatures (SST) posing one of the main threats to coral survival. Successful recruitment of new colonies is important for the recovery of degraded reefs following mortality events. Coral larvae require relatively uncontaminated substratum on which to metamorphose into sessile polyps, and the increasing pollution of coastal waters therefore constitutes an additional threat to reef resilience. Here we develop and analyse a model of larval metamorphosis success for two common coral species to quantify the interactive effects of water pollution (copper contamination) and SST. We identify thresholds of temperature and pollution that prevent larval metamorphosis, and evaluate synergistic interactions between these stressors. Our analyses show that halving the concentration of Cu can protect corals from the negative effects of a 2–3°C increase in SST. These results demonstrate that effective mitigation of local impacts can reduce negative effects of global stressors

    CERT1 mutations perturb human development by disrupting sphingolipid homeostasis

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    Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT autoregulation in the control of sphingolipid biosynthetic flux, provide unexpected insight into the structural organization of CERT, and suggest a possible therapeutic approach for patients with CerTra syndrome.This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS), NIH (R01NS109858, to VAG); the Paul A. Marks Scholar Program at the Columbia University Vagelos College of Physicians and Surgeons (to VAG); a TIGER grant from the TAUB Institute at the Columbia Vagelos College of Physicians and Scientists (to VAG); the Swiss National Science Foundation (SNF 31003A-179371, to TH); the European Joint Program on Rare Diseases (EJP RD+SNF 32ER30-187505, to TH); the Swiss Cancer League (KFS-4999-02-2020, to GD); the EPFL institutional fund (to GD); the Kristian Gerhard Jebsen Foundation (to GD); the Swiss National Science Foundation (SNSF) (310030_184926, to GD); the Swiss Foundation for Research on Muscle Disease (FSRMM, to MAL); the Natural Science and Engineering Research Council of Canada (Discovery Grant 2020-04241, to JEB); the Italian Ministry of Health Young Investigator Grant (GR-2011-02347754, to EL); the Fondazione Istituto di Ricerca Pediatrica – Città della Speranza (18-04, to EL); the Wroclaw Medical University (SUB.E160.21.004, to RS); the National Science Centre, Poland (2017/27/B/NZ5/0222, to RS); Telethon Undiagnosed Diseases Program (TUDP) (GSP15001); the Temple Street Foundation/Children’s Health Foundation Ireland (RPAC 19-02, to IK); the Deutsche Forschungsgemeinschaft (DFG) (PO2366/2–1, to BP); the Instituto de Salud Carlos III, Spain (to ELM, EBS, and BMD); the National Natural Science Foundation of China (81871079 and 81730036, to HG and KX); and the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH (R01 DK115574, to SSC).The DEFIDIAG study is funded by grants from the French Ministry of Health in the framewok of the national French initiative for genomic medicine. The funders were not involved in the study design, data acquisition, analysis, or writing of the manuscript. Funding for the DECIPHER project was provided by Wellcome. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051). The views expressed in this publication are those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12, granted by the Republic of Ireland REC). The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network.S

    The hydration structure of dissolved carbon dioxide from X-ray absorption spectroscopy

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    Abstract The dissolution of carbon dioxide in water and its subsequent hydrolysis reactions comprise one of the most central processes in all of science, yet it remains incompletely understood despite enormous effort. We report the detailed characterization of dissolved CO2 gas through the combination of X-ray spectroscopy and first principles theory. The molecule acts as a hydrophobe in water with an average hydrogen bond number of 0.56. The carbon atom interacts weakly with a single water at a distance of >2.67 Å and the carbonyl oxygens serve as weak hydrogen bond acceptors, thus locally enhancing the tetrahedral water hydrogen bonding structure

    Theoretical constraints on the effects of pH, salinity, and temperature on clumped isotope signatures of dissolved inorganic carbon species and precipitating carbonate minerals

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    The use of carbonate 'clumped isotope' thermometry as a geochemical technique to determine temperature of formation of a carbonate mineral is predicated on the assumption that the mineral has attained an internal thermodynamic equilibrium. If true, then the clumped isotope signature is dependent solely upon the temperature of formation of the mineral without the need to know the isotopic or elemental composition of coeval fluids. However, anomalous signatures can arise under disequilibrium conditions that can make the estimation of temperatures uncertain by several degrees Celsius. Here we use ab initio calculations to examine the potential disequilibrium mineral signatures that may arise from the incorporation of dissolved inorganic carbon (DIC) species (predominantly aqueous carbonate and bicarbonate ions) into growing crystals without full equilibration with the crystal lattice.We explore theoretically the nature of clumping in the individual DIC species and the composite DIC pool under varying pH, salinity, temperature, and isotopic composition, and speculate about their effects upon the resultant disequilibrium clumping of the precipitates. We also calculate equilibrium clumped signatures for the carbonate minerals calcite, aragonite, and witherite. Our models indicate that each DIC species has a distinct equilibrium clumped isotope signature such that, δ47(H2CO3)>δ47HCO3->δ47(equilibrium calcite)>δ47CO32-, and predict a difference between δ47HCO3-andδ47CO32->0.033‰ at 25°C, and that δ47 (aragonite)>δ47 (calcite)>δ47 (witherite). We define the calcite clumped crossover pH as the pH at which the composite δ47 (DIC pool)=δ47 (equilibrium calcite). If disequilibrium δ47 (calcite) is misinterpreted as equilibrium δ47 (calcite), it is possible to overestimate or underestimate the growth temperature by small but significant amounts. Increases in salinity lower the clumped crossover pH and may cause larger effects. Extreme effects of pH, salinity, and temperature, such as between cold freshwater lakes at high latitudes to hot hypersaline environments, are predicted to have sizeable effects on the clumped isotope composition of aqueous DIC pools.In order to determine the most reliable and efficient modeling methods to represent aqueous dissolved inorganic carbon (DIC) species and carbonate minerals, we performed convergence and sensitivity testing on several different levels of theory. We used 4 different techniques for modeling the hydration of DIC: gas phase, implicit solvation (PCM and SMD), explicit solvation (ion with 3 water molecules) and supermolecular clusters (ion plus 21 to 32 water molecules with geometries generated by molecular dynamics). For each solvation technique, we performed sensitivity testing by combining different levels of theory (up to 8 ab initio/hybrid methods, each with up to 5 different sizes of basis sets) to understand the limits of each technique. We looked at the degree of convergence with the most complex (and accurate) models in order to select the most reliable and efficient modeling methods. The B3LYP method combined with the 6-311++G(2d,2p) basis set with supermolecular clusters worked well. © 2013 Elsevier Ltd
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