WorldWideScience

Sample records for single mutational event

  1. Mutation Scanning in a Single and a Stacked Genetically Modified (GM) Event by Real-Time PCR and High Resolution Melting (HRM) Analysis

    Science.gov (United States)

    Ben Ali, Sina-Elisabeth; Madi, Zita Erika; Hochegger, Rupert; Quist, David; Prewein, Bernhard; Haslberger, Alexander G.; Brandes, Christian

    2014-01-01

    Genetic mutations must be avoided during the production and use of seeds. In the European Union (EU), Directive 2001/18/EC requires any DNA construct introduced via transformation to be stable. Establishing genetic stability is critical for the approval of genetically modified organisms (GMOs). In this study, genetic stability of two GMOs was examined using high resolution melting (HRM) analysis and real-time polymerase chain reaction (PCR) employing Scorpion primers for amplification. The genetic variability of the transgenic insert and that of the flanking regions in a single oilseed rape variety (GT73) and a stacked maize (MON88017 × MON810) was studied. The GT73 and the 5' region of MON810 showed no instabilities in the examined regions. However; two out of 100 analyzed samples carried a heterozygous point mutation in the 3' region of MON810 in the stacked variety. These results were verified by direct sequencing of the amplified PCR products as well as by sequencing of cloned PCR fragments. The occurrence of the mutation suggests that the 5' region is more suitable than the 3' region for the quantification of MON810. The identification of the single nucleotide polymorphism (SNP) in a stacked event is in contrast to the results of earlier studies of the same MON810 region in a single event where no DNA polymorphism was found. PMID:25365178

  2. Crystal ball single event display

    International Nuclear Information System (INIS)

    Grosnick, D.; Gibson, A.; Allgower, C.; Alyea, J.; Argonne National Lab., IL

    1997-01-01

    The Single Event Display (SED) is a routine that is designed to provide information graphically about a triggered event within the Crystal Ball. The SED is written entirely in FORTRAN and uses the CERN-based HICZ graphing package. The primary display shows the amount of energy deposited in each of the NaI crystals on a Mercator-like projection of the crystals. Ten different shades and colors correspond to varying amounts of energy deposited within a crystal. Information about energy clusters is displayed on the crystal map by outlining in red the thirteen (or twelve) crystals contained within a cluster and assigning each cluster a number. Additional information about energy clusters is provided in a series of boxes containing useful data about the energy distribution among the crystals within the cluster. Other information shown on the event display include the event trigger type and data about π o 's and η's formed from pairs of clusters as found by the analyzer. A description of the major features is given, along with some information on how to install the SED into the analyzer

  3. Investigation of single event latchup

    International Nuclear Information System (INIS)

    Xue Yuxiong; Yang Shengsheng; Cao Zhou; Ba Dedong; An Heng; Chen Luojing; Guo Gang

    2012-01-01

    Radiation effects on avionics microelectronics are important reliability issues for many space applications. In particular, single-event latchup (SEL) phenomenon is a major threat to CMOS integrated circuits in space systems. To effectively circumvent the failure, it is important to know the behavior of such devices during latchup. In this paper, the mechanisms for SEL in CMOS devices are investigated. Several microelectronic devices used in avionics are tested using heavy ion beams, pulsed laser and 252 Cf source. Based on the SEL test results, SEL-hardening and monitoring methods for preventing SEL from the systems design level are proposed. (authors)

  4. Single event upset test programs

    International Nuclear Information System (INIS)

    Russen, L.C.

    1984-11-01

    It has been shown that the heavy ions in cosmic rays can give rise to single event upsets in VLSI random access memory devices (RAMs). Details are given of the programs written to test 1K, 4K, 16K and 64K memories during their irradiation with heavy charged ions, in order to simulate the effects of cosmic rays in space. The test equipment, which is used to load the memory device to be tested with a known bit pattern, and subsequently interrogate it for upsets, or ''flips'', is fully described. (author)

  5. Adverse events in families with hypertrophic or dilated cardiomyopathy and mutations in the MYBPC3 gene

    Directory of Open Access Journals (Sweden)

    Lehrke Stephanie

    2008-10-01

    Full Text Available Abstract Background Mutations in MYBPC3 encoding myosin binding protein C belong to the most frequent causes of hypertrophic cardiomyopathy (HCM and may also lead to dilated cardiomyopathy (DCM. MYBPC3 mutations initially were considered to cause a benign form of HCM. The aim of this study was to examine the clinical outcome of patients and their relatives with 18 different MYBPC3 mutations. Methods 87 patients with HCM and 71 patients with DCM were screened for MYBPC3 mutations by denaturing gradient gel electrophoresis and sequencing. Close relatives of mutation carriers were genotyped for the respective mutation. Relatives with mutation were then evaluated by echocardiography and magnetic resonance imaging. A detailed family history regarding adverse clinical events was recorded. Results In 16 HCM (18.4% and two DCM (2.8% index patients a mutation was detected. Seven mutations were novel. Mutation carriers exhibited no additional mutations in genes MYH7, TNNT2, TNNI3, ACTC and TPM1. Including relatives of twelve families, a total number of 42 mutation carriers was identified of which eleven (26.2% had at least one adverse event. Considering the twelve families and six single patients with mutations, 45 individuals with cardiomyopathy and nine with borderline phenotype were identified. Among the 45 patients, 23 (51.1% suffered from an adverse event. In eleven patients of seven families an unexplained sudden death was reported at the age between 13 and 67 years. Stroke or a transient ischemic attack occurred in six patients of five families. At least one adverse event occurred in eleven of twelve families. Conclusion MYBPC3 mutations can be associated with cardiac events such as progressive heart failure, stroke and sudden death even at younger age. Therefore, patients with MYBPC3 mutations require thorough clinical risk assessment.

  6. Multiple Hotspot Mutations Scanning by Single Droplet Digital PCR.

    Science.gov (United States)

    Decraene, Charles; Silveira, Amanda B; Bidard, François-Clément; Vallée, Audrey; Michel, Marc; Melaabi, Samia; Vincent-Salomon, Anne; Saliou, Adrien; Houy, Alexandre; Milder, Maud; Lantz, Olivier; Ychou, Marc; Denis, Marc G; Pierga, Jean-Yves; Stern, Marc-Henri; Proudhon, Charlotte

    2018-02-01

    Progress in the liquid biopsy field, combined with the development of droplet digital PCR (ddPCR), has enabled noninvasive monitoring of mutations with high detection accuracy. However, current assays detect a restricted number of mutations per reaction. ddPCR is a recognized method for detecting alterations previously characterized in tumor tissues, but its use as a discovery tool when the mutation is unknown a priori remains limited. We established 2 ddPCR assays detecting all genomic alterations within KRAS exon 2 and EGFR exon 19 mutation hotspots, which are of clinical importance in colorectal and lung cancer, with use of a unique pair of TaqMan ® oligoprobes. The KRAS assay scanned for the 7 most common mutations in codons 12/13 but also all other mutations found in that region. The EGFR assay screened for all in-frame deletions of exon 19, which are frequent EGFR-activating events. The KRAS and EGFR assays were highly specific and both reached a limit of detection of <0.1% in mutant allele frequency. We further validated their performance on multiple plasma and formalin-fixed and paraffin-embedded tumor samples harboring a panel of different KRAS or EGFR mutations. This method presents the advantage of detecting a higher number of mutations with single-reaction ddPCRs while consuming a minimum of patient sample. This is particularly useful in the context of liquid biopsy because the amount of circulating tumor DNA is often low. This method should be useful as a discovery tool when the tumor tissue is unavailable or to monitor disease during therapy. © 2017 American Association for Clinical Chemistry.

  7. Single-event effect ground test issues

    International Nuclear Information System (INIS)

    Koga, R.

    1996-01-01

    Ground-based single event effect (SEE) testing of microcircuits permits characterization of device susceptibility to various radiation induced disturbances, including: (1) single event upset (SEU) and single event latchup (SEL) in digital microcircuits; (2) single event gate rupture (SEGR), and single event burnout (SEB) in power transistors; and (3) bit errors in photonic devices. These characterizations can then be used to generate predictions of device performance in the space radiation environment. This paper provides a general overview of ground-based SEE testing and examines in critical depth several underlying conceptual constructs relevant to the conduct of such tests and to the proper interpretation of results. These more traditional issues are contrasted with emerging concerns related to the testing of modern, advanced microcircuits

  8. Diversity of [beta]-globin mutations in Israeli ethnic groups reflects recent historic events

    Energy Technology Data Exchange (ETDEWEB)

    Filon, D.; Oron, V.; Krichevski, S.; Shaag, A.; Goldfarb, A.; Aker, M.; Rachmilewitz, E.A.; Rund, D.; Oppenheim, A. (Hebrew Univ. Hadassah-Medical School, Jerusalem (Israel)) (and others)

    1994-05-01

    The authors characterized nearly 500 [beta]-thalassemia genes from the Israeli population representing a variety of ethnic subgroups. They found 28 different mutations in the [beta]-globin gene, including three mutations ([beta][sup S], [beta][sup C], and [beta][sup O-Arab]) causing hemoglobinopathies. Marked genetic heterogeneity was observed in both the Arab (20 mutations) and Jewish (17 mutations) populations. On the other hand, two ethnic isolates - Druze and Samaritans - had a single mutation each. Fifteen of the [beta]-thalassemia alleles are Mediterranean in type, 5 originated in Kurdistan, 2 are of Indian origin, and 2 sporadic alleles came from Europe. Only one mutant allele-nonsense codon 37-appears to be indigenous to Israel. While human habitation in Israel dates back to early prehistory, the present-day spectrum of [beta]-globin mutations can be largely explained by migration events that occurred in the past millennium. 26 refs., 2 figs., 3 tabs.

  9. Parkinson's disease-related LRRK2 G2019S mutation results from independent mutational events in humans.

    Science.gov (United States)

    Lesage, Suzanne; Patin, Etienne; Condroyer, Christel; Leutenegger, Anne-Louise; Lohmann, Ebba; Giladi, Nir; Bar-Shira, Anat; Belarbi, Soraya; Hecham, Nassima; Pollak, Pierre; Ouvrard-Hernandez, Anne-Marie; Bardien, Soraya; Carr, Jonathan; Benhassine, Traki; Tomiyama, Hiroyuki; Pirkevi, Caroline; Hamadouche, Tarik; Cazeneuve, Cécile; Basak, A Nazli; Hattori, Nobutaka; Dürr, Alexandra; Tazir, Meriem; Orr-Urtreger, Avi; Quintana-Murci, Lluis; Brice, Alexis

    2010-05-15

    Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson's disease (PD) and in sporadic cases; the G2019S mutation is the single most frequent. Intriguingly, the frequency of this mutation in PD patients varies greatly among ethnic groups and geographic origins: it is present at <0.1% in East Asia, approximately 2% in European-descent patients and can reach frequencies of up to 15-40% in PD Ashkenazi Jews and North African Arabs. To ascertain the evolutionary dynamics of the G2019S mutation in different populations, we genotyped 74 markers spanning a 16 Mb genomic region around G2019S, in 191 individuals carrying the mutation from 126 families of different origins. Sixty-seven families were of North-African Arab origin, 18 were of North/Western European descent, 37 were of Jewish origin, mostly from Eastern Europe, one was from Japan, one from Turkey and two were of mixed origins. We found the G2019S mutation on three different haplotypes. Network analyses of the three carrier haplotypes showed that G2019S arose independently at least twice in humans. In addition, the population distribution of the intra-allelic diversity of the most widespread carrier haplotype, together with estimations of the age of G2019S determined by two different methods, suggests that one of the founding G2019S mutational events occurred in the Near East at least 4000 years ago.

  10. Dynamic of Mutational Events in Variable Number Tandem Repeats of Escherichia coli O157:H7

    Directory of Open Access Journals (Sweden)

    A. V. Bustamante

    2013-01-01

    Full Text Available VNTRs regions have been successfully used for bacterial subtyping; however, the hypervariability in VNTR loci is problematic when trying to predict the relationships among isolates. Since few studies have examined the mutation rate of these markers, our aim was to estimate mutation rates of VNTRs specific for verotoxigenic E. coli O157:H7. The knowledge of VNTR mutational rates and the factors affecting them would make MLVA more effective for epidemiological or microbial forensic investigations. For this purpose, we analyzed nine loci performing parallel, serial passage experiments (PSPEs on 9 O157:H7 strains. The combined 9 PSPE population rates for the 8 mutating loci ranged from 4.4 × 10−05 to 1.8 × 10−03 mutations/generation, and the combined 8-loci mutation rate was of 2.5 × 10−03 mutations/generation. Mutations involved complete repeat units, with only one point mutation detected. A similar proportion between single and multiple repeat changes was detected. Of the 56 repeat mutations, 59% were insertions and 41% were deletions, and 72% of the mutation events corresponded to O157-10 locus. For alleles with up to 13 UR, a constant and low mutation rate was observed; meanwhile longer alleles were associated with higher and variable mutation rates. Our results are useful to interpret data from microevolution and population epidemiology studies and particularly point out that the inclusion or not of O157-10 locus or, alternatively, a differential weighting data according to the mutation rates of loci must be evaluated in relation with the objectives of the proposed study.

  11. The effect of a single recombination event

    DEFF Research Database (Denmark)

    Schierup, Mikkel Heide; Jensen, Thomas Mailund; Wiuf, Carsten

    We investigate the variance in how visible a single recombination event is in a SNP data set as a function of the type of recombination event and its age. Data is simulated under the coalescent with recombination and inference is by the popular composite likelihood methods. The major determinant...

  12. Volatility of Mutator Phenotypes at Single Cell Resolution.

    Directory of Open Access Journals (Sweden)

    Scott R Kennedy

    2015-04-01

    Full Text Available Mutator phenotypes accelerate the evolutionary process of neoplastic transformation. Historically, the measurement of mutation rates has relied on scoring the occurrence of rare mutations in target genes in large populations of cells. Averaging mutation rates over large cell populations assumes that new mutations arise at a constant rate during each cell division. If the mutation rate is not constant, an expanding mutator population may contain subclones with widely divergent rates of evolution. Here, we report mutation rate measurements of individual cell divisions of mutator yeast deficient in DNA polymerase ε proofreading and base-base mismatch repair. Our data are best fit by a model in which cells can assume one of two distinct mutator states, with mutation rates that differ by an order of magnitude. In error-prone cell divisions, mutations occurred on the same chromosome more frequently than expected by chance, often in DNA with similar predicted replication timing, consistent with a spatiotemporal dimension to the hypermutator state. Mapping of mutations onto predicted replicons revealed that mutations were enriched in the first half of the replicon as well as near termination zones. Taken together, our findings show that individual genome replication events exhibit an unexpected volatility that may deepen our understanding of the evolution of mutator-driven malignancies.

  13. Mutation dynamics and fitness effects followed in single cells.

    Science.gov (United States)

    Robert, Lydia; Ollion, Jean; Robert, Jerome; Song, Xiaohu; Matic, Ivan; Elez, Marina

    2018-03-16

    Mutations have been investigated for more than a century but remain difficult to observe directly in single cells, which limits the characterization of their dynamics and fitness effects. By combining microfluidics, time-lapse imaging, and a fluorescent tag of the mismatch repair system in Escherichia coli , we visualized the emergence of mutations in single cells, revealing Poissonian dynamics. Concomitantly, we tracked the growth and life span of single cells, accumulating ~20,000 mutations genome-wide over hundreds of generations. This analysis revealed that 1% of mutations were lethal; nonlethal mutations displayed a heavy-tailed distribution of fitness effects and were dominated by quasi-neutral mutations with an average cost of 0.3%. Our approach has enabled the investigation of single-cell individuality in mutation rate, mutation fitness costs, and mutation interactions. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  14. Destructive Single-Event Effects in Diodes

    Science.gov (United States)

    Casey, Megan C.; Lauenstein, Jean-Marie; Campola, Michael J.; Wilcox, Edward P.; Phan, Anthony M.; Label, Kenneth A.

    2017-01-01

    In this work, we discuss the observed single-event effects in a variety of types of diodes. In addition, we conduct failure analysis on several Schottky diodes that were heavy-ion irradiated. High- and low-magnitude optical microscope images, infrared camera images, and scanning electron microscope images are used to identify and describe the failure locations.

  15. Single event phenomena in atmospheric neutron environments

    International Nuclear Information System (INIS)

    Gossett, C.A.; Hughlock, B.W.; Katoozi, M.; LaRue, G.S.; Wender, S.A.

    1993-01-01

    As integrated circuit technology achieves higher density through smaller feature sizes and as the airplane manufacturing industry integrates more sophisticated electronic components into the design of new aircraft, it has become increasingly important to evaluate the contribution of single event effects, primarily Single Event Upset (SEU), to the safety and reliability of commercial aircraft. In contrast to the effects of radiation on electronic systems in space applications for which protons and heavy ions are of major concern, in commercial aircraft applications the interactions of high energy neutrons are the dominant cause of single event effects. These high energy neutrons are produced by the interaction of solar and galactic cosmic rays, principally protons and heavy ions, in the upper atmosphere. This paper will describe direct experimental measurements of neutron-induced Single Event Effect (SEE) rates in commercial high density static random access memories in a neutron environment characteristic of that at commercial airplane altitudes. The first experimental measurements testing current models for neutron-silicon burst generation rates will be presented, as well as measurements of charge collection in silicon test structures as a function of neutron energy. These are the first laboratory SEE and charge collection measurements using a particle beam having a continuum energy spectrum and with a shape nearly identical to that observed during flight

  16. Experimental Setups for Single Event Effect Studies

    OpenAIRE

    N. H. Medina; V. A. P. Aguiar; N. Added; F. Aguirre; E. L. A. Macchione; S. G. Alberton; M. A. G. Silveira; J. Benfica; F. Vargas; B. Porcher

    2016-01-01

    Experimental setups are being prepared to test and to qualify electronic devices regarding their tolerance to Single Event Effect (SEE). A multiple test setup and a new beam line developed especially for SEE studies at the São Paulo 8 UD Pelletron accelerator were prepared. This accelerator produces proton beams and heavy ion beams up to 107Ag. A Super conducting Linear accelerator, which is under construction, may fulfill all of the European Space Agency requirements to qualify electronic...

  17. Frequent beneficial mutations during single-colony serial transfer of Streptococcus pneumoniae.

    Directory of Open Access Journals (Sweden)

    Kathleen E Stevens

    2011-08-01

    Full Text Available The appearance of new mutations within a population provides the raw material for evolution. The consistent decline in fitness observed in classical mutation accumulation studies has provided support for the long-held view that deleterious mutations are more common than beneficial mutations. Here we present results of a study using a mutation accumulation design with the bacterium Streptococcus pneumoniae in which the fitness of the derived populations increased. This rise in fitness was associated specifically with adaptation to survival during brief stationary phase periods between single-colony population bottlenecks. To understand better the population dynamics behind this unanticipated adaptation, we developed a maximum likelihood model describing the processes of mutation and stationary-phase selection in the context of frequent population bottlenecks. Using this model, we estimate that the rate of beneficial mutations may be as high as 4.8×10(-4 events per genome for each time interval corresponding to the pneumococcal generation time. This rate is several orders of magnitude higher than earlier estimates of beneficial mutation rates in bacteria but supports recent results obtained through the propagation of small populations of Escherichia coli. Our findings indicate that beneficial mutations may be relatively frequent in bacteria and suggest that in S. pneumoniae, which develops natural competence for transformation, a steady supply of such mutations may be available for sampling by recombination.

  18. Single event upsets correlated with environment

    International Nuclear Information System (INIS)

    Vampola, A.L.; Albin, F.; Lauriente, M.; Wilkinson, D.C.; Allen, J.

    1994-01-01

    Single Event Upset rates on satellites in different Earth orbits are correlated with solar protons and geomagnetic activity and also with the NASA AP8 proton model to extract information about satellite anomalies caused by the space environment. An extensive discussion of the SEU data base from the TOMS solid state recorder and an algorithm for correcting spontaneous upsets in it are included as an Appendix. SAMPEX and TOMS, which have the same memory chips, have similar normalized responses in the South Atlantic Anomaly. SEU rates due to solar protons over the polar caps are within expectations. No geomagnetic activity effects can be discerned in the SEU rates

  19. Experimental study of single event burnout and single event gate rupture in power MOSFETs and IGBT

    International Nuclear Information System (INIS)

    Tang Benqi; Wang Yanping; Geng Bin

    2001-01-01

    An experimental study was carried out to determine the single event burnout and single event gate rupture sensitivities in power MOSFETs and IGBT which were exposed to heavy ions from 252 Cf source. The test method, test results, a description of observed burnout current waveforms and a discussion of a possible failure mechanism were presented. Current measurements have been performed with a specially designed circuit. The test results include the observed dependence upon applied drain or gate to source bias and versus with external capacitors and limited resistors

  20. An Updated Perspective of Single Event Gate Rupture and Single Event Burnout in Power MOSFETs

    Science.gov (United States)

    Titus, Jeffrey L.

    2013-06-01

    Studies over the past 25 years have shown that heavy ions can trigger catastrophic failure modes in power MOSFETs [e.g., single-event gate rupture (SEGR) and single-event burnout (SEB)]. In 1996, two papers were published in a special issue of the IEEE Transaction on Nuclear Science [Johnson, Palau, Dachs, Galloway and Schrimpf, “A Review of the Techniques Used for Modeling Single-Event Effects in Power MOSFETs,” IEEE Trans. Nucl. Sci., vol. 43, no. 2, pp. 546-560, April. 1996], [Titus and Wheatley, “Experimental Studies of Single-Event Gate Rupture and Burnout in Vertical Power MOSFETs,” IEEE Trans. Nucl. Sci., vol. 43, no. 2, pp. 533-545, Apr. 1996]. Those two papers continue to provide excellent information and references with regard to SEB and SEGR in vertical planar MOSFETs. This paper provides updated references/information and provides an updated perspective of SEB and SEGR in vertical planar MOSFETs as well as provides references/information to other device types that exhibit SEB and SEGR effects.

  1. Equivalent properties of single event burnout induced by different sources

    International Nuclear Information System (INIS)

    Yang Shiyu; Cao Zhou; Da Daoan; Xue Yuxiong

    2009-01-01

    The experimental results of single event burnout induced by heavy ions and 252 Cf fission fragments in power MOSFET devices have been investigated. It is concluded that the characteristics of single event burnout induced by 252 Cf fission fragments is consistent to that in heavy ions. The power MOSFET in the 'turn-off' state is more susceptible to single event burnout than it is in the 'turn-on' state. The thresholds of the drain-source voltage for single event burnout induced by 173 MeV bromine ions and 252 Cf fission fragments are close to each other, and the burnout cross section is sensitive to variation of the drain-source voltage above the threshold of single event burnout. In addition, the current waveforms of single event burnouts induced by different sources are similar. Different power MOSFET devices may have different probabilities for the occurrence of single event burnout. (authors)

  2. Evidence that adaptation in Drosophila is not limited by mutation at single sites.

    Directory of Open Access Journals (Sweden)

    Talia Karasov

    2010-06-01

    Full Text Available Adaptation in eukaryotes is generally assumed to be mutation-limited because of small effective population sizes. This view is difficult to reconcile, however, with the observation that adaptation to anthropogenic changes, such as the introduction of pesticides, can occur very rapidly. Here we investigate adaptation at a key insecticide resistance locus (Ace in Drosophila melanogaster and show that multiple simple and complex resistance alleles evolved quickly and repeatedly within individual populations. Our results imply that the current effective population size of modern D. melanogaster populations is likely to be substantially larger (> or = 100-fold than commonly believed. This discrepancy arises because estimates of the effective population size are generally derived from levels of standing variation and thus reveal long-term population dynamics dominated by sharp--even if infrequent--bottlenecks. The short-term effective population sizes relevant for strong adaptation, on the other hand, might be much closer to census population sizes. Adaptation in Drosophila may therefore not be limited by waiting for mutations at single sites, and complex adaptive alleles can be generated quickly without fixation of intermediate states. Adaptive events should also commonly involve the simultaneous rise in frequency of independently generated adaptive mutations. These so-called soft sweeps have very distinct effects on the linked neutral polymorphisms compared to the standard hard sweeps in mutation-limited scenarios. Methods for the mapping of adaptive mutations or association mapping of evolutionarily relevant mutations may thus need to be reconsidered.

  3. Preleukemic and second-hit mutational events in an acute myeloid leukemia patient with a novel germline RUNX1 mutation.

    Science.gov (United States)

    Ng, Isaac Ks; Lee, Joanne; Ng, Christopher; Kosmo, Bustamin; Chiu, Lily; Seah, Elaine; Mok, Michelle Meng Huang; Tan, Karen; Osato, Motomi; Chng, Wee-Joo; Yan, Benedict; Tan, Lip Kun

    2018-01-01

    Germline mutations in the RUNX1 transcription factor give rise to a rare autosomal dominant genetic condition classified under the entity: Familial Platelet Disorders with predisposition to Acute Myeloid Leukaemia (FPD/AML). While several studies have identified a myriad of germline RUNX1 mutations implicated in this disorder, second-hit mutational events are necessary for patients with hereditary thrombocytopenia to develop full-blown AML. The molecular picture behind this process remains unclear. We describe a patient of Malay descent with an unreported 7-bp germline RUNX1 frameshift deletion, who developed second-hit mutations that could have brought about the leukaemic transformation from a pre-leukaemic state. These mutations were charted through the course of the treatment and stem cell transplant, showing a clear correlation between her clinical presentation and the mutations present. The patient was a 27-year-old Malay woman who presented with AML on the background of hereditary thrombocytopenia affecting her father and 3 brothers. Initial molecular testing revealed the same novel RUNX1 mutation in all 5 individuals. The patient received standard induction, consolidation chemotherapy, and a haploidentical stem cell transplant from her mother with normal RUNX1 profile. Comprehensive genomic analyses were performed at diagnosis, post-chemotherapy and post-transplant. A total of 8 mutations ( RUNX1 , GATA2 , DNMT3A , BCORL1 , BCOR , 2 PHF6 and CDKN2A ) were identified in the pre-induction sample, of which 5 remained ( RUNX1 , DNMT3A , BCORL1 , BCOR and 1 out of 2 PHF6 ) in the post-treatment sample and none were present post-transplant. In brief, the 3 mutations which were lost along with the leukemic cells at complete morphological remission were most likely acquired leukemic driver mutations that were responsible for the AML transformation from a pre-leukemic germline RUNX1 -mutated state. On the contrary, the 5 mutations that persisted post

  4. Single event burnout sensitivity of embedded field effect transistors

    International Nuclear Information System (INIS)

    Koga, R.; Crain, S.H.; Crawford, K.B.; Yu, P.; Gordon, M.J.

    1999-01-01

    Observations of single event burnout (SEB) in embedded field effect transistors are reported. Both SEB and other single event effects are presented for several pulse width modulation and high frequency devices. The microscope has been employed to locate and to investigate the damaged areas. A model of the damage mechanism based on the results so obtained is described

  5. Measuring Single Event Upsets in the ATLAS Inner Tracker

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    When the HL-LHC starts collecting data, the electronics inside will be subject to massive amounts of radiation. As a result, single event upsets could pose a threat to the ATLAS readout chain. The ABC130, a prototype front-end ASIC for the ATLAS inner tracker, must be tested for its susceptibility to single event upsets.

  6. Single event burnout sensitivity of embedded field effect transistors

    Energy Technology Data Exchange (ETDEWEB)

    Koga, R.; Crain, S.H.; Crawford, K.B.; Yu, P.; Gordon, M.J.

    1999-12-01

    Observations of single event burnout (SEB) in embedded field effect transistors are reported. Both SEB and other single event effects are presented for several pulse width modulation and high frequency devices. The microscope has been employed to locate and to investigate the damaged areas. A model of the damage mechanism based on the results so obtained is described.

  7. Single base pair mutation analysis by PNA directed PCR clamping

    DEFF Research Database (Denmark)

    Ørum, H.; Nielsen, P.E.; Egholm, M.

    1993-01-01

    A novel method that allows direct analysis of single base mutation by the polymerase chain reaction (PCR) is described. The method utilizes the finding that PNAs (peptide nucleic acids) recognize and bind to their complementary nucleic acid sequences with higher thermal stability and specificity...... allows selective amplification/suppression of target sequences that differ by only one base pair. Finally we show that PNAs can be designed in such a way that blockage can be accomplished when the PNA target sequence is located between the PCR primers....

  8. Microbeam mapping of single event latchups and single event upsets in CMOS SRAMs

    International Nuclear Information System (INIS)

    Barak, J.; Adler, E.; Fischer, B.E.; Schloegl, M.; Metzger, S.

    1998-01-01

    The first simultaneous microbeam mapping of single event upset (SEU) and latchup (SEL) in the CMOS RAM HM65162 is presented. The authors found that the shapes of the sensitive areas depend on V DD , on the ions being used and on the site on the chip being hit by the ion. In particular, they found SEL sensitive sites close to the main power supply lines between the memory-bit-arrays by detecting the accompanying current surge. All these SELs were also accompanied by bit-flips elsewhere in the memory (which they call indirect SEUs in contrast to the well known SEUs induced in the hit memory cell only). When identical SEL sensitive sites were hit farther away from the supply lines only indirect SEL sensitive sites could be detected. They interpret these events as latent latchups in contrast to the classical ones detected by their induced current surge. These latent SELs were probably decoupled from the main supply lines by the high resistivity of the local supply lines

  9. The single European market - a Schumpeterian event?

    OpenAIRE

    Siebert, Horst

    1989-01-01

    It is now four years after the White Paper launched the project on the completion of the internal market [Commission, 1985]. 300 steps were packaged and sold in a manner by Delors and Lord Cockfield that "caught on". The basic strategy is simple: abolish or reduce market segmentations that still exist, facilitate free market access, as well as establish the free movement of people, goods, services, and capital (the so-called four freedoms). Will the single European market prove to be an insti...

  10. Heavy ion and proton-induced single event multiple upset

    International Nuclear Information System (INIS)

    Reed, R.A.; Carts, M.A.; Marshall, P.W.

    1997-01-01

    Individual ionizing heavy ion events are shown to cause two or more adjacent memory cells to change logic states in a high density CMOS SRAM. A majority of the upsets produced by normally incident heavy ions are due to single-particle events that causes a single cell to upset. However, for grazing angles a majority of the upsets produced by heavy-ion irradiation are due to single-particle events that cause two or more cells to change logic states. Experimental evidence of a single proton-induced spallation reaction that causes two adjacent memory cells to change logic states is presented. Results from a dual volume Monte-Carlo simulation code for proton-induced single-event multiple upsets are within a factor of three of experimental data for protons at normal incidence and 70 degrees

  11. Future challenges in single event effects for advanced CMOS technologies

    International Nuclear Information System (INIS)

    Guo Hongxia; Wang Wei; Luo Yinhong; Zhao Wen; Guo Xiaoqiang; Zhang Keying

    2010-01-01

    SEE have became a substantial Achilles heel for the reliability of space-based advanced CMOS technologies with features size downscaling. Future space and defense systems require identification and understanding of single event effects to develop hardening approaches for advanced technologies, including changes in device geometry and materials affect energy deposition, charge collection,circuit upset, parametric degradation devices. Topics covered include the impact of technology scaling on radiation response, including single event transients in high speed digital circuits, evidence for single event effects caused by proton direct ionization, and the impact for SEU induced by particle energy effects and indirect ionization. The single event effects in CMOS replacement technologies are introduced briefly. (authors)

  12. Variations in tritium levels during single storm events

    International Nuclear Information System (INIS)

    Smith, L.W.

    1979-06-01

    Precipitation samples have been taken over a period of one calendar year to determine the variables in environmental tritium during single storm events. Where possible, comment is made on the hydrological implications of these variations

  13. Non Invasive Instrumentation For Single Event Effects (NIISEE), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — On this Phase 1 project, Adventium will identify and address key hurdles to achieve Radiation Hardening by Software (RHS) for Single Event Effects (SEEs) for modern...

  14. Single Event Upsets in the ATLAS IBL Front End ASICs

    CERN Document Server

    Rozanov, Alexander; The ATLAS collaboration

    2018-01-01

    During operation at instantaneous luminosities of up to 2.1 10^{34} cm^{-2} s^{-1} the front end chips of the ATLAS innermost pixel layer (IBL) experienced single event upsets affecting its global registers as well as the settings for the individual pixels, causing, among other things loss of occupancy, noisy pixels, and silent pixels. A quantitative analysis of the single event upsets as well as the operational issues and mitigation techniques will be presented.

  15. Single Event Upsets in the ATLAS IBL Front End ASICs

    CERN Document Server

    Rozanov, Alexandre; The ATLAS collaboration

    2018-01-01

    During operation at instantaneous luminosities of up to 2.1 1034 cm2 s−1 frontend chips of the ATLAS innermost pixel layer (IBL) experienced single event upsets affecting its global registers as well as the settings for the individual pixels, causing, amongst other things loss of occupancy, noisy pixels, and silent pixels. A quantitative analysis of the single event upsets as well as the operational issues and mitigation techniques are presented.

  16. Adult eyewitness memory for single versus repeated traumatic events

    NARCIS (Netherlands)

    Theunissen, T.P.M.; Meyer, T.; Memon, A.; Weinsheimer, C.C.

    2017-01-01

    Reports from individuals who have witnessed multiple, similar emotional events may differ from reports from witnesses of only a single event. To test this, we had participants (N = 65) view a video of a road traffic accident. Half of the participants saw two additional (similar) aversive films.

  17. Near bed suspended sediment flux by single turbulent events

    Science.gov (United States)

    Amirshahi, Seyed Mohammad; Kwoll, Eva; Winter, Christian

    2018-01-01

    The role of small scale single turbulent events in the vertical mixing of near bed suspended sediments was explored in a shallow shelf sea environment. High frequency velocity and suspended sediment concentration (SSC; calibrated from the backscatter intensity) were collected using an Acoustic Doppler Velocimeter (ADV). Using quadrant analysis, the despiked velocity time series was divided into turbulent events and small background fluctuations. Reynolds stress and Turbulent Kinetic Energy (TKE) calculated from all velocity samples, were compared to the same turbulent statistics calculated only from velocity samples classified as turbulent events (Reevents and TKEevents). The comparison showed that Reevents and TKEevents was increased 3 and 1.6 times, respectively, when small background fluctuations were removed and that the correlation with SSC for TKE could be improved through removal of the latter. The correlation between instantaneous vertical turbulent flux (w ‧) and SSC fluctuations (SSC ‧) exhibits a tidal pattern with the maximum correlation at peak ebb and flood currents, when strong turbulent events appear. Individual turbulent events were characterized by type, strength, duration and length. Cumulative vertical turbulent sediment fluxes and average SSC associated with individual turbulent events were calculated. Over the tidal cycle, ejections and sweeps were the most dominant events, transporting 50% and 36% of the cumulative vertical turbulent event sediment flux, respectively. Although the contribution of outward interactions to the vertical turbulent event sediment flux was low (11%), single outward interaction events were capable of inducing similar SSC ‧ as sweep events. The results suggest that on time scales of tens of minutes to hours, TKE may be appropriate to quantify turbulence in sediment transport studies, but that event characteristics, particular the upward turbulent flux need to be accounted for when considering sediment transport

  18. European accelerator facilities for single event effects testing

    Energy Technology Data Exchange (ETDEWEB)

    Adams, L; Nickson, R; Harboe-Sorensen, R [ESA-ESTEC, Noordwijk (Netherlands); Hajdas, W; Berger, G

    1997-03-01

    Single event effects are an important hazard to spacecraft and payloads. The advances in component technology, with shrinking dimensions and increasing complexity will give even more importance to single event effects in the future. The ground test facilities are complex and expensive and the complexities of installing a facility are compounded by the requirement that maximum control is to be exercised by users largely unfamiliar with accelerator technology. The PIF and the HIF are the result of experience gained in the field of single event effects testing and represent a unique collaboration between space technology and accelerator experts. Both facilities form an essential part of the European infrastructure supporting space projects. (J.P.N.)

  19. Short template switch events explain mutation clusters in the human genome.

    Science.gov (United States)

    Löytynoja, Ari; Goldman, Nick

    2017-06-01

    Resequencing efforts are uncovering the extent of genetic variation in humans and provide data to study the evolutionary processes shaping our genome. One recurring puzzle in both intra- and inter-species studies is the high frequency of complex mutations comprising multiple nearby base substitutions or insertion-deletions. We devised a generalized mutation model of template switching during replication that extends existing models of genome rearrangement and used this to study the role of template switch events in the origin of short mutation clusters. Applied to the human genome, our model detects thousands of template switch events during the evolution of human and chimp from their common ancestor and hundreds of events between two independently sequenced human genomes. Although many of these are consistent with a template switch mechanism previously proposed for bacteria, our model also identifies new types of mutations that create short inversions, some flanked by paired inverted repeats. The local template switch process can create numerous complex mutation patterns, including hairpin loop structures, and explains multinucleotide mutations and compensatory substitutions without invoking positive selection, speculative mechanisms, or implausible coincidence. Clustered sequence differences are challenging for current mapping and variant calling methods, and we show that many erroneous variant annotations exist in human reference data. Local template switch events may have been neglected as an explanation for complex mutations because of biases in commonly used analyses. Incorporation of our model into reference-based analysis pipelines and comparisons of de novo assembled genomes will lead to improved understanding of genome variation and evolution. © 2017 Löytynoja and Goldman; Published by Cold Spring Harbor Laboratory Press.

  20. Multiple-Event, Single-Photon Counting Imaging Sensor

    Science.gov (United States)

    Zheng, Xinyu; Cunningham, Thomas J.; Sun, Chao; Wang, Kang L.

    2011-01-01

    The single-photon counting imaging sensor is typically an array of silicon Geiger-mode avalanche photodiodes that are monolithically integrated with CMOS (complementary metal oxide semiconductor) readout, signal processing, and addressing circuits located in each pixel and the peripheral area of the chip. The major problem is its single-event method for photon count number registration. A single-event single-photon counting imaging array only allows registration of up to one photon count in each of its pixels during a frame time, i.e., the interval between two successive pixel reset operations. Since the frame time can t be too short, this will lead to very low dynamic range and make the sensor merely useful for very low flux environments. The second problem of the prior technique is a limited fill factor resulting from consumption of chip area by the monolithically integrated CMOS readout in pixels. The resulting low photon collection efficiency will substantially ruin any benefit gained from the very sensitive single-photon counting detection. The single-photon counting imaging sensor developed in this work has a novel multiple-event architecture, which allows each of its pixels to register as more than one million (or more) photon-counting events during a frame time. Because of a consequently boosted dynamic range, the imaging array of the invention is capable of performing single-photon counting under ultra-low light through high-flux environments. On the other hand, since the multiple-event architecture is implemented in a hybrid structure, back-illumination and close-to-unity fill factor can be realized, and maximized quantum efficiency can also be achieved in the detector array.

  1. Multi-Unit Initiating Event Analysis for a Single-Unit Internal Events Level 1 PSA

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong San; Park, Jin Hee; Lim, Ho Gon [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    The Fukushima nuclear accident in 2011 highlighted the importance of considering the risks from multi-unit accidents at a site. The ASME/ANS probabilistic risk assessment (PRA) standard also includes some requirements related to multi-unit aspects, one of which (IE-B5) is as follows: 'For multi-unit sites with shared systems, DO NOT SUBSUME multi-unit initiating events if they impact mitigation capability [1].' However, the existing single-unit PSA models do not explicitly consider multi-unit initiating events and hence systems shared by multiple units (e.g., alternate AC diesel generator) are fully credited for the single unit and ignores the need for the shared systems by other units at the same site [2]. This paper describes the results of the multi-unit initiating event (IE) analysis performed as a part of the at-power internal events Level 1 probabilistic safety assessment (PSA) for an OPR1000 single unit ('reference unit'). In this study, a multi-unit initiating event analysis for a single-unit PSA was performed, and using the results, dual-unit LOOP initiating event was added to the existing PSA model for the reference unit (OPR1000 type). Event trees were developed for dual-unit LOOP and dual-unit SBO which can be transferred from dual- unit LOOP. Moreover, CCF basic events for 5 diesel generators were modelled. In case of simultaneous SBO occurrences in both units, this study compared two different assumptions on the availability of the AAC D/G. As a result, when dual-unit LOOP initiating event was added to the existing single-unit PSA model, the total CDF increased by 1∼ 2% depending on the probability that the AAC D/G is available to a specific unit in case of simultaneous SBO in both units.

  2. Physical mechanisms of single-event effects in advanced microelectronics

    Energy Technology Data Exchange (ETDEWEB)

    Schrimpf, Ronald D. [Electrical Engineering and Computer Science, Vanderbilt University, 5635 Stevenson Center, Nashville, TN 37235 (United States)]. E-mail: ron.schrimpf@vanderbilt.edu; Weller, Robert A. [Electrical Engineering and Computer Science, Vanderbilt University, 5635 Stevenson Center, Nashville, TN 37235 (United States); Mendenhall, Marcus H. [Free Electron Laser Center, Vanderbilt University, Station B 351816, Nashville, TN 37235 (United States); Reed, Robert A. [Electrical Engineering and Computer Science, Vanderbilt University, 5635 Stevenson Center, Nashville, TN 37235 (United States); Massengill, Lloyd W. [Electrical Engineering and Computer Science, Vanderbilt University, 5635 Stevenson Center, Nashville, TN 37235 (United States)

    2007-08-15

    The single-event error rate in advanced semiconductor technologies can be estimated more accurately than conventional methods by using simulation based on accurate descriptions of a large number of individual particle interactions. The results can be used to select the ion types and energies for accelerator testing and to identify situations in which nuclear reactions will contribute to the error rate.

  3. Physical mechanisms of single-event effects in advanced microelectronics

    International Nuclear Information System (INIS)

    Schrimpf, Ronald D.; Weller, Robert A.; Mendenhall, Marcus H.; Reed, Robert A.; Massengill, Lloyd W.

    2007-01-01

    The single-event error rate in advanced semiconductor technologies can be estimated more accurately than conventional methods by using simulation based on accurate descriptions of a large number of individual particle interactions. The results can be used to select the ion types and energies for accelerator testing and to identify situations in which nuclear reactions will contribute to the error rate

  4. Analyzing Single-Event Gate Ruptures In Power MOSFET's

    Science.gov (United States)

    Zoutendyk, John A.

    1993-01-01

    Susceptibilities of power metal-oxide/semiconductor field-effect transistors (MOSFET's) to single-event gate ruptures analyzed by exposing devices to beams of energetic bromine ions while applying appropriate bias voltages to source, gate, and drain terminals and measuring current flowing into or out of each terminal.

  5. Single-event burnout of epitaxial bipolar transistors

    Energy Technology Data Exchange (ETDEWEB)

    Kuboyama, S.; Sugimoto, K.; Shugyo, S.; Matsuda, S. [National Space Development Agency of Japan, Tsukuba, Ibaraki (Japan); Hirao, T. [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan)

    1998-12-01

    Single-Event Burnout (SEB) of bipolar junction transistors (BJTs) has been observed nondestructively. It was revealed that all the NPN BJTs, including small signal transistors, with thinner epitaxial layers were inherently susceptible to the SEB phenomenon. It was demonstrated that several design parameters of BJTs were responsible for SEB susceptibility. Additionally, destructive and nondestructive modes of SEB were identified.

  6. Single-event burnout of epitaxial bipolar transistors

    Energy Technology Data Exchange (ETDEWEB)

    Kuboyama, Satoshi; Sugimoto, Kenji; Matsuda, Sumio [National Space Development Agency of Japan, Ysukuba, Ibaraki (Japan); Hirao, Toshio

    1998-10-01

    Single-event burnout (SEB) of bipolar junction transistors (BJTs) has been observed nondestructively. It was revealed that all the NPN BJTs including small signal transistors with thinner epitaxial layer were inherently susceptible to the SEB phenomenon. It was demonstrated that several design parameters of BJTs were responsible for SEB susceptibility. Additionally, destructive and nondestructive modes of SEB were identified. (author)

  7. Single Event Effects in FPGA Devices 2015-2016

    Science.gov (United States)

    Berg, Melanie; LaBel, Kenneth; Pellish, Jonathan

    2016-01-01

    This presentation provides an overview of single event effects in FPGA devices 2015-2016 including commercial Xilinx V5 heavy ion accelerated testing, Xilinx Kintex-7 heavy ion accelerated testing, mitigation study, and investigation of various types of triple modular redundancy (TMR) for commercial SRAM based FPGAs.

  8. The association of JAK2V617F mutation and leukocytosis with thrombotic events in essential thrombocythemia.

    Science.gov (United States)

    Hsiao, Hui-Hua; Yang, Ming-Yu; Liu, Yi-Chang; Lee, Ching-Ping; Yang, Wen-Chi; Liu, Ta-Chih; Chang, Chao-Sung; Lin, Sheng-Fung

    2007-11-01

    The Janus kinase 2 mutation, JAK2 (V617F), and megakaryocytic mutations, MPL (W515L/K), have been identified and correlated with a subtype of essential thrombocythemia (ET) patients. We investigated the frequency of mutations in ET patients and analyzed the relationship with their clinical features. Fifty-three ET patients were enrolled in the study. The amplification refractory mutation system was applied for the mutation survey of the JAK2V617F, while the polymerase chain reaction with sequencing was used for the mutation survey of MPLW515L/K. Thirty-five (66%) patients harboring the JAK2 (V617F) mutation, including 3 homozygous and 32 heterozygous changes, but no MPLW515L/K mutation, were found. During follow-up, 17 (32.1%) patients suffered from documented thrombotic events, with 15 having JAK2V617F mutations. Statistical analysis showed that patients with the JAK2 mutation had significantly higher leukocytes, hemoglobin level, and thrombotic event (p = 0.043, p = 0.001, and p = 0.029, respectively). Thrombotic events were also significantly correlated with leukocytosis and older age. The JAK2V617F mutation was noted in a certain population of ET patients and correlated with leukocytosis, high hemoglobin level, and thrombosis. Therefore, detection of the JAK2V617F mutation can affect not only the diagnosis, but also the management of ET patients.

  9. Charge collection and SEU (Single Event Upset) mechanisms

    International Nuclear Information System (INIS)

    Musseau, O.

    1994-01-01

    The purpose of this paper is to review the mechanisms of single event upset in microelectronic devices due to interaction with cosmic ions. Experimental and theoretical results are presented, and actual questions and problems are discussed. A brief introduction recalls the creation of the dense plasma of electron-hole pairs along the ion track. The basic processes for charge collection in a simple np junction (drift and diffusion) are presented. The funneling-field effect is discussed and experimental results are compared to numerical simulations and semi-empirical models. Charge collection in actual microelectronic structures is then presented. Single event upset of memory cells is discussed, based on numerical and experimental data. The main parameters for device characterization are presented. From the physical interpretation of charge collection mechanisms, the intrinsic sensitivity of various microelectronic technologies is determined and compared to experimental data. Scaling laws and future trends are discussed. (author)

  10. Applications of heavy ion microprobe for single event effects analysis

    International Nuclear Information System (INIS)

    Reed, Robert A.; Vizkelethy, Gyorgy; Pellish, Jonathan A.; Sierawski, Brian; Warren, Kevin M.; Porter, Mark; Wilkinson, Jeff; Marshall, Paul W.; Niu, Guofu; Cressler, John D.; Schrimpf, Ronald D.; Tipton, Alan; Weller, Robert A.

    2007-01-01

    The motion of ionizing-radiation-induced rogue charge carriers in a semiconductor can create unwanted voltage and current conditions within a microelectronic circuit. If sufficient unwanted charge or current occurs on a sensitive node, a variety of single event effects (SEEs) can occur with consequences ranging from trivial to catastrophic. This paper describes the application of heavy ion microprobes to assist with calibration and validation of SEE modeling approaches

  11. Single event effects in pulse width modulation controllers

    International Nuclear Information System (INIS)

    Penzin, S.H.; Crain, W.R.; Crawford, K.B.; Hansel, S.J.; Kirshman, J.F.; Koga, R.

    1996-01-01

    SEE testing was performed on pulse width modulation (PWM) controllers which are commonly used in switching mode power supply systems. The devices are designed using both Set-Reset (SR) flip-flops and Toggle (T) flip-flops which are vulnerable to single event upset (SEU) in a radiation environment. Depending on the implementation of the different devices the effect can be significant in spaceflight hardware

  12. Single-Event Effects in Silicon Carbide Power Devices

    Science.gov (United States)

    Lauenstein, Jean-Marie; Casey, Megan C.; LaBel, Kenneth A.; Ikpe, Stanley; Topper, Alyson D.; Wilcox, Edward P.; Kim, Hak; Phan, Anthony M.

    2015-01-01

    This report summarizes the NASA Electronic Parts and Packaging Program Silicon Carbide Power Device Subtask efforts in FY15. Benefits of SiC are described and example NASA Programs and Projects desiring this technology are given. The current status of the radiation tolerance of silicon carbide power devices is given and paths forward in the effort to develop heavy-ion single-event effect hardened devices indicated.

  13. Analyzing System on A Chip Single Event Upset Responses using Single Event Upset Data, Classical Reliability Models, and Space Environment Data

    Science.gov (United States)

    Berg, Melanie; LaBel, Kenneth; Campola, Michael; Xapsos, Michael

    2017-01-01

    We are investigating the application of classical reliability performance metrics combined with standard single event upset (SEU) analysis data. We expect to relate SEU behavior to system performance requirements. Our proposed methodology will provide better prediction of SEU responses in harsh radiation environments with confidence metrics. single event upset (SEU), single event effect (SEE), field programmable gate array devises (FPGAs)

  14. Vascular events in Korean patients with myeloproliferative neoplasms and their relationship to JAK2 mutation.

    Science.gov (United States)

    Bang, Soo-Mee; Lee, Jong-Seok; Ahn, Jeong Yeal; Lee, Jae Hoon; Hyun, Myung Soo; Kim, Bong Seog; Park, Moo Rim; Chi, Hyun-Sook; Kim, Ho Young; Kim, Hyo Jung; Lee, Moon Hee; Kim, Hwak; Won, Jong Ho; Yoon, Hwi Joong; Oh, Do-Yeun; Nam, Eun-Mi; Bae, Sung Hwa; Kim, Byoung-Kook

    2009-03-01

    Evaluation of the Janus kinase 2 (JAK2) V617F mutation has been widely used for the diagnosis of myeloproliferative neoplasms (MPN). However, its prognostic relevance to clinical outcome is not completely understood. We investigated the association of JAK2 V617F with vascular events in Korean patients with myeloproliferative neoplasms (MPN). We studied 283 patients from 15 centers, who were diagnosed with MPN. The JAK2 V617F status was evaluated by allele-specific polymerase chain reaction (PCR) and sequencing. The patients' diagnoses were essential thrombocythemia (ET n = 146), polycythemia vera (PV n = 120), primary myelofibrosis (n = 12), and unclassifiable MPN (MPNu n = 5). JAK2 V617F was detected in 89 (61%) patients with ET, 103 (86%) with PV, four (33%) with myelofibrosis, and four (80%) with MPNu. A higher number of leukocytes, haemoglobin levels and BM cellularity as well as an older age, lower platelet counts, and diagnosis of PV were significantly correlated with JAK2 V617F. Eighty-three and 43 episodes of thrombosis and bleeding occurred in 100 patients each before and after the diagnosis. Vascular events more frequently occurred in 37% of patients with JAK2 V617F than in 29% of those without the mutation (p = 0.045). Among 175 patients whose samples were available for sequencing, 28 patients with homozygous JAK2 V617F had vascular events more frequently (57%) than those who were heterozygotes (39%) or had the wild type (27%) (p = 0.03). The multivariate analysis showed that a JAK2 homozygous mutation, hypercholesterolemia and older age were independent risk factors for a vascular event. The results of this study showed that Korean patients with MPN had a similar JAK2 mutation rate and frequency of vascular events when compared to Western patients. The presence of V617F was significantly related to vascular events. Therefore, initial evaluation for the JAK2 mutation and careful monitoring for vascular events should be performed in MPN patients.

  15. Event-by-event simulation of single-neutron experiments to test uncertainty relations

    International Nuclear Information System (INIS)

    Raedt, H De; Michielsen, K

    2014-01-01

    Results from a discrete-event simulation of a recent single-neutron experiment that tests Ozawa's generalization of Heisenberg's uncertainty relation are presented. The event-based simulation algorithm reproduces the results of the quantum theoretical description of the experiment but does not require the knowledge of the solution of a wave equation, nor does it rely on detailed concepts of quantum theory. In particular, the data from these non-quantum simulations satisfy uncertainty relations derived in the context of quantum theory. (paper)

  16. Fast recognition of single molecules based on single-event photon statistics

    International Nuclear Information System (INIS)

    Dong Shuangli; Huang Tao; Liu Yuan; Wang Jun; Zhang Guofeng; Xiao Liantuan; Jia Suotang

    2007-01-01

    Mandel's Q parameter, which is determined from single-event photon statistics, provides an alternative way to recognize single molecules with fluorescence detection, other than the second-order correlation function. It is shown that the Q parameter of an assumed ideal double-molecule fluorescence with the same average photon number as that of the sample fluorescence can act as the criterion for single-molecule recognition. The influence of signal-to-background ratio and the error estimates for photon statistics are also presented. We have applied this method to ascertain single Cy5 dye molecules within hundreds of milliseconds

  17. Mild and severe muscular dystrophy caused by a single {gamma}-sarcoglycan mutation

    Energy Technology Data Exchange (ETDEWEB)

    McNally, E.M.; Boennemann, C.G.; Lidov, H.G.W. [Brigham and Women`s Hospital, Boston, MA (United States)] [and others

    1996-11-01

    Autosomal recessive muscular dystrophy is genetically heterogeneous. One form of this disorder, limb-girdle muscular dystrophy type 2C (LGMD 2C), is prevalent in northern Africa and has been shown to be associated with a single mutation in the gene encoding the dystrophin-associated protein {gamma}-sarcoglycan. The previous mutation analysis of {gamma}-sarcoglycan required the availability of muscle biopsies. To establish a mutation assay for genomic DNA, the intron-exon structure of the {gamma}-sarcoglycan gene was determined, and primers were designed to amplify each of the exons encoding {gamma}-sarcoglycan. We studied a group of Brazilian muscular dystrophy patients for mutations in the {gamma}-sarcoglycan gene. These patients were selected on the basis of autosomal inheritance and/or the presence of normal dystrophin and/or deficiency of {alpha}-sarcoglycan immunostaining. Four of 19 patients surveyed had a single, homozygous mutation in the {gamma}-sarcoglycan gene. The mutation identified in these patients, all of African-Brazilian descent, is identical to that seen in the North African population, suggesting that even patients of remote African descent may carry this mutation. The phenotype in these patients varied considerably. Of four families with an identical mutation, three have a severe Duchenne-like muscular dystrophy. However, one family has much milder symptoms, suggesting that other loci may be present that modify the severity of the clinical course resulting from {gamma}-sarcoglycan gene mutations. 19 refs., 5 figs., 3 tabs.

  18. Electrical signatures of single-stranded DNA with single base mutations in a nanopore capacitor

    International Nuclear Information System (INIS)

    Gracheva, Maria E; Aksimentiev, Aleksei; Leburton, Jean-Pierre

    2006-01-01

    In this paper, we evaluate the magnitude of the electrical signals produced by DNA translocation through a 1 nm diameter nanopore in a capacitor membrane with a numerical multi-scale approach, and assess the possibility of resolving individual nucleotides as well as their types in the absence of conformational disorder. We show that the maximum recorded voltage caused by the DNA translocation is about 35 mV, while the maximum voltage signal due to the DNA backbone is about 30 mV, and the maximum voltage of a DNA base is about 8 mV. Signals from individual nucleotides can be identified in the recorded voltage traces, suggesting a 1 nm diameter pore in a capacitor can be used to accurately count the number of nucleotides in a DNA strand. Furthermore, we study the effect of a single base substitution on the voltage trace, and calculate the differences among the voltage traces due to a single base mutation for the sequences C 3 AC 7 , C 3 CC 7 , C 3 GC 7 and C 3 TC 7 . The calculated voltage differences are in the 5-10 mV range. The calculated maximum voltage caused by the translocation of individual bases varies from 2 to 9 mV, which is experimentally detectable

  19. Validation of an "Intelligent Mouthguard" Single Event Head Impact Dosimeter.

    Science.gov (United States)

    Bartsch, Adam; Samorezov, Sergey; Benzel, Edward; Miele, Vincent; Brett, Daniel

    2014-11-01

    Dating to Colonel John Paul Stapp MD in 1975, scientists have desired to measure live human head impacts with accuracy and precision. But no instrument exists to accurately and precisely quantify single head impact events. Our goal is to develop a practical single event head impact dosimeter known as "Intelligent Mouthguard" and quantify its performance on the benchtop, in vitro and in vivo. In the Intelligent Mouthguard hardware, limited gyroscope bandwidth requires an algorithm-based correction as a function of impact duration. After we apply gyroscope correction algorithm, Intelligent Mouthguard results at time of CG linear acceleration peak correlate to the Reference Hybrid III within our tested range of pulse durations and impact acceleration profiles in American football and Boxing in vitro tests: American football, IMG=1.00REF-1.1g, R2=0.99; maximum time of peak XYZ component imprecision 3.6g and 370 rad/s2; maximum time of peak azimuth and elevation imprecision 4.8° and 2.9°; maximum average XYZ component temporal imprecision 3.3g and 390 rad/s2. Boxing, IMG=1.00REF-0.9 g, R2=0.99, R2=0.98; maximum time of peak XYZ component imprecision 3.9 g and 390 rad/s2, maximum time of peak azimuth and elevation imprecision 2.9° and 2.1°; average XYZ component temporal imprecision 4.0 g and 440 rad/s2. In vivo Intelligent Mouthguard true positive head impacts from American football players and amateur boxers have temporal characteristics (first harmonic frequency from 35 Hz to 79 Hz) within our tested benchtop (first harmonic frequencyIntelligent Mouthguard qualifies as a single event dosimeter in American football and Boxing.

  20. Single Event Upset Studies Using the ATLAS SCT

    CERN Document Server

    Weidberg, A R; The ATLAS collaboration

    2013-01-01

    Single Event Upsets (SEU) are expected to occur during high luminosity running of the ATLAS SemiConductor Tracker (SCT). The SEU cross sections were measured in pion beams with momenta in the range 200 to 465 MeV/c and proton test beams at 24 GeV/c but the extrapolation to LHC conditions is non-trivial because of the range of particle types and momenta. The SEUs studied occur in the \\emph{p-i-n} photodiode and the registers in the ABCD chip. Comparisons between predicted SEU rates and those measured from ATLAS data are presented. The implications for ATLAS operation are discussed.

  1. Single Event Upset Studies Using the ATLAS SCT

    CERN Document Server

    Dafinca, A; The ATLAS collaboration; Weidberg, A R

    2014-01-01

    Single Event Upsets (SEU) are expected to occur during high luminosity running of the ATLAS SemiConductor Tracker (SCT). The SEU cross sections were measured in pion beams with momenta in the range 200 to 465 MeV/c and proton test beams at 24 GeV/c but the extrapolation to LHC conditions is non-trivial because of the range of particle types and momenta. The SEUs studied occur in the p-i-n photodiode and the registers in the ABCD chip. Comparisons between predicted SEU rates and those measured from ATLAS data are presented. The implications for ATLAS operation are discussed

  2. Single-event transients (SET) in analog circuits

    International Nuclear Information System (INIS)

    Chen Panxun; Zhou Kaiming

    2006-01-01

    A new phenomenon of single- event upset is introduced. The transient signal is produced in the output of analog circuits after a heavy ion strikes. The transient upset can influence the circuit connected with the output of analog circuits. For example, the output of operational amplifier can be connected with the input of a digital counter, and the pulse of sufficiently high transient output induced by an ion can increase counts of the counter. On the other hand, the transient voltage signal at the output of analog circuits can change the stage of other circuits. (authors)

  3. Device simulation of charge collection and single-event upset

    International Nuclear Information System (INIS)

    Dodd, P.E.

    1996-01-01

    In this paper the author reviews the current status of device simulation of ionizing-radiation-induced charge collection and single-event upset (SEU), with an emphasis on significant results of recent years. The author presents an overview of device-modeling techniques applicable to the SEU problem and the unique challenges this task presents to the device modeler. He examines unloaded simulations of radiation-induced charge collection in simple p/n diodes, SEU in dynamic random access memories (DRAM's), and SEU in static random access memories (SRAM's). The author concludes with a few thoughts on future issues likely to confront the SEU device modeler

  4. Single-event burnout of power bipolar junction transistors

    International Nuclear Information System (INIS)

    Titus, J.L.; Johnson, G.H.; Schrimpf, R.D.; Galloway, K.F.

    1991-01-01

    Experimental evidence of single-event burnout of power bipolar junctions transistors (BJTs) is reported for the first time. Several commercial power BJTs were characterized in a simulated cosmic ray environment using mono-energetic ions at the tandem Van de Graaff accelerator facility at Brookhaven National Laboratory. Most of the device types exposed to this simulated environment exhibited burnout behavior. In this paper the experimental technique, data, and results are presented, while a qualitative model is used to help explain those results and trends observed in this experiment

  5. Thermomechanical Stresses Analysis of a Single Event Burnout Process

    Science.gov (United States)

    Tais, Carlos E.; Romero, Eduardo; Demarco, Gustavo L.

    2009-06-01

    This work analyzes the thermal and mechanical effects arising in a power Diffusion Metal Oxide Semiconductor (DMOS) during a Single Event Burnout (SEB) process. For studying these effects we propose a more detailed simulation structure than the previously used by other authors, solving the mathematical models by means of the Finite Element Method. We use a cylindrical heat generation region, with 5 W, 10 W, 50 W and 100 W for emulating the thermal phenomena occurring during SEB processes, avoiding the complexity of the mathematical treatment of the ion-semiconductor interaction.

  6. Applicability of LET to single events in microelectronic structures

    Science.gov (United States)

    Xapsos, Michael A.

    1992-12-01

    LET is often used as a single parameter to determine the energy deposited in a microelectronic structure by a single event. The accuracy of this assumption is examined for ranges of ion energies and volumes of silicon appropriate for modern microelectronics. It is shown to be accurate only under very restricted conditions. Significant differences arise because (1) LET is related to energy lost by the ion, not energy deposited in the volume; and (2) LET is an average value and does not account for statistical variations in energy deposition. Criteria are suggested for determining when factors other than LET should be considered, and new analytical approaches are presented to account for them. One implication of these results is that improvements can be made in space upset rate predictions by incorporating the new methods into currently used codes such as CREME and CRUP.

  7. Hierarchical mutational events compensate for glutamate auxotrophy of a Bacillus subtilis gltC mutant.

    Science.gov (United States)

    Dormeyer, Miriam; Lübke, Anastasia L; Müller, Peter; Lentes, Sabine; Reuß, Daniel R; Thürmer, Andrea; Stülke, Jörg; Daniel, Rolf; Brantl, Sabine; Commichau, Fabian M

    2017-06-01

    Glutamate is the major donor of nitrogen for anabolic reactions. The Gram-positive soil bacterium Bacillus subtilis either utilizes exogenously provided glutamate or synthesizes it using the gltAB-encoded glutamate synthase (GOGAT). In the absence of glutamate, the transcription factor GltC activates expression of the GOGAT genes for glutamate production. Consequently, a gltC mutant strain is auxotrophic for glutamate. Using a genetic selection and screening system, we could isolate and differentiate between gltC suppressor mutants in one step. All mutants had acquired the ability to synthesize glutamate, independent of GltC. We identified (i) gain-of-function mutations in the gltR gene, encoding the transcription factor GltR, (ii) mutations in the promoter of the gltAB operon and (iii) massive amplification of the genomic locus containing the gltAB operon. The mutants belonging to the first two classes constitutively expressed the gltAB genes and produced sufficient glutamate for growth. By contrast, mutants that belong to the third class appeared most frequently and solved glutamate limitation by increasing the copy number of the poorly expressed gltAB genes. Thus, glutamate auxotrophy of a B. subtilis gltC mutant can be relieved in multiple ways. Moreover, recombination-dependent amplification of the gltAB genes is the predominant mutational event indicating a hierarchy of mutations. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  8. Heavy ion microbeam system for study of single event effects

    International Nuclear Information System (INIS)

    Kamiya, Tomihiro; Utsunomiya, Nobuhiro; Minehara, Eiichi; Tanaka, Ryuichi; Ohmura, Miyoshi; Kohno, Kazuhiro; Iwamoto, Eiji.

    1992-01-01

    A high-energy heavy ion microbeam system has been developed and installed on a beam line of a 3 MV tandem electrostatic accelerator mainly for analysis of basic mechanism of single event upset (SEU) of semiconductor devices in spacecraft. The SEU is now the most serious problem for highly reliable spacecraft electronics system with long space mission. However, the mechanism has not been understood on the basis of microscopic process of SEU. The SEU phenomena depends not only upon hitting particles, but also upon the hit position on the microcircuit. To observe the transient charge pulse from a SEU, a single ion particle must hit exactly the desired position of the microcircuit. Such an experiment requires the microbeam spot size within 1 μm, the beam positioning accuracy within ±1 μm, and single ion hitting. The microbeam system has been designed to meet the above technical requirements. The system is equipped with two lens systems: one to control the target beam current in a wide range down to extremely low current without any change of the beam optics, and the other to focus heavy ion beams within a spot size of 1 μm. The final goal is to hit a microscopic target area with a single 15 MeV nickel ion. The beam spot size has been evaluated by Gaussian fitting of secondary electron profiles with microbeam scanning across the fine Cu mesh. The single ion detection has been also tested to generate a trigger signal for closing beam shutter to prevent further hits. This paper outlines the new microbeam system and describes methods to realize these techniques. (author)

  9. Mutational jackpot events generate effective frequency-dependent selection in adapting populations

    Science.gov (United States)

    Hallatschek, Oskar

    The site-frequency spectrum is one the most easily measurable quantities that characterize the genetic diversity of a population. While most neutral models predict that site frequency spectra should decay with increasing frequency, a high-frequency uptick has been reported in many populations. Anomalies in the high-frequency tail are particularly unsettling because the highest frequencies can be measured with greatest accuracy. Here, we show that an uptick in the spectrum of neutral mutations generally arises when mutant frequencies are dominated by rare jackpot events, mutational events with large descendant numbers. This leads to an effective pattern of frequency-dependent selection (or unstable internal equilibrium at one half frequency) that causes an accumulation of high-frequency polymorphic sites. We reproduce the known uptick occurring for recurrent hitchhiking (genetic draft) as well as rapid adaptation, and (in the future) generalize the shape of the high-frequency tail to other scenarios that are dominated by jackpot events, such as frequent range expansions. We also tackle (in the future) the inverse approach to use the high-frequency uptick for learning about the tail of the offspring number distribution. Positively selected alleles need to surpass, typically, an u NSF Career Award (PoLS), NIH NIGMS R01, Simons Foundation.

  10. Intramolecular electron transfer in single-site-mutated azurins

    DEFF Research Database (Denmark)

    Farver, O; Skov, L K; Pascher, T

    1993-01-01

    . Natl. Acad. Sci. U.S.A. 86, 6968-6972]. The RSSR- radical produced in the above reaction was reoxidized in a slower intramolecular electron-transfer process (30-70 s-1 at 298 K) concomitant with a further reduction of the Cu(II) ion. The temperature dependence of the latter rates was determined......, lambda = 135 kJ mol-1 for the reorganization energy was derived. When Trp48, situated midway between the donor and the acceptor, was replaced by Leu or Met, only a small change in the rate of intramolecular electron transfer was observed, indicating that the aromatic residue in this position...... is apparently only marginally involved in electron transfer in wild-type azurin. Pathway calculations also suggest that a longer, through-backbone path is more efficient than the shorter one involving Trp48. The former pathway yields an exponential decay factor, beta, of 6.6 nm-1. Another mutation, raising...

  11. A single nucleotide mutation in Nppc is associated with a long bone abnormality in lbab mice

    Directory of Open Access Journals (Sweden)

    Roe Bruce A

    2007-04-01

    Full Text Available Abstract Background The long bone abnormality (lbab mouse is a new autosomal recessive mutant characterized by overall smaller body size with proportionate dwarfing of all organs and shorter long bones. Previous linkage analysis has located the lbab mutation on chromosome 1 between the markers D1Mit9 and D1Mit488. Results A genome-based positional approach was used to identify a mutation associated with lbab disease. A total of 122 genes and expressed sequence tags at the lbab region were screened for possible mutation by using genomic DNA from lbabl/lbab, lbab/+, and +/+ B6 mice and high throughput temperature gradient capillary electrophoresis. A sequence difference was identified in one of the amplicons of gene Nppc between lbab/lbab and +/+ mice. One-step reverse transcriptase polymerase chain reaction was performed to validate the difference of Nppc in different types of mice at the mRNA level. The mutation of Nppc was unique in lbab/lbab mice among multiple mouse inbred strains. The mutation of Nppc is co-segregated with lbab disease in 200 progenies produced from heterozygous lbab/+ parents. Conclusion A single nucleotide mutation of Nppc is associated with dwarfism in lbab/lbab mice. Current genome information and technology allow us to efficiently identify single nucleotide mutations from roughly mapped disease loci. The lbab mouse is a useful model for hereditary human achondroplasia.

  12. A single nucleotide mutation in Nppc is associated with a long bone abnormality in lbab mice.

    Science.gov (United States)

    Jiao, Yan; Yan, Jian; Jiao, Feng; Yang, Hongbin; Donahue, Leah Rae; Li, Xinmin; Roe, Bruce A; Stuart, John; Gu, Weikuan

    2007-04-17

    The long bone abnormality (lbab) mouse is a new autosomal recessive mutant characterized by overall smaller body size with proportionate dwarfing of all organs and shorter long bones. Previous linkage analysis has located the lbab mutation on chromosome 1 between the markers D1Mit9 and D1Mit488. A genome-based positional approach was used to identify a mutation associated with lbab disease. A total of 122 genes and expressed sequence tags at the lbab region were screened for possible mutation by using genomic DNA from lbabl/lbab, lbab/+, and +/+ B6 mice and high throughput temperature gradient capillary electrophoresis. A sequence difference was identified in one of the amplicons of gene Nppc between lbab/lbab and +/+ mice. One-step reverse transcriptase polymerase chain reaction was performed to validate the difference of Nppc in different types of mice at the mRNA level. The mutation of Nppc was unique in lbab/lbab mice among multiple mouse inbred strains. The mutation of Nppc is co-segregated with lbab disease in 200 progenies produced from heterozygous lbab/+ parents. A single nucleotide mutation of Nppc is associated with dwarfism in lbab/lbab mice. Current genome information and technology allow us to efficiently identify single nucleotide mutations from roughly mapped disease loci. The lbab mouse is a useful model for hereditary human achondroplasia.

  13. Single event upset threshold estimation based on local laser irradiation

    International Nuclear Information System (INIS)

    Chumakov, A.I.; Egorov, A.N.; Mavritsky, O.B.; Yanenko, A.V.

    1999-01-01

    An approach for estimation of ion-induced SEU threshold based on local laser irradiation is presented. Comparative experiment and software simulation research were performed at various pulse duration and spot size. Correlation of single event threshold LET to upset threshold laser energy under local irradiation was found. The computer analysis of local laser irradiation of IC structures was developed for SEU threshold LET estimation. The correlation of local laser threshold energy with SEU threshold LET was shown. Two estimation techniques were suggested. The first one is based on the determination of local laser threshold dose taking into account the relation of sensitive area to local irradiated area. The second technique uses the photocurrent peak value instead of this relation. The agreement between the predicted and experimental results demonstrates the applicability of this approach. (authors)

  14. Single event effect testing of the Intel 80386 family and the 80486 microprocessor

    International Nuclear Information System (INIS)

    Moran, A.; LaBel, K.; Gates, M.; Seidleck, C.; McGraw, R.; Broida, M.; Firer, J.; Sprehn, S.

    1996-01-01

    The authors present single event effect test results for the Intel 80386 microprocessor, the 80387 coprocessor, the 82380 peripheral device, and on the 80486 microprocessor. Both single event upset and latchup conditions were monitored

  15. Causal relationships between solar proton events and single event upsets for communication satellites

    Science.gov (United States)

    Lohmeyer, W. Q.; Cahoy, K.; Liu, Shiyang

    In this work, we analyze a historical archive of single event upsets (SEUs) maintained by Inmarsat, one of the world's leading providers of global mobile satellite communications services. Inmarsat has operated its geostationary communication satellites and collected extensive satellite anomaly and telemetry data since 1990. Over the course of the past twenty years, the satellites have experienced more than 226 single event upsets (SEUs), a catch-all term for anomalies that occur in a satellite's electronics such as bit-flips, trips in power supplies, and memory changes in attitude control systems. While SEUs are seemingly random and difficult to predict, we correlate their occurrences to space weather phenomena, and specifically show correlations between SEUs and solar proton events (SPEs). SPEs are highly energetic protons that originate from solar coronal mass ejections (CMEs). It is thought that when these particles impact geostationary (GEO) satellites they can cause SEUs as well as solar array degradation. We calculate the associated statistical correlations that each SEU occurs within one day, one week, two weeks, and one month of 10 MeV SPEs between 10 - 10,000 particle flux units (pfu). However, we find that SPEs are most prevalent at solar maximum and that the SEUs on Inmarsat's satellites occur out of phase with the solar maximum. Ultimately, this suggests that SPEs are not the primary cause of the Inmarsat SEUs. A better understanding of the causal relationship between SPEs and SEUs will help the satellite communications industry develop component and operational space weather mitigation techniques as well as help the space weather community to refine radiation models.

  16. Retrotransposition and mutation events yield Rap1 GTPases with differential signalling capacity

    Directory of Open Access Journals (Sweden)

    Penzkofer Tobias

    2010-02-01

    Full Text Available Abstract Background Retrotransposition of mRNA transcripts gives occasionally rise to functional retrogenes. Through acquiring tempero-spatial expression patterns distinct from their parental genes and/or functional mutations in their coding sequences, such retrogenes may in principle reshape signalling networks. Results Here we present evidence for such a scenario, involving retrogenes of Rap1 belonging to the Ras family of small GTPases. We identified two murine and one human-specific retrogene of Rap1A and Rap1B, which encode proteins that differ by only a few amino acids from their parental Rap1 proteins. Markedly, human hRap1B-retro and mouse mRap1A-retro1 acquired mutations in the 12th and 59th amino acids, respectively, corresponding to residues mutated in constitutively active oncogenic Ras proteins. Statistical and structural analyses support a functional evolution scenario, where Rap1 isoforms of retrogenic origin are functionally distinct from their parental proteins. Indeed, all retrogene-encoded GTPases have an increased GTP/GDP binding ratio in vivo, indicating that their conformations resemble that of active GTP-bound Rap1. We furthermore demonstrate that these three Rap1 isoforms exhibit distinct affinities for the Ras-binding domain of RalGDS. Finally, when tested for their capacity to induce key cellular processes like integrin-mediated cell adhesion or cell spreading, marked differences are seen. Conclusions Together, these data lend strong support for an evolution scenario, where retrotransposition and subsequent mutation events generated species-specific Rap1 isoforms with differential signaling potential. Expression of the constitutively active human Rap1B-retro in cells like those derived from Ramos Burkitt's lymphoma and bone marrow from a patient with myelodysplastic syndrome (MDS warrants further investigation into its role in disease development.

  17. Frequency and spectrum of mutations induced by gamma irradiation in single, double and triple dwarf wheats

    International Nuclear Information System (INIS)

    Dhonukshe, B.L.

    1981-01-01

    Induced mutation studies were carried with three dwarf wheat varieties viz., ''Sonalika'', ''Chhoti Lerma'' and ''Hira'', considered to be single, double and trible dwarfs, respectively. Gamma-rays were used as a source of irradiation. Frequency of chlorophyll mutations were comparatively low and the spectrum was narrow. Chlorophyll mutations were altogether absent in the variety ''Sonalika''. A very wide spectrum of viable mutations affecting stem, leaf, ear growth habit, maturity and fertility characteristics was observed in the M 2 . The cumulative frequency of all the mutants together was quite high, which varied with the varieties. There were varietal differences in the composition and width of the spectrum induced by gamma-rays. The dwarf mutants having desirable leaf and spike characters were isolated in all the three varieties. (author)

  18. AIP mutations in Brazilian patients with sporadic pituitary adenomas: a single-center evaluation

    Science.gov (United States)

    Kasuki, Leandro; de Azeredo Lima, Carlos Henrique; Ogino, Liana; Camacho, Aline H S; Chimelli, Leila; Korbonits, Márta

    2017-01-01

    Aryl hydrocarbon receptor-interacting protein (AIP) gene mutations (AIPmut) are the most frequent germline mutations found in apparently sporadic pituitary adenomas (SPA). Our aim was to evaluate the frequency of AIPmut among young Brazilian patients with SPA. We performed an observational cohort study between 2013 and 2016 in a single referral center. AIPmut screening was carried out in 132 SPA patients with macroadenomas diagnosed up to 40 years or in adenomas of any size diagnosed until 18 years of age. Twelve tumor samples were also analyzed. Leukocyte DNA and tumor tissue DNA were sequenced for the entire AIP-coding region for evaluation of mutations. Eleven (8.3%) of the 132 patients had AIPmut, comprising 9/74 (12%) somatotropinomas, 1/38 (2.6%) prolactinoma, 1/10 (10%) corticotropinoma and no non-functioning adenomas. In pediatric patients (≤18 years), AIPmut frequency was 13.3% (2/15). Out of the 5 patients with gigantism, two had AIPmut, both truncating mutations. The Y268* mutation was described in Brazilian patients and the K273Rfs*30 mutation is a novel mutation in our patient. No somatic AIP mutations were found in the 12 tumor samples. A tumor sample from an acromegaly patient harboring the A299V AIPmut showed loss of heterozygosity. In conclusion, AIPmut frequency in SPA Brazilian patients is similar to other populations. Our study identified two mutations exclusively found in Brazilians and also shows, for the first time, loss of heterozygosity in tumor DNA from an acromegaly patient harboring the A299V AIPmut. Our findings corroborate previous observations that AIPmut screening should be performed in young patients with SPA. PMID:29074612

  19. Identification of five novel FBN1 mutations by non-radioactive single-strand conformation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, W.; Qian, C.; Comeau, K.; Francke, U. [Stanford Univ. Medical Center, Stanford, CA (United States)

    1994-09-01

    Marfan syndrome (MFS), one of the most common genetic disorders of connective tissue, is characterized by variable manifestations in skeletal, cardiovascular and ocular systems. Mutations in the fibrillin gene on chromosome 15 (FBN1) have been shown to cause MFS. To examine the relationship between FBN1 gene mutations, fibrillin protein function and MFS phenotypes, we screened for alternations in the fibrillin coding sequence in fibroblast derived cDNA from MFS patients. To date, abnormally migrating bands in more than 20 unrelated MFS patients have been identified by using non-radioactive single-strand conformation analysis and silver staining. Five altered bands have been directly sequenced. Two missense mutations and three splice site mutations have been identified. Both missense mutations substitute another amino acid for a cysteine residue (C1402W and C1672R) in EGF-like motifs of the fibrillin polypeptide chain. The two splice site mutations are at nucleotide positions 6994+1 (G{yields}A), and 7205-2 (A{yields}G) and result in in-frame skipping of exon 56 and 58, respectively. Skipping of exon 56 occurs in 50% of mutant transcripts. Use of a cryptic splice site 51 bp upstream of the normal donor site results in half of the mutant transcripts containing part of exon 56. Both products contain in-frame deletions. Another splice site mutation, identified by exon screening from patient genomic DNA using intron primers, is at nucleotide position 2293+2 (T{yields}A), but the predicted exon skipping has not been detected at the RT-PCR level. This may be due to instability of the mutant transcript. Including the mutations reported here, a total of 8 out of 36 published FBN1 gene mutations involve exon skipping. It may be inferred that FBN1 exon skipping plays an important pathogenic role in MFS.

  20. AIP mutations in Brazilian patients with sporadic pituitary adenomas: a single-center evaluation

    Directory of Open Access Journals (Sweden)

    Paula Bruna Araujo

    2017-11-01

    Full Text Available Aryl hydrocarbon receptor-interacting protein (AIP gene mutations (AIPmut are the most frequent germline mutations found in apparently sporadic pituitary adenomas (SPA. Our aim was to evaluate the frequency of AIPmut among young Brazilian patients with SPA. We performed an observational cohort study between 2013 and 2016 in a single referral center. AIPmut screening was carried out in 132 SPA patients with macroadenomas diagnosed up to 40 years or in adenomas of any size diagnosed until 18 years of age. Twelve tumor samples were also analyzed. Leukocyte DNA and tumor tissue DNA were sequenced for the entire AIP-coding region for evaluation of mutations. Eleven (8.3% of the 132 patients had AIPmut, comprising 9/74 (12% somatotropinomas, 1/38 (2.6% prolactinoma, 1/10 (10% corticotropinoma and no non-functioning adenomas. In pediatric patients (≤18 years, AIPmut frequency was 13.3% (2/15. Out of the 5 patients with gigantism, two had AIPmut, both truncating mutations. The Y268* mutation was described in Brazilian patients and the K273Rfs*30 mutation is a novel mutation in our patient. No somatic AIP mutations were found in the 12 tumor samples. A tumor sample from an acromegaly patient harboring the A299V AIPmut showed loss of heterozygosity. In conclusion, AIPmut frequency in SPA Brazilian patients is similar to other populations. Our study identified two mutations exclusively found in Brazilians and also shows, for the first time, loss of heterozygosity in tumor DNA from an acromegaly patient harboring the A299V AIPmut. Our findings corroborate previous observations that AIPmut screening should be performed in young patients with SPA.

  1. Approaches to proton single-event rate calculations

    International Nuclear Information System (INIS)

    Petersen, E.L.

    1996-01-01

    This article discusses the fundamentals of proton-induced single-event upsets and of the various methods that have been developed to calculate upset rates. Two types of approaches are used based on nuclear-reaction analysis. Several aspects can be analyzed using analytic methods, but a complete description is not available. The paper presents an analytic description for the component due to elastic-scattering recoils. There have been a number of studies made using Monte Carlo methods. These can completely describe the reaction processes, including the effect of nuclear reactions occurring outside the device-sensitive volume. They have not included the elastic-scattering processes. The article describes the semiempirical approaches that are most widely used. The quality of previous upset predictions relative to space observations is discussed and leads to comments about the desired quality of future predictions. Brief sections treat the possible testing limitation due to total ionizing dose effects, the relationship of proton and heavy-ion upsets, upsets due to direct proton ionization, and relative proton and cosmic-ray upset rates

  2. Search for Flavour Changing Neutral Currents in single top events

    CERN Document Server

    CMS Collaboration

    2013-01-01

    A study of top-quark anomalous couplings is performed through the search for a single top-quark produced in association with a $Z$ boson. The event selection requires the presence of three isolated leptons, electrons or muons, and of at least one jet. The signal extraction is done using kinematic variables and information related to b-tagging, combined using a Boosted Decision Tree. The search is performed in a data sample corresponding to about 5 fb$^{-1}$ of proton-proton collisions at $\\sqrt{s}=7$ TeV recorded with the CMS detector. No evidence of flavor-changing neutral currents is observed and upper limits at 95\\% confidence level are determined. The corresponding upper limits on the coupling strengths of an effective model are found to be $\\kappa_{gut}/\\Lambda < 0.10$ TeV$^{-1}$, $\\kappa_{gct}/\\Lambda < 0.35$ TeV$^{-1}$, $\\kappa_{Zut}/\\Lambda < 0.45$ TeV$^{-1}$ and $\\kappa_{Zct}/\\Lambda < 2.27$ TeV$^{-1}$, where $\\Lambda$ is the expected scale at which new physics could appear. The equivalen...

  3. Versatile single-chip event sequencer for atomic physics experiments

    Science.gov (United States)

    Eyler, Edward

    2010-03-01

    A very inexpensive dsPIC microcontroller with internal 32-bit counters is used to produce a flexible timing signal generator with up to 16 TTL-compatible digital outputs, with a time resolution and accuracy of 50 ns. This time resolution is easily sufficient for event sequencing in typical experiments involving cold atoms or laser spectroscopy. This single-chip device is capable of triggered operation and can also function as a sweeping delay generator. With one additional chip it can also concurrently produce accurately timed analog ramps, and another one-chip addition allows real-time control from an external computer. Compared to an FPGA-based digital pattern generator, this design is slower but simpler and more flexible, and it can be reprogrammed using ordinary `C' code without special knowledge. I will also describe the use of the same microcontroller with additional hardware to implement a digital lock-in amplifier and PID controller for laser locking, including a simple graphics-based control unit. This work is supported in part by the NSF.

  4. The single event upset environment for avionics at high latitude

    International Nuclear Information System (INIS)

    Sims, A.J.; Dyer, C.S.; Peerless, C.L.; Farren, J.

    1994-01-01

    Modern avionic systems for civil and military applications are becoming increasingly reliant upon embedded microprocessors and associated memory devices. The phenomenon of single event upset (SEU) is well known in space systems and designers have generally been careful to use SEU tolerant devices or to implement error detection and correction (EDAC) techniques where appropriate. In the past, avionics designers have had no reason to consider SEU effects but is clear that the more prevalent use of memory devices combined with increasing levels of IC integration will make SEU mitigation an important design consideration for future avionic systems. To this end, it is necessary to work towards producing models of the avionics SEU environment which will permit system designers to choose components and EDAC techniques which are based on predictions of SEU rates correct to much better than an order of magnitude. Measurements of the high latitude SEU environment at avionics altitude have been made on board a commercial airliner. Results are compared with models of primary and secondary cosmic rays and atmospheric neutrons. Ground based SEU tests of static RAMs are used to predict rates in flight

  5. Single Molecule Effects of Osteogenesis Imperfecta Mutations in Tropocollagen Protein Domains

    Science.gov (United States)

    2008-12-02

    Single molecule effects of osteogenesis imperfecta mutations in tropocollagen protein domains Alfonso Gautieri,1,2 Simone Vesentini,2 Alberto...2008 proteinscience.org Abstract: Osteogenesis imperfecta (OI) is a genetic disease characterized by fragile bones, skeletal deformities and, in severe...diagnosis and treatment, an effort referred to as materiomics. Keywords: steered molecular dynamics; osteogenesis imperfecta ; Young’s modulus; collagen

  6. Targeted mutations induced by a single acetylaminofluorene DNA adduct in mammalian cells and bacteria

    International Nuclear Information System (INIS)

    Moryia, M.; Takeshita, M.; Johnson, F.; Peden, K.; Will, S.; Grollman, A.P.

    1988-01-01

    Mutagenic specificity of 2-acetylaminofluorene (AAF) has been established in mammalian cells and several strains of bacteria by using a shuttle plasmid vector containing a single N-(deoxyguanosin-8-yl)acetylaminofluorene (C8-dG-AAF) adduct. The nucleotide sequence of the gene conferring tetracycline resistance was modified by conservative codon replacement so as to accommodate the sequence d(CCTTCGCTAC) flanked by two restriction sites, Bsm I and Xho I. The corresponding synthetic oligodeoxynucleotide underwent reaction with 2-(N-acetoxy-N-acetylamino)-fluorene (AAAF), forming a single dG-AAF adduct. This modified oligodeoxynucleotide was hybridized to its complementary strand and ligated between the Bsm I and Xho I sites of the vector. Plasmids containing the C8-dG-AAF adduct were used to transfect simian virus 40-transformed simian kidney (COS-1) cells and to transform several AB strains of Escherichia coli. Colonies containing mutant plasmides were detected by hybridization to 32 P-labeled oligodeoxynucleotides. Presence of the single DNA adduct increased the mutation frequency by 8-fold in both COS cells and E. coli. Over 80% of mutations detected in both systems were targeted and represented G x C → C x G or G x C → T x A transversions or single nucleotide deletions. The authors conclude that modification of a deoxyguanosine residue with AAF preferentially induces mutations targeted at this site when a plasmid containing a single C8-dG-AAF adduct is introduced into mammalian cells or bacteria

  7. Detecting β-thalassaemia mutations from a single cell by PEP and RDB

    Institute of Scientific and Technical Information of China (English)

    YI Ping; LI Li; YAO Hong; ZHOU Yuan-guo; DENG Bing; CHEN Zhu-qin

    2006-01-01

    Objective:To evaluate the possibility of the technology involving PEP and RDB for detecting β-thalassaemia multipoint mutations from a single cell simultaneously. Methods: A set of allele specific oligonucleotide (ASO) probes used for detecting 8 familiar β-thalassaemia mutations (CD41-42, IVS- Ⅱ -654, CD17, TATA box nt-28, CD71-72, TATA box nt-29, CD26, IVS- Ⅰ -5) were immobilized on a strip of nylon membrane. The genome of a individual cell was amplified by primer extension preamplification (PEP) with the mixture of15-base random oligonucleotides. The aliquots from PEP were used to amplify the objective gene fractions of β-thalassaemia gene by nested or semi-nested PCR. The membrane was hybridized with the final amplified products and then treated with Streptavidin-HRP and color development.Results :Totally 30 lymphocytes were picked up from blood samples of 1 healthy female and 4 patients with known β-thalassaemia mutations respectively. Each single lymphocyte was lysed in the proteinase K buffer. The amplification efficacy was 94.0% and alle drop-out(ADO) rate was 8.0%. Revert dot blot (RDB) was applied to the final amplified products from the 5 participants. The results of diagnosis were the same to the expected, and their genotypes were N/N, CD17 (A→T)/N, IVS- Ⅱ -654(C→T)/CD17(A → T), CD41-42 (-CTTT)/N and TATA box nt-28 (A→G)/N, respectively. Conclusion: The technology involving PEP and RDB could detectmultiple β-thalassaemia mutations from a single cell simultaneously,and the research provides experimental evidences for the feasibility of applying PEP and DNA array technology to screening multiple genetic mutations from a single cell, and will be applied to preimplantation genetic diagnosis and non-invasive prenatal diagnosis for β-thalassaemia.

  8. Detection of HIV drug resistance mutations in pregnant women receiving single dose Nevirapine in south India

    Directory of Open Access Journals (Sweden)

    Mini S Jacob

    2011-01-01

    Full Text Available Background: Single dose of Nevirapine to prevent mother to child transmission of HIV is the commonest preventive regimen in resource-limited countries. Objectives: The objective of this study was to detect drug-resistant virus after single dose of Nevirapine (sdNVP provided to delivering HIV seropositive (HIV+ve women and to evaluate the time taken for its decay. Results: Of the 36 consenting HIV+ve pregnant women enrolled into the study, the mean hemoglobin and total lymphocyte counts were 10.8 g/dl and 1843 cells/mm 3 , respectively. Mean CD4 counts in 64% of women was 363 cells/mm 3 and mean viral load for 16/36 women was 28,143 copies/ml of plasma. Nevirapine-resistance mutations were detected in 28% of women at delivery; using OLA (Oligonucleotide Ligation Assay. K103N mutations were seen in 19.4% of women while the Y181C mutation was seen in 5%. Both the mutations were detected in 2.7% of women. Sequential blood samples collected at delivery, 7-10 days, 6 weeks, 4 months, 6 months and one year postpartum showed that 81% of K103N mutations and 66.7% of Y181C mutations were detected at 6 weeks postpartum . Wild-type virus had replaced the mutants by one year postpartum in all women except one. Conclusion : These observations are relevant for future treatment with antiretroviral therapy in these women for their HIV disease.

  9. Development of Guidelines for Use of Proton Single-Event Test Data to Bound Single-Event Effect Susceptibility Due to Light Ions

    Data.gov (United States)

    National Aeronautics and Space Administration — Conventional methods for Single-Event Effects (SEE) Hardness Assurance have proven difficult to adapt to Explorer, Cubesat and other risk tolerant platforms with...

  10. Structure Based Thermostability Prediction Models for Protein Single Point Mutations with Machine Learning Tools.

    Directory of Open Access Journals (Sweden)

    Lei Jia

    Full Text Available Thermostability issue of protein point mutations is a common occurrence in protein engineering. An application which predicts the thermostability of mutants can be helpful for guiding decision making process in protein design via mutagenesis. An in silico point mutation scanning method is frequently used to find "hot spots" in proteins for focused mutagenesis. ProTherm (http://gibk26.bio.kyutech.ac.jp/jouhou/Protherm/protherm.html is a public database that consists of thousands of protein mutants' experimentally measured thermostability. Two data sets based on two differently measured thermostability properties of protein single point mutations, namely the unfolding free energy change (ddG and melting temperature change (dTm were obtained from this database. Folding free energy change calculation from Rosetta, structural information of the point mutations as well as amino acid physical properties were obtained for building thermostability prediction models with informatics modeling tools. Five supervised machine learning methods (support vector machine, random forests, artificial neural network, naïve Bayes classifier, K nearest neighbor and partial least squares regression are used for building the prediction models. Binary and ternary classifications as well as regression models were built and evaluated. Data set redundancy and balancing, the reverse mutations technique, feature selection, and comparison to other published methods were discussed. Rosetta calculated folding free energy change ranked as the most influential features in all prediction models. Other descriptors also made significant contributions to increasing the accuracy of the prediction models.

  11. TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA.

    Science.gov (United States)

    Wang, Na; Liu, Tiantian; Sofiadis, Anastasios; Juhlin, C Christofer; Zedenius, Jan; Höög, Anders; Larsson, Catharina; Xu, Dawei

    2014-10-01

    The telomerase reverse transcriptase (TERT) promoter mutations C228T and C250T have been found in many malignancies, including in thyroid carcinomas. However, it is unclear how early these mutations occur in thyroid tumorigenesis. The study included primary tumors from 58 patients initially diagnosed with follicular thyroid adenoma (FTA), a benign entity, 18 with atypical FTA (AFTA) having an uncertain malignant potential, and 52 with follicular thyroid carcinoma (FTC). Sanger sequencing was used to investigate the mutational status of the TERT promoter. Telomere length and TERT messenger RNA (mRNA) expression were determined using quantitative polymerase chain reaction (PCR). Telomerase activity was assessed using a Telomerase PCR enzyme-linked immunosorbent assay kit. The C228T mutation was identified in 1 of 58 FTA (2%) and 3 of 18 AFTA (17%) samples. These 4 tumors all expressed TERT mRNA and telomerase activity, whereas the majority of C228T-negative adenomas lacked TERT expression (C228T versus wild-type, P = .008). The C228T mutation was associated with NRAS gene mutations (P = .016). The patient with C228T-mutated FTA later developed a scar recurrence and died of FTC, whereas none of the remaining 57 patients with FTA had recurrence. No recurrence occurred in 3 patients with AFTA who carried C228T during the follow-up period (36-285 months). Nine of the 52 FTCs (17%) exhibited the TERT mutation (8 of 9 C228T and 1 of 9 C250T), and the presence of the mutation was associated with shorter patient survival. TERT promoter mutations may occur as an early genetic event in thyroid follicular tumors that have not developed malignant features on routine histopathological workup. © 2014 American Cancer Society.

  12. Excess of mutational jackpot events in expanding populations revealed by spatial Luria–Delbrück experiments

    Science.gov (United States)

    Fusco, Diana; Gralka, Matti; Kayser, Jona; Anderson, Alex; Hallatschek, Oskar

    2016-01-01

    The genetic diversity of growing cellular populations, such as biofilms, solid tumours or developing embryos, is thought to be dominated by rare, exceptionally large mutant clones. Yet, the emergence of these mutational jackpot events is only understood in well-mixed populations, where they stem from mutations that arise during the first few cell divisions. To study jackpot events in spatially structured populations, we track mutant clones in microbial populations using fluorescence microscopy and population sequencing. High-frequency mutations are found to be massively enriched in microbial colonies compared with well-shaken liquid cultures, as a result of late-occurring mutations surfing at the edge of range expansions. Thus, jackpot events can be generated not only when mutations arise early but also when they occur at favourable locations, which exacerbates their role in adaptation and disease. In particular, because spatial competition with the wild type keeps most mutant clones in a quiescent state, strong selection pressures that kill the wild type promote drug resistance. PMID:27694797

  13. Excess of mutational jackpot events in expanding populations revealed by spatial Luria-Delbrück experiments.

    Science.gov (United States)

    Fusco, Diana; Gralka, Matti; Kayser, Jona; Anderson, Alex; Hallatschek, Oskar

    2016-10-03

    The genetic diversity of growing cellular populations, such as biofilms, solid tumours or developing embryos, is thought to be dominated by rare, exceptionally large mutant clones. Yet, the emergence of these mutational jackpot events is only understood in well-mixed populations, where they stem from mutations that arise during the first few cell divisions. To study jackpot events in spatially structured populations, we track mutant clones in microbial populations using fluorescence microscopy and population sequencing. High-frequency mutations are found to be massively enriched in microbial colonies compared with well-shaken liquid cultures, as a result of late-occurring mutations surfing at the edge of range expansions. Thus, jackpot events can be generated not only when mutations arise early but also when they occur at favourable locations, which exacerbates their role in adaptation and disease. In particular, because spatial competition with the wild type keeps most mutant clones in a quiescent state, strong selection pressures that kill the wild type promote drug resistance.

  14. Single event effects induced by 15.14 MeV/u 136Xe ions

    International Nuclear Information System (INIS)

    Hou Mingdong; Zhang Qingxiang; Liu Jie; Wang Zhiguang; Jin Yunfan; Zhu Zhiyong; Zhen Honglou; Liu Changlong; Chen Xiaoxi; Wei Xinguo; Zhang Lin; Fan Youcheng; Zhu Zhourong; Zhang Yiting

    2002-01-01

    Single event effects induced by 15.14 MeV/u 136 Xe ions in different batches of 32k x 8 bits static random access memory are studied. The incident angle dependences of the cross sections for single event upset and single event latch up are presented. The SEE cross sections are plotted versus energy loss instead of linear energy transfer value in sensitive region. The depth of sensitive volume and thickness of 'dead' layer above the sensitive volume are estimated

  15. The single-event effect evaluation technology for nano integrated circuits

    International Nuclear Information System (INIS)

    Zheng Hongchao; Zhao Yuanfu; Yue Suge; Fan Long; Du Shougang; Chen Maoxin; Yu Chunqing

    2015-01-01

    Single-event effects of nano scale integrated circuits are investigated. Evaluation methods for single-event transients, single-event upsets, and single-event functional interrupts in nano circuits are summarized and classified in detail. The difficulties in SEE testing are discussed as well as the development direction of test technology, with emphasis placed on the experimental evaluation of a nano circuit under heavy ion, proton, and laser irradiation. The conclusions in this paper are based on many years of testing at accelerator facilities and our present understanding of the mechanisms for SEEs, which have been well verified experimentally. (paper)

  16. Induction of somatic mutations by low-dose X-rays: the challenge in recognizing radiation-induced events.

    Science.gov (United States)

    Nagashima, Haruki; Shiraishi, Kumiko; Ohkawa, Saori; Sakamoto, Yuki; Komatsu, Kenshi; Matsuura, Shinya; Tachibana, Akira; Tauchi, Hiroshi

    2017-10-19

    It is difficult to distinguish radiation-induced events from spontaneous events during induction of stochastic effects, especially in the case of low-dose or low-dose-rate exposures. By using a hypersensitive system for detecting somatic mutations at the HPRT1 locus, we investigated the frequency and spectrum of mutations induced by low-dose X-rays. The mutant frequencies induced by doses of >0.15 Gy were statistically significant when compared with the spontaneous frequency, and a clear dose dependency was also observed for mutant frequencies at doses of >0.15 Gy. In contrast, mutant frequencies at doses of 0.2 Gy. Our observations suggest that there could be a critical dose for mutation induction at between 0.1 Gy and 0.2 Gy, where mutagenic events are induced by multiple DNA double-strand breaks (DSBs). These observations also suggest that low-dose radiation delivered at doses of <0.1 Gy may not result in DSB-induced mutations but may enhance spontaneous mutagenesis events. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  17. Quantification of sequence exchange events between PMS2 and PMS2CL provides a basis for improved mutation scanning of Lynch syndrome patients.

    NARCIS (Netherlands)

    Klift, H.M. van der; Tops, C.M.; Bik, E.C.; Boogaard, M.W.; Borgstein, A.M.; Hansson, K.B.; Ausems, M.G.E.M.; Gomez Garcia, E.; Green, A.; Hes, F.J.; Izatt, L.; Hest, L.P. van; Alonso, A.M.; Vriends, A.H.; Wagner, A.; Zelst-Stams, W.A.G. van; Vasen, H.F.; Morreau, H.; Devilee, P.; Wijnen, J.T.

    2010-01-01

    Heterozygous mutations in PMS2 are involved in Lynch syndrome, whereas biallelic mutations are found in Constitutional mismatch repair-deficiency syndrome patients. Mutation detection is complicated by the occurrence of sequence exchange events between the duplicated regions of PMS2 and PMS2CL. We

  18. Conditions and consequences of a BRCA mutation in young, single women of childbearing age.

    Science.gov (United States)

    Hamilton, Rebekah; Hurley, Karen E

    2010-09-01

    To explore the experiences of young, single women who are at increased risk for hereditary breast and ovarian cancer (HBOC) because of a BRCA mutation. Qualitative. Seven states and Canada. 11 single women aged 18-35 years who tested positive for a BRCA mutation. Grounded theory with in-depth individual interviews conducted via e-mail or telephone. Analysis resulted in three conditions and three consequences. Conditions were dating or not dating, time in a relationship, and physical impact of surgery or breast cancer treatment. Consequences were explaining their choices, experiencing a sense of urgency, and experiencing a sense of loss. Young women who are at risk for HBOC face a complex array of decisions after finding out that they carry a BRCA mutation. Being single and childless adds to this complexity. Nurses can listen to young women with HBOC risk, help them clarify their fears and understanding of their risk, and provide nonthreatening support that goes beyond simply providing more information and includes a nonjudgmental understanding of the young women's experience.

  19. A single mutation in the envelope protein modulates flavivirus antigenicity, stability, and pathogenesis.

    Directory of Open Access Journals (Sweden)

    Leslie Goo

    2017-02-01

    Full Text Available The structural flexibility or 'breathing' of the envelope (E protein of flaviviruses allows virions to sample an ensemble of conformations at equilibrium. The molecular basis and functional consequences of virus conformational dynamics are poorly understood. Here, we identified a single mutation at residue 198 (T198F of the West Nile virus (WNV E protein domain I-II hinge that regulates virus breathing. The T198F mutation resulted in a ~70-fold increase in sensitivity to neutralization by a monoclonal antibody targeting a cryptic epitope in the fusion loop. Increased exposure of this otherwise poorly accessible fusion loop epitope was accompanied by reduced virus stability in solution at physiological temperatures. Introduction of a mutation at the analogous residue of dengue virus (DENV, but not Zika virus (ZIKV, E protein also increased accessibility of the cryptic fusion loop epitope and decreased virus stability in solution, suggesting that this residue modulates the structural ensembles sampled by distinct flaviviruses at equilibrium in a context dependent manner. Although the T198F mutation did not substantially impair WNV growth kinetics in vitro, studies in mice revealed attenuation of WNV T198F infection. Overall, our study provides insight into the molecular basis and the in vitro and in vivo consequences of flavivirus breathing.

  20. Single genome retrieval of context-dependent variability in mutation rates for human germline.

    Science.gov (United States)

    Sahakyan, Aleksandr B; Balasubramanian, Shankar

    2017-01-13

    Accurate knowledge of the core components of substitution rates is of vital importance to understand genome evolution and dynamics. By performing a single-genome and direct analysis of 39,894 retrotransposon remnants, we reveal sequence context-dependent germline nucleotide substitution rates for the human genome. The rates are characterised through rate constants in a time-domain, and are made available through a dedicated program (Trek) and a stand-alone database. Due to the nature of the method design and the imposed stringency criteria, we expect our rate constants to be good estimates for the rates of spontaneous mutations. Benefiting from such data, we study the short-range nucleotide (up to 7-mer) organisation and the germline basal substitution propensity (BSP) profile of the human genome; characterise novel, CpG-independent, substitution prone and resistant motifs; confirm a decreased tendency of moieties with low BSP to undergo somatic mutations in a number of cancer types; and, produce a Trek-based estimate of the overall mutation rate in human. The extended set of rate constants we report may enrich our resources and help advance our understanding of genome dynamics and evolution, with possible implications for the role of spontaneous mutations in the emergence of pathological genotypes and neutral evolution of proteomes.

  1. Single Event Burnout in DC-DC Converters for the LHC Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Claudio H. Rivetta et al.

    2001-09-24

    High voltage transistors in DC-DC converters are prone to catastrophic Single Event Burnout in the LHC radiation environment. This paper presents a systematic methodology to analyze single event effects sensitivity in converters and proposes solutions based on de-rating input voltage and output current or voltage.

  2. Cosmic and terrestrial single-event radiation effects in dynamic random access memories

    International Nuclear Information System (INIS)

    Massengill, L.W.

    1996-01-01

    A review of the literature on single-event radiation effects (SEE) on MOS integrated-circuit dynamic random access memories (DRAM's) is presented. The sources of single-event (SE) radiation particles, causes of circuit information loss, experimental observations of SE information upset, technological developments for error mitigation, and relationships of developmental trends to SE vulnerability are discussed

  3. Single-well moment tensor inversion of tensile microseismic events

    Czech Academy of Sciences Publication Activity Database

    Grechka, V.; Li, Z.; Howell, B.; Vavryčuk, Václav

    2016-01-01

    Roč. 81, č. 6 (2016), KS219-KS229 ISSN 0016-8033 R&D Projects: GA ČR(CZ) GAP210/12/1491; GA ČR(CZ) GC16-19751J Institutional support: RVO:67985530 Keywords : microseismic events * moment tensor inversion * mathematical formulation Subject RIV: DC - Siesmology, Volcanology, Earth Structure Impact factor: 2.391, year: 2016

  4. Circulating mutational portrait of cancer: manifestation of aggressive clonal events in both early and late stages

    Directory of Open Access Journals (Sweden)

    Meng Yang

    2017-05-01

    Full Text Available Abstract Background Solid tumors residing in tissues and organs leave footprints in circulation through circulating tumor cells (CTCs and circulating tumor DNAs (ctDNA. Characterization of the ctDNA portraits and comparison with tumor DNA mutational portraits may reveal clinically actionable information on solid tumors that is traditionally achieved through more invasive approaches. Methods We isolated ctDNAs from plasma of patients of 103 lung cancer and 74 other solid tumors of different tissue origins. Deep sequencing using the Guardant360 test was performed to identify mutations in 73 clinically actionable genes, and the results were associated with clinical characteristics of the patient. The mutation profiles of 37 lung cancer cases with paired ctDNA and tumor genomic DNA sequencing were used to evaluate clonal representation of tumor in circulation. Five lung cancer cases with longitudinal ctDNA sampling were monitored for cancer progression or response to treatments. Results Mutations in TP53, EGFR, and KRAS genes are most prevalent in our cohort. Mutation rates of ctDNA are similar in early (I and II and late stage (III and IV cancers. Mutation in DNA repair genes BRCA1, BRCA2, and ATM are found in 18.1% (32/177 of cases. Patients with higher mutation rates had significantly higher mortality rates. Lung cancer of never smokers exhibited significantly higher ctDNA mutation rates as well as higher EGFR and ERBB2 mutations than ever smokers. Comparative analysis of ctDNA and tumor DNA mutation data from the same patients showed that key driver mutations could be detected in plasma even when they were present at a minor clonal population in the tumor. Mutations of key genes found in the tumor tissue could remain in circulation even after frontline radiotherapy and chemotherapy suggesting these mutations represented resistance mechanisms. Longitudinal sampling of five lung cancer cases showed distinct changes in ctDNA mutation portraits that

  5. Identifying EGFR-Expressed Cells and Detecting EGFR Multi-Mutations at Single-Cell Level by Microfluidic Chip

    Science.gov (United States)

    Li, Ren; Zhou, Mingxing; Li, Jine; Wang, Zihua; Zhang, Weikai; Yue, Chunyan; Ma, Yan; Peng, Hailin; Wei, Zewen; Hu, Zhiyuan

    2018-03-01

    EGFR mutations companion diagnostics have been proved to be crucial for the efficacy of tyrosine kinase inhibitor targeted cancer therapies. To uncover multiple mutations occurred in minority of EGFR-mutated cells, which may be covered by the noises from majority of un-mutated cells, is currently becoming an urgent clinical requirement. Here we present the validation of a microfluidic-chip-based method for detecting EGFR multi-mutations at single-cell level. By trapping and immunofluorescently imaging single cells in specifically designed silicon microwells, the EGFR-expressed cells were easily identified. By in situ lysing single cells, the cell lysates of EGFR-expressed cells were retrieved without cross-contamination. Benefited from excluding the noise from cells without EGFR expression, the simple and cost-effective Sanger's sequencing, but not the expensive deep sequencing of the whole cell population, was used to discover multi-mutations. We verified the new method with precisely discovering three most important EGFR drug-related mutations from a sample in which EGFR-mutated cells only account for a small percentage of whole cell population. The microfluidic chip is capable of discovering not only the existence of specific EGFR multi-mutations, but also other valuable single-cell-level information: on which specific cells the mutations occurred, or whether different mutations coexist on the same cells. This microfluidic chip constitutes a promising method to promote simple and cost-effective Sanger's sequencing to be a routine test before performing targeted cancer therapy.[Figure not available: see fulltext.

  6. Screening for mutations in human alpha-globin genes by nonradioactive single-strand conformation polymorphism

    Directory of Open Access Journals (Sweden)

    Jorge S.B.

    2003-01-01

    Full Text Available Point mutations and small insertions or deletions in the human alpha-globin genes may produce alpha-chain structural variants and alpha-thalassemia. Mutations can be detected either by direct DNA sequencing or by screening methods, which select the mutated exon for sequencing. Although small (about 1 kb, 3 exons and 2 introns, the alpha-globin genes are duplicate (alpha2 and alpha1 and highy G-C rich, which makes them difficult to denature, reducing sequencing efficiency and causing frequent artifacts. We modified some conditions for PCR and electrophoresis in order to detect mutations in these genes employing nonradioactive single-strand conformation polymorphism (SSCP. Primers previously described by other authors for radioactive SSCP and phast-SSCP plus denaturing gradient gel electrophoresis were here combined and the resultant fragments (6 new besides 6 original per alpha-gene submitted to silver staining SSCP. Nine structural and one thalassemic mutations were tested, under different conditions including two electrophoretic apparatus (PhastSystem(TM and GenePhor(TM, Amersham Biosciences, different polyacrylamide gel concentrations, run temperatures and denaturing agents, and entire and restriction enzyme cut fragments. One hundred percent of sensitivity was achieved with four of the new fragments formed, using the PhastSystem(TM and 20% gels at 15ºC, without the need of restriction enzymes. This nonradioactive PCR-SSCP approach showed to be simple, rapid and sensitive, reducing the costs involved in frequent sequencing repetitions and increasing the reliability of the results. It can be especially useful for laboratories which do not have an automated sequencer.

  7. Stressful Life Event Experiences of Homeless Adults: A Comparison of Single Men, Single Women, and Women with Children

    Science.gov (United States)

    Zugazaga, Carole

    2004-01-01

    This article describes stressful life events experienced by a multi-shelter sample of 162 homeless adults in the Central Florida area. Participants included homeless single men (n = 54), homeless single women (n = 54), and homeless women with children (n = 54). Subjects were interviewed with a modified version of the List of Threatening…

  8. Anthology of the development of radiation transport tools as applied to single event effects

    International Nuclear Information System (INIS)

    Akkerman, A.; Barak, J.; Murat, M.; Duzellier, S.; Hubert, G.; Gaillardin, M.; Raine, M.; Jordan, T.; Jun, I.; Koontz, S.; Reddell, B.; O'Neill, P.; Foster, C.; Culpepper, W.; Lei, F.; McNulty, P.; Nieminen, P.; Saigne, F.; Wrobel, F.; Santin, G.; Sihver, L.; Tang, H.H.K.; Truscott, P.R.

    2013-01-01

    This anthology contains contributions from eleven different groups, each developing and/or applying Monte Carlo-based radiation transport tools to simulate a variety of effects that result from energy transferred to a semiconductor material by a single particle event. The topics span from basic mechanisms for single-particle induced failures to applied tasks like developing web sites to predict on-orbit single event failure rates using Monte Carlo radiation transport tools. (authors)

  9. Anthology of the Development of Radiation Transport Tools as Applied to Single Event Effects

    Science.gov (United States)

    Reed, R. A.; Weller, R. A.; Akkerman, A.; Barak, J.; Culpepper, W.; Duzellier, S.; Foster, C.; Gaillardin, M.; Hubert, G.; Jordan, T.; Jun, I.; Koontz, S.; Lei, F.; McNulty, P.; Mendenhall, M. H.; Murat, M.; Nieminen, P.; O'Neill, P.; Raine, M.; Reddell, B.; Saigné, F.; Santin, G.; Sihver, L.; Tang, H. H. K.; Truscott, P. R.; Wrobel, F.

    2013-06-01

    This anthology contains contributions from eleven different groups, each developing and/or applying Monte Carlo-based radiation transport tools to simulate a variety of effects that result from energy transferred to a semiconductor material by a single particle event. The topics span from basic mechanisms for single-particle induced failures to applied tasks like developing websites to predict on-orbit single event failure rates using Monte Carlo radiation transport tools.

  10. A Dual Phenotype of Periventricular Nodular Heterotopia and Frontometaphyseal Dysplasia in One Patient Caused by a Single FLNA Mutation Leading to Two Functionally Different Aberrant Transcripts

    Science.gov (United States)

    Zenker, Martin; Rauch, Anita; Winterpacht, Andreas; Tagariello, Andreas; Kraus, Cornelia; Rupprecht, Thomas; Sticht, Heinrich; Reis, André

    2004-01-01

    Two disorders, periventricular nodular heterotopia (PVNH) and a group of skeletal dysplasias belonging to the oto-palato-digital (OPD) spectrum, are caused by FLNA mutations. They are considered mutually exclusive because of the different presumed effects of the respective FLNA gene mutations, leading to loss of function (PVNH) and gain of function (OPD), respectively. We describe here the first patient manifesting PVNH in combination with frontometaphyseal dysplasia, a skeletal dysplasia of the OPD-spectrum. A novel de novo mutation, 7315C→A in exon 45 of the FLNA gene, was identified. It leads to two aberrant transcripts, one full-length transcript with the point mutation causing a substitution of a highly conserved leucine residue (L2439M) and a second shortened transcript lacking 21 bp due to the creation of an ectopic splice donor site in exon 45. We propose that the dual phenotype is caused by two functionally different, aberrant filamin A proteins and therefore represents an exceptional model case of allelic gain-of-function and loss-of-function phenotypes due to a single mutational event. PMID:14988809

  11. Domain-restricted mutation analysis to identify novel driver events in human cancer

    Directory of Open Access Journals (Sweden)

    Sanket Desai

    2017-10-01

    Full Text Available Analysis of mutational spectra across various cancer types has given valuable insights into tumorigenesis. Different approaches have been used to identify novel drivers from the set of somatic mutations, including the methods which use sequence conservation, geometric localization and pathway information. Recent computational methods suggest use of protein domain information for analysis and understanding of the functional consequence of non-synonymous mutations. Similarly, evidence suggests recurrence at specific position in proteins is robust indicators of its functional impact. Building on this, we performed a systematic analysis of TCGA exome derived somatic mutations across 6089 PFAM domains and significantly mutated domains were identified using randomization approach. Multiple alignment of individual domain allowed us to prioritize for conserved residues mutated at analogous positions across different proteins in a statistically disciplined manner. In addition to the known frequently mutated genes, this analysis independently identifies low frequency Meprin and TRAF-Homology (MATH domain in Speckle Type BTB/POZ (SPOP protein, in prostate adenocarcinoma. Results from this analysis will help generate hypotheses about the downstream molecular mechanism resulting in cancer phenotypes.

  12. Research on generation mechanism of single event transient current generated in the semiconductor using ion accelerator

    International Nuclear Information System (INIS)

    Hirao, Toshio

    2007-01-01

    Single-event upset (SEU) is triggered when an amount of electric charges induced by energetic ion incidence exceeds a value known as a critical charge in a very short time period. Therefore, accurate evaluation of electric charge and understanding of basic mechanism of SEU are necessary for the improvement of SEU torrance of electronic devices. In this paper, the collected charges for the single event transient current induced on semiconductor by heavy ion microbeams, and application to use microbeam for single event studies are presented. (author)

  13. Variable myopathic presentation in a single family with novel skeletal RYR1 mutation.

    Directory of Open Access Journals (Sweden)

    Ruben Attali

    Full Text Available We describe an autosomal recessive heterogeneous congenital myopathy in a large consanguineous family. The disease is characterized by variable severity, progressive course in 3 of 4 patients, myopathic face without ophthalmoplegia and proximal muscle weakness. Absence of cores was noted in all patients. Genome wide linkage analysis revealed a single locus on chromosome 19q13 with Zmax = 3.86 at θ = 0.0 and homozygosity of the polymorphic markers at this locus in patients. Direct sequencing of the main candidate gene within the candidate region, RYR1, was performed. A novel homozygous A to G nucleotide substitution (p.Y3016C within exon 60 of the RYR1 gene was found in patients. ARMS PCR was used to screen for the mutation in all available family members and in an additional 150 healthy individuals. This procedure confirmed sequence analysis and did not reveal the A to G mutation (p.Y3016C in 300 chromosomes from healthy individuals. Functional analysis on EBV immortalized cell lines showed no effect of the mutation on RyR1 pharmacological activation or the content of intracellular Ca(2+ stores. Western blot analysis demonstrated a significant reduction of the RyR1 protein in the patient's muscle concomitant with a reduction of the DHPRα1.1 protein. This novel mutation resulting in RyR1 protein decrease causes heterogeneous clinical presentation, including slow progression course and absence of centrally localized cores on muscle biopsy. We suggest that RYR1 related myopathy should be considered in a wide variety of clinical and pathological presentation in childhood myopathies.

  14. Single-trial event-related potentials to significant stimuli.

    Science.gov (United States)

    Rushby, Jacqueline A; Barry, Robert J

    2009-11-01

    The stimulus-response pattern of the skin conductance response (SCR) was used as a model of the Orienting Reflex (OR) to assess the P1, N1, P2, N2 and late positive complex (LPC/P300) components of the ERP in a simple habituation paradigm, in which a single series of 12 innocuous tones were presented at a very long interstimulus interval (2 min). To maintain their waking state during this boring task, participants were instructed to alternately close or open their eyes to each stimulus. None of the baseline-to-peak ERP measures showed trials effects comparable with the marked habituation over trials shown by the SCRs. Principal Components Analysis was used to decompose the ERP, yielding factors identified as the N1, N2, P3a, P3b and Novelty P3 components. An additional factor represented later eye-movement activity. No trial effects were apparent for the N1, N2, P3a or P3b components. The Novelty P3 showed marked response decrement over trials. These results are discussed in relation to current conceptualisations of the OR.

  15. A single geophone to locate seismic events on Mars

    Science.gov (United States)

    Roques, Aurélien; Berenguer, Jean-Luc; Bozdag, Ebru

    2016-04-01

    Knowing the structure of Mars is a key point in understanding the formation of Earth-like planets as plate tectonics and erosion have erased the original suface of the Earth formation. Installing a seismometer on Mars surface makes it possible to identify its structure. An important step in the identification of the structure of a planet is the epicenter's location of a seismic source, typically a meteoric impact or an earthquake. On Earth, the classical way of locating epicenters is triangulation, which requires at least 3 stations. The Mars InSight Project plans to set a single station with 3 components. We propose a software to locate seismic sources on Mars thanks to the 3-components simulated data of an earthquake given by Geoazur (Nice Sophia-Antipolis University, CNRS) researchers. Instrumental response of a sensor is crucial for data interpretation. We study the oscillations of geophone in several situations so as to awaken students to the meaning of damping in second order modeling. In physics, car shock absorbers are often used to illustrate the principle of damping but rarely in practical experiments. We propose the use of a simple seismometer (a string with a mass and a damper) that allows changing several parameters (inductive damping, temperature and pressure) so as to see the effects of these parameters on the impulse response and, in particular, on the damping coefficient. In a second step, we illustrate the effect of damping on a seismogram with the difficulty of identifying and interpreting the different phase arrival times with low damping.

  16. Comprehensive detection of diverse exon 19 deletion mutations of EGFR in lung Cancer by a single probe set.

    Science.gov (United States)

    Bae, Jin Ho; Jo, Seong-Min; Kim, Hak-Sung

    2015-12-15

    Detection of exon 19 deletion mutation of EGFR, one of the most frequently occurring mutations in lung cancer, provides the crucial information for diagnosis and treatment guideline in non-small-cell lung cancer (NSCLC). Here, we demonstrate a simple and efficient method to detect various exon 19 deletion mutations of EGFR using a single probe set comprising of an oligo-quencher (oligo-Q) and a molecular beacon (MB). While the MB hybridizes to both the wild and mutant target DNA, the oligo-Q only binds to the wild target DNA, leading to a fluorescent signal in case of deletion mutation. This enables the comprehensive detection of the diverse exon 19 deletion mutations using a single probe set. We demonstrated the utility and efficiency of the approach by detecting the frequent exon 19 deletion mutations of EGFR through a real-time PCR and in situ fluorescence imaging. Our approach enabled the detection of genomic DNA as low as 0.02 ng, showing a detection limit of 2% in a heterogeneous DNA mixture, and could be used for detecting mutations in a single cell level. The present MB and oligo-Q dual probe system can be used for diagnosis and treatment guideline in NSCLC. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Single-Cell Analysis of Human Pancreas Reveals Transcriptional Signatures of Aging and Somatic Mutation Patterns.

    Science.gov (United States)

    Enge, Martin; Arda, H Efsun; Mignardi, Marco; Beausang, John; Bottino, Rita; Kim, Seung K; Quake, Stephen R

    2017-10-05

    As organisms age, cells accumulate genetic and epigenetic errors that eventually lead to impaired organ function or catastrophic transformation such as cancer. Because aging reflects a stochastic process of increasing disorder, cells in an organ will be individually affected in different ways, thus rendering bulk analyses of postmitotic adult cells difficult to interpret. Here, we directly measure the effects of aging in human tissue by performing single-cell transcriptome analysis of 2,544 human pancreas cells from eight donors spanning six decades of life. We find that islet endocrine cells from older donors display increased levels of transcriptional noise and potential fate drift. By determining the mutational history of individual cells, we uncover a novel mutational signature in healthy aging endocrine cells. Our results demonstrate the feasibility of using single-cell RNA sequencing (RNA-seq) data from primary cells to derive insights into genetic and transcriptional processes that operate on aging human tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Single nucleotide polymorphism array lesions, TET2, DNMT3A, ASXL1 and CBL mutations are present in systemic mastocytosis.

    Directory of Open Access Journals (Sweden)

    Fabiola Traina

    Full Text Available We hypothesized that analysis of single nucleotide polymorphism arrays (SNP-A and new molecular defects may provide new insight in the pathogenesis of systemic mastocytosis (SM. SNP-A karyotyping was applied to identify recurrent areas of loss of heterozygosity and bidirectional sequencing was performed to evaluate the mutational status of TET2, DNMT3A, ASXL1, EZH2, IDH1/IDH2 and the CBL gene family. Overall survival (OS was analyzed using the Kaplan-Meier method. We studied a total of 26 patients with SM. In 67% of SM patients, SNP-A karyotyping showed new chromosomal abnormalities including uniparental disomy of 4q and 2p spanning TET2/KIT and DNMT3A. Mutations in TET2, DNMT3A, ASXL1 and CBL were found in 23%, 12%, 12%, and 4% of SM patients, respectively. No mutations were observed in EZH2 and IDH1/IDH2. Significant differences in OS were observed for SM mutated patients grouped based on the presence of combined TET2/DNMT3A/ASXL1 mutations independent of KIT (P = 0.04 and sole TET2 mutations (P<0.001. In conclusion, TET2, DNMT3A and ASXL1 mutations are also present in mastocytosis and these mutations may affect prognosis, as demonstrated by worse OS in mutated patients.

  19. Clinical and mutation analysis of 51 probands with anophthalmia and/or severe microphthalmia from a single center

    Science.gov (United States)

    Gerth-Kahlert, Christina; Williamson, Kathleen; Ansari, Morad; Rainger, Jacqueline K; Hingst, Volker; Zimmermann, Theodor; Tech, Stefani; Guthoff, Rudolf F; van Heyningen, Veronica; FitzPatrick, David R

    2013-01-01

    Clinical evaluation and mutation analysis was performed in 51 consecutive probands with severe eye malformations – anophthalmia and/or severe microphthalmia – seen in a single specialist ophthalmology center. The mutation analysis consisted of bidirectional sequencing of the coding regions of SOX2, OTX2, PAX6 (paired domain), STRA6, BMP4, SMOC1, FOXE3, and RAX, and genome-wide array-based copy number assessment. Fifteen (29.4%) of the 51 probands had likely causative mutations affecting SOX2 (9/51), OTX2 (5/51), and STRA6 (1/51). Of the cases with bilateral anophthalmia, 9/12 (75%) were found to be mutation positive. Three of these mutations were large genomic deletions encompassing SOX2 (one case) or OTX2 (two cases). Familial inheritance of three intragenic, plausibly pathogenic, and heterozygous mutations was observed. An unaffected carrier parent of an affected child with an identified OTX2 mutation confirmed the previously reported nonpenetrance for this disorder. Two families with SOX2 mutations demonstrated a parent and child both with significant but highly variable eye malformations. Heterozygous loss-of-function mutations in SOX2 and OTX2 are the most common genetic pathology associated with severe eye malformations and bi-allelic loss-of-function in STRA6 is confirmed as an emerging cause of nonsyndromal eye malformations. PMID:24498598

  20. Calculation of cosmic ray induced single event upsets: Program CRUP (Cosmic Ray Upset Program)

    Science.gov (United States)

    Shapiro, P.

    1983-09-01

    This report documents PROGRAM CRUP, COSMIC RAY UPSET PROGRAM. The computer program calculates cosmic ray induced single-event error rates in microelectronic circuits exposed to several representative cosmic-ray environments.

  1. Single-Event Effects in Silicon and Silicon Carbide Power Devices

    Science.gov (United States)

    Lauenstein, Jean-Marie; Casey, Megan C.; LaBel, Kenneth A.; Topper, Alyson D.; Wilcox, Edward P.; Kim, Hak; Phan, Anthony M.

    2014-01-01

    NASA Electronics Parts and Packaging program-funded activities over the past year on single-event effects in silicon and silicon carbide power devices are presented, with focus on SiC device failure signatures.

  2. Current Single Event Effects Results for Candidate Spacecraft Electronics for NASA

    Science.gov (United States)

    OBryan, Martha V.; Seidleck, Christina M.; Carts, Martin A.; LaBel, Kenneth A.; Marshall, Cheryl J.; Reed, Robert A.; Sanders, Anthony B.; Hawkins, Donald K.; Cox, Stephen R.; Kniffin, Scott D.

    2004-01-01

    We present data on the vulnerability of a variety of candidate spacecraft electronics to proton and heavy ion induced single event effects. Devices tested include digital, analog, linear bipolar, and hybrid devices, among others.

  3. Single event monitoring system based on Java 3D and XML data binding

    International Nuclear Information System (INIS)

    Wang Liang; Chinese Academy of Sciences, Beijing; Zhu Kejun; Zhao Jingwei

    2007-01-01

    Online single event monitoring is important to BESIII DAQ System. Java3D is extension of Java Language in 3D technology, XML data binding is more efficient to handle XML document than SAX and DOM. This paper mainly introduce the implementation of BESIII single event monitoring system with Java3D and XML data binding, and interface for track fitting software with JNI technology. (authors)

  4. NEPP Update of Independent Single Event Upset Field Programmable Gate Array Testing

    Science.gov (United States)

    Berg, Melanie; Label, Kenneth; Campola, Michael; Pellish, Jonathan

    2017-01-01

    This presentation provides a NASA Electronic Parts and Packaging (NEPP) Program update of independent Single Event Upset (SEU) Field Programmable Gate Array (FPGA) testing including FPGA test guidelines, Microsemi RTG4 heavy-ion results, Xilinx Kintex-UltraScale heavy-ion results, Xilinx UltraScale+ single event effect (SEE) test plans, development of a new methodology for characterizing SEU system response, and NEPP involvement with FPGA security and trust.

  5. Heavy Ion Irradiation Fluence Dependence for Single-Event Upsets of NAND Flash Memory

    Science.gov (United States)

    Chen, Dakai; Wilcox, Edward; Ladbury, Raymond; Kim, Hak; Phan, Anthony; Seidleck, Christina; LaBel, Kenneth

    2016-01-01

    We investigated the single-event effect (SEE) susceptibility of the Micron 16 nm NAND flash, and found the single-event upset (SEU) cross section varied inversely with fluence. The SEU cross section decreased with increasing fluence. We attribute the effect to the variable upset sensitivities of the memory cells. The current test standards and procedures assume that SEU follow a Poisson process and do not take into account the variability in the error rate with fluence. Therefore, heavy ion irradiation of devices with variable upset sensitivity distribution using typical fluence levels may underestimate the cross section and on-orbit event rate.

  6. Single-event effects in analog and mixed-signal integrated circuits

    International Nuclear Information System (INIS)

    Turflinger, T.L.

    1996-01-01

    Analog and mixed-signal integrated circuits are also susceptible to single-event effects, but they have rarely been tested. Analog circuit single-particle transients require modified test techniques and data analysis. Existing work is reviewed and future concerns are outlined

  7. The effect of driving force on intramolecular electron transfer in proteins. Studies on single-site mutated azurins

    DEFF Research Database (Denmark)

    Farver, O; Skov, L K; van de Kamp, M

    1992-01-01

    -6972]. To further investigate the nature of this long-range electron transfer (LRET) proceeding within the protein matrix, we have now investigated it in two azurins where amino acids have been substituted by single-site mutation of the wild-type Pseudomonas aeruginosa azurin. In one mutated protein, a methionine...... the reorganization energy, lambda and electronic coupling factor, beta. The calculated values fit very well with a through-bond LRET mechanism....

  8. Discrimination of three mutational events that result in a disruption of the R122 primary autolysis site of the human cationic trypsinogen (PRSS1 by denaturing high performance liquid chromatography

    Directory of Open Access Journals (Sweden)

    Férec Claude

    2001-11-01

    Full Text Available Abstract Background R122, the primary autolysis site of the human cationic trypsinogen (PRSS1, constitutes an important "self-destruct" or "fail-safe" defensive mechanism against premature trypsin activation within the pancreas. Disruption of this site by a missense mutation, R122H, was found to cause hereditary pancreatitis. In addition to a c.365G>A (CGC>CAC single nucleotide substitution, a c.365~366GC>AT (CGC>CAT gene conversion event in exon 3 of PRSS1 was also found to result in a R122H mutation. This imposes a serious concern on the genotyping of pancreatitis by a widely used polymerase chain reaction-restriction fragment length polymorphism assay, which could only detect the commonest c.365G>A variant. Materials and methods DNA samples containing either the known c.365G>A or c.365~366GC>AT variant in exon 3 of PRSS1 were used as positive controls to establish a denaturing high performance liquid chromatography (DHPLC assay. Results DHPLC could readily discriminate the two known different mutational events resulting in the R122H mutation. More importantly, under the same experimental conditions, it identified a further mutational event that also occurs in the R122 primary autolysis site but results in a different amino acid substitution: c.364C>T (CGC>TGC; R122C. Conclusions A rapid, simple, and low-cost assay for detecting both the known and new mutations occuring in the R122 primary autolysis site of PRSS1 was established. In addition, the newly found R122C variant represents a likely pancreatitis-predisposing mutation.

  9. Single-Event Transgene Product Levels Predict Levels in Genetically Modified Breeding Stacks.

    Science.gov (United States)

    Gampala, Satyalinga Srinivas; Fast, Brandon J; Richey, Kimberly A; Gao, Zhifang; Hill, Ryan; Wulfkuhle, Bryant; Shan, Guomin; Bradfisch, Greg A; Herman, Rod A

    2017-09-13

    The concentration of transgene products (proteins and double-stranded RNA) in genetically modified (GM) crop tissues is measured to support food, feed, and environmental risk assessments. Measurement of transgene product concentrations in breeding stacks of previously assessed and approved GM events is required by many regulatory authorities to evaluate unexpected transgene interactions that might affect expression. Research was conducted to determine how well concentrations of transgene products in single GM events predict levels in breeding stacks composed of these events. The concentrations of transgene products were compared between GM maize, soybean, and cotton breeding stacks (MON-87427 × MON-89034 × DAS-Ø15Ø7-1 × MON-87411 × DAS-59122-7 × DAS-40278-9 corn, DAS-81419-2 × DAS-44406-6 soybean, and DAS-21023-5 × DAS-24236-5 × SYN-IR102-7 × MON-88913-8 × DAS-81910-7 cotton) and their component single events (MON-87427, MON-89034, DAS-Ø15Ø7-1, MON-87411, DAS-59122-7, and DAS-40278-9 corn, DAS-81419-2, and DAS-44406-6 soybean, and DAS-21023-5, DAS-24236-5, SYN-IR102-7, MON-88913-8, and DAS-81910-7 cotton). Comparisons were made within a crop and transgene product across plant tissue types and were also made across transgene products in each breeding stack for grain/seed. Scatter plots were generated comparing expression in the stacks to their component events, and the percent of variability accounted for by the line of identity (y = x) was calculated (coefficient of identity, I 2 ). Results support transgene concentrations in single events predicting similar concentrations in breeding stacks containing the single events. Therefore, food, feed, and environmental risk assessments based on concentrations of transgene products in single GM events are generally applicable to breeding stacks composed of these events.

  10. Investigation of the Semicoa 2N7616 and 2N7425 and the Microsemi 2N7480 for Single-Event Gate Rupture and Single-Event Burnout

    Science.gov (United States)

    Scheick, Leif

    2014-01-01

    Single-event-effect test results for hi-rel total-dose-hardened power MOSFETs are presented in this report. The 2N7616 and the 2N7425 from Semicoa and the 2N7480 from International Rectifier were tested to NASA test condition standards and requirements. The 2N7480 performed well and the data agree with the manufacture's data. The 2N7616 and 2N7425 were entry parts from Semicoa using a new device architecture. Unfortunately, the device performed poorly and Semicoa is withdrawing power MOSFETs from it line due to these data. Vertical metal-oxide-semiconductor field-effect transistors (MOSFETs) are the most commonly used power transistor. MOSFETs are typically employed in power supplies and high current switching applications. Due to the inherent high electric fields in the device, power MOSFETs are sensitive to heavy ion irradiation and can fail catastrophically as a result of single-event gate rupture (SEGR) or single-event burnout (SEB). Manufacturers have designed radiation-hardened power MOSFETs for space applications. See [1] through [5] for more information. The objective of this effort was to investigate the SEGR and SEB responses of two power MOSFETs recently produced. These tests will serve as a limited verification of these parts. It is acknowledged that further testing on the respective parts may be needed for some mission profiles.

  11. Can tokamaks PFC survive a single event of any plasma instabilities?

    Energy Technology Data Exchange (ETDEWEB)

    Hassanein, A., E-mail: hassanein@purdue.edu [Center for Materials under Extreme Environment, School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47907 (United States); Sizyuk, V.; Miloshevsky, G.; Sizyuk, T. [Center for Materials under Extreme Environment, School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47907 (United States)

    2013-07-15

    Plasma instability events such as disruptions, edge-localized modes (ELMs), runaway electrons (REs), and vertical displacement events (VDEs) are continued to be serious events and most limiting factors for successful tokamak reactor concept. The plasma-facing components (PFCs), e.g., wall, divertor, and limited surfaces of a tokamak as well as coolant structure materials are subjected to intense particle and heat loads and must maintain a clean and stable surface environment among them and the core/edge plasma. Typical ITER transient events parameters are used for assessing the damage from these four different instability events. HEIGHTS simulation showed that a single event of a disruption, giant ELM, VDE, or RE can cause significant surface erosion (melting and vaporization) damage to PFC, nearby components, and/or structural materials (VDE, RE) melting and possible burnout of coolant tubes that could result in shut down of reactor for extended repair time.

  12. Can tokamaks PFC survive a single event of any plasma instabilities?

    Science.gov (United States)

    Hassanein, A.; Sizyuk, V.; Miloshevsky, G.; Sizyuk, T.

    2013-07-01

    Plasma instability events such as disruptions, edge-localized modes (ELMs), runaway electrons (REs), and vertical displacement events (VDEs) are continued to be serious events and most limiting factors for successful tokamak reactor concept. The plasma-facing components (PFCs), e.g., wall, divertor, and limited surfaces of a tokamak as well as coolant structure materials are subjected to intense particle and heat loads and must maintain a clean and stable surface environment among them and the core/edge plasma. Typical ITER transient events parameters are used for assessing the damage from these four different instability events. HEIGHTS simulation showed that a single event of a disruption, giant ELM, VDE, or RE can cause significant surface erosion (melting and vaporization) damage to PFC, nearby components, and/or structural materials (VDE, RE) melting and possible burnout of coolant tubes that could result in shut down of reactor for extended repair time.

  13. Can tokamaks PFC survive a single event of any plasma instabilities?

    International Nuclear Information System (INIS)

    Hassanein, A.; Sizyuk, V.; Miloshevsky, G.; Sizyuk, T.

    2013-01-01

    Plasma instability events such as disruptions, edge-localized modes (ELMs), runaway electrons (REs), and vertical displacement events (VDEs) are continued to be serious events and most limiting factors for successful tokamak reactor concept. The plasma-facing components (PFCs), e.g., wall, divertor, and limited surfaces of a tokamak as well as coolant structure materials are subjected to intense particle and heat loads and must maintain a clean and stable surface environment among them and the core/edge plasma. Typical ITER transient events parameters are used for assessing the damage from these four different instability events. HEIGHTS simulation showed that a single event of a disruption, giant ELM, VDE, or RE can cause significant surface erosion (melting and vaporization) damage to PFC, nearby components, and/or structural materials (VDE, RE) melting and possible burnout of coolant tubes that could result in shut down of reactor for extended repair time

  14. Mutations altering the gammaretrovirus endoproteolytic motif affect glycosylation of the envelope glycoprotein and early events of the virus life cycle

    Energy Technology Data Exchange (ETDEWEB)

    Argaw, Takele; Wilson, Carolyn A., E-mail: carolyn.wilson@fda.hhs.gov

    2015-01-15

    Previously, we found that mutation of glutamine to proline in the endoproteolytic cleavage signal of the PERV-C envelope (RQKK to RPKK) resulted in non-infectious vectors. Here, we show that RPKK results in a non-infectious vector when placed in not only a PERV envelope, but also the envelope of a related gammaretrovirus, FeLV-B. The amino acid substitutions do not prevent envelope precursor cleavage, viral core and genome assembly, or receptor binding. Rather, the mutations result in the formation of hyperglycosylated glycoprotein and a reduction in the reverse transcribed minus strand synthesis and undetectable 2-LTR circular DNA in cells exposed to vectors with these mutated envelopes. Our findings suggest novel functions associated with the cleavage signal sequence that may affect trafficking through the glycosylation machinery of the cell. Further, the glycosylation status of the envelope appears to impact post-binding events of the viral life cycle, either membrane fusion, internalization, or reverse transcription. - Highlights: • Env cleavage signal impacts infectivity of gammaretroviruses. • Non-infectious mutants have hyper-glycosylated envelope that bind target cells. • Non-infectious mutants have defects in the formation of the double-stranded DNA. • Env cleavage motif has functions beyond cleavage of the env precursor.

  15. Low-energy neutron-induced single-event upsets in static random access memory

    International Nuclear Information System (INIS)

    Guo Xiaoqiang; Guo Hongxia; Wang Guizhen; Ling Dongsheng; Chen Wei; Bai Xiaoyan; Yang Shanchao; Liu Yan

    2009-01-01

    The visual analysis method of data process was provided for neutron-induced single-event upset(SEU) in static random access memory(SRAM). The SEU effects of six CMOS SRAMs with different feature size(from 0.13 μm to 1.50 μm) were studied. The SEU experiments were performed using the neutron radiation environment at Xi'an pulsed reactor. And the dependence of low-energy neutron-induced SEU cross section on SRAM's feature size was given. The results indicate that the decreased critical charge is the dominant factor for the increase of single event effect sensitivity of SRAM devices with decreased feature size. Small-sized SRAM devices are more sensitive than large-sized ones to single event effect induced by low-energy neutrons. (authors)

  16. Single event effects and total ionizing dose effects of typical VDMOSFET devices

    International Nuclear Information System (INIS)

    Lou Jianshe; Cai Nan; Liu Jiaxin; Wu Qinzhi; Wang Jia

    2012-01-01

    In this work, single event effects and total ionizing dose effects of typical VDMOSFET irradiated by 60 Co γ-rays and 252 Cf source were studied. The single event burnout and single event gate rupture (SEB/SEGR) effects were investigated, and the relationship between drain-source breakdown voltage and ionizing dose was obtained. The results showed that the VDMOSFET devices were sensitive to SEB and SEGR, and measures to improve their resistance to SEB and SEGR should be considered seriously for their space applications. The drain-source breakdown voltage was sensitive to total ionizing dose effects as the threshold voltage. In assessing the devices' resistance to the total ionizing dose effects, both the threshold voltage and the drain-source breakdown voltage should be taken into account. (authors)

  17. Modeling and simulation of single-event effect in CMOS circuit

    International Nuclear Information System (INIS)

    Yue Suge; Zhang Xiaolin; Zhao Yuanfu; Liu Lin; Wang Hanning

    2015-01-01

    This paper reviews the status of research in modeling and simulation of single-event effects (SEE) in digital devices and integrated circuits. After introducing a brief historical overview of SEE simulation, different level simulation approaches of SEE are detailed, including material-level physical simulation where two primary methods by which ionizing radiation releases charge in a semiconductor device (direct ionization and indirect ionization) are introduced, device-level simulation where the main emerging physical phenomena affecting nanometer devices (bipolar transistor effect, charge sharing effect) and the methods envisaged for taking them into account are focused on, and circuit-level simulation where the methods for predicting single-event response about the production and propagation of single-event transients (SETs) in sequential and combinatorial logic are detailed, as well as the soft error rate trends with scaling are particularly addressed. (review)

  18. Heavy Ion Irradiation Fluence Dependence for Single-Event Upsets in a NAND Flash Memory

    Science.gov (United States)

    Chen, Dakai; Wilcox, Edward; Ladbury, Raymond L.; Kim, Hak; Phan, Anthony; Seidleck, Christina; Label, Kenneth

    2016-01-01

    We investigated the single-event effect (SEE) susceptibility of the Micron 16 nm NAND flash, and found that the single-event upset (SEU) cross section varied inversely with cumulative fluence. We attribute the effect to the variable upset sensitivities of the memory cells. Furthermore, the effect impacts only single cell upsets in general. The rate of multiple-bit upsets remained relatively constant with fluence. The current test standards and procedures assume that SEU follow a Poisson process and do not take into account the variability in the error rate with fluence. Therefore, traditional SEE testing techniques may underestimate the on-orbit event rate for a device with variable upset sensitivity.

  19. Rapid detection of single nucleotide mutation in p53 gene based on ...

    Indian Academy of Sciences (India)

    mutation.27 Nevertheless, more than 50% of all human tumors contain p53 mutation; ... gene mutation detection in various fields of biology and medicine persuaded us to find ..... Yola M L, Eren T and Atar N 2014 Electrochim. Acta. 125 38. 26.

  20. Mutation of NRAS but not KRAS significantly reduces myeloma sensitivity to single-agent bortezomib therapy

    NARCIS (Netherlands)

    G. Mulligan (George); D.I. Lichter (David); A.D. Bacco (Alessandra Di); S.J. Blakemore (Stephen); A. Berger (Allison); E. Koenig (Erik); H. Bernard (Hugues); W.L. Trepicchio (William); B. Li (Bin); R. Neuwirth (Rachel); N. Chattopadhyay (Nibedita); J.B. Bolen (Joseph); A.J. Dorner (Andrew); H. van de Velde (Helgi); D. Ricci (Deborah); S. Jagannath (Sundar); J.R. Berenson (James); P.G. Richardson (Paul Gerard); E.A. Stadtmauer (Edward); R.Z. Orlowski (Robert); S. Lonial (Sagar); K.C. Anderson (Kenneth); P. Sonneveld (Pieter); J.F. San Miguel (Jesús Fernando); D.-L. Esseltine (Dixie-Lee); M. Schu (Matthew)

    2014-01-01

    textabstractVarious translocations and mutations have been identified in myeloma, and certain aberrations, such as t(4;14) and del17, are linked with disease prognosis. To investigate mutational prevalence in myeloma and associations between mutations and patient outcomes, we tested a panel of 41

  1. Multifragmentation of a very heavy nuclear system (I): selection of single-source events

    Energy Technology Data Exchange (ETDEWEB)

    Frankland, J.D.; Bacri, Ch.O.; Borderie, B. [Paris-11 Univ., Inst. de Physique Nucleaire, 91 - Orsay (France)] [and others

    2000-07-01

    A sample of 'single-source' events, compatible with the multifragmentation of very heavy fused systems, are isolated among well-measured {sup 155}Gd + {sup nat}U 36 A.MeV reactions by examining the evolution of the kinematics of fragments with Z {>=} 5 as a function of the dissipated energy and loss of memory of the entrance channel. Single-source events are found to be the result of very central collisions. Such central collisions may also lead to multiple fragment emission due to the decay of excited projectile- and target-like nuclei and so-called 'neck' emission, and for this reason the isolation of single-source events is very difficult. Event-selection criteria based on centrality of collisions, or on the isotropy of the emitted fragments in each event, are found to be inefficient to separate the two mechanisms, unless they take into account the redistribution of fragments' kinetic energies into directions perpendicular to the beam axis. The selected events are good candidates to look for bulk effects in the multifragmentation process. (authors)

  2. Multifragmentation of a very heavy nuclear system (I): selection of single-source events

    International Nuclear Information System (INIS)

    Frankland, J.D.; Bacri, Ch.O.; Borderie, B.; Rivet, M.F.; Squalli, M.; Auger, G.; Bellaize, N.; Bocage, F.; Bougault, R.; Brou, R.; Buchet, Ph.; Chbihi, A.; Colin, J.; Cussol, D.; Dayras, R.; Demeyer, A.; Dore, D.; Durand, D.; Galichet, E.; Genouin-Duhamel, E.; Gerlic, E.; Guinet, D.; Lautesse, Ph.; Laville, J.L.; Lecolley, J.F.; Legrain, R.; Le Neindre, N.; Lopez, O.; Louvel, M.; Maskay, A.M.; Nalpas, L.; Nguyen, A.D.; Parlog, M.; Peter, J.; Plagnol, E.; Rosato, E.; Saint-Laurent, F.; Salou, S.; Steckmeyer, J.C.; Stern, M.; Tabacaru, G.; Tamain, B.; Tirel, O.; Tassan-Got, L.; Vient, E.; Volant, C.; Wieleczko, J.P.

    2001-01-01

    A sample of 'single-source' events, compatible with the multifragmentation of very heavy fused systems, are isolated among well-measured 155 Gd+ nat U 36 A MeV reactions by examining the evolution of the kinematics of fragments with Z≥5 as a function of the dissipated energy and loss of memory of the entrance channel. Single-source events are found to be the result of very central collisions. Such central collisions may also lead to multiple fragment emission due to the decay of excited projectile- and target-like nuclei and so-called 'neck' emission, and for this reason the isolation of single-source events is very difficult. Event-selection criteria based on centrality of collisions, or on the isotropy of the emitted fragments in each event, are found to be inefficient to separate the two mechanisms, unless they take into account the redistribution of fragments' kinetic energies into directions perpendicular to the beam axis. The selected events are good candidates to look for bulk effects in the multifragmentation process

  3. Impact of NBTI Aging on the Single-Event Upset of SRAM Cells

    CERN Document Server

    Bagatin, M; Gerardin, Simone; Paccagnella, Alessandro; Bagatin, Marta

    2010-01-01

    We analyzed the impact of negative bias temperature instability (NBTI) on the single-event upset rate of SRAM cells through experiments and SPICE simulations. We performed critical charge simulations introducing different degradation patterns in the cells, in three technology nodes, from 180 to 90 nm. The simulations results were checked with alpha-particle and heavy-ion irradiations on a 130-nm technology. Both simulations and experimental results show that NBTI degradation does not significantly affect the single-event upset SRAM cell rate as long as the parametric drift induced by aging is within 10\\%.

  4. Experimental study on heavy-ion single event effect on nanometer DDR SRAM

    International Nuclear Information System (INIS)

    Luo Yinhong; Zhang Fengqi; Guo Hongxia; Zhou Hui; Wang Yanping; Zhang Keying

    2013-01-01

    Single event effect experimental study on 90 nm and 65 nm DDR SRAM were carried out, single event upset (SEU) cross section was discussed as a function of several parameters such as feature size, test pattern, incidence angle, supply voltage. Key influence factors and effect rule were analyzed. Feasibility of the current test method was discussed. Results indicate that, SEU cross section reduces as technologies scale down; the influence of test pattern and power supply on SEU cross section is small; tilt angle increases SEU cross section due to multiple upset increasement. The applicability of cosine tilt test method is correlative to ion species and linear energy transfer (LET) values. (authors)

  5. A Biofunctional Molecular Beacon for Detecting Single Base Mutations in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Haiyan Dong

    2016-01-01

    Full Text Available The development of a convenient and sensitive biosensing system to detect specific DNA sequences is an important issue in the field of genetic disease therapy. As a classic DNA detection technique, molecular beacon (MB is often used in the biosensing system. However, it has intrinsic drawbacks, including high assay cost, complicated chemical modification, and operational complexity. In this study, we developed a simple and cost-effective label-free multifunctional MB (LMMB by integrating elements of polymerization primer, template, target recognition, and G-quadruplex into one entity to detect target DNA. The core technique was accomplished by introducing a G-hairpin that features fragments of both G-quadruplex and target DNA recognition in the G-hairpin stem. Hybridization between LMMB and target DNA triggered conformational change between the G-hairpin and the common C-hairpin, resulting in significant SYBR-green signal amplification. The hybridization continues to the isothermal circular strand-displacement polymerization and accumulation of the double-stranded fragments, causing the uninterrupted extension of the LMMB without a need of chemical modification and other assistant DNA sequences. The novel and programmable LMMB could detect target DNA with sensitivity at 250 pmol/l with a linear range from 2 to 100 nmol/l and the relative standard deviation of 7.98%. The LMMB could sense a single base mutation from the normal DNA, and polymerase chain reaction (PCR amplicons of the mutant-type cell line from the wild-type one. The total time required for preparation and assaying was only 25 minutes. Apparently, the LMMB shows great potential for detecting DNA and its mutations in biosamples, and therefore it opens up a new prospect for genetic disease therapy.

  6. Investigation of photobleaching and saturation of single molecules by fluorophore recrossing events

    Energy Technology Data Exchange (ETDEWEB)

    Burrows, Sean M.; Reif, Randall D. [Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061 (United States); Pappas, Dimitri [Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061 (United States)], E-mail: d.pappas@ttu.edu

    2007-08-15

    A method for investigation of photobleaching and saturation of single molecules by fluorophore recrossing events in a laser beam is described. The diffraction-limited probe volumes encountered in single-molecule detection (SMD) produce high excitation irradiance, which can decrease available signal. The single molecules of several dyes were detected and the data was used to extract interpeak times above a defined threshold value. The interpeak times revealed the number of fluorophore recrossing events. The number of molecules detected that were within 2 ms of each other represented a molecular recrossing for this work. Calcein, fluorescein and R-phycoerythrin were analyzed and the saturation irradiance and photobleaching effects were determined as a function of irradiance. This approach is simple and it serves as a method of optimizing experimental conditions for single-molecule detection.

  7. Detection of MPLW515L/K mutations and determination of allele frequencies with a single-tube PCR assay.

    Science.gov (United States)

    Takei, Hiraku; Morishita, Soji; Araki, Marito; Edahiro, Yoko; Sunami, Yoshitaka; Hironaka, Yumi; Noda, Naohiro; Sekiguchi, Yuji; Tsuneda, Satoshi; Ohsaka, Akimichi; Komatsu, Norio

    2014-01-01

    A gain-of-function mutation in the myeloproliferative leukemia virus (MPL) gene, which encodes the thrombopoietin receptor, has been identified in patients with essential thrombocythemia and primary myelofibrosis, subgroups of classic myeloproliferative neoplasms (MPNs). The presence of MPL gene mutations is a critical diagnostic criterion for these diseases. Here, we developed a rapid, simple, and cost-effective method of detecting two major MPL mutations, MPLW515L/K, in a single PCR assay; we termed this method DARMS (dual amplification refractory mutation system)-PCR. DARMS-PCR is designed to produce three different PCR products corresponding to MPLW515L, MPLW515K, and all MPL alleles. The amplicons are later detected and quantified using a capillary sequencer to determine the relative frequencies of the mutant and wild-type alleles. Applying DARMS-PCR to human specimens, we successfully identified MPL mutations in MPN patients, with the exception of patients bearing mutant allele frequencies below the detection limit (5%) of this method. The MPL mutant allele frequencies determined using DARMS-PCR correlated strongly with the values determined using deep sequencing. Thus, we demonstrated the potential of DARMS-PCR to detect MPL mutations and determine the allele frequencies in a timely and cost-effective manner.

  8. Detection of MPLW515L/K mutations and determination of allele frequencies with a single-tube PCR assay.

    Directory of Open Access Journals (Sweden)

    Hiraku Takei

    Full Text Available A gain-of-function mutation in the myeloproliferative leukemia virus (MPL gene, which encodes the thrombopoietin receptor, has been identified in patients with essential thrombocythemia and primary myelofibrosis, subgroups of classic myeloproliferative neoplasms (MPNs. The presence of MPL gene mutations is a critical diagnostic criterion for these diseases. Here, we developed a rapid, simple, and cost-effective method of detecting two major MPL mutations, MPLW515L/K, in a single PCR assay; we termed this method DARMS (dual amplification refractory mutation system-PCR. DARMS-PCR is designed to produce three different PCR products corresponding to MPLW515L, MPLW515K, and all MPL alleles. The amplicons are later detected and quantified using a capillary sequencer to determine the relative frequencies of the mutant and wild-type alleles. Applying DARMS-PCR to human specimens, we successfully identified MPL mutations in MPN patients, with the exception of patients bearing mutant allele frequencies below the detection limit (5% of this method. The MPL mutant allele frequencies determined using DARMS-PCR correlated strongly with the values determined using deep sequencing. Thus, we demonstrated the potential of DARMS-PCR to detect MPL mutations and determine the allele frequencies in a timely and cost-effective manner.

  9. Impact of repeated single-metal and multi-metal pollution events on soil quality.

    Science.gov (United States)

    Burges, Aritz; Epelde, Lur; Garbisu, Carlos

    2015-02-01

    Most frequently, soil metal pollution results from the occurrence of repeated single-metal and, above all, multi-metal pollution events, with concomitant adverse consequences for soil quality. Therefore, in this study, we evaluated the impact of repeated single-metal and multi-metal (Cd, Pb, Cu, Zn) pollution events on soil quality, as reflected by the values of a variety of soil microbial parameters with potential as bioindicators of soil functioning. Specifically, parameters of microbial activity (potentially mineralizable nitrogen, β-glucosidase and acid phosphatase activity) and biomass (fungal and bacterial gene abundance by RT-qPCR) were determined, in the artificially metal-polluted soil samples, at regular intervals over a period of 26 weeks. Similarly, we studied the evolution over time of CaCl2-extractable metal fractions, in order to estimate metal bioavailability in soil. Different metals showed different values of bioavailability and relative bioavailability ([metal]bio/[metal]tot) in soil throughout the experiment, under both repeated single-metal and multi-metal pollution events. Both repeated Zn-pollution and multi-metal pollution events led to a significant reduction in the values of acid phosphatase activity, and bacterial and fungal gene abundance, reflecting the negative impact of these repeated events on soil microbial activity and biomass, and, hence, soil quality. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. High-energy heavy ion testing of VLSI devices for single event ...

    Indian Academy of Sciences (India)

    Unknown

    per describes the high-energy heavy ion radiation testing of VLSI devices for single event upset (SEU) ... The experimental set up employed to produce low flux of heavy ions viz. silicon ... through which they pass, leaving behind a wake of elec- ... for use in Bus Management Unit (BMU) and bulk CMOS ... was scheduled.

  11. Single Event Upset Energy Dependence In a Buck-Converter Power Supply Design

    CERN Document Server

    Drake, G; The ATLAS collaboration; Gopalakrishnan, A; Mahadik, S; Mellado, B; Proudfoot, J; Reed, R; Senthilkumaran, A; Stanek, R

    2012-01-01

    We present a study of Single Event Upsets (SEU) performed on a commercial pulse-width modulator controller chip for switching power supplies. We performed tests to study the probability of an SEU occurring as a function of incident particle (hadron) energy. We discuss the performance of the circuit, and present a solution using external circuitry to effectively eliminate the effect.

  12. Single Event Effects (SEE) for Power Metal-Oxide-Semiconductor Field-Effect Transistors (MOSFETs)

    Science.gov (United States)

    Lauenstein, Jean-Marie

    2011-01-01

    Single-event gate rupture (SEGR) continues to be a key failure mode in power MOSFETs. (1) SEGR is complex, making rate prediction difficult SEGR mechanism has two main components: (1) Oxide damage-- Reduces field required for rupture (2) Epilayer response -- Creates transient high field across the oxide.

  13. First nondestructive measurements of power MOSFET single event burnout cross sections

    International Nuclear Information System (INIS)

    Oberg, D.L.; Wert, J.L.

    1987-01-01

    A new technique to nondestructively measure single event burnout cross sections for N-channel power MOSFETs is presented. Previous measurements of power MOSFET burnout susceptibility have been destructive and thus not conducive to providing statistically meaningful burnout probabilities. The nondestructive technique and data for various device types taken at several accelerators, including the LBL Bevalac, are documented. Several new phenomena are observed

  14. Single-event burnout of power MOSFET devices for satellite application

    International Nuclear Information System (INIS)

    Xue Yuxiong; Tian Kai; Cao Zhou; Yang Shiyu; Liu Gang; Cai Xiaowu; Lu Jiang

    2008-01-01

    Single-event burnout (SEB) sensitivity was tested for power MOSFET devices, JTMCS081 and JTMCS062, which were made in Institute of Microelectronics, Chinese Academy of Sciences, using californium-252 simulation source. SEB voltage threshold was found for devices under test (DUT). It is helpful for engineers to choose devices used in satellites. (authors)

  15. Re-Verification of the IRHN57133SE and IRHN57250SE for Single Event Gate Rupture and Single Event Burnout

    Science.gov (United States)

    Scheick, Leif

    2010-01-01

    The vertical metal oxide semiconductor field-effect transistor (MOSFET) is a widely used power transistor onboard a spacecraft. The MOSFET is typically employed in power supplies and high current switching applications. Due to the inherent high electric fields in the device, power MOSFETs are sensitive to heavy ion irradiation and can fail catastrophically as a result of single event gate rupture (SEGR) or single event burnout (SEB). Manufacturers have designed radiation-hardened power MOSFETs for space applications. These radiation hardened devices are not immune to SEGR or SEB but, rather, can exhibit them at a much more damaging ion than their non-radiation hardened counterparts. See [1] through [5] for more information.This effort was to investigate the SEGR and SEB responses of two power MOSFETs from IR(the IRHN57133SE and the IRHN57250SE) that have recently been produced on a new fabrication line. These tests will serve as a limited verification of these parts, but it is acknowledged that further testing on the respective parts may be needed for some mission profiles.

  16. A Single Missense Mutation in 77% of Prostate Cancer Bone Metastases: Novel Opportunity for Genetic Biomarker and Novel Therapeutic Mitochondrial Target

    Science.gov (United States)

    2017-10-01

    goal of this application is to identify targets for the treatment of androgen receptor null castration-resistant prostate cancer in in vitro and pre...AWARD NUMBER: W81XWH-16-1-0584 TITLE : A Single Missense Mutation in 77% of Prostate Cancer Bone Metastases: Novel Opportunity for Genetic...Missense Mutation in 77% of Prostate Cancer Bone Metastases: 5a. CONTRACT NUMBER A Single Missense Mutation in 77% of Prostate Cancer Bone Metastases

  17. Single Event Effects Test Facility Options at the Oak Ridge National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Riemer, Bernie [ORNL; Gallmeier, Franz X [ORNL; Dominik, Laura J [ORNL

    2015-01-01

    Increasing use of microelectronics of ever diminishing feature size in avionics systems has led to a growing Single Event Effects (SEE) susceptibility arising from the highly ionizing interactions of cosmic rays and solar particles. Single event effects caused by atmospheric radiation have been recognized in recent years as a design issue for avionics equipment and systems. To ensure a system meets all its safety and reliability requirements, SEE induced upsets and potential system failures need to be considered, including testing of the components and systems in a neutron beam. Testing of integrated circuits (ICs) and systems for use in radiation environments requires the utilization of highly advanced laboratory facilities that can run evaluations on microcircuits for the effects of radiation. This paper provides a background of the atmospheric radiation phenomenon and the resulting single event effects, including single event upset (SEU) and latch up conditions. A study investigating requirements for future single event effect irradiation test facilities and developing options at the Spallation Neutron Source (SNS) is summarized. The relatively new SNS with its 1.0 GeV proton beam, typical operation of 5000 h per year, expertise in spallation neutron sources, user program infrastructure, and decades of useful life ahead is well suited for hosting a world-class SEE test facility in North America. Emphasis was put on testing of large avionics systems while still providing tunable high flux irradiation conditions for component tests. Makers of ground-based systems would also be served well by these facilities. Three options are described; the most capable, flexible, and highest-test-capacity option is a new stand-alone target station using about one kW of proton beam power on a gas-cooled tungsten target, with dual test enclosures. Less expensive options are also described.

  18. Single event effects and performance predictions for space applications of RISC processors

    International Nuclear Information System (INIS)

    Kimbrough, J.R.; Colella, N.J.; Denton, S.M.; Shaeffer, D.L.; Shih, D.; Wilburn, J.W.; Coakley, P.G.; Casteneda, C.; Koga, R.; Clark, D.A.; Ullmann, J.L.

    1994-01-01

    Proton and ion Single Event Phenomena (SEP) tests were performed on 32-b processors including R3000A's from all commercial manufacturers along with the Performance PR3400 family, Integrated Device Technology Inc. 79R3081, LSI Logic Corporation LR33000HC, and Intel i80960MX parts. The microprocessors had acceptable upset rates for operation in a low earth orbit or a lunar mission such as CLEMENTINE with a wide range in proton total dose failure. Even though R3000A devices are 60% smaller in physical area than R3000 devices, there was a 340% increase in device Single Event Upset (SEU) cross section. Software tests of varying complexity demonstrate that registers and other functional blocks using register architecture dominate the cross section. The current approach of giving a single upset cross section can lead to erroneous upset rates depending on the application software

  19. Design of thermostable rhamnogalacturonan lyase mutants from Bacillus licheniformis by combination of targeted single point mutations

    DEFF Research Database (Denmark)

    da Silva, Ines Isabel Cardoso Rodrigues; Jers, Carsten; Otten, Harm

    2014-01-01

    Rhamnogalacturonan I lyases (RGI lyases) (EC 4.2.2.-) catalyze cleavage of α-1,4 bonds between rhamnose and galacturonic acid in the backbone of pectins by β-elimination. In the present study, targeted improvement of the thermostability of a PL family 11 RGI lyase from Bacillus licheniformis (DSM......, were obtained due to additive stabilizing effects of single amino acid mutations (E434L, G55V, and G326E) compared to the wild type. The crystal structure of the B. licheniformis wild-type RGI lyase was also determined; the structural analysis corroborated that especially mutation of charged amino...

  20. Properties of Coronal Shocks at the Origin of SEP events Observed by Only One Single Spacecraft

    Science.gov (United States)

    Lario, D.; Kwon, R.

    2017-12-01

    The simultaneous observation of solar energetic particle (SEP) events by multiple spacecraft distributed in the interplanetary medium depends not only on the spatial separation among the different spacecraft, but also on the properties of the particle sources and the characteristics of the SEP transport in interplanetary space. Among the SEP events observed by STEREO-A, STEREO-B and/or near-Earth spacecraft during solar cycle 24, we select SEP events observed by a single spacecraft (specifically, the SEP events observed only by near-Earth spacecraft on 2012 April 5, 2011 September 4, and 2013 August 17). We analyze whether the properties of the coronal shock associated with the origin of the events (as seen in extreme-ultraviolet and white-light coronal images) differ from those associated with SEP events observed by two or three spacecraft. For the selected events we find that the associated CMEs are, in general, narrower than those associated with SEP events observed by two or three spacecraft. The confined extension of the parent coronal shock and the absence of magnetic connection between distant spacecraft and the regions of the expanding coronal shock able to efficiently accelerate SEPs seem to be the conditions leading to intense SEP events observed only over narrow regions of interplanetary space by spacecraft magnetically connected to regions close to the parent eruption site. Weak and gradual intensity increases observed in extended regions of space might involve transport processes and/or later connections established with interplanetary shocks. Systematic analyses of a larger number of events are required before drawing firm conclusions.

  1. Quantification of sequence exchange events between PMS2 and PMS2CL provides a basis for improved mutation scanning of Lynch syndrome patients.

    Science.gov (United States)

    van der Klift, Heleen M; Tops, Carli M J; Bik, Elsa C; Boogaard, Merel W; Borgstein, Anne-Marijke; Hansson, Kerstin B M; Ausems, Margreet G E M; Gomez Garcia, Encarna; Green, Andrew; Hes, Frederik J; Izatt, Louise; van Hest, Liselotte P; Alonso, Angel M; Vriends, Annette H J T; Wagner, Anja; van Zelst-Stams, Wendy A G; Vasen, Hans F A; Morreau, Hans; Devilee, Peter; Wijnen, Juul T

    2010-05-01

    Heterozygous mutations in PMS2 are involved in Lynch syndrome, whereas biallelic mutations are found in Constitutional mismatch repair-deficiency syndrome patients. Mutation detection is complicated by the occurrence of sequence exchange events between the duplicated regions of PMS2 and PMS2CL. We investigated the frequency of such events with a nonspecific polymerase chain reaction (PCR) strategy, co-amplifying both PMS2 and PMS2CL sequences. This allowed us to score ratios between gene and pseudogene-specific nucleotides at 29 PSV sites from exon 11 to the end of the gene. We found sequence transfer at all investigated PSVs from intron 12 to the 3' end of the gene in 4 to 52% of DNA samples. Overall, sequence exchange between PMS2 and PMS2CL was observed in 69% (83/120) of individuals. We demonstrate that mutation scanning with PMS2-specific PCR primers and MLPA probes, designed on PSVs, in the 3' duplicated region is unreliable, and present an RNA-based mutation detection strategy to improve reliability. Using this strategy, we found 19 different putative pathogenic PMS2 mutations. Four of these (21%) are lying in the region with frequent sequence transfer and are missed or called incorrectly as homozygous with several PSV-based mutation detection methods. (c) 2010 Wiley-Liss, Inc.

  2. A pan-cancer analysis of transcriptome changes associated with somatic mutations in U2AF1 reveals commonly altered splicing events.

    Directory of Open Access Journals (Sweden)

    Angela N Brooks

    Full Text Available Although recurrent somatic mutations in the splicing factor U2AF1 (also known as U2AF35 have been identified in multiple cancer types, the effects of these mutations on the cancer transcriptome have yet to be fully elucidated. Here, we identified splicing alterations associated with U2AF1 mutations across distinct cancers using DNA and RNA sequencing data from The Cancer Genome Atlas (TCGA. Using RNA-Seq data from 182 lung adenocarcinomas and 167 acute myeloid leukemias (AML, in which U2AF1 is somatically mutated in 3-4% of cases, we identified 131 and 369 splicing alterations, respectively, that were significantly associated with U2AF1 mutation. Of these, 30 splicing alterations were statistically significant in both lung adenocarcinoma and AML, including three genes in the Cancer Gene Census, CTNNB1, CHCHD7, and PICALM. Cell line experiments expressing U2AF1 S34F in HeLa cells and in 293T cells provide further support that these altered splicing events are caused by U2AF1 mutation. Consistent with the function of U2AF1 in 3' splice site recognition, we found that S34F/Y mutations cause preferences for CAG over UAG 3' splice site sequences. This report demonstrates consistent effects of U2AF1 mutation on splicing in distinct cancer cell types.

  3. Early Events in Retinal Degeneration Caused by Rhodopsin Mutation or Pigment Epithelium Malfunction: Differences and Similarities

    Science.gov (United States)

    Di Pierdomenico, Johnny; García-Ayuso, Diego; Pinilla, Isabel; Cuenca, Nicolás; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Villegas-Pérez, María P.

    2017-01-01

    To study the course of photoreceptor cell death and macro and microglial reactivity in two rat models of retinal degeneration with different etiologies. Retinas from P23H-1 (rhodopsin mutation) and Royal College of Surgeon (RCS, pigment epithelium malfunction) rats and age-matched control animals (Sprague-Dawley and Pievald Viro Glaxo, respectively) were cross-sectioned at different postnatal ages (from P10 to P60) and rhodopsin, L/M- and S-opsin, ionized calcium-binding adapter molecule 1 (Iba1), glial fibrillary acid protein (GFAP), and proliferating cell nuclear antigen (PCNA) proteins were immunodetected. Photoreceptor nuclei rows and microglial cells in the different retinal layers were quantified. Photoreceptor degeneration starts earlier and progresses quicker in P23H-1 than in RCS rats. In both models, microglial cell activation occurs simultaneously with the initiation of photoreceptor death while GFAP over-expression starts later. As degeneration progresses, the numbers of microglial cells increase in the retina, but decreasing in the inner retina and increasing in the outer retina, more markedly in RCS rats. Interestingly, and in contrast with healthy animals, microglial cells reach the outer nuclei and outer segment layers. The higher number of microglial cells in dystrophic retinas cannot be fully accounted by intraretinal migration and PCNA immunodetection revealed microglial proliferation in both models but more importantly in RCS rats. The etiology of retinal degeneration determines the initiation and pattern of photoreceptor cell death and simultaneously there is microglial activation and migration, while the macroglial response is delayed. The actions of microglial cells in the degeneration cannot be explained only in the basis of photoreceptor death because they participate more actively in the RCS model. Thus, the retinal degeneration caused by pigment epithelium malfunction is more inflammatory and would probably respond better to interventions

  4. Relationship between single-event upset immunity and fabrication processes of recent memories

    International Nuclear Information System (INIS)

    Nemoto, N.; Shindou, H.; Kuboyama, S.; Matsuda, S.; Itoh, H.; Okada, S.; Nashiyama, I.

    1999-01-01

    Single-Event upset (SEU) immunity for commercial devices were evaluated by irradiation tests using high-energy heavy ions. We show test results and describe the relationship between observed SEU and structures/fabrication processes. We have evaluated single-even upset (SEU) tolerance of recent commercial memory devices using high energy heavy ions in order to find relationship between SEU rate and their fabrication process. It was revealed that the change of the process parameter gives much effect for the SEU rate of the devices. (authors)

  5. Simulating single-event burnout of n-channel power MOSFET's

    International Nuclear Information System (INIS)

    Johnson, G.H.; Hohl, J.H.; Schrimpf, R.D.; Galloway, K.F.

    1993-01-01

    Heavy ions are ubiquitous in a space environment. Single-event burnout of power MOSFET's is a sudden catastrophic failure mechanism that is initiated by the passage of a heavy ion through the device structure. The passage of the heavy ion generates a current filament that locally turns on a parasitic n-p-n transistor inherent to the power MOSFET. Subsequent high currents and high voltage in the device induce second breakdown of the parasitic bipolar transistor and hence meltdown of the device. This paper presents a model that can be used for simulating the burnout mechanism in order to gain insight into the significant device parameters that most influence the single-event burnout susceptibility of n-channel power MOSFET's

  6. Capillary electrophoretic study of individual exocytotic events in single mast cells

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Andrea Ming-Wei [Iowa State Univ., Ames, IA (United States)

    1999-02-12

    The peak profile of individual degranulation events from the on-column release of serotonin from single rat peritoneal mast cells (RPMCs) was monitored using capillary electrophoresis with laser-induced native fluorescence detection (CE-LINF). Serotonin, an important biogenic amine, is contained in granules (0.25 fL) within RPMCs and is extruded by a process termed exocytosis. The secretagogue, Polymyxin B sulfate, was used as the CE running buffer after injection of a single RPMC into the separation capillary to stimulate the release of the granules. Because the release process occurs on a ms time scale, monitoring individual exocytotic events is possible with the coupling of high-speed CE and LINF detection.

  7. Evaluation of single-event upset tolerance on 64Mbit DRAM and 16Mbit DRAM

    Energy Technology Data Exchange (ETDEWEB)

    Nemoto, N; Shindou, H; Matsuzaki, K; Akutsu, T; Matsuda, S [National Space Development Agency of Japan, Tokyo (Japan); Hirao, T; Itoh, H; Nashiyama, I

    1997-11-01

    In recent years, reduction in the mission cost is regarded as one of the most important matters, and thus much effort has been made to reduce the cost of electronic components used in spacecrafts without diminishing their performance. On this policy, there has been a growing interest in space application of commercial devices such as highly integrated memory ICs because of low prices and high performance of such devices. To ensure success in this application, it is indispensable to investigate radiation effects, e.g., single-event and total-dose effects, on commercial devices precisely. In the present study, we have evaluated single-event upset (SEU) tolerance for 1Mbit, 4Mbit SRAM and 16Mbit, 64Mbit DRAM by irradiation of high energy heavy ions such as 175MeV-Ar{sup 8+} and 450MeV-Xe{sup 23+}. We observed these SEU tolerance in space. (author)

  8. NASA Electronic Parts and Packaging Field Programmable Gate Array Single Event Effects Test Guideline Update

    Science.gov (United States)

    Berg, Melanie D.; LaBel, Kenneth A.

    2018-01-01

    The following are updated or new subjects added to the FPGA SEE Test Guidelines manual: academic versus mission specific device evaluation, single event latch-up (SEL) test and analysis, SEE response visibility enhancement during radiation testing, mitigation evaluation (embedded and user-implemented), unreliable design and its affects to SEE Data, testing flushable architectures versus non-flushable architectures, intellectual property core (IP Core) test and evaluation (addresses embedded and user-inserted), heavy-ion energy and linear energy transfer (LET) selection, proton versus heavy-ion testing, fault injection, mean fluence to failure analysis, and mission specific system-level single event upset (SEU) response prediction. Most sections within the guidelines manual provide information regarding best practices for test structure and test system development. The scope of this manual addresses academic versus mission specific device evaluation and visibility enhancement in IP Core testing.

  9. Development of heavy-ion irradiation technique for single-event in semiconductor devices

    Energy Technology Data Exchange (ETDEWEB)

    Nemoto, Norio; Akutsu, Takao; Matsuda, Sumio [National Space Development Agency of Japan, Tsukuba, Ibaraki (Japan). Tsukuba Space Center; Naitoh, Ichiro; Itoh, Hisayoshi; Agematsu, Takashi; Kamiya, Tomihiro; Nashiyama, Isamu

    1997-03-01

    Heavy-ion irradiation technique has been developed for the evaluation of single-event effects on semiconductor devices. For the uniform irradiation of high energy heavy ions to device samples, we have designed and installed a magnetic beam-scanning system in a JAERI cyclotron beam course. It was found that scanned area was approximately 4 x 2 centimeters and that the deviation of ion fluence from the average value was less than 7%. (author)

  10. Prediction Methodology for Proton Single Event Burnout: Application to a STRIPFET Device

    CERN Document Server

    Siconolfi, Sara; Oser, Pascal; Spiezia, Giovanni; Hubert, Guillaume; David, Jean-Pierre

    2015-01-01

    This paper presents a single event burnout (SEB) sensitivity characterization for power MOSFETs, independent from tests, through a prediction model issued from TCAD analysis and the knowledge of device topology. The methodology is applied to a STRIPFET device and compared to proton data obtained at PSI, showing a good agreement in the order of magnitude of proton SEB cross section, and thus validating the prediction model as an alternative device characterization with respect to SEB.

  11. TDRS-1 single event upsets and the effect of the space environment

    International Nuclear Information System (INIS)

    Wilkinson, D.C.; Daughtridge, S.C.; Stone, J.L.; Sauer, H.H.; Darling, P.

    1991-01-01

    The systematic recording of Single Event Upsets on TDRS-1 from 1984 to 1990 allows correlations to be drawn between those upsets and the space environment. In this paper, ground based neutron monitor data are used to illustrate the long-term relationship between galactic cosmic rays and TDRS-1 upsets. The short-term effects of energetic solar particles are illustrated with space environment data from GOES-7

  12. Estimation of the LET threshold of single event upset of microelectronics in experiments with Cf-252

    International Nuclear Information System (INIS)

    Kuznetsov, N.V.; Nymmik, R.A.

    1996-01-01

    A method is proposed for analyzing single event upsets (SEU) in large scale integration circuits of random access memory (RAM) when exposed to Cf-252 fission fragments. The method makes is possible to find the RAM linear energy transfer (LET) threshold to be used for estimations of RAM SEU rates in space. The method is illustrated by analyzing experimental data for the 2 x 8 kbit CMOS/bulk RAM. (author)

  13. In-flight and ground testing of single event upset sensitivity in static RAMs

    International Nuclear Information System (INIS)

    Johansson, K.; Dyreklev, P.; Granbom, B.; Calvet, C.; Fourtine, S.; Feuillatre, O.

    1998-01-01

    This paper presents the results from in-flight measurements of single event upsets (SEU) in static random access memories (SRAM) caused by the atmospheric radiation environment at aircraft altitudes. The memory devices were carried on commercial airlines at high altitude and mainly high latitudes. The SEUs were monitored by a Component Upset Test Equipment (CUTE), designed for this experiment. The in flight results are compared to ground based testing with neutrons from three different sources

  14. Tuning and Switching Enantioselectivity of Asymmetric Carboligation in an Enzyme through Mutational Analysis of a Single Hot Spot.

    Science.gov (United States)

    Wechsler, Cindy; Meyer, Danilo; Loschonsky, Sabrina; Funk, Lisa-Marie; Neumann, Piotr; Ficner, Ralf; Brodhun, Florian; Müller, Michael; Tittmann, Kai

    2015-12-01

    Enantioselective bond making and breaking is a hallmark of enzyme action, yet switching the enantioselectivity of the reaction is a difficult undertaking, and typically requires extensive screening of mutant libraries and multiple mutations. Here, we demonstrate that mutational diversification of a single catalytic hot spot in the enzyme pyruvate decarboxylase gives access to both enantiomers of acyloins acetoin and phenylacetylcarbinol, important pharmaceutical precursors, in the case of acetoin even starting from the unselective wild-type protein. Protein crystallography was used to rationalize these findings and to propose a mechanistic model of how enantioselectivity is controlled. In a broader context, our studies highlight the efficiency of mechanism-inspired and structure-guided rational protein design for enhancing and switching enantioselectivity of enzymatic reactions, by systematically exploring the biocatalytic potential of a single hot spot. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Results of single-event multilevel orthopedic surgery in children with cerebral palsy

    Directory of Open Access Journals (Sweden)

    Akhmed Tomov

    2015-11-01

    Full Text Available Background: Single-event multilevel orthopedic surgery is a modern approach in the operative treatment of children with cerebral palsy. Methods: Single-event multilevel orthopedic surgery was carried out in 108 patients with cerebral palsy. Patients’ average age was 11.3±1.7 years. Surgical results were analyzed at follow-up after 18 to 24 months, by way of detailed physical examination, functional assessment, imaging, the Edinburgh Visual Gait Score and Gillette Functional Assessment Questionnaire. Results: In our series, 647 procedures were performed during 141 surgeries. Patients had an average of 4.59 procedures per surgery. Observational gait analysis showed an improvement in stance and swing gait phases in ambulatory children. According to the Gillette Functional Assessment Questionnaire, an increase of functional level was noted in 50 patients but did not change in 32 patients. Conclusions: For children with cerebral palsy, single-event multilevel surgery is defined as two or more surgical procedures of the soft tissue or bone at two or more anatomical levels during one operative procedure. In cases where a large volume of surgery is required, two separate operations with a short break in between, but requiring only one hospital admission and one rehabilitation period, are also included. This approach requires adapted methods of surgical intervention, and appropriate methods of anesthesia and pain control in the postoperative period to the start of rehabilitation. Compliance with the above principles allowed the necessary correction of orthopedic complications to be achieved in all cases.

  16. BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer: Primary or secondary genetic events in colorectal carcinogenesis?

    International Nuclear Information System (INIS)

    Velho, Sérgia; Moutinho, Cátia; Cirnes, Luís; Albuquerque, Cristina; Hamelin, Richard; Schmitt, Fernando; Carneiro, Fátima; Oliveira, Carla; Seruca, Raquel

    2008-01-01

    BRAF, KRAS and PIK3CA mutations are frequently found in sporadic colorectal cancer (CRC). In contrast to KRAS and PIK3CA mutations, BRAF mutations are associated with tumours harbouring CpG Island methylation phenotype (CIMP), MLH1 methylation and microsatellite instability (MSI). We aimed at determine the frequency of KRAS, BRAF and PIK3CA mutations in the process of colorectal tumourigenesis using a series of colorectal polyps and carcinomas. In the series of polyps CIMP, MLH1 methylation and MSI were also studied. Mutation analyses were performed by PCR/sequencing. Bisulfite treated DNA was used to study CIMP and MLH1 methylation. MSI was detected by pentaplex PCR and Genescan analysis of quasimonomorphic mononucleotide repeats. Chi Square test and Fisher's Exact test were used to perform association studies. KRAS, PIK3CA or BRAF occur in 71% of polyps and were mutually exclusive. KRAS mutations occur in 35% of polyps. PIK3CA was found in one of the polyps. V600E BRAF mutations occur in 29% of cases, all of them classified as serrated adenoma. CIMP phenotype occurred in 25% of the polyps and all were mutated for BRAF. MLH1 methylation was not detected and all the polyps were microsatellite stable. The comparison between the frequency of oncogenic mutations in polyps and CRC (MSI and MSS) lead us to demonstrate that KRAS and PIK3CA are likely to precede both types of CRC. BRAF mutations are likely to precede MSI carcinomas since the frequency found in serrated polyps is similar to what is found in MSI CRC (P = 0.9112), but statistically different from what is found in microsatellite stable (MSS) tumours (P = 0.0191). Our results show that BRAF, KRAS and PIK3CA mutations occur prior to malignant transformation demonstrating that these oncogenic alterations are primary genetic events in colorectal carcinogenesis. Further, we show that BRAF mutations occur in association with CIMP phenotype in colorectal serrated polyps and verified that colorectal serrated

  17. BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer: Primary or secondary genetic events in colorectal carcinogenesis?

    Directory of Open Access Journals (Sweden)

    Schmitt Fernando

    2008-09-01

    Full Text Available Abstract Background BRAF, KRAS and PIK3CA mutations are frequently found in sporadic colorectal cancer (CRC. In contrast to KRAS and PIK3CA mutations, BRAF mutations are associated with tumours harbouring CpG Island methylation phenotype (CIMP, MLH1 methylation and microsatellite instability (MSI. We aimed at determine the frequency of KRAS, BRAF and PIK3CA mutations in the process of colorectal tumourigenesis using a series of colorectal polyps and carcinomas. In the series of polyps CIMP, MLH1 methylation and MSI were also studied. Methods Mutation analyses were performed by PCR/sequencing. Bisulfite treated DNA was used to study CIMP and MLH1 methylation. MSI was detected by pentaplex PCR and Genescan analysis of quasimonomorphic mononucleotide repeats. Chi Square test and Fisher's Exact test were used to perform association studies. Results KRAS, PIK3CA or BRAF occur in 71% of polyps and were mutually exclusive. KRAS mutations occur in 35% of polyps. PIK3CA was found in one of the polyps. V600E BRAF mutations occur in 29% of cases, all of them classified as serrated adenoma. CIMP phenotype occurred in 25% of the polyps and all were mutated for BRAF. MLH1 methylation was not detected and all the polyps were microsatellite stable. The comparison between the frequency of oncogenic mutations in polyps and CRC (MSI and MSS lead us to demonstrate that KRAS and PIK3CA are likely to precede both types of CRC. BRAF mutations are likely to precede MSI carcinomas since the frequency found in serrated polyps is similar to what is found in MSI CRC (P = 0.9112, but statistically different from what is found in microsatellite stable (MSS tumours (P = 0.0191. Conclusion Our results show that BRAF, KRAS and PIK3CA mutations occur prior to malignant transformation demonstrating that these oncogenic alterations are primary genetic events in colorectal carcinogenesis. Further, we show that BRAF mutations occur in association with CIMP phenotype in colorectal

  18. Parasitic bipolar amplification in a single event transient and its temperature dependence

    International Nuclear Information System (INIS)

    Liu Zheng; Chen Shu-Ming; Chen Jian-Jun; Qin Jun-Rui; Liu Rong-Rong

    2012-01-01

    Using three-dimensional technology computer-aided design (TCAD) simulation, parasitic bipolar amplification in a single event transient (SET) current of a single transistor and its temperature dependence are studied. We quantify the contributions of different current components in a SET current pulse, and it is found that the proportion of parasitic bipolar amplification in total collected charge is about 30% in both 130-nm and 90-nm technologies. The temperature dependence of parasitic bipolar amplification and the mechanism of the SET pulse are also investigated and quantified. The results show that the proportion of charge induced by parasitic bipolar increases with rising temperature, which illustrates that the parasitic bipolar amplification plays an important role in the charge collection of a single transistor

  19. Computing in the presence of soft bit errors. [caused by single event upset on spacecraft

    Science.gov (United States)

    Rasmussen, R. D.

    1984-01-01

    It is shown that single-event-upsets (SEUs) due to cosmic rays are a significant source of single bit error in spacecraft computers. The physical mechanism of SEU, electron hole generation by means of Linear Energy Transfer (LET), it discussed with reference made to the results of a study of the environmental effects on computer systems of the Galileo spacecraft. Techniques for making software more tolerant of cosmic ray effects are considered, including: reducing the number of registers used by the software; continuity testing of variables; redundant execution of major procedures for error detection; and encoding state variables to detect single-bit changes. Attention is also given to design modifications which may reduce the cosmic ray exposure of on-board hardware. These modifications include: shielding components operating in LEO; removing low-power Schottky parts; and the use of CMOS diodes. The SEU parameters of different electronic components are listed in a table.

  20. Partial loss of heterozygosity events at the mutated gene in tumors from MLH1/MSH2 large genomic rearrangement carriers

    Energy Technology Data Exchange (ETDEWEB)

    Zavodna, Katarina; Krivulcik, Tomas; Bujalkova, Maria Gerykova [Laboratory of Cancer Genetics, Cancer Research Institute of Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava (Slovakia); Slamka, Tomas; Martinicky, David; Ilencikova, Denisa [National Cancer Institute, Department of Oncologic Genetics, Klenova 1, 833 01 Bratislava (Slovakia); Bartosova, Zdena [Laboratory of Cancer Genetics, Cancer Research Institute of Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava (Slovakia)

    2009-11-20

    Depending on the population studied, large genomic rearrangements (LGRs) of the mismatch repair (MMR) genes constitute various proportions of the germline mutations that predispose to hereditary non-polyposis colorectal cancer (HNPCC). It has been reported that loss of heterozygosity (LOH) at the LGR region occurs through a gene conversion mechanism in tumors from MLH1/MSH2 deletion carriers; however, the converted tracts were delineated only by extragenic microsatellite markers. We sought to determine the frequency of LGRs in Slovak HNPCC patients and to study LOH in tumors from LGR carriers at the LGR region, as well as at other heterozygous markers within the gene to more precisely define conversion tracts. The main MMR genes responsible for HNPCC, MLH1, MSH2, MSH6, and PMS2, were analyzed by MLPA (multiplex ligation-dependent probe amplification) in a total of 37 unrelated HNPCC-suspected patients whose MLH1/MSH2 genes gave negative results in previous sequencing experiments. An LOH study was performed on six tumors from LGR carriers by combining MLPA to assess LOH at LGR regions and sequencing to examine LOH at 28 SNP markers from the MLH1 and MSH2 genes. We found six rearrangements in the MSH2 gene (five deletions and dup5-6), and one aberration in the MLH1 gene (del5-6). The MSH2 deletions were of three types (del1, del1-3, del1-7). We detected LOH at the LGR region in the single MLH1 case, which was determined in a previous study to be LOH-negative in the intragenic D3S1611 marker. Three tumors displayed LOH of at least one SNP marker, including two cases that were LOH-negative at the LGR region. LGRs accounted for 25% of germline MMR mutations identified in 28 Slovakian HNPCC families. A high frequency of LGRs among the MSH2 mutations provides a rationale for a MLPA screening of the Slovakian HNPCC families prior scanning by DNA sequencing. LOH at part of the informative loci confined to the MLH1 or MSH2 gene (heterozygous LGR region, SNP, or

  1. Partial loss of heterozygosity events at the mutated gene in tumors from MLH1/MSH2 large genomic rearrangement carriers

    Directory of Open Access Journals (Sweden)

    Ilencikova Denisa

    2009-11-01

    Full Text Available Abstract Background Depending on the population studied, large genomic rearrangements (LGRs of the mismatch repair (MMR genes constitute various proportions of the germline mutations that predispose to hereditary non-polyposis colorectal cancer (HNPCC. It has been reported that loss of heterozygosity (LOH at the LGR region occurs through a gene conversion mechanism in tumors from MLH1/MSH2 deletion carriers; however, the converted tracts were delineated only by extragenic microsatellite markers. We sought to determine the frequency of LGRs in Slovak HNPCC patients and to study LOH in tumors from LGR carriers at the LGR region, as well as at other heterozygous markers within the gene to more precisely define conversion tracts. Methods The main MMR genes responsible for HNPCC, MLH1, MSH2, MSH6, and PMS2, were analyzed by MLPA (multiplex ligation-dependent probe amplification in a total of 37 unrelated HNPCC-suspected patients whose MLH1/MSH2 genes gave negative results in previous sequencing experiments. An LOH study was performed on six tumors from LGR carriers by combining MLPA to assess LOH at LGR regions and sequencing to examine LOH at 28 SNP markers from the MLH1 and MSH2 genes. Results We found six rearrangements in the MSH2 gene (five deletions and dup5-6, and one aberration in the MLH1 gene (del5-6. The MSH2 deletions were of three types (del1, del1-3, del1-7. We detected LOH at the LGR region in the single MLH1 case, which was determined in a previous study to be LOH-negative in the intragenic D3S1611 marker. Three tumors displayed LOH of at least one SNP marker, including two cases that were LOH-negative at the LGR region. Conclusion LGRs accounted for 25% of germline MMR mutations identified in 28 Slovakian HNPCC families. A high frequency of LGRs among the MSH2 mutations provides a rationale for a MLPA screening of the Slovakian HNPCC families prior scanning by DNA sequencing. LOH at part of the informative loci confined to the MLH1

  2. Partial loss of heterozygosity events at the mutated gene in tumors from MLH1/MSH2 large genomic rearrangement carriers

    International Nuclear Information System (INIS)

    Zavodna, Katarina; Krivulcik, Tomas; Bujalkova, Maria Gerykova; Slamka, Tomas; Martinicky, David; Ilencikova, Denisa; Bartosova, Zdena

    2009-01-01

    Depending on the population studied, large genomic rearrangements (LGRs) of the mismatch repair (MMR) genes constitute various proportions of the germline mutations that predispose to hereditary non-polyposis colorectal cancer (HNPCC). It has been reported that loss of heterozygosity (LOH) at the LGR region occurs through a gene conversion mechanism in tumors from MLH1/MSH2 deletion carriers; however, the converted tracts were delineated only by extragenic microsatellite markers. We sought to determine the frequency of LGRs in Slovak HNPCC patients and to study LOH in tumors from LGR carriers at the LGR region, as well as at other heterozygous markers within the gene to more precisely define conversion tracts. The main MMR genes responsible for HNPCC, MLH1, MSH2, MSH6, and PMS2, were analyzed by MLPA (multiplex ligation-dependent probe amplification) in a total of 37 unrelated HNPCC-suspected patients whose MLH1/MSH2 genes gave negative results in previous sequencing experiments. An LOH study was performed on six tumors from LGR carriers by combining MLPA to assess LOH at LGR regions and sequencing to examine LOH at 28 SNP markers from the MLH1 and MSH2 genes. We found six rearrangements in the MSH2 gene (five deletions and dup5-6), and one aberration in the MLH1 gene (del5-6). The MSH2 deletions were of three types (del1, del1-3, del1-7). We detected LOH at the LGR region in the single MLH1 case, which was determined in a previous study to be LOH-negative in the intragenic D3S1611 marker. Three tumors displayed LOH of at least one SNP marker, including two cases that were LOH-negative at the LGR region. LGRs accounted for 25% of germline MMR mutations identified in 28 Slovakian HNPCC families. A high frequency of LGRs among the MSH2 mutations provides a rationale for a MLPA screening of the Slovakian HNPCC families prior scanning by DNA sequencing. LOH at part of the informative loci confined to the MLH1 or MSH2 gene (heterozygous LGR region, SNP, or

  3. A new method for explicit modelling of single failure event within different common cause failure groups

    International Nuclear Information System (INIS)

    Kančev, Duško; Čepin, Marko

    2012-01-01

    Redundancy and diversity are the main principles of the safety systems in the nuclear industry. Implementation of safety components redundancy has been acknowledged as an effective approach for assuring high levels of system reliability. The existence of redundant components, identical in most of the cases, implicates a probability of their simultaneous failure due to a shared cause—a common cause failure. This paper presents a new method for explicit modelling of single component failure event within multiple common cause failure groups simultaneously. The method is based on a modification of the frequently utilised Beta Factor parametric model. The motivation for development of this method lays in the fact that one of the most widespread softwares for fault tree and event tree modelling as part of the probabilistic safety assessment does not comprise the option for simultaneous assignment of single failure event to multiple common cause failure groups. In that sense, the proposed method can be seen as an advantage of the explicit modelling of common cause failures. A standard standby safety system is selected as a case study for application and study of the proposed methodology. The results and insights implicate improved, more transparent and more comprehensive models within probabilistic safety assessment.

  4. Soft error rate analysis methodology of multi-Pulse-single-event transients

    International Nuclear Information System (INIS)

    Zhou Bin; Huo Mingxue; Xiao Liyi

    2012-01-01

    As transistor feature size scales down, soft errors in combinational logic because of high-energy particle radiation is gaining more and more concerns. In this paper, a combinational logic soft error analysis methodology considering multi-pulse-single-event transients (MPSETs) and re-convergence with multi transient pulses is proposed. In the proposed approach, the voltage pulse produced at the standard cell output is approximated by a triangle waveform, and characterized by three parameters: pulse width, the transition time of the first edge, and the transition time of the second edge. As for the pulse with the amplitude being smaller than the supply voltage, the edge extension technique is proposed. Moreover, an efficient electrical masking model comprehensively considering transition time, delay, width and amplitude is proposed, and an approach using the transition times of two edges and pulse width to compute the amplitude of pulse is proposed. Finally, our proposed firstly-independently-propagating-secondly-mutually-interacting (FIP-SMI) is used to deal with more practical re-convergence gate with multi transient pulses. As for MPSETs, a random generation model of MPSETs is exploratively proposed. Compared to the estimates obtained using circuit level simulations by HSpice, our proposed soft error rate analysis algorithm has 10% errors in SER estimation with speed up of 300 when the single-pulse-single-event transient (SPSET) is considered. We have also demonstrated the runtime and SER decrease with the increment of P0 using designs from the ISCAS-85 benchmarks. (authors)

  5. Lack of robustness of life extension associated with several single-gene P element mutations in Drosophila melanogaster.

    Science.gov (United States)

    Mockett, Robin J; Nobles, Amber C

    2013-10-01

    The hypothesis tested in this study was that single-gene mutations found previously to extend the life span of Drosophila melanogaster could do so consistently in both long-lived y w and standard w (1118) genetic backgrounds. GAL4 drivers were used to express upstream activation sequence (UAS)-responder transgenes globally or in the nervous system. Transgenes associated with oxidative damage prevention (UAS-hSOD1 and UAS-GCLc) or removal (EP-UAS-Atg8a and UAS-dTOR (FRB) ) failed to increase mean life spans in any expression pattern in either genetic background. Flies containing a UAS-EGFP-bMSRA (C) transgene associated with protein repair were found not to exhibit life extension or detectable enhanced green fluorescent protein (EGFP) activity. The presence of UAS-responder transgenes was confirmed by PCR amplification and sequencing at the 5' and 3' end of each insertion. These results cast doubt on the robustness of life extension in flies carrying single-gene mutations and suggest that the effects of all such mutations should be tested independently in multiple genetic backgrounds and laboratory environments.

  6. Mutation-Specific Mechanisms of Hyperactivation of Noonan Syndrome SOS Molecules Detected with Single-molecule Imaging in Living Cells.

    Science.gov (United States)

    Nakamura, Yuki; Umeki, Nobuhisa; Abe, Mitsuhiro; Sako, Yasushi

    2017-10-26

    Noonan syndrome (NS) is a congenital hereditary disorder associated with developmental and cardiac defects. Some patients with NS carry mutations in SOS, a guanine nucleotide exchange factor (GEF) for the small GTPase RAS. NS mutations have been identified not only in the GEF domain, but also in various domains of SOS, suggesting that multiple mechanisms disrupt SOS function. In this study, we examined three NS mutations in different domains of SOS to clarify the abnormality in its translocation to the plasma membrane, where SOS activates RAS. The association and dissociation kinetics between SOS tagged with a fluorescent protein and the living cell surface were observed in single molecules. All three mutants showed increased affinity for the plasma membrane, inducing excessive RAS signalling. However, the mechanisms by which their affinity was increased were specific to each mutant. Conformational disorder in the resting state, increased probability of a conformational change on the plasma membrane, and an increased association rate constant with the membrane receptor are the suggested mechanisms. These different properties cause the specific phenotypes of the mutants, which should be rescuable with different therapeutic strategies. Therefore, single-molecule kinetic analyses of living cells are useful for the pathological analysis of genetic diseases.

  7. Rapid formation of a modern bedrock canyon by a single flood event

    Science.gov (United States)

    Lamb, Michael P.; Fonstad, Mark A.

    2010-07-01

    Deep river canyons are thought to form slowly over geological time (see, for example, ref. 1), cut by moderate flows that reoccur every few years. In contrast, some of the most spectacular canyons on Earth and Mars were probably carved rapidly during ancient megaflood events. Quantification of the flood discharge, duration and erosion mechanics that operated during such events is hampered because we lack modern analogues. Canyon Lake Gorge, Texas, was carved in 2002 during a single catastrophic flood. The event offers a rare opportunity to analyse canyon formation and test palaeo-hydraulic-reconstruction techniques under known topographic and hydraulic conditions. Here we use digital topographic models and visible/near-infrared aerial images from before and after the flood, discharge measured during the event, field measurements and sediment-transport modelling to show that the flood moved metre-sized boulders, excavated ~7m of limestone and transformed a soil-mantled valley into a bedrock canyon in just ~3days. We find that canyon morphology is strongly dependent on rock type: plucking of limestone blocks produced waterfalls, inner channels and bedrock strath terraces, whereas abrasion of cemented alluvium sculpted walls, plunge pools and streamlined islands. Canyon formation was so rapid that erosion might have been limited by the ability of the flow to transport sediment. We suggest that our results might improve hydraulic reconstructions of similar megafloods on Earth and Mars.

  8. Top quark polarization in t-channel single top-quark events with the ATLAS detector

    CERN Document Server

    Chitishvili, Mariam

    2017-01-01

    This summary presents the measurement of the top‐quark polarization in t-channel single top quarks with the ATLAS detector at the LHC. Monte Carlo simulated events are used. Selected events contain one lepton, large missing transverse momentum and exactly two jets, with one of them identified as b-jet. Selection cuts are used to identify the t-channel topology at reconstruction level. The polarization is measured, from an asymmetry in an angular distribution, at parton level by correcting the reconstructed angular distribution for detector effects. This project provides an overview on how a "standard" physics analysis is performed within ATLAS. The analysis is performed in ROOT. Simulation data is reconstructed to perform an unfolded measurement of a given property of a fundamental particle within the Standard Model. Finally results are compared with theoretical predictions.

  9. Discrete event model-based simulation for train movement on a single-line railway

    International Nuclear Information System (INIS)

    Xu Xiao-Ming; Li Ke-Ping; Yang Li-Xing

    2014-01-01

    The aim of this paper is to present a discrete event model-based approach to simulate train movement with the considered energy-saving factor. We conduct extensive case studies to show the dynamic characteristics of the traffic flow and demonstrate the effectiveness of the proposed approach. The simulation results indicate that the proposed discrete event model-based simulation approach is suitable for characterizing the movements of a group of trains on a single railway line with less iterations and CPU time. Additionally, some other qualitative and quantitative characteristics are investigated. In particular, because of the cumulative influence from the previous trains, the following trains should be accelerated or braked frequently to control the headway distance, leading to more energy consumption. (general)

  10. Effectiveness Analysis of a Non-Destructive Single Event Burnout Test Methodology

    CERN Document Server

    Oser, P; Spiezia, G; Fadakis, E; Foucard, G; Peronnard, P; Masi, A; Gaillard, R

    2014-01-01

    It is essential to characterize power MosFETs regarding their tolerance to destructive Single Event Burnouts (SEB). Therefore, several non-destructive test methods have been developed to evaluate the SEB cross-section of power devices. A power MosFET has been evaluated using a test circuit, designed according to standard non-destructive test methods discussed in the literature. Guidelines suggest a prior adaptation of auxiliary components to the device sensitivity before the radiation test. With the first value chosen for the de-coupling capacitor, the external component initiated destructive events and affected the evaluation of the cross-section. As a result, the influence of auxiliary components on the device cross-section was studied. This paper presents the obtained experimental results, supported by SPICE simulations, to evaluate and discuss how the circuit effectiveness depends on the external components.

  11. Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers

    Directory of Open Access Journals (Sweden)

    Johnson Peter W

    2006-03-01

    Full Text Available Abstract Background The MDM2 gene encodes a negative regulator of the p53 tumour suppressor protein. A single nucleotide polymorphism (SNP in the MDM2 promoter (a T to G exchange at nucleotide 309 has been reported to produce accelerated tumour formation in individuals with inherited p53 mutations. We have investigated the effect of the MDM2 SNP309 on clinical outcome in a cohort of patients with germline mutations of BRCA1. Methods Genomic DNA was obtained for 102 healthy controls and 116 patients with established pathogenic mutations of BRCA1 and Pyrosequencing technology™ was used to determine the genotype at the MDM2 SNP309 locus. Results The polymorphism was present in 52.9% of the controls (G/T in 37.3% and G/G in 15.6% and 58.6% of the BRCA1 mutation carriers (47.4% G/T and 11.2% G/G. Incidence of malignancy in female BRCA1 carriers was not significantly higher in SNP309 carriers than in wildtype (T/T individuals (72.7% vs. 75.6%, p = 1.00. Mean age of diagnosis of first breast cancer was 41.2 years in the SNP309 G/G genotype carriers, 38.6 years in those with the SNP309 G/T genotype and 39.0 years in wildtype subjects (p = 0.80. Conclusion We found no evidence that the MDM2 SNP309 accelerates tumour development in carriers of known pathogenic germline mutations of BRCA1.

  12. Single event upsets in semiconductor devices induced by highly ionising particles.

    Science.gov (United States)

    Sannikov, A V

    2004-01-01

    A new model of single event upsets (SEUs), created in memory cells by heavy ions and high energy hadrons, has been developed. The model takes into account the spatial distribution of charge collection efficiency over the cell area not considered in previous approaches. Three-dimensional calculations made by the HADRON code have shown good agreement with experimental data for the energy dependence of proton SEU cross sections, sensitive depths and other SEU observables. The model is promising for prediction of SEU rates for memory chips exposed in space and in high-energy experiments as well as for the development of a high-energy neutron dosemeter based on the SEU effect.

  13. Calculation of neutron-induced single-event upset cross sections for semiconductor memory devices

    International Nuclear Information System (INIS)

    Ikeuchi, Taketo; Watanabe, Yukinobu; Nakashima, Hideki; Sun, Weili

    2001-01-01

    Neutron-induced single-event upset (SEU) cross sections for semiconductor memory devices are calculated by the Burst Generation Rate (BGR) method using LA150 data and QMD calculation in the neutron energy range between 20 MeV and 10 GeV. The calculated results are compared with the measured SEU cross sections for energies up to 160 MeV, and the validity of the calculation method and the nuclear data used is verified. The kind of reaction products and the neutron energy range that have the most effect on SEU are discussed. (author)

  14. Analysis of cosmic ray neutron-induced single-event phenomena

    International Nuclear Information System (INIS)

    Tukamoto, Yasuyuki; Watanabe, Yukinobu; Nakashima, Hideki

    2003-01-01

    We have developed a database of cross sections for the n+ 28 Si reaction in the energy range between 2 MeV and 3 GeV in order to analyze single-event upset (SEU) phenomena induced by cosmic-ray neutrons in semiconductor memory devices. The data are applied to calculations of SEU cross sections using the Burst Generation Rate (BGR) model including two parameters, critical charge and effective depth. The calculated results are compared with measured SEU cross-sections for energies up to 160 MeV, and the reaction products that provide important effects on SEU are mainly investigated. (author)

  15. Single Event Upset Energy Dependence In a Buck-Converter Power Supply Design

    CERN Document Server

    Drake, G; The ATLAS collaboration; De Lurgio, P; Stanek, R; Mellado, B; Gopalakrishnan, A; Mahadik, S; Reed, R; Senthilkumaran, A

    2012-01-01

    We present a study of Single Event Upsets performed on a commercial pulse-width modulator controller chip that we are using for a switching power supply design for the Atlas Tile Calorimeter at the LHC. We performed tests to study the probability of an SEU occurring as a function of incident particle (hadron) energy. We compare the results with prediction from theory. We discuss the performance of the circuit, and perform an analysis using Bendel parameters. We also present a solution that we found using external circuitry that eliminates the effect.

  16. An analog cell to detect single event transients in voltage references

    Energy Technology Data Exchange (ETDEWEB)

    Franco, F.J., E-mail: fjfranco@fis.ucm.es [Departamento de Física Aplicada III, Facultad de Físicas, Universidad Complutense de Madrid (UCM), 28040 Madrid (Spain); Palomar, C. [Departamento de Física Aplicada III, Facultad de Físicas, Universidad Complutense de Madrid (UCM), 28040 Madrid (Spain); Izquierdo, J.G. [Centro de Láseres Ultrarrápidos, Facultad de Químicas, Universidad Complutense de Madrid (UCM), 28040 Madrid (Spain); Agapito, J.A. [Departamento de Física Aplicada III, Facultad de Físicas, Universidad Complutense de Madrid (UCM), 28040 Madrid (Spain)

    2015-01-11

    A reliable voltage reference is mandatory in mixed-signal systems. However, this family of components can undergo very long single event transients when operating in radiation environments such as space and nuclear facilities due to the impact of heavy ions. The purpose of the present paper is to demonstrate how a simple cell can be used to detect these transients. The cell was implemented with typical COTS components and its behavior was verified by SPICE simulations and in a laser facility. Different applications of the cell are explored as well.

  17. Discussions On Worst-Case Test Condition For Single Event Burnout

    Science.gov (United States)

    Liu, Sandra; Zafrani, Max; Sherman, Phillip

    2011-10-01

    This paper discusses the failure characteristics of single- event burnout (SEB) on power MOSFETs based on analyzing the quasi-stationary avalanche simulation curves. The analyses show the worst-case test condition for SEB would be using the ion that has the highest mass that would result in the highest transient current due to charge deposition and displacement damage. The analyses also show it is possible to build power MOSFETs that will not exhibit SEB even when tested with the heaviest ion, which have been verified by heavy ion test data on SEB sensitive and SEB immune devices.

  18. Search for new phenomena using single photon events in the DELPHI detector at LEP

    CERN Document Server

    Abreu, P; Adye, T; Agasi, E; Ajinenko, I; Aleksan, Roy; Alekseev, G D; Alemany, R; Allport, P P; Almehed, S; Amaldi, Ugo; Amato, S; Andreazza, A; Andrieux, M L; Antilogus, P; Apel, W D; Arnoud, Y; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Bambade, P; Barão, F; Barate, R; Barbi, M S; Barbiellini, Guido; Bardin, Dimitri Yuri; Baroncelli, A; Bärring, O; Barrio, J A; Bartl, Walter; Bates, M J; Battaglia, Marco; Baubillier, M; Baudot, J; Becks, K H; Begalli, M; Beillière, P; Belokopytov, Yu A; Belous, K S; Benvenuti, Alberto C; Berggren, M; Bertrand, D; Bianchi, F; Bigi, M; Bilenky, S M; Billoir, P; Bloch, D; Blume, M; Blyth, S; Bolognese, T; Bonesini, M; Bonivento, W; Booth, P S L; Borisov, G; Bosio, C; Bosworth, S; Botner, O; Boudinov, E; Bouquet, B; Bourdarios, C; Bowcock, T J V; Bozzo, M; Branchini, P; Brand, K D; Brenke, T; Brenner, R A; Bricman, C; Brillault, L; Brown, R C A; Brückman, P; Brunet, J M; Bugge, L; Buran, T; Burgsmüller, T; Buschmann, P; Buys, A; Cabrera, S; Caccia, M; Calvi, M; Camacho-Rozas, A J; Camporesi, T; Canale, V; Canepa, M; Cankocak, K; Cao, F; Carena, F; Carroll, L; Caso, Carlo; Castillo-Gimenez, M V; Cattai, A; Cavallo, F R; Cerrito, L; Chabaud, V; Charpentier, P; Chaussard, L; Chauveau, J; Checchia, P; Chelkov, G A; Chen, M; Chierici, R; Chliapnikov, P V; Chochula, P; Chorowicz, V; Cindro, V; Collins, P; Contreras, J L; Contri, R; Cortina, E; Cosme, G; Cossutti, F; Crawley, H B; Crennell, D J; Crosetti, G; Cuevas-Maestro, J; Czellar, S; Dahl-Jensen, Erik; Dahm, J; D'Almagne, B; Dam, M; Damgaard, G; Dauncey, P D; Davenport, Martyn; Da Silva, W; Defoix, C; Deghorain, A; Della Ricca, G; Delpierre, P A; Demaria, N; De Angelis, A; de Boer, Wim; De Brabandere, S; De Clercq, C; La Vaissière, C de; De Lotto, B; De Min, A; De Paula, L S; De Saint-Jean, C; Dijkstra, H; Di Ciaccio, Lucia; Djama, F; Dolbeau, J; Dönszelmann, M; Doroba, K; Dracos, M; Drees, J; Drees, K A; Dris, M; Dufour, Y; Edsall, D M; Ehret, R; Eigen, G; Ekelöf, T J C; Ekspong, Gösta; Elsing, M; Engel, J P; Ershaidat, N; Erzen, B; Espirito-Santo, M C; Falk, E; Fassouliotis, D; Feindt, Michael; Fenyuk, A; Ferrer, A; Filippas-Tassos, A; Firestone, A; Fischer, P A; Föth, H; Fokitis, E; Fontanelli, F; Formenti, F; Franek, B J; Frenkiel, P; Fries, D E C; Frodesen, A G; Frühwirth, R; Fulda-Quenzer, F; Fuster, J A; Galloni, A; Gamba, D; Gandelman, M; García, C; García, J; Gaspar, C; Gasparini, U; Gavillet, P; Gazis, E N; Gelé, D; Gerber, J P; Gerdyukov, L N; Gibbs, M; Gokieli, R; Golob, B; Gopal, Gian P; Gorn, L; Górski, M; Guz, Yu; Gracco, Valerio; Graziani, E; Grosdidier, G; Grzelak, K; Gumenyuk, S A; Gunnarsson, P; Günther, M; Guy, J; Hahn, F; Hahn, S; Hajduk, Z; Hallgren, A; Hamacher, K; Hao, W; Harris, F J; Hedberg, V; Hernández, J J; Herquet, P; Herr, H; Hessing, T L; Higón, E; Hilke, Hans Jürgen; Hill, T S; Holmgren, S O; Holt, P J; Holthuizen, D J; Hoorelbeke, S; Houlden, M A; Huet, K; Hultqvist, K; Jackson, J N; Jacobsson, R; Jalocha, P; Janik, R; Jarlskog, C; Jarlskog, G; Jarry, P; Jean-Marie, B; Johansson, E K; Jönsson, L B; Jönsson, P E; Joram, Christian; Juillot, P; Kaiser, M; Kapusta, F; Karafasoulis, K; Karlsson, M; Karvelas, E; Katsanevas, S; Katsoufis, E C; Keränen, R; Khokhlov, Yu A; Khomenko, B A; Khovanskii, N N; King, B J; Kjaer, N J; Klein, H; Klovning, A; Kluit, P M; Köne, B; Kokkinias, P; Koratzinos, M; Korcyl, K; Kourkoumelis, C; Kuznetsov, O; Kramer, P H; Krammer, Manfred; Kreuter, C; Kronkvist, I J; Krumshtein, Z; Krupinski, W; Kubinec, P; Kucewicz, W; Kurvinen, K L; Lacasta, C; Laktineh, I; Lamblot, S; Lamsa, J; Lanceri, L; Lane, D W; Langefeld, P; Last, I; Laugier, J P; Lauhakangas, R; Leder, Gerhard; Ledroit, F; Lefébure, V; Legan, C K; Leitner, R; Lemoigne, Y; Lemonne, J; Lenzen, Georg; Lepeltier, V; Lesiak, T; Liko, D; Lindner, R; Lipniacka, A; Lippi, I; Lörstad, B; Lokajícek, M; Loken, J G; López, J M; Loukas, D; Lutz, P; Lyons, L; MacNaughton, J N; Maehlum, G; Maio, A; Malychev, V; Mandl, F; Marco, J; Marco, R P; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Maron, T; Martínez-Rivero, C; Martínez-Vidal, F; Martí i García, S; Matorras, F; Matteuzzi, C; Matthiae, Giorgio; Mazzucato, M; McCubbin, M L; McKay, R; McNulty, R; Medbo, J; Merk, M; Meroni, C; Meyer, S; Meyer, W T; Michelotto, M; Migliore, E; Mirabito, L; Mitaroff, Winfried A; Mjörnmark, U; Moa, T; Møller, R; Mönig, K; Monge, M R; Morettini, P; Müller, H; Mundim, L M; Murray, W J; Muryn, B; Myatt, Gerald; Naraghi, F; Navarria, Francesco Luigi; Navas, S; Nawrocki, K; Negri, P; Némécek, S; Neumann, W; Neumeister, N; Nicolaidou, R; Nielsen, B S; Nieuwenhuizen, M; Nikolaenko, V; Niss, P; Nomerotski, A; Normand, Ainsley; Oberschulte-Beckmann, W; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, Risto; Österberg, K; Ouraou, A; Paganini, P; Paganoni, M; Pagès, P; Palka, H; Papadopoulou, T D; Papageorgiou, K; Pape, L; Parkes, C; Parodi, F; Passeri, A; Pegoraro, M; Peralta, L; Pernegger, H; Pernicka, Manfred; Perrotta, A; Petridou, C; Petrolini, A; Petrovykh, M; Phillips, H T; Piana, G; Pierre, F; Pimenta, M; Pindo, M; Plaszczynski, S; Podobrin, O; Pol, M E; Polok, G; Poropat, P; Pozdnyakov, V; Prest, M; Privitera, P; Pukhaeva, N; Pullia, Antonio; Radojicic, D; Ragazzi, S; Rahmani, H; Rames, J; Ratoff, P N; Read, A L; Reale, M; Rebecchi, P; Redaelli, N G; Regler, Meinhard; Reid, D; Renton, P B; Resvanis, L K; Richard, F; Richardson, J; Rídky, J; Rinaudo, G; Ripp, I; Romero, A; Roncagliolo, I; Ronchese, P; Roos, L; Rosenberg, E I; Rosso, E; Roudeau, Patrick; Rovelli, T; Rückstuhl, W; Ruhlmann-Kleider, V; Ruiz, A; Rybicki, K; Saarikko, H; Sacquin, Yu; Sadovskii, A; Sajot, G; Salt, J; Sánchez, J; Sannino, M; Schimmelpfennig, M; Schneider, H; Schwickerath, U; Schyns, M A E; Sciolla, G; Scuri, F; Seager, P; Sedykh, Yu; Segar, A M; Seitz, A; Sekulin, R L; Shellard, R C; Siccama, I; Siegrist, P; Simonetti, S; Simonetto, F; Sissakian, A N; Sitár, B; Skaali, T B; Smadja, G; Smirnov, N; Smirnova, O G; Smith, G R; Solovyanov, O; Sosnowski, R; Souza-Santos, D; Spassoff, Tz; Spiriti, E; Sponholz, P; Squarcia, S; Stanescu, C; Stapnes, Steinar; Stavitski, I; Stichelbaut, F; Stocchi, A; Strauss, J; Strub, R; Stugu, B; Szczekowski, M; Szeptycka, M; Tabarelli de Fatis, T; Tavernet, J P; Chikilev, O G; Tilquin, A; Timmermans, J; Tkatchev, L G; Todorov, T; Toet, D Z; Tomaradze, A G; Tomé, B; Tonazzo, A; Tortora, L; Tranströmer, G; Treille, D; Trischuk, W; Tristram, G; Trombini, A; Troncon, C; Tsirou, A L; Turluer, M L; Tyapkin, I A; Tyndel, M; Tzamarias, S; Überschär, B; Ullaland, O; Uvarov, V; Valenti, G; Vallazza, E; Van der Velde, C; van Apeldoorn, G W; van Dam, P; Van Doninck, W K; Van Eldik, J; Vassilopoulos, N; Vegni, G; Ventura, L; Venus, W A; Verbeure, F; Verlato, M; Vertogradov, L S; Vilanova, D; Vincent, P; Vitale, L; Vlasov, E; Vodopyanov, A S; Vrba, V; Wahlen, H; Walck, C; Weierstall, M; Weilhammer, Peter; Weiser, C; Wetherell, Alan M; Wicke, D; Wickens, J H; Wielers, M; Wilkinson, G R; Williams, W S C; Winter, M; Witek, M; Woschnagg, K; Yip, K; Yushchenko, O P; Zach, F; Zaitsev, A; Zalewska-Bak, A; Zalewski, Piotr; Zavrtanik, D; Zevgolatakos, E; Zimin, N I; Zito, M; Zontar, D; Zuberi, R; Zucchelli, G C; Zumerle, G; Charpentier, Ph; Gavillet, Ph

    1997-01-01

    Data are presented on the reaction \\epem~\\into~\\gamma + no other detected particle at center-of-mass energies, \\sqs = 89.48 GeV, 91.26 GeV and 93.08 GeV. The cross section for this reaction is related directly to the number of light neutrino generations which couple to the \\zz boson, and to several other phenomena such as excited neutrinos, the production of an invisible `X' particle, a possible magnetic moment of the tau neutrino, and neutral monojets. Based on the observed number of single photon events, the number of light neutrinos which couple to the \\zz is measured to be N_\

  19. Monte Carlo study for the dynamical fluctuations inside a single jet in 2-jet events

    International Nuclear Information System (INIS)

    Zhang Kunshi; Liu Lianshou; Yin Jianwu; Chen Gang; Liu Chao

    2002-01-01

    The dynamical fluctuations inside a single jet in the 2-jet events produced in e + e - collisions at 91.2 GeV have been studied using Monte Carlo method. The results show that, the anisotropy of dynamical fluctuations inside a single jet changes remarkably with the variation of the cut parameter y cut . A transition point (γ p t = γ ψ ≠γ y ) exists, where the dynamical fluctuations are anisotropic in the longitudinal-transverse plan and isotropic in the transverse planes. It indicates that the y cut corresponding to the transition point is a physically reasonable cutting parameter for selecting jets and, meanwhile, the relative transverse momentum k t at the transition point is the scale for the determination of physical jets. This conclusion is in good agreement with the experimental fact that the third jet (gluon jet) was historically first discovered in the energy region 17-30 GeV in e + e - collisions

  20. Compendium of Single Event Effects, Total Ionizing Dose, and Displacement Damage for Candidate Spacecraft Electronics for NASA

    Science.gov (United States)

    LaBel, Kenneth A.; OBryan, Martha V.; Chen, Dakai; Campola, Michael J.; Casey, Megan C.; Pellish, Jonathan A.; Lauenstein, Jean-Marie; Wilcox, Edward P.; Topper, Alyson D.; Ladbury, Raymond L.; hide

    2014-01-01

    We present results and analysis investigating the effects of radiation on a variety of candidate spacecraft electronics to proton and heavy ion induced single event effects (SEE), proton-induced displacement damage (DD), and total ionizing dose (TID). Introduction: This paper is a summary of test results.NASA spacecraft are subjected to a harsh space environment that includes exposure to various types of ionizing radiation. The performance of electronic devices in a space radiation environment is often limited by its susceptibility to single event effects (SEE), total ionizing dose (TID), and displacement damage (DD). Ground-based testing is used to evaluate candidate spacecraft electronics to determine risk to spaceflight applications. Interpreting the results of radiation testing of complex devices is quite difficult. Given the rapidly changing nature of technology, radiation test data are most often application-specific and adequate understanding of the test conditions is critical. Studies discussed herein were undertaken to establish the application-specific sensitivities of candidate spacecraft and emerging electronic devices to single-event upset (SEU), single-event latchup (SEL), single-event gate rupture (SEGR), single-event burnout (SEB), single-event transient (SET), TID, enhanced low dose rate sensitivity (ELDRS), and DD effects.

  1. Kernel PLS Estimation of Single-trial Event-related Potentials

    Science.gov (United States)

    Rosipal, Roman; Trejo, Leonard J.

    2004-01-01

    Nonlinear kernel partial least squaes (KPLS) regressior, is a novel smoothing approach to nonparametric regression curve fitting. We have developed a KPLS approach to the estimation of single-trial event related potentials (ERPs). For improved accuracy of estimation, we also developed a local KPLS method for situations in which there exists prior knowledge about the approximate latency of individual ERP components. To assess the utility of the KPLS approach, we compared non-local KPLS and local KPLS smoothing with other nonparametric signal processing and smoothing methods. In particular, we examined wavelet denoising, smoothing splines, and localized smoothing splines. We applied these methods to the estimation of simulated mixtures of human ERPs and ongoing electroencephalogram (EEG) activity using a dipole simulator (BESA). In this scenario we considered ongoing EEG to represent spatially and temporally correlated noise added to the ERPs. This simulation provided a reasonable but simplified model of real-world ERP measurements. For estimation of the simulated single-trial ERPs, local KPLS provided a level of accuracy that was comparable with or better than the other methods. We also applied the local KPLS method to the estimation of human ERPs recorded in an experiment on co,onitive fatigue. For these data, the local KPLS method provided a clear improvement in visualization of single-trial ERPs as well as their averages. The local KPLS method may serve as a new alternative to the estimation of single-trial ERPs and improvement of ERP averages.

  2. Single event effects induced by 15.14 MeV/u sup 1 sup 3 sup 6 Xe ions

    CERN Document Server

    Hou Ming Dong; LiuJie; Wang Zhi Guang; Jin Yun Fan; Zhu Zhi Yong; Zhen Hong Lou; Liu Chang Long; Chen Xiao Xi; Wei Xin Guo; Zhang Li; Fan You Cheng; Zhu Zhou Rong; Zhang Yiting

    2002-01-01

    Single event effects induced by 15.14 MeV/u sup 1 sup 3 sup 6 Xe ions in different batches of 32k x 8 bits static random access memory are studied. The incident angle dependences of the cross sections for single event upset and single event latch up are presented. The SEE cross sections are plotted versus energy loss instead of linear energy transfer value in sensitive region. The depth of sensitive volume and thickness of 'dead' layer above the sensitive volume are estimated

  3. Single event effect hardness for the front-end ASICs in the DAMPE satellite BGO calorimeter

    Science.gov (United States)

    Gao, Shan-Shan; Jiang, Di; Feng, Chang-Qing; Xi, Kai; Liu, Shu-Bin; An, Qi

    2016-01-01

    The Dark Matter Particle Explorer (DAMPE) is a Chinese scientific satellite designed for cosmic ray studies with a primary scientific goal of indirect detection of dark matter particles. As a crucial sub-detector, the BGO calorimeter measures the energy spectrum of cosmic rays in the energy range from 5 GeV to 10 TeV. In order to implement high-density front-end electronics (FEE) with the ability to measure 1848 signals from 616 photomultiplier tubes on the strictly constrained satellite platform, two kinds of 32-channel front-end ASICs, VA160 and VATA160, are customized. However, a space mission period of more than 3 years makes single event effects (SEEs) become threats to reliability. In order to evaluate SEE sensitivities of these chips and verify the effectiveness of mitigation methods, a series of laser-induced and heavy ion-induced SEE tests were performed. Benefiting from the single event latch-up (SEL) protection circuit for power supply, the triple module redundancy (TMR) technology for the configuration registers and the optimized sequential design for the data acquisition process, 52 VA160 chips and 32 VATA160 chips have been applied in the flight model of the BGO calorimeter with radiation hardness assurance. Supported by Strategic Priority Research Program on Space Science of the Chinese Academy of Sciences (XDA04040202-4) and Fundamental Research Funds for the Central Universities (WK2030040048)

  4. Single-Event Effect Performance of a Conductive-Bridge Memory EEPROM

    Science.gov (United States)

    Chen, Dakai; Wilcox, Edward; Berg, Melanie; Kim, Hak; Phan, Anthony; Figueiredo, Marco; Seidleck, Christina; LaBel, Kenneth

    2015-01-01

    We investigated the heavy ion single-event effect (SEE) susceptibility of the industry’s first stand-alone memory based on conductive-bridge memory (CBRAM) technology. The device is available as an electrically erasable programmable read-only memory (EEPROM). We found that single-event functional interrupt (SEFI) is the dominant SEE type for each operational mode (standby, dynamic read, and dynamic write/read). SEFIs occurred even while the device is statically biased in standby mode. Worst case SEFIs resulted in errors that filled the entire memory space. Power cycle did not always clear the errors. Thus the corrupted cells had to be reprogrammed in some cases. The device is also vulnerable to bit upsets during dynamic write/read tests, although the frequency of the upsets are relatively low. The linear energy transfer threshold for cell upset is between 10 and 20 megaelectron volts per square centimeter per milligram, with an upper limit cross section of 1.6 times 10(sup -11) square centimeters per bit (95 percent confidence level) at 10 megaelectronvolts per square centimeter per milligram. In standby mode, the CBRAM array appears invulnerable to bit upsets.

  5. Automatic Single Event Effects Sensitivity Analysis of a 13-Bit Successive Approximation ADC

    Science.gov (United States)

    Márquez, F.; Muñoz, F.; Palomo, F. R.; Sanz, L.; López-Morillo, E.; Aguirre, M. A.; Jiménez, A.

    2015-08-01

    This paper presents Analog Fault Tolerant University of Seville Debugging System (AFTU), a tool to evaluate the Single-Event Effect (SEE) sensitivity of analog/mixed signal microelectronic circuits at transistor level. As analog cells can behave in an unpredictable way when critical areas interact with the particle hitting, there is a need for designers to have a software tool that allows an automatic and exhaustive analysis of Single-Event Effects influence. AFTU takes the test-bench SPECTRE design, emulates radiation conditions and automatically evaluates vulnerabilities using user-defined heuristics. To illustrate the utility of the tool, the SEE sensitivity of a 13-bits Successive Approximation Analog-to-Digital Converter (ADC) has been analysed. This circuit was selected not only because it was designed for space applications, but also due to the fact that a manual SEE sensitivity analysis would be too time-consuming. After a user-defined test campaign, it was detected that some voltage transients were propagated to a node where a parasitic diode was activated, affecting the offset cancelation, and therefore the whole resolution of the ADC. A simple modification of the scheme solved the problem, as it was verified with another automatic SEE sensitivity analysis.

  6. A review of the number and severity of injuries sustained following a single motocross event.

    Science.gov (United States)

    Dick, Charles G; White, Simon; Bopf, Daniel

    2014-03-01

    Competitive and recreational motocross is an increasingly popular sport in Australia and worldwide. Children as young as 4-year-old can participate in this activity. It is recognised that this is a high risk sport despite the use of protective equipment and developments in course design. Injuries sustained range from minor contusions and fractures to severe life threatening spine and head injuries in adults and the paediatric population. In addition organised events can generate a surge of trauma that can burden small local hospitals, resulting in an unpredicted increase in the workload with subsequent delays to treatment. We present the trauma workload generated in a district hospital following a single motocross event. All patients attending a district hospital emergency department with injuries sustained during a single motocross event were identified through hospital and ambulance records. The nature of their injuries and the treatment required, the length of hospital stay and operative theatre time generated by their injuries were obtained from hospital and theatre records. 14 patients attended the emergency department over a 24-hour period, requiring 5 ambulances from the scene. 7 patients required hospital admission with 7 operations performed, consuming 12.2 h of operating theatre time and 21 days of hospital beds. 2 patients sustained head injuries requiring observation, one of which was transferred to a spinal unit for management of their spinal injuries. Motocross is a popular sport and at times has unacceptable risks of injury in organised competitions, especially with regards to paediatric injuries. Better course design, restrictions on participant age and limitations in vehicle speeds may help reduce the number of severe injuries. These events can also generate a sudden trauma burden to local hospital facilities with knock on effects on waiting times for theatre and potentially compromising not only treatment of the injured participants but also

  7. Aftershock Sequences and Seismic-Like Organization of Acoustic Events Produced by a Single Propagating Crack

    Science.gov (United States)

    Alizee, D.; Bonamy, D.

    2017-12-01

    In inhomogeneous brittle solids like rocks, concrete or ceramics, one usually distinguish nominally brittle fracture, driven by the propagation of a single crack from quasibrittle one, resulting from the accumulation of many microcracks. The latter goes along with intermittent sharp noise, as e.g. revealed by the acoustic emission observed in lab scale compressive fracture experiments or at geophysical scale in the seismic activity. In both cases, statistical analyses have revealed a complex time-energy organization into aftershock sequences obeying a range of robust empirical scaling laws (the Omori-Utsu, productivity and Bath's law) that help carry out seismic hazard analysis and damage mitigation. These laws are usually conjectured to emerge from the collective dynamics of microcrack nucleation. In the experiments presented at AGU, we will show that such a statistical organization is not specific to the quasi-brittle multicracking situations, but also rules the acoustic events produced by a single crack slowly driven in an artificial rock made of sintered polymer beads. This simpler situation has advantageous properties (statistical stationarity in particular) permitting us to uncover the origins of these seismic laws: Both productivity law and Bath's law result from the scale free statistics for event energy and Omori-Utsu law results from the scale-free statistics of inter-event time. This yields predictions on how the associated parameters are related, which were analytically derived. Surprisingly, the so-obtained relations are also compatible with observations on lab scale compressive fracture experiments, suggesting that, in these complex multicracking situations also, the organization into aftershock sequences and associated seismic laws are also ruled by the propagation of individual microcrack fronts, and not by the collective, stress-mediated, microcrack nucleation. Conversely, the relations are not fulfilled in seismology signals, suggesting that

  8. High-quality Thermodynamic Data on the Stability Changes of Proteins Upon Single-site Mutations

    Energy Technology Data Exchange (ETDEWEB)

    Pucci, Fabrizio, E-mail: fapucci@ulb.ac.be; Bourgeas, Raphaël, E-mail: rbourgeas@ulb.ac.be; Rooman, Marianne, E-mail: mrooman@ulb.ac.be [Department of BioModeling, BioInformatics and BioProcesses, Université Libre de Bruxelles, CP 165/61, Roosevelt Avenue 50, 1050 Brussels, Belgium and Interuniversity Institute of Bioinformatics in Brussels, CP 263, Triumph Bld, 1050 Brussels (Belgium)

    2016-06-15

    We have set up and manually curated a dataset containing experimental information on the impact of amino acid substitutions in a protein on its thermal stability. It consists of a repository of experimentally measured melting temperatures (T{sub m}) and their changes upon point mutations (ΔT{sub m}) for proteins having a well-resolved x-ray structure. This high-quality dataset is designed for being used for the training or benchmarking of in silico thermal stability prediction methods. It also reports other experimentally measured thermodynamic quantities when available, i.e., the folding enthalpy (ΔH) and heat capacity (ΔC{sub P}) of the wild type proteins and their changes upon mutations (ΔΔH and ΔΔC{sub P}), as well as the change in folding free energy (ΔΔG) at a reference temperature. These data are analyzed in view of improving our insights into the correlation between thermal and thermodynamic stabilities, the asymmetry between the number of stabilizing and destabilizing mutations, and the difference in stabilization potential of thermostable versus mesostable proteins.

  9. Precise estimates of mutation rate and spectrum in yeast

    Science.gov (United States)

    Zhu, Yuan O.; Siegal, Mark L.; Hall, David W.; Petrov, Dmitri A.

    2014-01-01

    Mutation is the ultimate source of genetic variation. The most direct and unbiased method of studying spontaneous mutations is via mutation accumulation (MA) lines. Until recently, MA experiments were limited by the cost of sequencing and thus provided us with small numbers of mutational events and therefore imprecise estimates of rates and patterns of mutation. We used whole-genome sequencing to identify nearly 1,000 spontaneous mutation events accumulated over ∼311,000 generations in 145 diploid MA lines of the budding yeast Saccharomyces cerevisiae. MA experiments are usually assumed to have negligible levels of selection, but even mild selection will remove strongly deleterious events. We take advantage of such patterns of selection and show that mutation classes such as indels and aneuploidies (especially monosomies) are proportionately much more likely to contribute mutations of large effect. We also provide conservative estimates of indel, aneuploidy, environment-dependent dominant lethal, and recessive lethal mutation rates. To our knowledge, for the first time in yeast MA data, we identified a sufficiently large number of single-nucleotide mutations to measure context-dependent mutation rates and were able to (i) confirm strong AT bias of mutation in yeast driven by high rate of mutations from C/G to T/A and (ii) detect a higher rate of mutation at C/G nucleotides in two specific contexts consistent with cytosine methylation in S. cerevisiae. PMID:24847077

  10. Allogeneic Transplant in ELANE and MEFV Mutation Positive Severe Cyclic Neutropenia: Review of Prognostic Factors for Secondary Severe Events

    Directory of Open Access Journals (Sweden)

    Onyemaechi N. Okolo

    2017-01-01

    Full Text Available Objective and Importance. Cyclic neutropenia (CyN is a rare autosomal dominant inherited disorder due to the mutation ELANE primarily affecting bone marrow stem cells and is characterized by recurrent neutropenia every 2 to 4 weeks. Symptoms vary from benign to severe, including death. Postulations on the cause of wide spectrum in symptom presentation include the possibility of other genetic mutations, such as MEFV. Recommended treatment for CyN is G-CSF to keep ANC higher to minimize risk of infection. Case. A 25-year-old male diagnosed with CyN, on G-CSF but worsening quality of life. Pretransplant investigations revealed ELANE mutation positive severe CyN along with familial Mediterranean fever (MEFV mutation. Intervention. Bone marrow transplantation as treatment for dual mutation (ELANE and MEFV mutation positive severe CyN. Conclusion. BMT may be considered as an alternative treatment for severe CyN in patients who are refractory to G-CSF. It is postulated that in our patient the combined mutations (CyN and MEFV may have contributed to the severity of this individual’s symptoms. We suggest CyN patients who present with severe symptoms have evaluation with ELANE mutation testing, Periodic Fever Syndromes Panel, and routine marrow assessment with FISH, conventional cytogenetics, and morphological evaluation for MDS/AML.

  11. R-process enrichment from a single event in an ancient dwarf galaxy.

    Science.gov (United States)

    Ji, Alexander P; Frebel, Anna; Chiti, Anirudh; Simon, Joshua D

    2016-03-31

    Elements heavier than zinc are synthesized through the rapid (r) and slow (s) neutron-capture processes. The main site of production of the r-process elements (such as europium) has been debated for nearly 60 years. Initial studies of trends in chemical abundances in old Milky Way halo stars suggested that these elements are produced continually, in sites such as core-collapse supernovae. But evidence from the local Universe favours the idea that r-process production occurs mainly during rare events, such as neutron star mergers. The appearance of a plateau of europium abundance in some dwarf spheroidal galaxies has been suggested as evidence for rare r-process enrichment in the early Universe, but only under the assumption that no gas accretes into those dwarf galaxies; gas accretion favours continual r-process enrichment in these systems. Furthermore, the universal r-process pattern has not been cleanly identified in dwarf spheroidals. The smaller, chemically simpler, and more ancient ultrafaint dwarf galaxies assembled shortly after the first stars formed, and are ideal systems with which to study nucleosynthesis events such as the r-process. Reticulum II is one such galaxy. The abundances of non-neutron-capture elements in this galaxy (and others like it) are similar to those in other old stars. Here, we report that seven of the nine brightest stars in Reticulum II, observed with high-resolution spectroscopy, show strong enhancements in heavy neutron-capture elements, with abundances that follow the universal r-process pattern beyond barium. The enhancement seen in this 'r-process galaxy' is two to three orders of magnitude higher than that detected in any other ultrafaint dwarf galaxy. This implies that a single, rare event produced the r-process material in Reticulum II. The r-process yield and event rate are incompatible with the source being ordinary core-collapse supernovae, but consistent with other possible sources, such as neutron star mergers.

  12. Single event upsets calculated from new ENDF/B-VI proton and neutron data up to 150 MeV

    International Nuclear Information System (INIS)

    Chadwick, M.B.

    1999-01-01

    Single-event upsets (SEU) in microelectronics are calculated from newly-developed silicon nuclear reaction recoil data that extend up to 150 MeV, for incident protons and neutrons. Calculated SEU cross sections are compared with measured data

  13. Characterization of System Level Single Event Upset (SEU) Responses using SEU Data, Classical Reliability Models, and Space Environment Data

    Science.gov (United States)

    Berg, Melanie; Label, Kenneth; Campola, Michael; Xapsos, Michael

    2017-01-01

    We propose a method for the application of single event upset (SEU) data towards the analysis of complex systems using transformed reliability models (from the time domain to the particle fluence domain) and space environment data.

  14. Single-Event Effect Testing of the Cree C4D40120D Commercial 1200V Silicon Carbide Schottky Diode

    Science.gov (United States)

    Lauenstein, J.-M.; Casey, M. C.; Wilcox, E. P.; Kim, Hak; Topper, A. D.

    2014-01-01

    This study was undertaken to determine the single event effect (SEE) susceptibility of the commercial silicon carbide 1200V Schottky diode manufactured by Cree, Inc. Heavy-ion testing was conducted at the Texas A&M University Cyclotron Single Event Effects Test Facility (TAMU). Its purpose was to evaluate this device as a candidate for use in the Solar-Electric Propulsion flight project.

  15. Observation of Single Isolated Electrons of High Transverse Momentum in Events with Missing Transverse Energy at the CERN pp Collider

    DEFF Research Database (Denmark)

    Banner, M.; Kofoed-Hansen, O.

    1983-01-01

    We report the results of a search for single isolated electrons of high transverse momentum at the CERN collider. Above 15 GeV/c, four events are found having large missing transverse energy along a direction opposite in azimuth to that of the high-pT electron. Both the configuration of the events...

  16. Single-Point Mutation with a Rotamer Library Toolkit: Toward Protein Engineering.

    Science.gov (United States)

    Pottel, Joshua; Moitessier, Nicolas

    2015-12-28

    Protein engineers have long been hard at work to harness biocatalysts as a natural source of regio-, stereo-, and chemoselectivity in order to carry out chemistry (reactions and/or substrates) not previously achieved with these enzymes. The extreme labor demands and exponential number of mutation combinations have induced computational advances in this domain. The first step in our virtual approach is to predict the correct conformations upon mutation of residues (i.e., rebuilding side chains). For this purpose, we opted for a combination of molecular mechanics and statistical data. In this work, we have developed automated computational tools to extract protein structural information and created conformational libraries for each amino acid dependent on a variable number of parameters (e.g., resolution, flexibility, secondary structure). We have also developed the necessary tool to apply the mutation and optimize the conformation accordingly. For side-chain conformation prediction, we obtained overall average root-mean-square deviations (RMSDs) of 0.91 and 1.01 Å for the 18 flexible natural amino acids within two distinct sets of over 3000 and 1500 side-chain residues, respectively. The commonly used dihedral angle differences were also evaluated and performed worse than the state of the art. These two metrics are also compared. Furthermore, we generated a family-specific library for kinases that produced an average 2% lower RMSD upon side-chain reconstruction and a residue-specific library that yielded a 17% improvement. Ultimately, since our protein engineering outlook involves using our docking software, Fitted/Impacts, we applied our mutation protocol to a benchmarked data set for self- and cross-docking. Our side-chain reconstruction does not hinder our docking software, demonstrating differences in pose prediction accuracy of approximately 2% (RMSD cutoff metric) for a set of over 200 protein/ligand structures. Similarly, when docking to a set of over 100

  17. New insight into the parasitic bipolar amplification effect in single event transient production

    International Nuclear Information System (INIS)

    Chen Jian-Jun; Chen Shu-Ming; Liang Bin; Deng Ke-Feng

    2012-01-01

    In this paper, a new method is proposed to study the mechanism of charge collection in single event transient (SET) production in 90 nm bulk complementary metal oxide semiconductor (CMOS) technology. We find that different from the case in the pMOSFET, the parasitic bipolar amplification effect (bipolar effect) in the balanced inverter does not exist in the nMOSFET after the ion striking. The influence of the substrate process on the bipolar effect is also studied in the pMOSFET. We find that the bipolar effect can be effectively mitigated by a buried deep P + -well layer and can be removed by a buried SO 2 layer. (condensed matter: structural, mechanical, and thermal properties)

  18. Influence of edge effects on single event upset susceptibility of SOI SRAMs

    International Nuclear Information System (INIS)

    Gu, Song; Liu, Jie; Zhao, Fazhan; Zhang, Zhangang; Bi, Jinshun; Geng, Chao; Hou, Mingdong; Liu, Gang; Liu, Tianqi; Xi, Kai

    2015-01-01

    An experimental investigation of the single event upset (SEU) susceptibility for heavy ions at tilted incidence was performed. The differences of SEU cross-sections between tilted incidence and normal incidence at equivalent effective linear energy transfer were 21% and 57% for the silicon-on-insulator (SOI) static random access memories (SRAMs) of 0.5 μm and 0.18 μm feature size, respectively. The difference of SEU cross-section raised dramatically with increasing tilt angle for SOI SRAM of deep-submicron technology. The result of CRÈME-MC simulation for tilted irradiation of the sensitive volume indicates that the energy deposition spectrum has a substantial tail extending into the low energy region. The experimental results show that the influence of edge effects on SEU susceptibility cannot be ignored in particular with device scaling down

  19. Single Event Upset in Static Random Access Memories in Atmospheric Neutron Environments

    Science.gov (United States)

    Arita, Yutaka; Takai, Mikio; Ogawa, Izumi; Kishimoto, Tadafumi

    2003-07-01

    Single-event upsets (SEUs) in a 0.4 μm 4 Mbit complementary metal oxide semiconductor (CMOS) static random access memory (SRAM) were investigated in various atmospheric neutron environments at sea level, at an altitude of 2612 m mountain, at an altitude of commercial airplane, and at an underground depth of 476 m. Neutron-induced SEUs increase with the increase in altitude. For a device with a borophosphosilicate glass (BPSG) film, SEU rates induced by thermal neutrons increase with the decrease in the cell charge of a memory cell. A thermal neutron-induced SEU is significant in SRAMs with a small cell charge. With the conditions of small cell charge, thermal neutron-induced SEUs account for 60% or more of the total neutron-induced SEUs. The SEU rate induced by atmospheric thermal neutrons can be estimated by an acceleration test using 252Cf.

  20. Single-Event Effects in High-Frequency Linear Amplifiers: Experiment and Analysis

    Science.gov (United States)

    Zeinolabedinzadeh, Saeed; Ying, Hanbin; Fleetwood, Zachary E.; Roche, Nicolas J.-H.; Khachatrian, Ani; McMorrow, Dale; Buchner, Stephen P.; Warner, Jeffrey H.; Paki-Amouzou, Pauline; Cressler, John D.

    2017-01-01

    The single-event transient (SET) response of two different silicon-germanium (SiGe) X-band (8-12 GHz) low noise amplifier (LNA) topologies is fully investigated in this paper. The two LNAs were designed and implemented in 130nm SiGe HBT BiCMOS process technology. Two-photon absorption (TPA) laser pulses were utilized to induce transients within various devices in these LNAs. Impulse response theory is identified as a useful tool for predicting the settling behavior of the LNAs subjected to heavy ion strikes. Comprehensive device and circuit level modeling and simulations were performed to accurately simulate the behavior of the circuits under ion strikes. The simulations agree well with TPA measurements. The simulation, modeling and analysis presented in this paper can be applied for any other circuit topologies for SET modeling and prediction.

  1. A simple analytical model of single-event upsets in bulk CMOS

    Energy Technology Data Exchange (ETDEWEB)

    Sogoyan, Armen V.; Chumakov, Alexander I.; Smolin, Anatoly A., E-mail: aasmol@spels.ru; Ulanova, Anastasia V.; Boruzdina, Anna B.

    2017-06-01

    During the last decade, multiple new methods of single event upset (SEU) rate prediction for aerospace systems have been proposed. Despite different models and approaches being employed in these methods, they all share relatively high usage complexity and require information about a device that is not always available to an end user. This work presents an alternative approach to estimating SEU cross-section as a function of linear energy transfer (LET) that can be further developed into a method of SEU rate prediction. The goal is to propose a simple, yet physics-based, approach with just two parameters that can be used even in situations when only a process node of the device is known. The developed approach is based on geometrical interpretation of SEU cross-section and an analytical solution to the diffusion problem obtained for a simplified IC topology model. A good fit of the model to the experimental data encompassing 7 generations of SRAMs is demonstrated.

  2. Radiation Fields in High Energy Accelerators and their impact on Single Event Effects

    CERN Document Server

    García Alía, Rubén; Wrobel, Frédéric; Brugger, Markus

    Including calculation models and measurements for a variety of electronic components and their concerned radiation environments, this thesis describes the complex radiation field present in the surrounding of a high-energy hadron accelerator and assesses the risks related to it in terms of Single Event Effects (SEE). It is shown that this poses not only a serious threat to the respective operation of modern accelerators but also highlights the impact on other high-energy radiation environments such as those for ground and avionics applications. Different LHC-like radiation environments are described in terms of their hadron composition and energy spectra. They are compared with other environments relevant for electronic component operation such as the ground-level, avionics or proton belt. The main characteristic of the high-energy accelerator radiation field is its mixed nature, both in terms of hadron types and energy interval. The threat to electronics ranges from neutrons of thermal energies to GeV hadron...

  3. Talys calculations for evaluation of neutron-induced single-event upset cross sections

    Energy Technology Data Exchange (ETDEWEB)

    Bourselier, Jean-Christophe

    2005-08-15

    The computer code TALYS has been used to calculate interactions between cosmic-ray neutrons and silicon nuclei with the goal to describe single-event upset (SEU) cross sections in microelectronics devices. Calculations for the Si(n,X) reaction extend over an energy range of 2 to 200 MeV. The obtained energy spectra of the resulting residuals and light-ions have been integrated using several different critical charges as SEU threshold. It is found that the SEU cross section seems largely to be dominated by {sup 28}Si recoils from elastic scattering. Furthermore, the shape of the SEU cross section as a function of the energy of the incoming neutron changes drastically with decreasing critical charge. The results presented in this report stress the importance of performing studies at mono-energetic neutron beams to advance the understanding of the underlying mechanisms causing SEUs.

  4. Single event upset studies on the CMS tracker APV25 readout chip

    International Nuclear Information System (INIS)

    Noah, E.; Bauer, T.; Bisello, D.; Faccio, F.; Friedl, M.; Fulcher, J.R.; Hall, G.; Huhtinen, M.; Kaminsky, A.; Pernicka, M.; Raymond, M.; Wyss, J.

    2002-01-01

    The microstrip tracker for the CMS experiment at the CERN Large Hadron Collider will be read out using APV25 chips. During high luminosity running the tracker will be exposed to particle fluxes up to 10 7 cm -2 s -1 , which raises concerns that the APV25 could occasionally suffer Single Event Upsets (SEUs). The effect of SEU on the APV25 has been studied to investigate implications for CMS detector operation and from the viewpoint of detailed circuit operation, to improve the understanding of its origin and what factors affect its magnitude. Simulations were performed to reconstruct the effects created by highly ionising particles striking sensitive parts of the circuits, along with consideration of the underlying mechanisms of charge deposition, collection and the consequences. A model to predict the behaviour of the memory circuits in the APV25 has been developed and data collected from dedicated experiments using both heavy ions and hadrons have been shown to support it

  5. Experimental setup for Single Event Effects at the São Paulo 8UD Pelletron Accelerator

    Science.gov (United States)

    Aguiar, V. A. P.; Added, N.; Medina, N. H.; Macchione, E. L. A.; Tabacniks, M. H.; Aguirre, F. R.; Silveira, M. A. G.; Santos, R. B. B.; Seixas, L. E.

    2014-08-01

    In this work we present an experimental setup mounted in one of the beam lines at the São Paulo 8UD Pelletron Accelerator in order to study Single Event Effects in electronic devices. The basic idea is to use elastic scattering collisions to achieve a low-flux with a high-uniformity ion beam to irradiate several devices. 12C, 16O, 28Si, 35Cl and 63Cu beams were used to test the experimental setup. In this system it is possible to use efficiently LET values of 17 MeV/mg/cm2 for an external beam arrangement and up to 32 MeV/mg/cm2 for in-vacuum irradiation.

  6. Experimental setup for Single Event Effects at the São Paulo 8UD Pelletron Accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Aguiar, V.A.P. [Instituto de Física da Universidade de São Paulo, São Paulo, SP (Brazil); Added, N., E-mail: nemitala@if.usp.br [Instituto de Física da Universidade de São Paulo, São Paulo, SP (Brazil); Medina, N.H.; Macchione, E.L.A.; Tabacniks, M.H.; Aguirre, F.R. [Instituto de Física da Universidade de São Paulo, São Paulo, SP (Brazil); Silveira, M.A.G.; Santos, R.B.B. [Centro Universitário da FEI, São Bernardo do Campo, SP (Brazil); Seixas, L.E. [Centro de Tecnologia da Informação Renato Archer, Campinas, SP (Brazil)

    2014-08-01

    In this work we present an experimental setup mounted in one of the beam lines at the São Paulo 8UD Pelletron Accelerator in order to study Single Event Effects in electronic devices. The basic idea is to use elastic scattering collisions to achieve a low-flux with a high-uniformity ion beam to irradiate several devices. {sup 12}C, {sup 16}O, {sup 28}Si, {sup 35}Cl and {sup 63}Cu beams were used to test the experimental setup. In this system it is possible to use efficiently LET values of 17 MeV/mg/cm{sup 2} for an external beam arrangement and up to 32 MeV/mg/cm{sup 2} for in-vacuum irradiation.

  7. Talys calculations for evaluation of neutron-induced single-event upset cross sections

    International Nuclear Information System (INIS)

    Bourselier, Jean-Christophe

    2005-08-01

    The computer code TALYS has been used to calculate interactions between cosmic-ray neutrons and silicon nuclei with the goal to describe single-event upset (SEU) cross sections in microelectronics devices. Calculations for the Si(n,X) reaction extend over an energy range of 2 to 200 MeV. The obtained energy spectra of the resulting residuals and light-ions have been integrated using several different critical charges as SEU threshold. It is found that the SEU cross section seems largely to be dominated by 28 Si recoils from elastic scattering. Furthermore, the shape of the SEU cross section as a function of the energy of the incoming neutron changes drastically with decreasing critical charge. The results presented in this report stress the importance of performing studies at mono-energetic neutron beams to advance the understanding of the underlying mechanisms causing SEUs

  8. Acquisition and classification of static single-event upset cross section for SRAM-based FPGAs

    International Nuclear Information System (INIS)

    Yao Zhibin; Fan Ruyu; Guo Hongxia; Wang Zhongming; He Baoping; Zhang Fengqi; Zhang Keying

    2011-01-01

    In order to evaluate single event upsets (SEUs) in SRAM-based FPGAs and to find the sensitive resource in configuration memory, a heavy ions irradiation experiment was carried out on a Xilinx FPGAs device XCV300PQ240. The experiment was conducted to gain the static SEU cross section and classify the SEUs in configurations memory according to different resource uses. The results demonstrate that the inter-memory of SRAM-based FPGAs is extremely sensitive to heavy-ion-induced SEUs. The LUT and routing resources are the main source of SEUs in the configuration memory, which covers more than 97.46% of the total upsets. The SEU sensitivity of various resources is different. The IOB control bit and LUT elements are more sensitive,and more attention should be paid to the LUT elements in radiation hardening,which account for a quite large proportion of the configuration memory. (authors)

  9. Neutron-induced single event upsets in static RAMS observed at 10 km flight altitude

    International Nuclear Information System (INIS)

    Olsen, J.; Becher, P.E.; Fynbo, P.B.; Raaby, P. Schultz, J.

    1993-01-01

    Neutron induced single event upsets (SEUs) in static memory devices (SRAMs) have so far been seen only in laboratory environments. The authors report observations of 14 neutron induced SEUs at commercial aircraft flight altitudes as well. The observed SEU rate at 10 km flight altitude based on exposure of 160 standard 256 Kbit CMOS SRAMs is 4.8 · 10 -8 upsets/bit/day. In the laboratory 117 SRAMs of two different brands were irradiated with fast neutrons from a Pu-Be source. A total of 176 SEUs have been observed, among these are two SEU pairs. The upset rates from the laboratory tests are compared to those found in the airborne SRAMS

  10. Simulation study on single event burnout in linear doping buffer layer engineered power VDMOSFET

    International Nuclear Information System (INIS)

    Jia Yunpeng; Su Hongyuan; Hu Dongqing; Wu Yu; Jin Rui

    2016-01-01

    The addition of a buffer layer can improve the device's secondary breakdown voltage, thus, improving the single event burnout (SEB) threshold voltage. In this paper, an N type linear doping buffer layer is proposed. According to quasi-stationary avalanche simulation and heavy ion beam simulation, the results show that an optimized linear doping buffer layer is critical. As SEB is induced by heavy ions impacting, the electric field of an optimized linear doping buffer device is much lower than that with an optimized constant doping buffer layer at a given buffer layer thickness and the same biasing voltages. Secondary breakdown voltage and the parasitic bipolar turn-on current are much higher than those with the optimized constant doping buffer layer. So the linear buffer layer is more advantageous to improving the device's SEB performance. (paper)

  11. Engaged patients, engaged partnerships: singles and partners dealing with an acute cardiac event.

    Science.gov (United States)

    Bertoni, Anna; Donato, Silvia; Graffigna, Guendalina; Barello, Serena; Parise, Miriam

    2015-01-01

    A few studies examine patients' (and partners') individual and relational functioning after an acute cardiac event and no research focuses on the individual and relational factors associated with the patient's engagement in his/her disease management. The present study aimed at exploring these variables in male and female patients as well as their partners. We pursued our objectives by taking advantage of a dyadic research design that involved both partners in the data collection, when present, and by including women patients in the sample. Findings showed that patients in a couple, compared to single patients, perceive that their illness had less serious consequences for their life and they were more engaged in their health care; that patients and partners showed comparable levels of distress; and that less depressed, more confident, and better informed patients were more likely to actively engage in their treatment. Findings are discussed in light of their implications for clinical practice.

  12. Single event upset in static random access memories in atmospheric neutron environments

    CERN Document Server

    Arita, Y; Ogawa, I; Kishimoto, T

    2003-01-01

    Single-event upsets (SEUs) in a 0.4 mu m 4Mbit complementary metal oxide semiconductor (CMOS) static random access memory (SRAM) were investigated in various atmospheric neutron environments at sea level, at an altitude of 2612 m mountain, at an altitude of commercial airplane, and at an underground depth of 476m. Neutron-induced SEUs increase with the increase in altitude. For a device with a borophosphosilicate glass (BPSG) film, SEU rates induced by thermal neutrons increase with the decrease in the cell charge of a memory cell. A thermal neutron-induced SEU is significant in SRAMs with a small cell charge. With the conditions of small cell charge, thermal neutron-induced SEUs account for 60% or more of the total neutron-induced SEUs. The SEU rate induced by atmospheric thermal neutrons can be estimated by an acceleration test using sup 2 sup 5 sup 2 Cf. (author)

  13. Study on relations between heavy ions single event upset cross sections and γ accumulated doses

    International Nuclear Information System (INIS)

    He Chaohui; Geng Bin; Wang Yanping; Peng Honglun; Yang Hailiang; Chen Xiaohua; Li Guozheng

    2002-01-01

    Experiments were done under 252 Cf and 60 Co γ source to study the relation between heavy ion Single Event Upset (SEU) cross sections and γ accumulated doses. There was no obvious rule and little influence of γ accumulated doses on SEU cross sections when Static Random Access Memories were in power off mode and static power on mode. In active measuring mode, the SEU cross section increased as the accumulated doses increasing when same data were written in memory cells. If reverse data, such as '55' and 'AA', were written in memory cells during the experiment, the SEU cross sections decreased to the level when memories were not irradiated under 60 Co γ source, even more small. It implied that the influence of γ accumulated doses on SEU cross sections can be set off by this method

  14. A simple analytical model of single-event upsets in bulk CMOS

    International Nuclear Information System (INIS)

    Sogoyan, Armen V.; Chumakov, Alexander I.; Smolin, Anatoly A.; Ulanova, Anastasia V.; Boruzdina, Anna B.

    2017-01-01

    During the last decade, multiple new methods of single event upset (SEU) rate prediction for aerospace systems have been proposed. Despite different models and approaches being employed in these methods, they all share relatively high usage complexity and require information about a device that is not always available to an end user. This work presents an alternative approach to estimating SEU cross-section as a function of linear energy transfer (LET) that can be further developed into a method of SEU rate prediction. The goal is to propose a simple, yet physics-based, approach with just two parameters that can be used even in situations when only a process node of the device is known. The developed approach is based on geometrical interpretation of SEU cross-section and an analytical solution to the diffusion problem obtained for a simplified IC topology model. A good fit of the model to the experimental data encompassing 7 generations of SRAMs is demonstrated.

  15. Events

    Directory of Open Access Journals (Sweden)

    Igor V. Karyakin

    2016-02-01

    Full Text Available The 9th ARRCN Symposium 2015 was held during 21st–25th October 2015 at the Novotel Hotel, Chumphon, Thailand, one of the most favored travel destinations in Asia. The 10th ARRCN Symposium 2017 will be held during October 2017 in the Davao, Philippines. International Symposium on the Montagu's Harrier (Circus pygargus «The Montagu's Harrier in Europe. Status. Threats. Protection», organized by the environmental organization «Landesbund für Vogelschutz in Bayern e.V.» (LBV was held on November 20-22, 2015 in Germany. The location of this event was the city of Wurzburg in Bavaria.

  16. WINHAC - the Monte Carlo event generator for single W-boson production in hadronic collisions

    International Nuclear Information System (INIS)

    Placzek, W.; Jadach, P.

    2009-01-01

    The charged-current Drell-Yan process, i.e. single W-boson production with leptonic decays in hadronic collisions, will play an important role in the experimental programme at the LHC. It will be used for improved measurements of some Standard Model parameters (such as the W-boson mass and widths, etc.), for better determination of the Higgs-boson mass limits, in '' new physics '' searches, as a '' standard candle '' process, etc. In order to achieve all these goals, precise theoretical predictions for this process in terms of a Monte Carlo event generator are indispensable. In this talk the Monte Carlo event generator WINHAC for the charged-current Drell-Yan process will be presented. It features higher-order QED corrections within the exclusive Yennie-Frautschi-Suura exponentiation scheme with the 1 st order electroweak corrections. It is interfaced with PYTHIA for QCD/QED initial-state parton shower as well as hadronization. It includes options for proton-proton, proton-antiproton and nucleus-nucleus collisions. Moreover, it allows for longitudinally and transversely polarized W-boson production. It has been cross-checked numerically to high precision against independent programs/calculations. Some numerical results from WINHAC will also be presented. Finally, interplay between QCD and electroweak effects will briefly be discussed. (author)

  17. Widespread Amazon forest tree mortality from a single cross-basin squall line event

    Science.gov (United States)

    Negrón-Juárez, Robinson I.; Chambers, Jeffrey Q.; Guimaraes, Giuliano; Zeng, Hongcheng; Raupp, Carlos F. M.; Marra, Daniel M.; Ribeiro, Gabriel H. P. M.; Saatchi, Sassan S.; Nelson, Bruce W.; Higuchi, Niro

    2010-08-01

    Climate change is expected to increase the intensity of extreme precipitation events in Amazonia that in turn might produce more forest blowdowns associated with convective storms. Yet quantitative tree mortality associated with convective storms has never been reported across Amazonia, representing an important additional source of carbon to the atmosphere. Here we demonstrate that a single squall line (aligned cluster of convective storm cells) propagating across Amazonia in January, 2005, caused widespread forest tree mortality and may have contributed to the elevated mortality observed that year. Forest plot data demonstrated that the same year represented the second highest mortality rate over a 15-year annual monitoring interval. Over the Manaus region, disturbed forest patches generated by the squall followed a power-law distribution (scaling exponent α = 1.48) and produced a mortality of 0.3-0.5 million trees, equivalent to 30% of the observed annual deforestation reported in 2005 over the same area. Basin-wide, potential tree mortality from this one event was estimated at 542 ± 121 million trees, equivalent to 23% of the mean annual biomass accumulation estimated for these forests. Our results highlight the vulnerability of Amazon trees to wind-driven mortality associated with convective storms. Storm intensity is expected to increase with a warming climate, which would result in additional tree mortality and carbon release to the atmosphere, with the potential to further warm the climate system.

  18. Femtomolar detection of single mismatches by discriminant analysis of DNA hybridization events using gold nanoparticles.

    Science.gov (United States)

    Ma, Xingyi; Sim, Sang Jun

    2013-03-21

    Even though DNA-based nanosensors have been demonstrated for quantitative detection of analytes and diseases, hybridization events have never been numerically investigated for further understanding of DNA mediated interactions. Here, we developed a nanoscale platform with well-designed capture and detection gold nanoprobes to precisely evaluate the hybridization events. The capture gold nanoprobes were mono-laid on glass and the detection probes were fabricated via a novel competitive conjugation method. The two kinds of probes combined in a suitable orientation following the hybridization with the target. We found that hybridization efficiency was markedly dependent on electrostatic interactions between DNA strands, which can be tailored by adjusting the salt concentration of the incubation solution. Due to the much lower stability of the double helix formed by mismatches, the hybridization efficiencies of single mismatched (MMT) and perfectly matched DNA (PMT) were different. Therefore, we obtained an optimized salt concentration that allowed for discrimination of MMT from PMT without stringent control of temperature or pH. The results indicated this to be an ultrasensitive and precise nanosensor for the diagnosis of genetic diseases.

  19. Applications Of Monte Carlo Radiation Transport Simulation Techniques For Predicting Single Event Effects In Microelectronics

    International Nuclear Information System (INIS)

    Warren, Kevin; Reed, Robert; Weller, Robert; Mendenhall, Marcus; Sierawski, Brian; Schrimpf, Ronald

    2011-01-01

    MRED (Monte Carlo Radiative Energy Deposition) is Vanderbilt University's Geant4 application for simulating radiation events in semiconductors. Geant4 is comprised of the best available computational physics models for the transport of radiation through matter. In addition to basic radiation transport physics contained in the Geant4 core, MRED has the capability to track energy loss in tetrahedral geometric objects, includes a cross section biasing and track weighting technique for variance reduction, and additional features relevant to semiconductor device applications. The crucial element of predicting Single Event Upset (SEU) parameters using radiation transport software is the creation of a dosimetry model that accurately approximates the net collected charge at transistor contacts as a function of deposited energy. The dosimetry technique described here is the multiple sensitive volume (MSV) model. It is shown to be a reasonable approximation of the charge collection process and its parameters can be calibrated to experimental measurements of SEU cross sections. The MSV model, within the framework of MRED, is examined for heavy ion and high-energy proton SEU measurements of a static random access memory.

  20. Allogeneic Transplant in ELANE and MEFV Mutation Positive Severe Cyclic Neutropenia: Review of Prognostic Factors for Secondary Severe Events

    OpenAIRE

    Okolo, Onyemaechi N.; Katsanis, Emmanuel; Yun, Seongseok; Reveles, Candace Y.; Anwer, Faiz

    2017-01-01

    Objective and Importance. Cyclic neutropenia (CyN) is a rare autosomal dominant inherited disorder due to the mutation ELANE primarily affecting bone marrow stem cells and is characterized by recurrent neutropenia every 2 to 4 weeks. Symptoms vary from benign to severe, including death. Postulations on the cause of wide spectrum in symptom presentation include the possibility of other genetic mutations, such as MEFV. Recommended treatment for CyN is G-CSF to keep ANC higher to minimize risk o...

  1. Investigation of HZETRN 2010 as a Tool for Single Event Effect Qualification of Avionics Systems

    Science.gov (United States)

    Rojdev, Kristina; Koontz, Steve; Atwell, William; Boeder, Paul

    2014-01-01

    NASA's future missions are focused on long-duration deep space missions for human exploration which offers no options for a quick emergency return to Earth. The combination of long mission duration with no quick emergency return option leads to unprecedented spacecraft system safety and reliability requirements. It is important that spacecraft avionics systems for human deep space missions are not susceptible to Single Event Effect (SEE) failures caused by space radiation (primarily the continuous galactic cosmic ray background and the occasional solar particle event) interactions with electronic components and systems. SEE effects are typically managed during the design, development, and test (DD&T) phase of spacecraft development by using heritage hardware (if possible) and through extensive component level testing, followed by system level failure analysis tasks that are both time consuming and costly. The ultimate product of the SEE DD&T program is a prediction of spacecraft avionics reliability in the flight environment produced using various nuclear reaction and transport codes in combination with the component and subsystem level radiation test data. Previous work by Koontz, et al.1 utilized FLUKA, a Monte Carlo nuclear reaction and transport code, to calculate SEE and single event upset (SEU) rates. This code was then validated against in-flight data for a variety of spacecraft and space flight environments. However, FLUKA has a long run-time (on the order of days). CREME962, an easy to use deterministic code offering short run times, was also compared with FLUKA predictions and in-flight data. CREME96, though fast and easy to use, has not been updated in several years and underestimates secondary particle shower effects in spacecraft structural shielding mass. Thus, this paper will investigate the use of HZETRN 20103, a fast and easy to use deterministic transport code, similar to CREME96, that was developed at NASA Langley Research Center primarily for

  2. Application of high energy accelerator to study of single event burn-out (SEB)

    Energy Technology Data Exchange (ETDEWEB)

    Hada, Takashi; Aoki, Shiro; Nakamura, Masao; Matsuda, Sumio [National Space Development Agency of Japan, Tokyo (Japan); Hirao, Toshio; Nashiyama, Isamu; Hirose, Takayuki; Ohira, Hideharu; Nagai, Yuki

    1996-12-01

    Hitherto, as nuclear fission fragments of 252-Cf, one of radioactive matters have been used for elucidation of single event mechanism, this method has a limit for analysis of power MOSFET with long charge collection region (generally, empty layer) and is difficult to form the experiment simulating the space environment, because of their wide LET (Linear Energy Transfer) range and of short flying distance of about 15 micrometer. As a result, some irradiation experiments using an accelerator capable of forming charged particle beam with long flying distance and single energy became essential to elucidate the SEB mechanism. In this paper, an experiment result of SEB phenomenon using high energy accelerator was reported. As a result, following items were found: (1) With increase of impressed charge, collected charge shows two peaks, and also increases, (2) commercial power MOSFET shows about 280 V in SEB resistance, and power MOSFET developed for the space use shows about 320 V, which is improved about 40 V for the commercial one, and so forth. (G.K.)

  3. Single-Trial Event-Related Potential Based Rapid Image Triage System

    Directory of Open Access Journals (Sweden)

    Ke Yu

    2011-06-01

    Full Text Available Searching for points of interest (POI in large-volume imagery is a challenging problem with few good solutions. In this work, a neural engineering approach called rapid image triage (RIT which could offer about a ten-fold speed up in POI searching is developed. It is essentially a cortically-coupled computer vision technique, whereby the user is presented bursts of images at a speed of 6–15 images per second and then neural signals called event-related potential (ERP is used as the ‘cue’ for user seeing images of high relevance likelihood. Compared to past efforts, the implemented system has several unique features: (1 it applies overlapping frames in image chip preparation, to ensure rapid image triage performance; (2 a novel common spatial-temporal pattern (CSTP algorithm that makes use of both spatial and temporal patterns of ERP topography is proposed for high-accuracy single-trial ERP detection; (3 a weighted version of probabilistic support-vector-machine (SVM is used to address the inherent unbalanced nature of single-trial ERP detection for RIT. High accuracy, fast learning, and real-time capability of the developed system shown on 20 subjects demonstrate the feasibility of a brainmachine integrated rapid image triage system for fast detection of POI from large-volume imagery.

  4. Single charging events on colloidal particles in a nonpolar liquid with surfactant

    Science.gov (United States)

    Schreuer, Caspar; Vandewiele, Stijn; Brans, Toon; Strubbe, Filip; Neyts, Kristiaan; Beunis, Filip

    2018-01-01

    Electrical charging of colloidal particles in nonpolar liquids due to surfactant additives is investigated intensively, motivated by its importance in a variety of applications. Most methods rely on average electrophoretic mobility measurements of many particles, which provide only indirect information on the charging mechanism. In the present work, we present a method that allows us to obtain direct information on the charging mechanism, by measuring the charge fluctuations on individual particles with a precision higher than the elementary charge using optical trapping electrophoresis. We demonstrate the capabilities of the method by studying the influence of added surfactant OLOA 11000 on the charging of single colloidal PMMA particles in dodecane. The particle charge and the frequency of charging events are investigated both below and above the critical micelle concentration (CMC) and with or without applying a DC offset voltage. It is found that at least two separate charging mechanisms are present below the critical micelle concentration. One mechanism is a process where the particle is stripped from negatively charged ionic molecules. An increase in the charging frequency with increased surfactant concentration suggests a second mechanism that involves single surfactant molecules. Above the CMC, neutral inverse micelles can also be involved in the charging process.

  5. The dual role of multiple-transistor charge sharing collection in single-event transients

    International Nuclear Information System (INIS)

    Guo Yang; Chen Jian-Jun; He Yi-Bai; Liang Bin; Liu Bi-Wei

    2013-01-01

    As technologies scale down in size, multiple-transistors being affected by a single ion has become a universal phenomenon, and some new effects are present in single event transients (SETs) due to the charge sharing collection of the adjacent multiple-transistors. In this paper, not only the off-state p-channel metal—oxide semiconductor field-effect transistor (PMOS FET), but also the on-state PMOS is struck by a heavy-ion in the two-transistor inverter chain, due to the charge sharing collection and the electrical interaction. The SET induced by striking the off-state PMOS is efficiently mitigated by the pulse quenching effect, but the SET induced by striking the on-state PMOS becomes dominant. It is indicated in this study that in the advanced technologies, the SET will no longer just be induced by an ion striking the off-state transistor, and the SET sensitive region will no longer just surround the off-state transistor either, as it is in the older technologies. We also discuss this issue in a three-transistor inverter in depth, and the study illustrates that the three-transistor inverter is still a better replacement for spaceborne integrated circuit design in advanced technologies. (condensed matter: structural, mechanical, and thermal properties)

  6. Single photon and multiphoton events with missing energy in $e^{+} e^{-}$ collisions at LEP

    CERN Document Server

    Achard, P; Aguilar-Benítez, M; Alcaraz, J; Alemanni, G; Allaby, James V; Aloisio, A; Alviggi, M G; Anderhub, H; Andreev, V P; Anselmo, F; Arefev, A; Azemoon, T; Aziz, T; Bagnaia, P; Bajo, A; Baksay, G; Baksay, L; Baldew, S V; Banerjee, S; Banerjee, Sw; Barczyk, A; Barillère, R; Bartalini, P; Basile, M; Batalova, N; Battiston, R; Bay, A; Becattini, F; Becker, U; Behner, F; Bellucci, L; Berbeco, R; Berdugo, J; Berges, P; Bertucci, B; Betev, B L; Biasini, M; Biglietti, M; Biland, A; Blaising, J J; Blyth, S C; Bobbink, Gerjan J; Böhm, A; Boldizsar, L; Borgia, B; Bottai, S; Bourilkov, D; Bourquin, Maurice; Braccini, S; Branson, J G; Brochu, F; Burger, J D; Burger, W J; Cai, X D; Capell, M; Cara Romeo, G; Carlino, G; Cartacci, A M; Casaus, J; Cavallari, F; Cavallo, N; Cecchi, C; Cerrada, M; Chamizo-Llatas, M; Chang, Y H; Chemarin, M; Chen, A; Chen, G; Chen, G M; Chen, H F; Chen, H S; Chiefari, G; Cifarelli, Luisa; Cindolo, F; Clare, I; Clare, R; Coignet, G; Colino, N; Costantini, S; de la Cruz, B; Cucciarelli, S; van Dalen, J A; De Asmundis, R; Déglon, P L; Debreczeni, J; Degré, A; Dehmelt, K; Deiters, K; Della Volpe, D; Delmeire, E; Denes, P; De Notaristefani, F; De Salvo, A; Diemoz, M; Dierckxsens, M; Dionisi, C; Dittmar, M; Doria, A; Dova, M T; Duchesneau, D; Duda, M; Echenard, B; Eline, A; El-Hage, A; El-Mamouni, H; Engler, A; Eppling, F J; Extermann, P; Falagán, M A; Falciano, S; Favara, A; Fay, J; Fedin, O; Felcini, M; Ferguson, T; Fesefeldt, H S; Fiandrini, E; Field, J H; Filthaut, F; Fisher, P H; Fisher, W; Fisk, I; Forconi, G; Freudenreich, Klaus; Furetta, C; Galaktionov, Yu; Ganguli, S N; García-Abia, P; Gataullin, M; Gentile, S; Giagu, S; Gong, Z F; Grenier, G; Grimm, O; Grünewald, M W; Guida, M; van Gulik, R; Gupta, V K; Gurtu, A; Gutay, L J; Haas, D; Hatzifotiadou, D; Hebbeker, T; Hervé, A; Hirschfelder, J; Hofer, H; Hohlmann, M; Holzner, G; Hou, S R; Hu, Y; Jin, B N; Jones, L W; de Jong, P; Josa-Mutuberria, I; Käfer, D; Kaur, M; Kienzle-Focacci, M N; Kim, J K; Kirkby, Jasper; Kittel, E W; Klimentov, A; König, A C; Kopal, M; Koutsenko, V F; Kräber, M H; Krämer, R W; Krüger, A; Kunin, A; Ladrón de Guevara, P; Laktineh, I; Landi, G; Lebeau, M; Lebedev, A; Lebrun, P; Lecomte, P; Lecoq, P; Le Coultre, P; Le Goff, J M; Leiste, R; Levtchenko, M; Levchenko, P M; Li, C; Likhoded, S; Lin, C H; Lin, W T; Linde, Frank L; Lista, L; Liu, Z A; Lohmann, W; Longo, E; Lü, Y S; Luci, C; Luminari, L; Lustermann, W; Ma Wen Gan; Malgeri, L; Malinin, A; Maña, C; Mans, J; Martin, J P; Marzano, F; Mazumdar, K; McNeil, R R; Mele, S; Merola, L; Meschini, M; Metzger, W J; Mihul, A; Milcent, H; Mirabelli, G; Mnich, J; Mohanty, G B; Muanza, G S; Muijs, A J M; Musicar, B; Musy, M; Nagy, S; Natale, S; Napolitano, M; Nessi-Tedaldi, F; Newman, H; Nisati, A; Novák, T; Nowak, H; Ofierzynski, R A; Organtini, G; Pal, I; Palomares, C; Paolucci, P; Paramatti, R; Passaleva, G; Patricelli, S; Paul, T; Pauluzzi, M; Paus, C; Pauss, Felicitas; Pedace, M; Pensotti, S; Perret-Gallix, D; Petersen, B; Piccolo, D; Pierella, F; Pioppi, M; Piroué, P A; Pistolesi, E; Plyaskin, V; Pohl, M; Pozhidaev, V; Pothier, J; Prokofev, D; Prokofiev, D O; Quartieri, J; Rahal-Callot, G; Rahaman, M A; Raics, P; Raja, N; Ramelli, R; Rancoita, P G; Ranieri, R; Raspereza, A V; Razis, P A; Ren, D; Rescigno, M; Reucroft, S; Riemann, S; Riles, K; Roe, B P; Romero, L; Rosca, A; Rosenbleck, C; Rosier-Lees, S; Roth, S; Rubio, J A; Ruggiero, G; Rykaczewski, H; Sakharov, A; Saremi, S; Sarkar, S; Salicio, J; Sánchez, E; Schäfer, C; Shchegelskii, V; Schopper, Herwig Franz; Schotanus, D J; Sciacca, C; Servoli, L; Shevchenko, S; Shivarov, N; Shoutko, V; Shumilov, E; Shvorob, A V; Son, D; Souga, C; Spillantini, P; Steuer, M; Stickland, D P; Stoyanov, B; Strässner, A; Sudhakar, K; Sultanov, G G; Sun, L Z; Sushkov, S; Suter, H; Swain, J D; Szillási, Z; Tang, X W; Tarjan, P; Tauscher, Ludwig; Taylor, L; Tellili, B; Teyssier, D; Timmermans, C; Ting, Samuel C C; Ting, S M; Tonwar, S C; Tóth, J; Tully, C; Tung, K L; Ulbricht, J; Valente, E; Van de Walle, R T; Vásquez, R; Veszpremi, V; Vesztergombi, G; Vetlitskii, I; Vicinanza, D; Viertel, Gert M; Villa, S; Vivargent, M; Vlachos, S; Vodopyanov, I; Vogel, H; Vogt, H; Vorobev, I; Vorobyov, A A; Wadhwa, M; Wang, Q; Wang, X L; Wang, Z M; Weber, M; Wienemann, P; Wilkens, H; Wynhoff, S; Xia, L; Xu, Z Z; Yamamoto, J; Yang, B Z; Yang, C G; Yang, H J; Yang, M; Yeh, S C; Zalite, A; Zalite, Yu; Zhang, Z P; Zhao, J; Zhu, G Y; Zhu, R Y; Zhuang, H L; Zichichi, A; Zimmermann, B; Zöller, M

    2004-01-01

    Single- and multi-photon events with missing energy are selected in 619/pb of data collected by the L3 detector at LEP at centre-of-mass energies between 189GeV and 209GeV. The cross sections of the process e^+e^- -> nu nu gamma (gamma) are found to be in agreement with the Standard Model expectations, and the number of light neutrino species is determined, including lower energy data, to be N_nu = 2.98 +/- 0.05 +/- 0.04. Selection results are also given in the form of tables which can be used to test future models involving single- and multi-photon signatures at LEP. These final states are also predicted by models with large extra dimensions and by several supersymmetric models. No evidence for such models is found. Among others, lower limits between 1.5TeV and 0.65TeV are set, at 95% confidence level, on the new scale of gravity for the number of extra dimensions between 2 and 8.

  7. Modeling of Single Event Transients With Dual Double-Exponential Current Sources: Implications for Logic Cell Characterization

    Science.gov (United States)

    Black, Dolores A.; Robinson, William H.; Wilcox, Ian Z.; Limbrick, Daniel B.; Black, Jeffrey D.

    2015-08-01

    Single event effects (SEE) are a reliability concern for modern microelectronics. Bit corruptions can be caused by single event upsets (SEUs) in the storage cells or by sampling single event transients (SETs) from a logic path. An accurate prediction of soft error susceptibility from SETs requires good models to convert collected charge into compact descriptions of the current injection process. This paper describes a simple, yet effective, method to model the current waveform resulting from a charge collection event for SET circuit simulations. The model uses two double-exponential current sources in parallel, and the results illustrate why a conventional model based on one double-exponential source can be incomplete. A small set of logic cells with varying input conditions, drive strength, and output loading are simulated to extract the parameters for the dual double-exponential current sources. The parameters are based upon both the node capacitance and the restoring current (i.e., drive strength) of the logic cell.

  8. Mechanism of DNA–binding loss upon single-point mutation in p53

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    loss in protein−DNA binding affinity and specificity upon single point ..... we computed the root–mean–square–deviations (RMSDs) of each residue's ...... Petsko G and Ringe D 1984 Fluctuations in protein structure from. X-ray diffraction; Annu.

  9. Four Gaucher disease type II patients with three novel mutations: a single centre experience from Turkey.

    Science.gov (United States)

    Bulut, Fatma Derya; Kör, Deniz; Şeker-Yılmaz, Berna; Hergüner, Özlem; Ceylaner, Serdar; Özkınay, Ferda; Kılavuz, Sebile; Önenli-Mungan, Neslihan

    2018-04-14

    Gaucher disease is the most common lysosomal storage disorder due to glucosylceramidase enzyme deficiency. There are three subtypes of the disease. Neurological involvement accompanies visceral and haematological findings only in type II and type III Gaucher patients. Type II is the acute progressive neuronopathic form which is the most severe and rare subtype. Clinical findings are recognized prenatally or in the first months of life and followed by death within the first two years of age. Among our 81 Gaucher patients, we identified 4 (4,9%) type II patients in our metabolic centre. This rate is significantly higher than the rate reported in the literature (Gaucher patients with three novel mutations and one perinatal lethal form with generalized ichthyosis which is a very rare disorder. Additionally, we would like to highlight the phenotypic heterogeneity not only between the subtypes, also even in the same type.

  10. Event-specific qualitative and quantitative detection of five genetically modified rice events using a single standard reference molecule.

    Science.gov (United States)

    Kim, Jae-Hwan; Park, Saet-Byul; Roh, Hyo-Jeong; Shin, Min-Ki; Moon, Gui-Im; Hong, Jin-Hwan; Kim, Hae-Yeong

    2017-07-01

    One novel standard reference plasmid, namely pUC-RICE5, was constructed as a positive control and calibrator for event-specific qualitative and quantitative detection of genetically modified (GM) rice (Bt63, Kemingdao1, Kefeng6, Kefeng8, and LLRice62). pUC-RICE5 contained fragments of a rice-specific endogenous reference gene (sucrose phosphate synthase) as well as the five GM rice events. An existing qualitative PCR assay approach was modified using pUC-RICE5 to create a quantitative method with limits of detection correlating to approximately 1-10 copies of rice haploid genomes. In this quantitative PCR assay, the square regression coefficients ranged from 0.993 to 1.000. The standard deviation and relative standard deviation values for repeatability ranged from 0.02 to 0.22 and 0.10% to 0.67%, respectively. The Ministry of Food and Drug Safety (Korea) validated the method and the results suggest it could be used routinely to identify five GM rice events. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Novel inborn error of folate metabolism: identification by exome capture and sequencing of mutations in the MTHFD1 gene in a single proband.

    Science.gov (United States)

    Watkins, David; Schwartzentruber, Jeremy A; Ganesh, Jaya; Orange, Jordan S; Kaplan, Bernard S; Nunez, Laura Dempsey; Majewski, Jacek; Rosenblatt, David S

    2011-09-01

    An infant was investigated because of megaloblastic anaemia, atypical hemolytic uraemic syndrome, severe combined immune deficiency, elevated blood levels of homocysteine and methylmalonic acid, and a selective decreased synthesis of methylcobalamin in cultured fibroblasts. Exome sequencing was performed on patient genomic DNA. Two mutations were identified in the MTHFD1 gene, which encodes a protein that catalyses three reactions involved in cellular folate metabolism. This protein is essential for the generation of formyltetrahydrofolate and methylenetetrahydrofolate and important for nucleotide and homocysteine metabolism. One mutation (c.727+1G>A) affects the splice acceptor site of intron 8. The second mutation, c.517C>T (p.R173C), changes a critical arginine residue in the NADP-binding site of the protein. Mutations affecting this arginine have previously been shown to affect enzyme activity. Both parents carry a single mutation and an unaffected sibling carries neither mutation. The combination of two mutations in the MTHFRD1 gene, predicted to have severe consequences, in the patient and their absence in the unaffected sibling, supports causality. This patient represents the first case of an inborn error of folate metabolism affecting the trifunctional MTHFD1 protein. This report reinforces the power of exome capture and sequencing for the discovery of novel genes, even when only a single proband is available for study.

  12. Single mutation confers vanadate resistance to the plasma membrane H+-ATPase from the yeast Schizosaccharomyces pombe

    International Nuclear Information System (INIS)

    Ulaszewski, S.; Van Herck, J.C.; Dufour, J.P.; Kulpa, J.; Nieuwenhuis, B.; Goffeau, A.

    1987-01-01

    A single-gene nuclear mutant has been selected from the yeast Schizosaccharomyces pombe for growth resistance to Dio-9, a plasma membrane H+-ATPase inhibitor. From this mutant, called pma1, an ATPase activity has been purified. It contains a Mr = 100,000 major polypeptide which is phosphorylated by [gamma- 32 P] ATP. Proton pumping is not impaired since the isolated mutant ATPase is able, in reconstituted proteoliposomes, to quench the fluorescence of the delta pH probe 9-amino-6-chloro-2-methoxy acridine. The isolated mutant ATPase is sensitive to Dio-9 as well as to seven other plasma membrane H+-ATPase inhibitors. The mutant H+-ATPase activity tested in vitro is, however, insensitive to vanadate. Its Km for MgATP is modified and its ATPase specific activity is decreased. The pma1 mutation decreases the rate of extracellular acidification induced by glucose when cells are incubated at pH 4.5 under nongrowing conditions. During growth, the intracellular mutant pH is more acid than the wild type one. The derepression by ammonia starvation of methionine transport is decreased in the mutant. The growth rate of pma1 mutants is reduced in minimal medium compared to rich medium, especially when combined to an auxotrophic mutation. It is concluded that the H+-ATPase activity from yeast plasma membranes controls the intracellular pH as well as the derepression of amino acid, purine, and pyrimidine uptakes. The pma1 mutation modifies several transport properties of the cells including those responsible for the uptake of Dio-9 and other inhibitors

  13. Investigation of the Semicoa SCF9550 and the International Rectifier IRHM57260SE for Single-Event Gate Rapture and Single-Event Burnout : NASA Electronic Parts and Packaging (NEPP) Program Office of Safety and Mission Assurance

    Science.gov (United States)

    Scheick, Leif

    2011-01-01

    Single-event-effect test results for hi-rel total-dose-hardened power MOSFETs are presented in this report. TheSCF9550 from Semicoa and the IRHM57260SE from International Rectifier were tested to NASA test condition/standards and requirements.The IRHM57260SE performed much better when compared to previous testing. These initial results confirm that parts from the Temecula line are marginally comparable to the El Segundo line. The SCF9550 from Semicoa was also tested and represents the initial parts offering from this vendor. Both parts experienced single-event gate rupture (SEGR) and single-event burnout (SEB). All of the SEGR was from gate to drain.

  14. Single-event multilevel surgery for children with cerebral palsy: a systematic review.

    Science.gov (United States)

    McGinley, Jennifer L; Dobson, Fiona; Ganeshalingam, Rekha; Shore, Benjamin J; Rutz, Erich; Graham, H Kerr

    2012-02-01

    To conduct a systematic review of single-event multilevel surgery (SEMLS) for children with cerebral palsy, with the aim of evaluating the quality of the evidence and developing recommendations for future research. The systematic review was conducted using standard search and extraction methods in Medline, EMBASE, CINAHL, and Cochrane electronic databases. For the purposes of this review, SEMLS was defined as two or more soft-tissue or bony surgical procedures at two or more anatomical levels during one operative procedure, requiring only one hospital admission and one period of rehabilitation. Studies were included if: (1) the primary focus was to examine the effect of SEMLS in children with cerebral palsy; (2) the results focused on multiple anatomic levels and reported findings of one or more World Health Organization International Classification of Functioning, Disability and Health (ICF) domains. Studies that focused on a single intervention or level, or on the utility of a specific outcome measure were excluded. Study quality was appraised with the Methodological Index for Non-Randomized Studies (MINORS) and the Oxford Centre for Evidence-Based Medicine scale. The review also examined the reporting of surgery, adverse events, and rehabilitation. Thirty-one studies fulfilled the criteria for inclusion, over the period 1985 to October 2010. The MINORS score for these studies varied from 4 to 19, with marked variation in the quality of reporting. Study quality has improved over recent years. Valid measures of gait and function have been introduced and several of the most recent studies have addressed multiple dimensions of the ICF. A statistical synthesis of the outcome data was not conducted, although a trend towards favourable outcomes in gait was evident. Caution is advised with interpretation owing to the variable study quality. Uncontrolled studies may have resulted in an overestimation of treatment efficacy. The design and reporting of studies of SEMLS are

  15. Phenylketonuria in The Netherlands : 93% of the mutations are detected by single-strand conformation analysis

    NARCIS (Netherlands)

    vanderSijsBos, CJM; Diepstraten, CM; Juyn, JA; Plaisier, M; Giltay, JC; vanSpronsen, FJ; Smit, GPA; Berger, R; Smeitink, JAM; PollThe, BT; vanAmstel, JKP

    1996-01-01

    Single-strand conformational analysis was used to screen for genetic defects in all thirteen exons of the phenylalanine hydroxylase gene (PAH) in phenylketonuria and hyperphenylalaninemia patients in the Netherlands. Exons that showed a bandshift were sequenced directly, In this way, we were able to

  16. Dedicator of cytokinesis 8 mutation related combined immune deficiency: A single centre experience from India

    Directory of Open Access Journals (Sweden)

    Dhwanee Thakkar

    2017-10-01

    Full Text Available The Dedicator of cytokinesis 8 (DOCK8 related combined immune deficiency is a recently discovered entity which differs from the classic STAT3 associated autosomal dominant hyper-IgE syndrome with respect to the genetic origin and the clinical manifestations. It is characterised by increased risk of autoimmunity, malignancy and neurological complications in addition to increased risk of recurrent cutaneous, sinopulmonary and gastrointestinal infections. We report a series 11 children from three families suffering from DOCK8 related combined immunodeficiency. Out of 11 children only 5 were alive at diagnosis and rest 6 were siblings who had died of similar complaints. Among the 5 children only one underwent allogeneic haploidentical stem cell transplant (SCT from his mother but died before engraftment due to infection. Other 4 are alive without SCT but have multiple co-morbidities. A constellation of cutaneous lesions, recurrent sinopulmonary & gastro intestinal infections and allergic manifestations in a child who may have a similar family history should arouse a suspicion of combined immunodeficiency associated with DOCK8 mutation. Early diagnosis in such children can expedite the appropriate management with SCT. Keywords: Combined immunodeficiency, DOCK8, Children

  17. A single amino acid mutation in SNAP-25 induces anxiety-related behavior in mouse.

    Directory of Open Access Journals (Sweden)

    Masakazu Kataoka

    Full Text Available Synaptosomal-associated protein of 25 kDa (SNAP-25 is a presynaptic protein essential for neurotransmitter release. Previously, we demonstrate that protein kinase C (PKC phosphorylates Ser(187 of SNAP-25, and enhances neurotransmitter release by recruiting secretory vesicles near to the plasma membrane. As PKC is abundant in the brain and SNAP-25 is essential for synaptic transmission, SNAP-25 phosphorylation is likely to play a crucial role in the central nervous system. We therefore generated a mutant mouse, substituting Ser(187 of SNAP-25 with Ala using "knock-in" technology. The most striking effect of the mutation was observed in their behavior. The homozygous mutant mice froze readily in response to environmental change, and showed strong anxiety-related behavior in general activity and light and dark preference tests. In addition, the mutant mice sometimes exhibited spontaneously occurring convulsive seizures. Microdialysis measurements revealed that serotonin and dopamine release were markedly reduced in amygdala. These results clearly indicate that PKC-dependent SNAP-25 phosphorylation plays a critical role in the regulation of emotional behavior as well as the suppression of epileptic seizures, and the lack of enhancement of monoamine release is one of the possible mechanisms underlying these defects.

  18. Single Event Resolution of Plant Plasma Membrane Protein Endocytosis by TIRF Microscopy.

    Science.gov (United States)

    Johnson, Alexander; Vert, Grégory

    2017-01-01

    Endocytosis is a key process in the internalization of extracellular materials and plasma membrane proteins, such as receptors and transporters, thereby controlling many aspects of cell signaling and cellular homeostasis. Endocytosis in plants has an essential role not only for basic cellular functions but also for growth and development, nutrient delivery, toxin avoidance, and pathogen defense. The precise mechanisms of endocytosis in plants remain quite elusive. The lack of direct visualization and examination of single events of endocytosis has greatly hampered our ability to precisely monitor the cell surface lifetime and the recruitment profile of proteins driving endocytosis or endocytosed cargos in plants. Here, we discuss the necessity to systematically implement total internal reflection fluorescence microcopy (TIRF) in the Plant Cell Biology community and present reliable protocols for high spatial and temporal imaging of endocytosis in plants using clathrin-mediated endocytosis as a test case, since it represents the major route for internalization of cell-surface proteins in plants. We developed a robust method to directly visualize cell surface proteins using TIRF microscopy combined to a high throughput, automated and unbiased analysis pipeline to determine the temporal recruitment profile of proteins to single sites of endocytosis, using the departure of clathrin as a physiological reference for scission. Using this 'departure assay', we assessed the recruitment of two different AP-2 subunits, alpha and mu, to the sites of endocytosis and found that AP2A1 was recruited in concert with clathrin, while AP2M was not. This validated approach therefore offers a powerful solution to better characterize the plant endocytic machinery and the dynamics of one's favorite cargo protein.

  19. A nonadaptive origin of a beneficial trait: in silico selection for free energy of folding leads to the neutral emergence of mutational robustness in single domain proteins.

    Science.gov (United States)

    Pagan, Rafael F; Massey, Steven E

    2014-02-01

    Proteins are regarded as being robust to the deleterious effects of mutations. Here, the neutral emergence of mutational robustness in a population of single domain proteins is explored using computer simulations. A pairwise contact model was used to calculate the ΔG of folding (ΔG folding) using the three dimensional protein structure of leech eglin C. A random amino acid sequence with low mutational robustness, defined as the average ΔΔG resulting from a point mutation (ΔΔG average), was threaded onto the structure. A population of 1,000 threaded sequences was evolved under selection for stability, using an upper and lower energy threshold. Under these conditions, mutational robustness increased over time in the most common sequence in the population. In contrast, when the wild type sequence was used it did not show an increase in robustness. This implies that the emergence of mutational robustness is sequence specific and that wild type sequences may be close to maximal robustness. In addition, an inverse relationship between ∆∆G average and protein stability is shown, resulting partly from a larger average effect of point mutations in more stable proteins. The emergence of mutational robustness was also observed in the Escherichia coli colE1 Rop and human CD59 proteins, implying that the property may be common in single domain proteins under certain simulation conditions. The results indicate that at least a portion of mutational robustness in small globular proteins might have arisen by a process of neutral emergence, and could be an example of a beneficial trait that has not been directly selected for, termed a "pseudaptation."

  20. JAK2 V617F, MPL, and CALR mutations in essential thrombocythaemia and major thrombotic complications: a single-institute retrospective analysis.

    Science.gov (United States)

    Pósfai, Éva; Marton, Imelda; Király, Péter Attila; Kotosz, Balázs; Kiss-László, Zsuzsanna; Széll, Márta; Borbényi, Zita

    2015-07-01

    Thrombo-haemorrhagic events are the main cause of morbidity and mortality in essential thrombocythemia. The aim of this study was to estimate the incidence of thrombotic events and the impact of the JAK2V617F, MPL (W515L, W515K, W515R, W515A and S505N) and CALR (type-1, type-2) mutations on 101 essential thrombocythaemia patients (72 females and 29 males with a mean age of 61 years) diagnosed in a Southern Hungarian regional academic centre. The incidence of major thrombosis was 13.86 %. Sixty percent of the patients carried the JAK2V617F mutation. The MPL mutations were analysed by sequencing and the W515L was the only one we could identify with an incidence of 3.96 %. Type-2 CALR mutation could be identified in 3 cases among the patients who had JAK2/MPL-unmutated ET. Statistical analyses revealed that the JAK2V617F mutation was associated with significantly increased levels of platelet (p = 0.042), haemoglobin (p = 0.000), red blood cell (p = 0.000) and haematocrit (p = 0.000) and hepatomegaly (p = 0.045) at diagnosis compared to JAK2V617F negative counterparts, however there was no significant association between the JAK2V617F mutation status (relative risk: 1.297, 95 % CI 0.395-4.258; p = 0.668) and subsequent thrombotic complications. The impact of JAK2V617F, MPL W515L and CALR mutations on the clinical findings at the diagnosis of ET was obvious, but their statistically significant role in the prediction of thrombotic events could not be proven in this study. Our results indirectly support the concept that, besides the quantitative and qualitative changes in the platelets, the mechanisms leading to thrombosis are more complex and multifactorial.

  1. Advantages of a single-cycle production assay to study cell culture-adaptive mutations of hepatitis C virus

    DEFF Research Database (Denmark)

    Russell, Rodney S; Meunier, Jean-Christophe; Takikawa, Shingo

    2008-01-01

    mutations that were selected during serial passage in Huh-7.5 cells were studied. Recombinant genomes containing all five mutations produced 3-4 logs more infectious virions than did wild type. Neither a coding mutation in NS5A nor a silent mutation in E2 was adaptive, whereas coding mutations in E2, p7......The JFH1 strain of hepatitis C virus (HCV) is unique among HCV isolates, in that the wild-type virus can traverse the entire replication cycle in cultured cells. However, without adaptive mutations, only low levels of infectious virus are produced. In the present study, the effects of five...

  2. Triggering Mechanism for Neutron Induced Single-Event Burnout in Power Devices

    Science.gov (United States)

    Shoji, Tomoyuki; Nishida, Shuichi; Hamada, Kimimori

    2013-04-01

    Cosmic ray neutrons can trigger catastrophic failures in power devices. It has been reported that parasitic transistor action causes single-event burnout (SEB) in power metal-oxide-semiconductor field-effect transistors (MOSFETs) and insulated gate bipolar transistors (IGBTs). However, power diodes do not have an inherent parasitic transistor. In this paper, we describe the mechanism triggering SEB in power diodes for the first time using transient device simulation. Initially, generated electron-hole pairs created by incident recoil ions generate transient current, which increases the electron density in the vicinity of the n-/n+ boundary. The space charge effect of the carriers leads to an increase in the strength of the electric field at the n-/n+ boundary. Finally, the onset of impact ionization at the n-/n+ boundary can trigger SEB. Furthermore, this failure is closely related to diode secondary breakdown. It was clarified that the impact ionization at the n-/n+ boundary is a key point of the mechanism triggering SEB in power devices.

  3. Simulation study on single event burnout in linear doping buffer layer engineered power VDMOSFET

    Science.gov (United States)

    Yunpeng, Jia; Hongyuan, Su; Rui, Jin; Dongqing, Hu; Yu, Wu

    2016-02-01

    The addition of a buffer layer can improve the device's secondary breakdown voltage, thus, improving the single event burnout (SEB) threshold voltage. In this paper, an N type linear doping buffer layer is proposed. According to quasi-stationary avalanche simulation and heavy ion beam simulation, the results show that an optimized linear doping buffer layer is critical. As SEB is induced by heavy ions impacting, the electric field of an optimized linear doping buffer device is much lower than that with an optimized constant doping buffer layer at a given buffer layer thickness and the same biasing voltages. Secondary breakdown voltage and the parasitic bipolar turn-on current are much higher than those with the optimized constant doping buffer layer. So the linear buffer layer is more advantageous to improving the device's SEB performance. Project supported by the National Natural Science Foundation of China (No. 61176071), the Doctoral Fund of Ministry of Education of China (No. 20111103120016), and the Science and Technology Program of State Grid Corporation of China (No. SGRI-WD-71-13-006).

  4. The application of particle filters in single trial event-related potential estimation

    International Nuclear Information System (INIS)

    Mohseni, Hamid R; Nazarpour, Kianoush; Sanei, Saeid; Wilding, Edward L

    2009-01-01

    In this paper, an approach for the estimation of single trial event-related potentials (ST-ERPs) using particle filters (PFs) is presented. The method is based on recursive Bayesian mean square estimation of ERP wavelet coefficients using their previous estimates as prior information. To enable a performance evaluation of the approach in the Gaussian and non-Gaussian distributed noise conditions, we added Gaussian white noise (GWN) and real electroencephalogram (EEG) signals recorded during rest to the simulated ERPs. The results were compared to that of the Kalman filtering (KF) approach demonstrating the robustness of the PF over the KF to the added GWN noise. The proposed method also outperforms the KF when the assumption about the Gaussianity of the noise is violated. We also applied this technique to real EEG potentials recorded in an odd-ball paradigm and investigated the correlation between the amplitude and the latency of the estimated ERP components. Unlike the KF method, for the PF there was a statistically significant negative correlation between amplitude and latency of the estimated ERPs, matching previous neurophysiological findings

  5. Single-event burnout hardening of planar power MOSFET with partially widened trench source

    Science.gov (United States)

    Lu, Jiang; Liu, Hainan; Cai, Xiaowu; Luo, Jiajun; Li, Bo; Li, Binhong; Wang, Lixin; Han, Zhengsheng

    2018-03-01

    We present a single-event burnout (SEB) hardened planar power MOSFET with partially widened trench sources by three-dimensional (3D) numerical simulation. The advantage of the proposed structure is that the work of the parasitic bipolar transistor inherited in the power MOSFET is suppressed effectively due to the elimination of the most sensitive region (P-well region below the N+ source). The simulation result shows that the proposed structure can enhance the SEB survivability significantly. The critical value of linear energy transfer (LET), which indicates the maximum deposited energy on the device without SEB behavior, increases from 0.06 to 0.7 pC/μm. The SEB threshold voltage increases to 120 V, which is 80% of the rated breakdown voltage. Meanwhile, the main parameter characteristics of the proposed structure remain similar with those of the conventional planar structure. Therefore, this structure offers a potential optimization path to planar power MOSFET with high SEB survivability for space and atmospheric applications. Project supported by the National Natural Science Foundation of China (Nos. 61404161, 61404068, 61404169).

  6. 3D Thermal and Mechanical Analysis of a Single Event Burnout

    Science.gov (United States)

    Peretti, Gabriela; Demarco, Gustavo; Romero, Eduardo; Tais, Carlos

    2015-08-01

    This paper presents a study related to thermal and mechanical behavior of power DMOS transistors during a Single Event Burnout (SEB) process. We use a cylindrical heat generation region for emulating the thermal and mechanical phenomena related to the SEB. In this way, it is avoided the complexity of the mathematical treatment of the ion-device interaction. This work considers locating the heat generation region in positions that are more realistic than the ones used in previous work. For performing the study, we formulate and validate a new 3D model for the transistor that maintains the computational cost at reasonable level. The resulting mathematical models are solved by means of the Finite Element Method. The simulations results show that the failure dynamics is dominated by the mechanical stress in the metal layer. Additionally, the time to failure depends on the heat source position, for a given power and dimension of the generation region. The results suggest that 3D modeling should be considered for a detailed study of thermal and mechanical effects induced by SEBs.

  7. Incorporation of aurochs into a cattle herd in Neolithic Europe: single event or breeding?

    Science.gov (United States)

    Schibler, Jörg; Elsner, Julia; Schlumbaum, Angela

    2014-07-01

    Domestication is an ongoing process continuously changing the lives of animals and humans and the environment. For the majority of European cattle (Bos taurus) genetic and archaeozoological evidence support initial domestication ca. 11'000 BP in the Near East from few founder aurochs (Bos primigenius) belonging to the mitochondrial DNA T macro-haplogroup. Gene flow between wild European aurochs of P haplogroup and domestic cattle of T haplogroup, coexisting over thousands of years, appears to have been sporadic. We report archaeozoological and ancient DNA evidence for the incorporation of wild stock into a domestic cattle herd from a Neolithic lake-dwelling in Switzerland. A complete metacarpus of a small and compact adult bovid is morphologically and genetically a female. With withers height of ca. 112 cm, it is comparable in size with small domestic cattle from contemporaneous sites in the area. The bone is directly dated to 3360-3090 cal BC and associated to the Horgen culture, a period of the secondary products revolution. The cow possessed a novel mtDNA P haplotype variant of the European aurochs. We argue this is either a single event or, based on osteological characteristics of the Horgen cattle, a rare instance of intentional breeding with female aurochs.

  8. Radiation induced Single Event Effects in the ATLAS MDT-ASD front-end chip

    CERN Document Server

    Posch, C

    2002-01-01

    Single Event Effect (SEE) tests of the MDT-ASD, the ATLAS MDT front-end chip have been performed at the Harvard Cyclotron Lab. The MDT-ASD is an 8-channel drift tube read-out ASIC fabricated in a commercial 0.5um CMOS process (AMOS14TB). The chip contains a 53 bit register which holds the setup information and an associated shift register of the same length plus some additional control logic. 10 test devices were exposed to a 160 MeV proton beam with a fluence of 1.05E9 p.cm-2.s-1 up to >4.4E p.cm-2 per device. After a total fluence of 4.46E13 p.cm-2, 7 soft SEEs (non-permanent bit flips in the registers) and 0 hard/destructive SEE (e.g. latch-ups, SEL) had occurred. The simulated fluence for 10 years of LHC operation at nominal luminosity for worst case location MDT components is 2.67E11 h.cm-2. The rate of SEUs in the ASD setup register for all of ATLAS, derived from these numbers, is 2.4 per day. It is foreseen to update the active registers of the on-detector electronics at regular intervals. Depending on...

  9. Medium-energy heavy-ion single-event-burnout imaging of power MOSFETs

    Energy Technology Data Exchange (ETDEWEB)

    Musseau, O.; Torres, A.; Campbell, A.B.; Knudson, A.R.; Buchner, S.; Fischer, B.; Schloegl, M.; Briand, P.

    1999-12-01

    The authors present the first experimental determination of the SEB sensitive area in a power MOSFET irradiated with a high-LET heavy-ion microbeam. They used a spectroscopy technique to perform coincident measurements of the charge collected in both source and drain junctions together, with a non-destructive technique (current limitation). The resulting charge collection images are related to the physical structure of the individual cells. These experimental data reveal the complex 3-dimensional behavior of a real structure, which can not easily be simulated using available tools. As the drain voltage is increased, the onset of burnout is reached, characterized by a sudden change in the charge collection image. Hot spots are observed where the collected charge reaches its maximum value. Those spots, due to burnout triggering events, correspond to areas where the silicon is degraded through thermal effects along a single ion track. This direct observation of SEB sensitive areas as applications for, either device hardening, by modifying doping profiles or layout of the cells, or for code calibration and device simulation.

  10. Line-edge roughness induced single event transient variation in SOI FinFETs

    International Nuclear Information System (INIS)

    Wu Weikang; An Xia; Jiang Xiaobo; Chen Yehua; Liu Jingjing; Zhang Xing; Huang Ru

    2015-01-01

    The impact of process induced variation on the response of SOI FinFET to heavy ion irradiation is studied through 3-D TCAD simulation for the first time. When FinFET biased at OFF state configuration (V gs = 0, V ds = V dd ) is struck by a heavy ion, the drain collects ionizing charges under the electric field and a current pulse (single event transient, SET) is consequently formed. The results reveal that with the presence of line-edge roughness (LER), which is one of the major variation sources in nano-scale FinFETs, the device-to-device variation in terms of SET is observed. In this study, three types of LER are considered: type A has symmetric fin edges, type B has irrelevant fin edges and type C has parallel fin edges. The results show that type A devices have the largest SET variation while type C devices have the smallest variation. Further, the impact of the two main LER parameters, correlation length and root mean square amplitude, on SET variation is discussed as well. The results indicate that variation may be a concern in radiation effects with the down scaling of feature size. (paper)

  11. Single event upset susceptibilities of latchup immune CMOS process programmable gate arrays

    Science.gov (United States)

    Koga, R.; Crain, W. R.; Crawford, K. B.; Hansel, S. J.; Lau, D. D.; Tsubota, T. K.

    Single event upsets (SEU) and latchup susceptibilities of complementary metal oxide semiconductor programmable gate arrays (CMOS PPGA's) were measured at the Lawrence Berkeley Laboratory 88-in. cyclotron facility with Xe (603 MeV), Cu (290 MeV), and Ar (180 MeV) ion beams. The PPGA devices tested were those which may be used in space. Most of the SEU measurements were taken with a newly constructed tester called the Bus Access Storage and Comparison System (BASACS) operating via a Macintosh II computer. When BASACS finds that an output does not match a prerecorded pattern, the state of all outputs, position in the test cycle, and other necessary information is transmitted and stored in the Macintosh. The upset rate was kept between 1 and 3 per second. After a sufficient number of errors are stored, the test is stopped and the total fluence of particles and total errors are recorded. The device power supply current was closely monitored to check for occurrence of latchup. Results of the tests are presented, indicating that some of the PPGA's are good candidates for selected space applications.

  12. Position sensitive regions in a generic radiation sensor based on single event upsets in dynamic RAMs

    International Nuclear Information System (INIS)

    Darambara, D.G.; Spyrou, N.M.

    1997-01-01

    Modern integrated circuits are highly complex systems and, as such, are susceptible to occasional failures. Semiconductor memory devices, particularly dynamic random access memories (dRAMs), are subject to random, transient single event upsets (SEUs) created by energetic ionizing radiation. These radiation-induced soft failures in the stored data of silicon based memory chips provide the foundation for a new, highly efficient, low cost generic radiation sensor. The susceptibility and the detection efficiency of a given dRAM device to SEUs is a complicated function of the circuit design and geometry, the operating conditions and the physics of the charge collection mechanisms involved. Typically, soft error rates measure the cumulative response of all sensitive regions of the memory by broad area chip exposure in ionizing radiation environments. However, this study shows that many regions of a dynamic memory are competing charge collection centres having different upset thresholds. The contribution to soft fails from discrete regions or individual circuit elements of the memory device is unambiguously separated. Hence the use of the dRAM as a position sensitive radiation detector, with high spatial resolution, is assessed and demonstrated. (orig.)

  13. Impact of temperature on single event upset measurement by heavy ions in SRAM devices

    International Nuclear Information System (INIS)

    Liu Tianqi; Geng Chao; Zhang Zhangang; Gu Song; Tong Teng; Xi Kai; Hou Mingdong; Liu Jie; Zhao Fazhan; Liu Gang; Han Zhengsheng

    2014-01-01

    The temperature dependence of single event upset (SEU) measurement both in commercial bulk and silicon on insulator (SOI) static random access memories (SRAMs) has been investigated by experiment in the Heavy Ion Research Facility in Lanzhou (HIRFL). For commercial bulk SRAM, the SEU cross section measured by 12 C ions is very sensitive to the temperature. The temperature test of SEU in SOI SRAM was conducted by 209 Bi and 12 C ions, respectively, and the SEU cross sections display a remarkable growth with the elevated temperature for 12 C ions but keep constant for 209 Bi ions. The impact of temperature on SEU measurement was analyzed by Monte Carlo simulation. It is revealed that the SEU cross section is significantly affected by the temperature around the threshold linear energy transfer of SEU occurrence. As the SEU occurrence approaches saturation, the SEU cross section gradually exhibits less temperature dependency. Based on this result, the experimental data measured in HIRFL was analyzed, and then a reasonable method of predicting the on-orbit SEU rate was proposed. (semiconductor devices)

  14. Integrated genetic and epigenetic analysis of bladder cancer reveals an additive diagnostic value of FGFR3 mutations and hypermethylation events

    DEFF Research Database (Denmark)

    Serizawa, Reza R; Ralfkiaer, Ulrik; Steven, Kenneth

    2011-01-01

    The bladder cancer genome harbors numerous oncogenic mutations and aberrantly methylated gene promoters. The aim of our study was to generate a profile of these alterations and investigate their use as biomarkers in urine sediments for noninvasive detection of bladder cancer. We systematically sc...... noninvasive, DNA-based detection of bladder cancer....

  15. DNA detection and single nucleotide mutation identification using SERS for molecular diagnostics and global health

    Science.gov (United States)

    Ngo, Hoan T.; Gandra, Naveen; Fales, Andrew M.; Taylor, Steve M.; Vo-Dinh, Tuan

    2017-02-01

    Nucleic acid-based molecular diagnostics at the point-of-care (POC) and in resource-limited settings is still a challenge. We present a sensitive yet simple DNA detection method with single nucleotide polymorphism (SNP) identification capability. The detection scheme involves sandwich hybridization of magnetic beads conjugated with capture probes, target sequences, and ultrabright surface-enhanced Raman Scattering (SERS) nanorattles conjugated with reporter probes. Upon hybridization, the sandwich probes are concentrated at the detection focus controlled by a magnetic system for SERS measurements. The ultrabright SERS nanorattles, consisting of a core and a shell with resonance Raman reporters loaded in the gap space between the core and the shell, serve as SERS tags for ultrasensitive signal detection. Specific DNA sequences of the malaria parasite Plasmodium falciparum and dengue virus 1 (DENV1) were used as the model marker system. Detection limit of approximately 100 attomoles was achieved. Single nucleotide polymorphism (SNP) discrimination of wild type malaria DNA and mutant malaria DNA, which confers resistance to artemisinin drugs, was also demonstrated. The results demonstrate the molecular diagnostic potential of the nanorattle-based method to both detect and genotype infectious pathogens. The method's simplicity makes it a suitable candidate for molecular diagnosis at the POC and in resource-limited settings.

  16. A single splice site mutation in human-specific ARHGAP11B causes basal progenitor amplification

    Science.gov (United States)

    Florio, Marta; Namba, Takashi; Pääbo, Svante; Hiller, Michael; Huttner, Wieland B.

    2016-01-01

    The gene ARHGAP11B promotes basal progenitor amplification and is implicated in neocortex expansion. It arose on the human evolutionary lineage by partial duplication of ARHGAP11A, which encodes a Rho guanosine triphosphatase–activating protein (RhoGAP). However, a lack of 55 nucleotides in ARHGAP11B mRNA leads to loss of RhoGAP activity by GAP domain truncation and addition of a human-specific carboxy-terminal amino acid sequence. We show that these 55 nucleotides are deleted by mRNA splicing due to a single C→G substitution that creates a novel splice donor site. We reconstructed an ancestral ARHGAP11B complementary DNA without this substitution. Ancestral ARHGAP11B exhibits RhoGAP activity but has no ability to increase basal progenitors during neocortex development. Hence, a single nucleotide substitution underlies the specific properties of ARHGAP11B that likely contributed to the evolutionary expansion of the human neocortex. PMID:27957544

  17. Single-Event Latchup Testing of the Micrel MIC4424 Dual Power MOSFET Driver

    Science.gov (United States)

    Pellish, J. A.; Boutte, A.; Kim, H.; Phan, A.; Topper, A.

    2016-01-01

    We conducted 47 exposures of four different MIC4424 devices and did not observe any SEL or high-current events. This included worst-case conditions with a LET of 81 MeV-sq cm/mg, applied voltage of 18.5 V, a case temperature greater than 120 C, and a final fluence of 1x10(exp 7)/sq cm. We also monitored both the outputs for the presence of SETs. While the period of the 1 MHz square wave was slightly altered in some cases, no pulses were added or deleted. 1. Purpose: The purpose of this testing is to characterize the BiCMOS/DMOS Micrel MIC4424 dual, non-inverting MOSFET driver for single-event latchup (SEL) susceptibility. These data will be used for flight lot evaluation purposes. 2. Devices Tested: The MIC4423/4424/4425 family are highly reliable BiCMOS/DMOS buffer/driver MOSFET drivers. They are higher output current versions of the MIC4426/4427/4428. They can survive up to 5V of noise spiking, of either polarity, on the ground pin. They can accept, without either damage or logic upset, up to half an amp of reverse current (either polarity) forced back into their outputs. Primarily intended for driving power MOSFETs, the MIC4423/4424/4425 drivers are suitable for driving other loads (capacitive, resistive, or inductive) which require low-impedance, high peak currents, and fast switching times. Heavily loaded clock lines, coaxial cables, or piezoelectric transducers are some examples. The only known limitation on loading is that total power dissipated in the driver must be kept within the maximum power dissipation limits of the package. Five (5) parts were provided for SEL testing. We prepared four parts for irradiation and reserved one piece as an un-irradiated control. More information about the devices can be found in Table 1. The parts were prepared for testing by removing the lid from the CDIP package to expose the target die. The parts were then soldered to small copper circuit adapter boards for easy handling. These parts are fabricated in a bulk Bi

  18. TALEN-mediated single-base-pair editing identification of an intergenic mutation upstream of BUB1B as causative of PCS (MVA) syndrome

    Science.gov (United States)

    Ochiai, Hiroshi; Miyamoto, Tatsuo; Kanai, Akinori; Hosoba, Kosuke; Sakuma, Tetsushi; Kudo, Yoshiki; Asami, Keiko; Ogawa, Atsushi; Watanabe, Akihiro; Kajii, Tadashi; Yamamoto, Takashi; Matsuura, Shinya

    2014-01-01

    Cancer-prone syndrome of premature chromatid separation with mosaic variegated aneuploidy [PCS (MVA) syndrome] is a rare autosomal recessive disorder characterized by constitutional aneuploidy and a high risk of childhood cancer. We previously reported monoallelic mutations in the BUB1B gene (encoding BUBR1) in seven Japanese families with the syndrome. No second mutation was found in the opposite allele of any of the families studied, although a conserved BUB1B haplotype and a decreased transcript were identified. To clarify the molecular pathology of the second allele, we extended our mutational search to a candidate region surrounding BUB1B. A unique single nucleotide substitution, G > A at ss802470619, was identified in an intergenic region 44 kb upstream of a BUB1B transcription start site, which cosegregated with the disorder. To examine whether this is the causal mutation, we designed a transcription activator-like effector nuclease–mediated two-step single-base pair editing strategy and biallelically introduced this substitution into cultured human cells. The cell clones showed reduced BUB1B transcripts, increased PCS frequency, and MVA, which are the hallmarks of the syndrome. We also encountered a case of a Japanese infant with PCS (MVA) syndrome carrying a homozygous single nucleotide substitution at ss802470619. These results suggested that the nucleotide substitution identified was the causal mutation of PCS (MVA) syndrome. PMID:24344301

  19. The chlorophyll-deficient golden leaf mutation in cucumber is due to a single nucleotide substitution in CsChlI for magnesium chelatase I subunit.

    Science.gov (United States)

    Gao, Meiling; Hu, Liangliang; Li, Yuhong; Weng, Yiqun

    2016-10-01

    The cucumber chlorophyll-deficient golden leaf mutation is due to a single nucleotide substitution in the CsChlI gene for magnesium chelatase I subunit which plays important roles in the chlorophyll biosynthesis pathway. The Mg-chelatase catalyzes the insertion of Mg(2+) into the protoporphyrin IX in the chlorophyll biosynthesis pathway, which is a protein complex encompassing three subunits CHLI, CHLD, and CHLH. Chlorophyll-deficient mutations in genes encoding the three subunits have played important roles in understanding the structure, function and regulation of this important enzyme. In an EMS mutagenesis population, we identified a chlorophyll-deficient mutant C528 with golden leaf color throughout its development which was viable and able to set fruits and seeds. Segregation analysis in multiple populations indicated that this leaf color mutation was recessively inherited and the green color showed complete dominance over golden color. Map-based cloning identified CsChlI as the candidate gene for this mutation which encoded the CHLI subunit of cucumber Mg-chelatase. The 1757-bp CsChlI gene had three exons and a single nucleotide change (G to A) in its third exon resulted in an amino acid substitution (G269R) and the golden leaf color in C528. This mutation occurred in the highly conserved nucleotide-binding domain of the CHLI protein in which chlorophyll-deficient mutations have been frequently identified. The mutant phenotype, CsChlI expression pattern and the mutated residue in the CHLI protein suggested the mutant allele in C528 is unique among mutations identified so far in different species. This golden leaf mutant not only has its potential in cucumber breeding, but also provides a useful tool in understanding the CHLI function and its regulation in the chlorophyll biosynthesis pathway as well as chloroplast development.

  20. A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors

    Energy Technology Data Exchange (ETDEWEB)

    de Vries, Robert P.; Tzarum, Netanel; Peng, Wenjie; Thompson, Andrew J.; Ambepitiya Wickramasinghe, Iresha N.; de la Pena, Alba T. Torrents; van Breemen, Marielle J.; Bouwman, Kim M.; Zhu, Xueyong; McBride, Ryan; Yu, Wenli; Sanders, Rogier W.; Verheije, Monique H.; Wilson, Ian A.; Paulson, James C.

    2017-07-10

    In June 2013, the first case of human infection with an avian H6N1 virus was reported in a Taiwanese woman. Although this was a single non-fatal case, the virus continues to circulate in Taiwanese poultry. As with any emerging avian virus that infects humans, there is concern that acquisition of human-type receptor specificity could enable transmission in the human population. Despite mutations in the receptor-binding pocket of the human H6N1 isolate, it has retained avian-type (NeuAcα2-3Gal) receptor specificity. However, we show here that a single nucleotide substitution, resulting in a change from Gly to Asp at position 225 (G225D), completely switches specificity to human-type (NeuAcα2-6Gal) receptors. Significantly, G225D H6 loses binding to chicken trachea epithelium and is now able to bind to human tracheal tissue. Structural analysis reveals that Asp225 directly interacts with the penultimate Gal of the human-type receptor, stabilizing human receptor binding.

  1. CHASM and SNVBox: toolkit for detecting biologically important single nucleotide mutations in cancer.

    Science.gov (United States)

    Wong, Wing Chung; Kim, Dewey; Carter, Hannah; Diekhans, Mark; Ryan, Michael C; Karchin, Rachel

    2011-08-01

    Thousands of cancer exomes are currently being sequenced, yielding millions of non-synonymous single nucleotide variants (SNVs) of possible relevance to disease etiology. Here, we provide a software toolkit to prioritize SNVs based on their predicted contribution to tumorigenesis. It includes a database of precomputed, predictive features covering all positions in the annotated human exome and can be used either stand-alone or as part of a larger variant discovery pipeline. MySQL database, source code and binaries freely available for academic/government use at http://wiki.chasmsoftware.org, Source in Python and C++. Requires 32 or 64-bit Linux system (tested on Fedora Core 8,10,11 and Ubuntu 10), 2.5*≤ Python 5.0, 60 GB available hard disk space (50 MB for software and data files, 40 GB for MySQL database dump when uncompressed), 2 GB of RAM.

  2. Increased Cardiovascular Events and Subclinical Atherosclerosis in Rheumatoid Arthritis Patients: 1 Year Prospective Single Centre Study.

    Directory of Open Access Journals (Sweden)

    Piero Ruscitti

    Full Text Available Several studies showed the close relationship between Rheumatoid Arthritis (RA and cerebro-cardiovascular events (CVEs and subclinical atherosclerosis. In this study, we investigated the occurrence of CVEs and subclinical atherosclerosis during the course of RA and we evaluated the possible role of both traditional cardiovascular (CV and disease related risk factors to predict the occurrence of new CVEs and the onset of subclinical atherosclerosis.We designed a single centre, bias-adjusted, prospective, observational study to investigate, in a homogeneous subset of RA patients, the occurrence of new onset of CVEs and subclinical atherosclerosis. Statistical analyses were performed to evaluate the role of traditional CV and disease-related risk factors to predict the occurrence of new CVEs and subclinical atherosclerosis.We enrolled 347 RA patients prospectively followed for 12 months. An increased percentage of patients experienced CVEs, developed subclinical atherosclerosis and was affected by systemic arterial hypertension (SAH, type 2 diabetes mellitus and metabolic syndrome (MS, at the end of follow up. Our analysis showed that the insurgence of both SAH and MS, during the follow up, the older age, the CVE familiarity and the lack of clinical response, were associated with a significantly increased risk to experience CVEs and to develop subclinical atherosclerosis.Our study quantifies the increased expected risk for CVEs in a cohort of RA patients prospectively followed for 1 year. The occurrence of both new CVEs and subclinical atherosclerosis in RA patients may be explained by inflammatory burden as well as traditional CV risk factors.

  3. Single event upset mitigation techniques for FPGAs utilized in nuclear power plant digital instrumentation and control

    International Nuclear Information System (INIS)

    Wang Xin; Holbert, Keith E.; Clark, Lawrence T.

    2011-01-01

    Highlights: → Triple modular redundancy (TMR) implementation is the best solution for digital I and C. → Maximal probability of two simultaneous errors with TMR maximum partition is 4.44%. → Dual modular redundancy minimum logic partitioning design is an additional option. - Abstract: Field programmable gate arrays (FPGAs) are integrated circuits being increasingly used for digital instrumentation and control (I and C) in nuclear power plants (NPPs) because of low cost, re-configurability and low design turn-around time. However, to ensure reliability, proper design techniques must be employed since the memory and logic in FPGAs are susceptible to single event upsets (SEUs). Triple modular redundancy (TMR) has become a common SEU mitigation design technique because of its straightforward implementation and reliable results. Partitioned TMR approaches are introduced in this paper, and formulae derived indicate that the maximum probability of two simultaneous errors [P E ] max is inversely proportional to the number of logic partitions in a TMR design, when each redundant logic block in every logic partition has the same number of sensitive nodes. However, the maximum logic partitioning design cannot completely eliminate the possibility of two simultaneous upsets. For the example test circuit it is found that [P E ] max is reduced dramatically from 66.67% for minimum logic partitioning to 4.44% for maximum logic partitioning. Because TMR introduces significant overhead due to its full hardware redundancy, a dual modular redundancy approach is also examined for application to less demanding situations. By comparative analysis this study reaches the conclusion that the maximum logic partitioning TMR implementation is the best solution for digital I and C applications in NPPs where obtaining robustness is of the highest importance, despite its higher area overhead.

  4. Swift heavy ion induced single event upsets in high density UV-EPROM's

    Energy Technology Data Exchange (ETDEWEB)

    Dahiwale, S.S. [Department of Physics, University of Pune, Pune 7 (India); Shinde, N.S. [Department of Chemical Engineering, Mie University (Japan); Kanjilal, D. [Inter University Accelerator Center, New Delhi (India); Bhoraskar, V.N. [Department of Physics, University of Pune, Pune 7 (India); Dhole, S.D. [Department of Physics, University of Pune, Pune 7 (India)], E-mail: sanjay@physics.unipune.ernet.in

    2008-04-15

    A few high density UV-EPROM's (32Kb x 8) were irradiated with 5.41 MeV energy {alpha}-particles with fluences from 10{sup 4} to 10{sup 8} alphas/cm{sup 2} and 100 MeV nickel, iodine and silver ions for low fluences between 5 x 10{sup 7} and 10{sup 8} ions/cm{sup 2}. The energy and ion species was selected on the basis of predicted threshold values of linear energy transfer (LET) in silicon. The program which was stored in the memory found to be changed from 0 to 1 and 1 to 0 state, respectively. On the basis of changed states, the cross-sections ({sigma}) were calculated to investigate the single event effects/upsets. No upset was observed in case of {alpha}-particle since it has very low LET, but the SEU cross-section found to be more in case of Iodine i.e. 2.29 x 10{sup -3} cm{sup 2} than that of nickel, 2.12 x 10{sup -3} cm{sup 2} and silver, 2.26 x 10{sup -3}. This mainly attributes that LET for iodine is more as compared to silver and nickel ions, which deposits large amount of energy near the sensitive node of memory cell in the form of electron-hole pairs required to change the state. These measured SEU cross-section were also compared with theoretically predicted values along with the Weibull distribution fit to the ion induced experimental SEU data. The theoretical predicted SEU cross-section 3.27 x 10{sup -3} cm{sup 2} found to be in good agreement with the measured SEU cross-section.

  5. Development of Single-Event Upset hardened programmable logic devices in deep submicron CMOS

    International Nuclear Information System (INIS)

    Bonacini, S.

    2007-11-01

    The electronics associated to the particle detectors of the Large Hadron Collider (LHC), under construction at CERN, will operate in a very harsh radiation environment. Commercial Off-The-Shelf (COTS) components cannot be used in the vicinity of particle collision due to their poor radiation tolerance. This thesis is a contribution to the effort to cover the need for radiation-tolerant SEU-robust (Single Event Upset) programmable components for application in high energy physics experiments. Two components are under development: a Programmable Logic Device (PLD) and a Field-Programmable Gate Array (FPGA). The PLD is a fuse-based, 10-input, 8-I/O general architecture device in 0.25 μm CMOS technology. The FPGA under development is a 32*32 logic block array, equivalent to ∼ 25 k gates, in 0.13 μm CMOS. The irradiation test results obtained in the CMOS 0.25 μm technology demonstrate good robustness of the circuit up to an LET (Linear Energy Transfer) of 79.6 cm 2 *MeV/mg, which make it suitable for the target environment. The CMOS 0.13 μm circuit has showed robustness to an LET of 37.4 cm 2 *MeV/mg in the static test mode and has increased sensitivity in the dynamic test mode. This work focused also on the research for an SEU-robust register in both the mentioned technologies. The SEU-robust register is employed as a user data flip-flop in the FPGA and PLD designs and as a configuration cell as well in the FPGA design

  6. Accurate prediction of the functional significance of single nucleotide polymorphisms and mutations in the ABCA1 gene.

    Directory of Open Access Journals (Sweden)

    Liam R Brunham

    2005-12-01

    Full Text Available The human genome contains an estimated 100,000 to 300,000 DNA variants that alter an amino acid in an encoded protein. However, our ability to predict which of these variants are functionally significant is limited. We used a bioinformatics approach to define the functional significance of genetic variation in the ABCA1 gene, a cholesterol transporter crucial for the metabolism of high density lipoprotein cholesterol. To predict the functional consequence of each coding single nucleotide polymorphism and mutation in this gene, we calculated a substitution position-specific evolutionary conservation score for each variant, which considers site-specific variation among evolutionarily related proteins. To test the bioinformatics predictions experimentally, we evaluated the biochemical consequence of these sequence variants by examining the ability of cell lines stably transfected with the ABCA1 alleles to elicit cholesterol efflux. Our bioinformatics approach correctly predicted the functional impact of greater than 94% of the naturally occurring variants we assessed. The bioinformatics predictions were significantly correlated with the degree of functional impairment of ABCA1 mutations (r2 = 0.62, p = 0.0008. These results have allowed us to define the impact of genetic variation on ABCA1 function and to suggest that the in silico evolutionary approach we used may be a useful tool in general for predicting the effects of DNA variation on gene function. In addition, our data suggest that considering patterns of positive selection, along with patterns of negative selection such as evolutionary conservation, may improve our ability to predict the functional effects of amino acid variation.

  7. Single Versus Multiple Events Error Potential Detection in a BCI-Controlled Car Game With Continuous and Discrete Feedback.

    Science.gov (United States)

    Kreilinger, Alex; Hiebel, Hannah; Müller-Putz, Gernot R

    2016-03-01

    This work aimed to find and evaluate a new method for detecting errors in continuous brain-computer interface (BCI) applications. Instead of classifying errors on a single-trial basis, the new method was based on multiple events (MEs) analysis to increase the accuracy of error detection. In a BCI-driven car game, based on motor imagery (MI), discrete events were triggered whenever subjects collided with coins and/or barriers. Coins counted as correct events, whereas barriers were errors. This new method, termed ME method, combined and averaged the classification results of single events (SEs) and determined the correctness of MI trials, which consisted of event sequences instead of SEs. The benefit of this method was evaluated in an offline simulation. In an online experiment, the new method was used to detect erroneous MI trials. Such MI trials were discarded and could be repeated by the users. We found that, even with low SE error potential (ErrP) detection rates, feasible accuracies can be achieved when combining MEs to distinguish erroneous from correct MI trials. Online, all subjects reached higher scores with error detection than without, at the cost of longer times needed for completing the game. Findings suggest that ErrP detection may become a reliable tool for monitoring continuous states in BCI applications when combining MEs. This paper demonstrates a novel technique for detecting errors in online continuous BCI applications, which yields promising results even with low single-trial detection rates.

  8. Application of RADSAFE to Model Single Event Upset Response of a 0.25 micron CMOS SRAM

    Science.gov (United States)

    Warren, Kevin M.; Weller, Robert A.; Sierawski, Brian; Reed, Robert A.; Mendenhall, Marcus H.; Schrimpf, Ronald D.; Massengill, Lloyd; Porter, Mark; Wilkerson, Jeff; LaBel, Kenneth A.; hide

    2006-01-01

    The RADSAFE simulation framework is described and applied to model Single Event Upsets (SEU) in a 0.25 micron CMOS 4Mbit Static Random Access Memory (SRAM). For this circuit, the RADSAFE approach produces trends similar to those expected from classical models, but more closely represents the physical mechanisms responsible for SEU in the SRAM circuit.

  9. Definition of Capabilities Needed for a Single Event Effects Test Facility

    International Nuclear Information System (INIS)

    Riemer, Bernie; Gallmeier, Franz X.

    2014-01-01

    The Federal Aviation Administration (FAA) is contemplating new regulations mandating testing of the vulnerability of flight-critical avionics to single event effects (SEE). A limited number of high-energy neutron test facilities currently serve the SEE industrial and institutional research community. The FAA recognizes that existing facilities have insufficient test capacity to meet new demand from such mandates; it desires more flexible irradiation capabilities to test complete, large systems and would like capabilities to address greater concerns for thermal neutrons. For this reason, the FAA funded this study by Spallation Neutron Source (SNS) staff with the ultimate aim of developing options for SEE test facilities using high-energy neutrons at the SNS complex. After an investigation of current SEE test practices and assessment of future testing requirements, three concepts were identified covering a range of test functionality, neutron flux levels, and fidelity to the atmospheric neutron spectrum. The costs and times required to complete each facility were also estimated. SEE testing is generally performed by accelerating the event rate to a point where the effects are still dominated by single events and double event causes of failures are negligible. In practice, acceleration factors of as high as 10 6 are applicable for component testing, whereas for systems testing acceleration factors of 10 4 seem to be the upper limit. It is strongly desirable that the irradiation facility be tunable over a large range of high-energy neutron fluxes of 10 2 - 10 4 n/cm 2 /s for systems testing and from 10 4 - 10 7 n/cm 2 /s for components testing. The most capable, most flexible, and highest-test-capacity option is a new stand-alone target station named the High-Energy neutron Test Station (HETS). It is also the most expensive option, with a cost to complete of approximately $100 million. Dual test enclosures would allow for simultaneous testing activity effectively

  10. Definition of Capabilities Needed for a Single Event Effects Test Facility

    Energy Technology Data Exchange (ETDEWEB)

    Riemer, Bernie [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Spallation Neutron Source (SNS); Gallmeier, Franz X. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Spallation Neutron Source (SNS)

    2014-12-01

    The Federal Aviation Administration (FAA) is contemplating new regulations mandating testing of the vulnerability of flight-critical avionics to single event effects (SEE). A limited number of high-energy neutron test facilities currently serve the SEE industrial and institutional research community. The FAA recognizes that existing facilities have insufficient test capacity to meet new demand from such mandates; it desires more flexible irradiation capabilities to test complete, large systems and would like capabilities to address greater concerns for thermal neutrons. For this reason, the FAA funded this study by Spallation Neutron Source (SNS) staff with the ultimate aim of developing options for SEE test facilities using high-energy neutrons at the SNS complex. After an investigation of current SEE test practices and assessment of future testing requirements, three concepts were identified covering a range of test functionality, neutron flux levels, and fidelity to the atmospheric neutron spectrum. The costs and times required to complete each facility were also estimated. SEE testing is generally performed by accelerating the event rate to a point where the effects are still dominated by single events and double event causes of failures are negligible. In practice, acceleration factors of as high as 106 are applicable for component testing, whereas for systems testing acceleration factors of 104 seem to be the upper limit. It is strongly desirable that the irradiation facility be tunable over a large range of high-energy neutron fluxes of 102 - 104 n/cm²/s for systems testing and from 104 - 107 n/cm²/s for components testing. The most capable, most flexible, and highest-test-capacity option is a new stand-alone target station named the High-Energy neutron Test Station (HETS). It is also the most expensive option, with a cost to complete of approximately $100 million. Dual test enclosures would

  11. Potential impact of single-risk-factor versus total risk management for the prevention of cardiovascular events in Seychelles.

    Science.gov (United States)

    Ndindjock, Roger; Gedeon, Jude; Mendis, Shanthi; Paccaud, Fred; Bovet, Pascal

    2011-04-01

    To assess the prevalence of cardiovascular (CV) risk factors in Seychelles, a middle-income African country, and compare the cost-effectiveness of single-risk-factor management (treating individuals with arterial blood pressure ≥ 140/90 mmHg and/or total serum cholesterol ≥ 6.2 mmol/l) with that of management based on total CV risk (treating individuals with a total CV risk ≥ 10% or ≥ 20%). CV risk factor prevalence and a CV risk prediction chart for Africa were used to estimate the 10-year risk of suffering a fatal or non-fatal CV event among individuals aged 40-64 years. These figures were used to compare single-risk-factor management with total risk management in terms of the number of people requiring treatment to avert one CV event and the number of events potentially averted over 10 years. Treatment for patients with high total CV risk (≥ 20%) was assumed to consist of a fixed-dose combination of several drugs (polypill). Cost analyses were limited to medication. A total CV risk of ≥ 10% and ≥ 20% was found among 10.8% and 5.1% of individuals, respectively. With single-risk-factor management, 60% of adults would need to be treated and 157 cardiovascular events per 100000 population would be averted per year, as opposed to 5% of adults and 92 events with total CV risk management. Management based on high total CV risk optimizes the balance between the number requiring treatment and the number of CV events averted. Total CV risk management is much more cost-effective than single-risk-factor management. These findings are relevant for all countries, but especially for those economically and demographically similar to Seychelles.

  12. The relationship of the factor V Leiden mutation or the deletion-deletion polymorphism of the angiotensin converting enzyme to postoperative thromboembolic events following total joint arthroplasty

    Directory of Open Access Journals (Sweden)

    Fang Carrie

    2001-04-01

    Full Text Available Abstract Background Although all patients undergoing total joint arthroplasty are subjected to similar risk factors that predispose to thromboembolism, only a subset of patients develop this complication. The objective of this study was to determine whether a specific genetic profile is associated with a higher risk of developing a postoperative thromboembolic complication. Specifically, we examined if the Factor V Leiden (FVL mutation or the deletion polymorphism of the angiotensin-converting enzyme (ACE gene increased a patient's risk for postoperative thromboembolic events. The FVL mutation has been associated with an increased risk of idiopathic thromboembolism and the deletion polymorphism of the ACE gene has been associated with increased vascular tone, attenuated fibrinolysis and increased platelet aggregation. Methods The presence of these genetic profiles was determined for 38 patients who had a postoperative symptomatic pulmonary embolus or proximal deep venous thrombosis and 241 control patients without thrombosis using molecular biological techniques. Results The Factor V Leiden mutation was present in none of the 38 experimental patients and in 3% or 8 of the 241 controls (p = 0.26. Similarly there was no difference detected in the distribution of polymorphisms for the ACE gene with the deletion-deletion genotype present in 36% or 13 of the 38 experimental patients and in 31% or 74 of the 241 controls (p = 0.32. Conclusions Our results suggest that neither of these potentially hypercoaguable states are associated with an increased risk of symptomatic thromboembolic events following total hip or knee arthroplasty in patients receiving pharmacological thromboprophylaxis.

  13. Observed differences in event structures of high-p/sub T/ π0 and single photon events produced in pp collisions at the CERN ISR

    International Nuclear Information System (INIS)

    Rahm, D.C.

    1980-01-01

    The direct photon production in pp collisions for c.m. energies 31 less than or equal to 63 GeV and transverse momenta of up to 9 GeV/c were measured at the ISR by use of a segmented lead/liquid argon calorimeter. The observed γ/π 0 ratio was found to be a significantly larger than zero at 4 GeV/c in p/sub T/, increasing to 0.4 at 9 GeV/c. The average multiplicity on the trigger side for the single-photon events was found to be significantly lower than for π 0 events. The correlations in Δy and Δphi between the trigger particle and an additional particle were found to differe mainly at small Δy and Δphi. 3 figures

  14. Number distribution of leakage neutrons for single neutron emission event and one source emission event in multiplying medium for two variables - a GEANT4 study

    International Nuclear Information System (INIS)

    Roy, Arup Singha; Raman, Anand; Chaudhury, Probal; Thomas, Renju G.

    2018-01-01

    A quantitative knowledge about the neutron multiplying character of a neutron multiplying medium such as High enriched Uranium (HEU), Weapon Graded plutonium (WGPu) and similar special nuclear materials is essential for improving the probability of detection of these materials to check against illicit trafficking. The objective of this study is to gain a deeper insight in to the neutron and gamma multiplication behaviour of these materials. The leakage number distribution of neutron and gamma initiated by a source emission event (Spontaneous Fission) as well as single neutron emission event has been obtained in the course of this study. The computations for this study were carried out through GEANT4 simulation and also with the help of FREYA incorporated into it. This helped to carry out a detailed analysis of each history more realistically and obtain more reliable results

  15. HER2 mutated breast cancer responds to treatment with single agent neratinib, a second generation HER2/EGFR tyrosine kinase inhibitor

    Science.gov (United States)

    Ben–Baruch, Noa Efrat; Bose, Ron; Kavuri, Shyam M.; Ma, Cynthia X.; Ellis, Matthew J.

    2015-01-01

    Activating mutations in the HER2 tyrosine kinase have been identified in human breast cancers that lack HER2 gene amplification. These patients are not candidates for HER2 targeted drugs under current standards of care, but preclinical data strongly suggest that these patients will benefit from anti-HER2 drugs. In this case report, we describe a young woman with metastatic breast cancer whose tumor was found to carry a HER2 L755S mutation, which is in the kinase domain of HER2. Treatment with the second generation HER2/EGFR tyrosine kinase inhibitor, neratinib, resulted in partial response and dramatic improvement in the patient’s function status. This partial response lasted 11 months and when the patient’s cancer progressed, she was treated with neratinib plus capecitabine and her cancer again responded. This second response parallels the benefit seen with continuing trastuzumab in HER2 amplified breast cancer after disease progression. This case is the first report, to our knowledge, of successful single agent treatment of HER2 mutated breast cancer. Two clinical trials of neratinib for HER2 mutated, metastatic breast cancer are currently enrolling patients. Further, data from The Cancer Genome Atlas project have identified HER2 mutations in a wide range of solid tumors, including bladder, colorectal, and non-small cell lung cancer, suggesting that clinical trials of neratinib or neratinib-based combinations for HER2 mutated solid tumors is warranted. PMID:26358790

  16. HER2-Mutated Breast Cancer Responds to Treatment With Single-Agent Neratinib, a Second-Generation HER2/EGFR Tyrosine Kinase Inhibitor.

    Science.gov (United States)

    Ben-Baruch, Noa Efrat; Bose, Ron; Kavuri, Shyam M; Ma, Cynthia X; Ellis, Matthew J

    2015-09-01

    Activating mutations in the HER2 tyrosine kinase have been identified in human breast cancers that lack HER2 gene amplification. These patients are not candidates for HER2-targeted drugs under current standards of care, but preclinical data strongly suggest that these patients will benefit from anti-HER2 drugs. This case report describes a young woman with metastatic breast cancer whose tumor was found to carry a HER2 L755S mutation, which is in the kinase domain of HER2. Treatment with the second-generation HER2/EGFR tyrosine kinase inhibitor neratinib resulted in partial response and dramatic improvement in the patient's functional status. This partial response lasted 11 months, and when the patient's cancer progressed, she was treated with neratinib plus capecitabine and her cancer again responded. This second response parallels the benefit seen with continuing trastuzumab in HER2-amplified breast cancer after disease progression. This case represents the first report, to our knowledge, of successful single-agent treatment of HER2-mutated breast cancer. Two clinical trials of neratinib for HER2-mutated metastatic breast cancer are currently enrolling patients. Further, data from The Cancer Genome Atlas project have identified HER2 mutations in a wide range of solid tumors, including bladder, colorectal, and non-small cell lung cancers, suggesting that clinical trials of neratinib or neratinib-based combinations for HER2-mutated solid tumors is warranted. Copyright © 2015 by the National Comprehensive Cancer Network.

  17. Combining Single Strand Oligodeoxynucleotides and CRISPR/Cas9 to Correct Gene Mutations in β-Thalassemia-induced Pluripotent Stem Cells.

    Science.gov (United States)

    Niu, Xiaohua; He, Wenyin; Song, Bing; Ou, Zhanhui; Fan, Di; Chen, Yuchang; Fan, Yong; Sun, Xiaofang

    2016-08-05

    β-Thalassemia (β-Thal) is one of the most common genetic diseases in the world. The generation of patient-specific β-Thal-induced pluripotent stem cells (iPSCs), correction of the disease-causing mutations in those cells, and then differentiation into hematopoietic stem cells offers a new therapeutic strategy for this disease. Here, we designed a CRISPR/Cas9 to specifically target the Homo sapiens hemoglobin β (HBB) gene CD41/42(-CTTT) mutation. We demonstrated that the combination of single strand oligodeoxynucleotides with CRISPR/Cas9 was capable of correcting the HBB gene CD41/42 mutation in β-Thal iPSCs. After applying a correction-specific PCR assay to purify the corrected clones followed by sequencing to confirm mutation correction, we verified that the purified clones retained full pluripotency and exhibited normal karyotyping. Additionally, whole-exome sequencing showed that the mutation load to the exomes was minimal after CRISPR/Cas9 targeting. Furthermore, the corrected iPSCs were selected for erythroblast differentiation and restored the expression of HBB protein compared with the parental iPSCs. This method provides an efficient and safe strategy to correct the HBB gene mutation in β-Thal iPSCs. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Monitoring of seismic events from a specific source region using a single regional array: A case study

    Science.gov (United States)

    Gibbons, S. J.; Kværna, T.; Ringdal, F.

    2005-07-01

    In the monitoring of earthquakes and nuclear explosions using a sparse worldwide network of seismic stations, it is frequently necessary to make reliable location estimates using a single seismic array. It is also desirable to screen out routine industrial explosions automatically in order that analyst resources are not wasted upon detections which can, with a high level of confidence, be associated with such a source. The Kovdor mine on the Kola Peninsula of NW Russia is the site of frequent industrial blasts which are well recorded by the ARCES regional seismic array at a distance of approximately 300 km. We describe here an automatic procedure for identifying signals which are likely to result from blasts at the Kovdor mine and, wherever possible, for obtaining single array locations for such events. Carefully calibrated processing parameters were chosen using measurements from confirmed events at the mine over a one-year period for which the operators supplied Ground Truth information. Phase arrival times are estimated using an autoregressive method and slowness and azimuth are estimated using broadband f{-} k analysis in fixed frequency bands and time-windows fixed relative to the initial P-onset time. We demonstrate the improvement to slowness estimates resulting from the use of fixed frequency bands. Events can be located using a single array if, in addition to the P-phase, at least one secondary phase is found with both an acceptable slowness estimate and valid onset-time estimate. We evaluate the on-line system over a twelve month period; every event known to have occured at the mine is detected by the process and 32 out of 53 confirmed events were located automatically. The remaining events were classified as “very likely” Kovdor events and were subsequently located by an analyst. The false alarm rate is low; only 84 very likely Kovdor events were identified during the whole of 2003 and none of these were subsequently located at a large distance from

  19. FinFET memory cell improvements for higher immunity against single event upsets

    Science.gov (United States)

    Sajit, Ahmed Sattar

    The 21st century is witnessing a tremendous demand for transistors. Life amenities have incorporated the transistor in every aspect of daily life, ranging from toys to rocket science. Day by day, scaling down the transistor is becoming an imperious necessity. However, it is not a straightforward process; instead, it faces overwhelming challenges. Due to these scaling changes, new technologies, such as FinFETs for example, have emerged as alternatives to the conventional bulk-CMOS technology. FinFET has more control over the channel, therefore, leakage current is reduced. FinFET could bridge the gap between silicon devices and non-silicon devices. The semiconductor industry is now incorporating FinFETs in systems and subsystems. For example, Intel has been using them in their newest processors, delivering potential saving powers and increased speeds to memory circuits. Memory sub-systems are considered a vital component in the digital era. In memory, few rows are read or written at a time, while the most rows are static; hence, reducing leakage current increases the performance. However, as a transistor shrinks, it becomes more vulnerable to the effects from radioactive particle strikes. If a particle hits a node in a memory cell, the content might flip; consequently, leading to corrupting stored data. Critical fields, such as medical and aerospace, where there are no second chances and cannot even afford to operate at 99.99% accuracy, has induced me to find a rigid circuit in a radiated working environment. This research focuses on a wide spectrum of memories such as 6T SRAM, 8T SRAM, and DICE memory cells using FinFET technology and finding the best platform in terms of Read and Write delay, susceptibility level of SNM, RSNM, leakage current, energy consumption, and Single Event Upsets (SEUs). This research has shown that the SEU tolerance that 6T and 8T FinFET SRAMs provide may not be acceptable in medical and aerospace applications where there is a very high

  20. Single-Event Gate Rupture in Power MOSFETs: A New Radiation Hardness Assurance Approach

    Science.gov (United States)

    Lauenstein, Jean-Marie

    2011-01-01

    Almost every space mission uses vertical power metal-semiconductor-oxide field-effect transistors (MOSFETs) in its power-supply circuitry. These devices can fail catastrophically due to single-event gate rupture (SEGR) when exposed to energetic heavy ions. To reduce SEGR failure risk, the off-state operating voltages of the devices are derated based upon radiation tests at heavy-ion accelerator facilities. Testing is very expensive. Even so, data from these tests provide only a limited guide to on-orbit performance. In this work, a device simulation-based method is developed to measure the response to strikes from heavy ions unavailable at accelerator facilities but posing potential risk on orbit. This work is the first to show that the present derating factor, which was established from non-radiation reliability concerns, is appropriate to reduce on-orbit SEGR failure risk when applied to data acquired from ions with appropriate penetration range. A second important outcome of this study is the demonstration of the capability and usefulness of this simulation technique for augmenting SEGR data from accelerator beam facilities. The mechanisms of SEGR are two-fold: the gate oxide is weakened by the passage of the ion through it, and the charge ionized along the ion track in the silicon transiently increases the oxide electric field. Most hardness assurance methodologies consider the latter mechanism only. This work demonstrates through experiment and simulation that the gate oxide response should not be neglected. In addition, the premise that the temporary weakening of the oxide due to the ion interaction with it, as opposed to due to the transient oxide field generated from within the silicon, is validated. Based upon these findings, a new approach to radiation hardness assurance for SEGR in power MOSFETs is defined to reduce SEGR risk in space flight projects. Finally, the potential impact of accumulated dose over the course of a space mission on SEGR

  1. Genetic diagnosis of Duchenne and Becker muscular dystrophy using next-generation sequencing technology: comprehensive mutational search in a single platform.

    Science.gov (United States)

    Lim, Byung Chan; Lee, Seungbok; Shin, Jong-Yeon; Kim, Jong-Il; Hwang, Hee; Kim, Ki Joong; Hwang, Yong Seung; Seo, Jeong-Sun; Chae, Jong Hee

    2011-11-01

    Duchenne muscular dystrophy or Becker muscular dystrophy might be a suitable candidate disease for application of next-generation sequencing in the genetic diagnosis because the complex mutational spectrum and the large size of the dystrophin gene require two or more analytical methods and have a high cost. The authors tested whether large deletions/duplications or small mutations, such as point mutations or short insertions/deletions of the dystrophin gene, could be predicted accurately in a single platform using next-generation sequencing technology. A custom solution-based target enrichment kit was designed to capture whole genomic regions of the dystrophin gene and other muscular-dystrophy-related genes. A multiplexing strategy, wherein four differently bar-coded samples were captured and sequenced together in a single lane of the Illumina Genome Analyser, was applied. The study subjects were 25 16 with deficient dystrophin expression without a large deletion/duplication and 9 with a known large deletion/duplication. Nearly 100% of the exonic region of the dystrophin gene was covered by at least eight reads with a mean read depth of 107. Pathogenic small mutations were identified in 15 of the 16 patients without a large deletion/duplication. Using these 16 patients as the standard, the authors' method accurately predicted the deleted or duplicated exons in the 9 patients with known mutations. Inclusion of non-coding regions and paired-end sequence analysis enabled accurate identification by increasing the read depth and providing information about the breakpoint junction. The current method has an advantage for the genetic diagnosis of Duchenne muscular dystrophy and Becker muscular dystrophy wherein a comprehensive mutational search may be feasible using a single platform.

  2. A single amino acid mutation in Spo0A results in sporulation deficiency of Paenibacillus polymyxa SC2.

    Science.gov (United States)

    Hou, Xiaoyang; Yu, Xiaoning; Du, Binghai; Liu, Kai; Yao, Liangtong; Zhang, Sicheng; Selin, C; Fernando, W G D; Wang, Chengqiang; Ding, Yanqin

    2016-01-01

    Sporulating bacteria such as Bacillus subtilis and Paenibacillus polymyxa exhibit sporulation deficiencies during their lifetime in a laboratory environment. In this study, spontaneous mutants SC2-M1 and SC2-M2, of P. polymyxa SC2 lost the ability to form endospores. A global genetic and transcriptomic analysis of wild-type SC2 and spontaneous mutants was carried out. Genome resequencing analysis revealed 14 variants in the genome of SC2-M1, including three insertions and deletions (indels), 10 single nucleotide variations (SNVs) and one intrachromosomal translocation (ITX). There were nine variants in the genome of SC2-M2, including two indels and seven SNVs. Transcriptomic analysis revealed that 266 and 272 genes showed significant differences in expression in SC2-M1 and SC2-M2, respectively, compared with the wild-type SC2. Besides sporulation-related genes, genes related to exopolysaccharide biosynthesis (eps), antibiotic (fusaricidin) synthesis, motility (flgB) and other functions were also affected in these mutants. In SC2-M2, reversion of spo0A resulted in the complete recovery of sporulation. This is the first global analysis of mutations related to sporulation deficiency in P. polymyxa. Our results demonstrate that a SNV within spo0A caused the sporulation deficiency of SC2-M2 and provide strong evidence that an arginine residue at position 211 is essential for the function of Spo0A. Copyright © 2016 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.

  3. A Single Recessive Mutated Gene (Sd237-1) Controlling Semi-Dwarf Plant Stature of Rice

    International Nuclear Information System (INIS)

    Sobrizal

    2009-01-01

    Dwarfism is a valuable trait in crop breeding, because it increases lodging resistance and decreases damages due to wind and rain. During the course of this study, a semi-dwarf mutant was successfully induced through 200 Gy gamma ray irradiated KI 237 seeds. KI 237 is a pure line with high yield potency, developed through an Indica-Japonica cross of IR36 / Koshihikari. The selected semi-dwarf plant reached 60 - 62 % of plant height of original plant KI 237 at the mature stage. The length of inter nodes, panicle, and seed were also compared between these two plants. The retardation of the 1 st (uppermost) inter nodes was 24 %, moreover, the retardation of panicle and seed length were only 10 % and 2 %, respectively. The elongation pattern of the inter nodes in this mutant was almost the same as sd1 (Dee-geo-woo-gen), the original parent of the first release modern rice variety, but their performances were different. Based on the segregation analysis in M 2 and M 3 generation it was concluded that this mutant was controlled by a single recessive mutated gene. This gene was designated as sd 237-1 . This mutant should be useful as a genetic resource for the improvement of KI 237 line through back-cross breeding as well as be developed further in breeding program directly to be a new high yielding mutant variety. (author)

  4. Role of single-point mutations and deletions on transition temperatures in ideal proteinogenic heteropolymer chains in the gas phase.

    Science.gov (United States)

    Olivares-Quiroz, L

    2016-07-01

    A coarse-grained statistical mechanics-based model for ideal heteropolymer proteinogenic chains of non-interacting residues is presented in terms of the size K of the chain and the set of helical propensities [Formula: see text] associated with each residue j along the chain. For this model, we provide an algorithm to compute the degeneracy tensor [Formula: see text] associated with energy level [Formula: see text] where [Formula: see text] is the number of residues with a native contact in a given conformation. From these results, we calculate the equilibrium partition function [Formula: see text] and characteristic temperature [Formula: see text] at which a transition from a low to a high entropy states is observed. The formalism is applied to analyze the effect on characteristic temperatures [Formula: see text] of single-point mutations and deletions of specific amino acids [Formula: see text] along the chain. Two probe systems are considered. First, we address the case of a random heteropolymer of size K and given helical propensities [Formula: see text] on a conformational phase space. Second, we focus our attention to a particular set of neuropentapeptides, [Met-5] and [Leu-5] enkephalins whose thermodynamic stability is a key feature on their coupling to [Formula: see text] and [Formula: see text] receptors and the triggering of biochemical responses.

  5. Detection of single amino acid mutation in human breast cancer by disordered plasmonic self-similar chain

    KAUST Repository

    Coluccio, M. L.

    2015-09-04

    Control of the architecture and electromagnetic behavior of nanostructures offers the possibility of designing and fabricating sensors that, owing to their intrinsic behavior, provide solutions to new problems in various fields. We show detection of peptides in multicomponent mixtures derived from human samples for early diagnosis of breast cancer. The architecture of sensors is based on a matrix array where pixels constitute a plasmonic device showing a strong electric field enhancement localized in an area of a few square nanometers. The method allows detection of single point mutations in peptides composing the BRCA1 protein. The sensitivity demonstrated falls in the picomolar (10−12 M) range. The success of this approach is a result of accurate design and fabrication control. The residual roughness introduced by fabrication was taken into account in optical modeling and was a further contributing factor in plasmon localization, increasing the sensitivity and selectivity of the sensors. This methodology developed for breast cancer detection can be considered a general strategy that is applicable to various pathologies and other chemical analytical cases where complex mixtures have to be resolved in their constitutive components.

  6. Detection of single amino acid mutation in human breast cancer by disordered plasmonic self-similar chain

    KAUST Repository

    Coluccio, M. L.; Gentile, F.; Das, Gobind; Nicastri, A.; Perri, A. M.; Candeloro, P.; Perozziello, G.; Proietti Zaccaria, R.; Gongora, J. S. Totero; Alrasheed, Salma; Fratalocchi, Andrea; Limongi, Tania; Cuda, G.; Di Fabrizio, Enzo M.

    2015-01-01

    Control of the architecture and electromagnetic behavior of nanostructures offers the possibility of designing and fabricating sensors that, owing to their intrinsic behavior, provide solutions to new problems in various fields. We show detection of peptides in multicomponent mixtures derived from human samples for early diagnosis of breast cancer. The architecture of sensors is based on a matrix array where pixels constitute a plasmonic device showing a strong electric field enhancement localized in an area of a few square nanometers. The method allows detection of single point mutations in peptides composing the BRCA1 protein. The sensitivity demonstrated falls in the picomolar (10−12 M) range. The success of this approach is a result of accurate design and fabrication control. The residual roughness introduced by fabrication was taken into account in optical modeling and was a further contributing factor in plasmon localization, increasing the sensitivity and selectivity of the sensors. This methodology developed for breast cancer detection can be considered a general strategy that is applicable to various pathologies and other chemical analytical cases where complex mixtures have to be resolved in their constitutive components.

  7. Success in treating renal calculi with single-access, single-event percutaneous nephrolithotomy: is a routine "second look" necessary?

    Science.gov (United States)

    Davol, Patrick E; Wood, Craig; Fulmer, Brant

    2006-05-01

    Percutaneous nephrolithotomy (PCNL) is an effective procedure for the treatment of large renal calculi. An important consideration for patients undergoing PCNL is the management of any residual stone burden, which may include "second-look" nephroscopy. The utility of this practice is unproven, and we present our data on a series of patients in which second-look procedures were not performed. We retrospectively reviewed the records of 43 consecutive patients undergoing a total of 45 procedures by a single surgeon at a tertiary-care center. Patients were considered stone free if no calculi were evident by either plain film or noncontrast CT scan. Statistical analysis was used to look for correlations between radiographic stone clearance and various patient and stone characteristics. Of these procedures, 15% had immediate postoperative evidence of residual fragments. At a mean follow-up of 8 months, 32.5% had residual or recurrent stone. There were statistically significant correlations between both patient age and stone size and the risk of recurrent or residual stone. In our study, PCNL was effective for the single-stage treatment of large renal calculi. Aggressive stone clearance obviated the need for routine second-look nephroscopy. Factors leading to an increased risk of residual or recurrent calculi included the presence of a staghorn calculus and younger patient age. The excellent stone-free rates achieved suggest that routine second-look nephroscopy may not be necessary for the majority of patients undergoing PCNL.

  8. Two-dimensional numerical simulation of the effect of single event burnout for n-channel VDMOSFET

    International Nuclear Information System (INIS)

    Guo Hongxia; Chen Yusheng; Wang Wei; Zhao Jinlong; Zhang Yimen; Zhou Hui

    2004-01-01

    2D MEDICI simulator is used to investigate the effect of Single Event Burnout (SEB) for n-channel power VDMOSFETs. The simulation results are consistent with experimental results which have been published. The simulation results are of great interest for a better understanding of the occurrence of events. The effects of the minority carrier lifetime in the base region, the base width and the emitter doping density on SEB susceptibility are verified. Some hardening solutions to SEB are provided. The work shows that the 2D simulator MEDICI is an useful tool for burnout prediction and for the evaluation of hardening solutions. (authors)

  9. Cortical atrophy and hypofibrinogenemia due to FGG and TBCD mutations in a single family: a case report.

    Science.gov (United States)

    Stephen, Joshi; Nampoothiri, Sheela; Vinayan, K P; Yesodharan, Dhanya; Remesh, Preetha; Gahl, William A; Malicdan, May Christine V

    2018-05-16

    Blended phenotypes or co-occurrence of independent phenotypically distinct conditions are extremely rare and are due to coincidence of multiple pathogenic mutations, especially due to consanguinity. Hereditary fibrinogen deficiencies result from mutations in the genes FGA, FGB, and FGG, encoding the three different polypeptide chains that comprise fibrinogen. Neurodevelopmental abnormalities have not been associated with fibrinogen deficiencies. In this study, we report an unusual patient with a combination of two independently inherited genetic conditions; fibrinogen deficiency and early onset cortical atrophy. The study describes a male child from consanguineous family presented with hypofibrinogenemia, diffuse cortical atrophy, microcephaly, hypertonia and axonal motor neuropathy. Through a combination of homozygosity mapping and exome sequencing, we identified bi-allelic pathogenic mutations in two genes: a homozygous novel truncating mutation in FGG (c.554del; p.Lys185Argfs*14) and a homozygous missense mutation in TBCD (c.1423G > A;p.Ala475Thr). Loss of function mutations in FGG have been associated with fibrinogen deficiency, while the c.1423G > A mutation in TBCD causes a novel syndrome of neurodegeneration and early onset encephalopathy. Our study highlights the importance of homozygosity mapping and exome sequencing in molecular prenatal diagnosis, especially when multiple gene mutations are responsible for the phenotype.

  10. NASA Electronic Parts and Packaging (NEPP) Field Programmable Gate Array (FPGA) Single Event Effects (SEE) Test Guideline Update

    Science.gov (United States)

    Berg, Melanie D.; LaBel, Kenneth A.

    2018-01-01

    The following are updated or new subjects added to the FPGA SEE Test Guidelines manual: academic versus mission specific device evaluation, single event latch-up (SEL) test and analysis, SEE response visibility enhancement during radiation testing, mitigation evaluation (embedded and user-implemented), unreliable design and its affects to SEE Data, testing flushable architectures versus non-flushable architectures, intellectual property core (IP Core) test and evaluation (addresses embedded and user-inserted), heavy-ion energy and linear energy transfer (LET) selection, proton versus heavy-ion testing, fault injection, mean fluence to failure analysis, and mission specific system-level single event upset (SEU) response prediction. Most sections within the guidelines manual provide information regarding best practices for test structure and test system development. The scope of this manual addresses academic versus mission specific device evaluation and visibility enhancement in IP Core testing.

  11. Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.

    Science.gov (United States)

    Hitti, Jane; Halvas, Elias K; Zheng, Lu; Panousis, Constantinos G; Kabanda, Joseph; Taulo, Frank; Kumarasamy, Nagalingeswaran; Pape, Jean William; Lalloo, Umesh; Sprenger, Heather; Klingman, Karin L; Chan, Ellen S; McMahon, Deborah; Mellors, John W

    2014-11-01

    Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy. This analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/μL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1-infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list. Perinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. Infants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.

  12. Investigations on heavy ion induced Single-Event Transients (SETs) in highly-scaled FinFETs

    Energy Technology Data Exchange (ETDEWEB)

    Gaillardin, M., E-mail: marc.gaillardin@cea.fr [CEA, DAM, DIF, F-91297 Arpajon (France); Raine, M.; Paillet, P. [CEA, DAM, DIF, F-91297 Arpajon (France); Adell, P.C. [Jet Propulsion Laboratory, Pasadena, CA 91101 (United States); Girard, S. [Université de Saint-Etienne, Laboratoire H. Curien, UMR-5516, 42000 Saint-Etienne (France); Duhamel, O. [CEA, DAM, DIF, F-91297 Arpajon (France); Andrieu, F.; Barraud, S.; Faynot, O. [CEA, LETI-Minatec, 17 avenue des Martyrs, 38000 Grenoble (France)

    2015-12-15

    We investigate Single-Event Transients (SET) in different designs of multiple-gate devices made of FinFETs with various geometries. Heavy ion experimental results are explained by using a thorough charge collection analysis of fast transients measured on dedicated test structures. Multi-level simulations are performed to get new insights into the charge collection mechanisms in multiple-gate devices. Implications for multiple-gate device design hardening are finally discussed.

  13. Single Event Upset Rate Estimates for a 16-K CMOS (Complementary Metal Oxide Semiconductor) SRAM (Static Random Access Memory).

    Science.gov (United States)

    1986-09-30

    4 . ~**..ft.. ft . - - - ft SI TABLES 9 I. SA32~40 Single Event Upset Test, 1140-MeV Krypton, 9/l8/8~4. . .. .. .. .. .. .16 II. CRUP Simulation...cosmic ray interaction analysis described in the remainder of this report were calculated using the CRUP computer code 3 modified for funneling. The... CRUP code requires, as inputs, the size of a depletion region specified as a retangular parallel piped with dimensions a 9 b S c, the effective funnel

  14. Temperature control system for the study of single event effects in integrated circuits using a cyclotron accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Bakerenkov, A.S., E-mail: as_bakerenkov@list.ru [National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Moscow (Russian Federation); Belyakov, V.V. [National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Moscow (Russian Federation); Kozyukov, A.E. [Joint-Stock Company Institute of Space Device Engineering (JSC ISDE), Moscow (Russian Federation); Pershenkov, V.S.; Solomatin, A.V.; Shurenkov, V.V. [National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Moscow (Russian Federation)

    2015-02-11

    The temperature control system for the study of single event disruptions produced by hard ion impacts in integrated circuits is described. Heating and cooling of the irradiated device are achieved using thermoelectric modules (Peltier modules). The thermodynamic performance of the system is estimated. The technique for the numerical estimation of the main parameters of the temperature control system for cooling and heating is considered. The results of a test of the system in a vacuum cell of an accelerator are presented.

  15. Temperature control system for the study of single event effects in integrated circuits using a cyclotron accelerator

    International Nuclear Information System (INIS)

    Bakerenkov, A.S.; Belyakov, V.V.; Kozyukov, A.E.; Pershenkov, V.S.; Solomatin, A.V.; Shurenkov, V.V.

    2015-01-01

    The temperature control system for the study of single event disruptions produced by hard ion impacts in integrated circuits is described. Heating and cooling of the irradiated device are achieved using thermoelectric modules (Peltier modules). The thermodynamic performance of the system is estimated. The technique for the numerical estimation of the main parameters of the temperature control system for cooling and heating is considered. The results of a test of the system in a vacuum cell of an accelerator are presented

  16. Study of single tagged multihadronic γγ* events at A 2> ≅ 12 GeV2/C4

    International Nuclear Information System (INIS)

    Batyunya, B.; Tyapkin, I.; Todorov, T.

    1993-01-01

    An analysis of single tagged two photon events was performed in the multihadronic channel. Data corresponding to a 26.0 pb -1 integrated luminosity was compared to a two component model prediction: a generalized Vector meson Dominance Model (VDM) for the non perturbative part and a Quark Parton Model (QPM) describing the perturbative regime. The obtained reasonable agreement between data and MC is the first step before unfolding the data and testing QCD. 16 refs., 13 figs., 1 tab

  17. A Novel Approach to Estimating Nitrous Oxide Emissions during Wetting Events from Single-Timepoint Flux Measurements.

    Science.gov (United States)

    Davis, Brian W; Needelman, Brian A; Cavigelli, Michel A; Yarwood, Stephanie A; Maul, Jude E; Bagley, Gwendolyn A; Mirsky, Steven B

    2017-03-01

    Precipitation and irrigation induce pulses of NO emissions in agricultural soils, but the magnitude, duration, and timing of these pulses remain uncertain. This uncertainty makes it difficult to accurately extrapolate emissions from unmeasured time periods between chamber sampling events. Therefore, we developed a modeling protocol to predict NO emissions from data collected daily for 7 d after wetting events. Within a cover crop-based corn ( L.) production system in Beltsville, MD, we conducted the 7-d time series during four time periods representing a range of corn growth stages in 2013 and 2014. Treatments included mixtures and monocultures of grass and legume cover crops that were fertilized with pelletized poultry litter or urea-ammonium nitrate solution (9-276 kg N ha). Most fluxes did not exhibit the expected exponential decay over time (82%); therefore, cumulative emissions were calculated using trapezoidal integration over 7 d after the wetting event. Cumulative 7-d emissions were well correlated with single point gas fluxes on the second day after a wetting event using a generalized linear mixed model (ln[emissions] = 0.809∙ln[flux] + 2.47). Soil chemical covariates before or after a wetting event were weakly associated with cumulative emissions. The ratio of dissolved organic C to total inorganic N was negatively correlated with cumulative emissions ( = 0.23-0.29), whereas nitrate was positively correlated with cumulative emissions ( = 0.23-0.33). Our model is an innovative approach that is calibrated using site-specific time series data, which may then be used to estimate short-term NO emissions after wetting events using only a single flux measurement. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  18. Brief Report: Human Acute Myeloid Leukemia Reprogramming to Pluripotency Is a Rare Event and Selects for Patient Hematopoietic Cells Devoid of Leukemic Mutations.

    Science.gov (United States)

    Lee, Jong-Hee; Salci, Kyle R; Reid, Jennifer C; Orlando, Luca; Tanasijevic, Borko; Shapovalova, Zoya; Bhatia, Mickie

    2017-09-01

    Induced pluripotent stem cell reprogramming has provided critical insights into disease processes by modeling the genetics and related clinical pathophysiology. Human cancer represents highly diverse genetics, as well as inter- and intra-patient heterogeneity, where cellular model systems capable of capturing this disease complexity would be invaluable. Acute myeloid leukemia (AML) represents one of most heterogeneous cancers and has been divided into genetic subtypes correlated with unique risk stratification over the decades. Here, we report our efforts to induce pluripotency from the heterogeneous population of human patients that represents this disease in the clinic. Using robust optimized reprogramming methods, we demonstrate that reprogramming of AML cells harboring leukemic genomic aberrations is a rare event with the exception of those with de novo mixed-lineage leukemia (MLL) mutations that can be reprogrammed and model drug responses in vitro. Our findings indicate that unlike hematopoietic cells devoid of genomic aberrations, AML cells harboring driver mutations are refractory to reprogramming. Expression of MLL fusion proteins in AML cells did not contribute to induced reprogramming success, which continued to select for patient derived cells devoid of AML patient-specific aberrations. Our study reveals that unanticipated blockades to achieving pluripotency reside within the majority of transformed AML patient cells. Stem Cells 2017;35:2095-2102. © 2017 AlphaMed Press.

  19. A Novel KCNJ2 Mutation Identified in an Autistic Proband Affects the Single Channel Properties of Kir2.1

    Directory of Open Access Journals (Sweden)

    Anna Binda

    2018-03-01

    Full Text Available Inwardly rectifying potassium channels (Kir have been historically associated to several cardiovascular disorders. In particular, loss-of-function mutations in the Kir2.1 channel have been reported in cases affected by Andersen-Tawil syndrome while gain-of-function mutations in the same channel cause the short QT3 syndrome. Recently, a missense mutation in Kir2.1, as well as mutations in the Kir4.1, were reported to be involved in autism spectrum disorders (ASDs suggesting a role of potassium channels in these diseases and introducing the idea of the existence of K+ channel ASDs. Here, we report the identification in an Italian affected family of a novel missense mutation (p.Phe58Ser in the KCNJ2 gene detected in heterozygosity in a proband affected by autism and borderline for short QT syndrome type 3. The mutation is located in the N-terminal region of the gene coding for the Kir2.1 channel and in particular in a very conserved domain. In vitro assays demonstrated that this mutation results in an increase of the channel conductance and in its open probability. This gain-of-function of the protein is consistent with the autistic phenotype, which is normally associated to an altered neuronal excitability.

  20. Tuning of the Lethal Response to Multiple Stressors with a Single-Site Mutation during Clinical Infection by Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Krishan Kumar

    2017-10-01

    Full Text Available The agr system of Staphylococcus aureus promotes invasion of host tissues, and as expected, agents that block agr quorum sensing have anti-infective properties. Paradoxically, agr-defective mutants are frequently recovered from patients, especially those persistently infected with S. aureus. We found that an agr deficiency increased survival of cultured bacteria during severe stress, such as treatment with gentamicin, ciprofloxacin, heat, or low pH. With daptomycin, deletion of agr decreased survival. Therefore, agr activity can be either detrimental or protective, depending on the type of lethal stress. Deletion of agr had no effect on the ability of the antimicrobials to block bacterial growth, indicating that agr effects are limited to lethal action. Thus, the effect of an agr deletion is on bacterial tolerance, not resistance. For gentamicin and daptomycin, activity can be altered by agr-regulated secreted factors. For ciprofloxacin, a detrimental function was downregulation of glutathione peroxidase (bsaA, an enzyme responsible for defense against oxidative stress. Deficiencies in agr and bsaA were epistatic for survival, consistent with agr having a destructive role mediated by reactive oxygen species. Enhanced susceptibility to lethal stress by wild-type agr, particularly antimicrobial stress, helps explain why inactivating mutations in S. aureus agr commonly occur in hospitalized patients during infection. Moreover, the agr quorum-sensing system of S. aureus provides a clinically relevant example in which a single-step change in the response to severe stress alters the evolutionary path of a pathogen during infection.

  1. Helicity of the $W$ boson in single - lepton $t \\bar{t}$ events

    Energy Technology Data Exchange (ETDEWEB)

    Canelli, Maria Florencia [Rochester U.

    2003-08-01

    We have applied a general approach for extracting information from data to a study of top quarks produced in proton-antiproton (pp) collisions in the process pp ! tt. This reaction can be calculated in the Standard Model (SM), in which the top (or antitop) quarks decay into b quarks and W bosons: t ! W+ b, t ! W b. We examine the decays of the W boson in these events in order to establish how the spin of the W correlates with its momentum vector. This is dened by the helicity of the W boson (pro jection of its spin along its line of ight), which is also predicted by the SM. The analysis is based on a direct calculation of a probability for each event as a function of the helicity of the W bosons in top-antitop events in the lepton+jets nal state. These events correspond to one W decaying into a lepton and its neutrino, and the other W into a quark-antiquark pair, with the quarks from the W and the two b quarks evolving into jets of particles. The probability is calculated by convoluting the dierential cross section with the resolution and acceptance of the detector. This measurement uses top quarks collected by the D experiment in 125 events/pb of data in pp collisions at p s=1.8 TeV during Run I of the Fermilab TeVatron. Assuming the \\V{A" coupling of the SM decay, we obtain a longitudinal helicity fraction of F0=0.560.31(stat)0.07(syst) for the W, which is consistent with the prediction of the Standard Model of F0=0.70 for a top-quark mass of 175 GeV/c2 . The method employed in this analysis oers the possibility of increasing statistical precision by using both of the decays of W bosons in these events. Also Monte Carlo studies indicate that the approach provides an unbiased result in the limit of poor statistics. Although our measurement is severely limited by the small event sample of Run I, this powerful technique will provide far greater sensitivity to any departures from the SM in the data anticipated from Run II.

  2. Measurement of the associated production of a single top quark and a W boson in single-lepton events with the ATLAS detector

    Energy Technology Data Exchange (ETDEWEB)

    Mergelmeyer, Sebastian

    2016-06-15

    The production of a single top quark in association with a W boson (Wt) is measured with the ATLAS detector using proton-proton collision events with one lepton, three jets and missing transverse energy at √(s)=8 TeV. Signal events are identified using an artificial neural network in an unconventional manner, addressing the large uncertainties due to the major background, which has an about 10 times larger cross section and a very similar signature compared with the Wt signal. State-of-the-art statistical methods are used to validate the modelling of the signal and the background, and to extract the cross section for Wt production. The cross section is found to be consistent with related measurements as well as the Standard Model prediction. In addition, a direct measurement of the CKM matrix element V{sub tb} is performed.

  3. Measurement of the associated production of a single top quark and a W boson in single-lepton events with the ATLAS detector

    International Nuclear Information System (INIS)

    Mergelmeyer, Sebastian

    2016-06-01

    The production of a single top quark in association with a W boson (Wt) is measured with the ATLAS detector using proton-proton collision events with one lepton, three jets and missing transverse energy at √(s)=8 TeV. Signal events are identified using an artificial neural network in an unconventional manner, addressing the large uncertainties due to the major background, which has an about 10 times larger cross section and a very similar signature compared with the Wt signal. State-of-the-art statistical methods are used to validate the modelling of the signal and the background, and to extract the cross section for Wt production. The cross section is found to be consistent with related measurements as well as the Standard Model prediction. In addition, a direct measurement of the CKM matrix element V_t_b is performed.

  4. Mutagenesis in Caenorhabditis elegans. II. A spectrum of mutational events induced with 1500 r of gamma-radiation

    International Nuclear Information System (INIS)

    Rosenbluth, R.E.; Cuddeford, C.; Baillie, D.L.

    1985-01-01

    The authors previously established a gamma-ray dose-response curve for recessive lethal events (lethals) captured over the eT1 balancer. In this paper they analyze the nature of lethal events produced, with a frequency of 0.04 per eT1 region, at a dose of 1500 r. To do so, they developed a protocol that, in the absence of cytogenetics, allows balanced lethals to be analyzed for associated chromosomal rearrangements. A set of 35 lethal strains was chosen for the analysis. Although the dosage was relatively low, a large number of multiple-break events were observed. The fraction of lethals associated with rearrangements was found to be 0.76. Currently most X- and gamma-ray dosages used for mutagenesis in C. elegans are 6000-8000 r. From the data it was conservatively estimated that 43% of rearrangements induced with 8000 r would be accompanied by additional chromosome breaks in the genome. With 1500 r the value was 5%. The 35 lethals studied were derived from 875 screened F1's. Among these lethals there were (1) at least two unc-36 duplications, (2) at least four translocations, (3) at least six deficiencies of chromosome V (these delete about 90% of the unc-60 to unc-42 region) and (4) several unanalyzed rearrangements. Thus, it is possible to recover desired rearrangements at reasonable rates with a dose of only 1500 r. The authors suggest that the levels of ionizing radiation employed in most published C. elegans studies are excessive and efforts should be made to use reduced levels in the future

  5. The Influence of Age at Single-Event Multilevel Surgery on Outcome in Children with Cerebral Palsy Who Walk with Flexed Knee Gait

    Science.gov (United States)

    Svehlik, Martin; Steinwender, Gerhard; Kraus, Tanja; Saraph, Vinay; Lehmann, Thomas; Linhart, Wolfgang E.; Zwick, Ernst B.

    2011-01-01

    Aim: Information on the timing and long-term outcome of single-event multilevel surgery in children with bilateral spastic cerebral palsy (CP) walking with flexed knee gait is limited. Based on our clinical experience, we hypothesized that older children with bilateral spastic CP would benefit more from single-event multilevel surgery than younger…

  6. A microprocessor-based single board computer for high energy physics event pattern recognition

    International Nuclear Information System (INIS)

    Bernstein, H.; Gould, J.J.; Imossi, R.; Kopp, J.K.; Love, W.A.; Ozaki, S.; Platner, E.D.; Kramer, M.A.

    1981-01-01

    A single board MC 68000 based computer has been assembled and bench marked against the CDC 7600 running portions of the pattern recognition code used at the MPS. This computer has a floating coprocessor to achieve throughputs equivalent to several percent that of the 7600. A major part of this work was the construction of a FORTRAN compiler including assembler, linker and library. The intention of this work is to assemble a large number of these single board computers in a parallel FASTBUS environment to act as an on-line and off-line filter for the raw data from MPS II and ISABELLE experiments. (orig.)

  7. Microprocessor-based single board computer for high energy physics event pattern recognition

    International Nuclear Information System (INIS)

    Bernstein, H.; Gould, J.J.; Imossi, R.; Kopp, J.K.; Love, W.A.; Ozaki, S.; Platner, E.D.; Kramer, M.A.

    1981-01-01

    A single board MC 68000 based computer has been assembled and bench marked against the CDC 7600 running portions of the pattern recognition code used at the MPS. This computer has a floating coprocessor to achieve throughputs equivalent to several percent that of the 7600. A major part of this work was the construction of a FORTRAN compiler including assembler, linker and library. The intention of this work is to assemble a large number of these single board computers in a parallel FASTBUS environment to act as an on-line and off-line filter for the raw data from MPS II and ISABELLE experiments

  8. Comparison between Radioisotopic and Non-radioisotopic Polymerase Chain Reaction-Single Strand Conformation Polymorphism (PCR-SSCP) Procedures in the Detection of Mutations at the rpoB Gene Associated with Rifampicin Resistance in Mycobacterium tuberculosis

    International Nuclear Information System (INIS)

    Lee, H.; Bang, H.E.; Johnson, R.; Jordaan, A.M.; Victor, T.C. . E-mail : tv@sun.ac.za; Dar, L.; Khan, B.K.; Cho, S.N. . E-mail : raycho@yonsei.ac.kr

    2006-01-01

    Rapid and sensitive detection of mutations at the rpoB gene of Mycobacterium tuberculosis would be of great importance for proper management of tuberculosis (TB) patients and control of multi-drug resistant TB. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) using both radioisotopic and non-radioisotopic methods have been widely used for detecting such mutations. However, the silver staining method, which is the most frequently employed in PCR-SSCP, has been reported to be producing results of varying sensitivity. Radioisotope-based methods have shown greater sensitivity in detecting the rpoB mutations than the silver staining method. The primary objective of this study was therefore to compare the radioisotopic method with the silver staining method detection of mutations of rpoB gene by PCR-SSCP in the same laboratory. Purified DNAs from M. tuberculosis H37Rv were serially diluted and used for PCR amplification with and without radionuclides. The PCR products were then detected by silver staining and autoradiography methods. In addition, clinical isolates were analyzed by PCR-SSCP. The radioisotopic method showed about four-fold increase in the detection of PCR products over ethidium bromide staining in agarose gel. When compared with silver staining, the radioisotopic method gave a sensitivity of more than 10-fold in detecting PCR products and about 8-fold in PCR-SSCP. Radioisotope-based detection methods provided a clearer resolution in PCR-SSCP than the silver staining method when applied to clinical isolates of M. tuberculosis. Radioisotope-based detection method was shown to be more sensitive than non-isotope-based method in detecting PCR products and mutations at the rpoB gene of M. tuberculosis by PCR-SSCP. It may be noted that mutations in the rpoB gene as a marker have significant clinical importance because of the increasing number of MDR-TB cases in the world. It is especially relevant to MDR and Extreme Drug Resistance TB

  9. A single-chip event sequencer and related microcontroller instrumentation for atomic physics research.

    Science.gov (United States)

    Eyler, E E

    2011-01-01

    A 16-bit digital event sequencer with 50 ns resolution and 50 ns trigger jitter is implemented by using an internal 32-bit timer on a dsPIC30F4013 microcontroller, controlled by an easily modified program written in standard C. It can accommodate hundreds of output events, and adjacent events can be spaced as closely as 1.5 μs. The microcontroller has robust 5 V inputs and outputs, allowing a direct interface to common laboratory equipment and other electronics. A USB computer interface and a pair of analog ramp outputs can be added with just two additional chips. An optional display/keypad unit allows direct interaction with the sequencer without requiring an external computer. Minor additions also allow simple realizations of other complex instruments, including a precision high-voltage ramp generator for driving spectrum analyzers or piezoelectric positioners, and a low-cost proportional integral differential controller and lock-in amplifier for laser frequency stabilization with about 100 kHz bandwidth.

  10. Mms Sensitivity of All Amino Acid-Requiring Mutants in Aspergillus and Its Suppression by Mutations in a Single Gene

    OpenAIRE

    Käfer, Etta

    1987-01-01

    All available amino acid-requiring mutants of Aspergillus nidulans were found to be hypersensitive to MMS (methyl methanesulfonate) to various degrees. On MMS media, secondary mutations could be selected which suppress this MMS sensitivity but do not affect the requirement. Many such mutations were analyzed and found to be alleles of one gene, smsA (= suppressor of MMS sensitivity), which mapped distal on the right arm of chromosome V. This gene is more likely to be involved in general regula...

  11. HFE gene mutation and iron overload in Egyptian pediatric acute lymphoblastic leukemia survivors: a single-center study.

    Science.gov (United States)

    El-Rashedi, Farida H; El-Hawy, Mahmoud A; El-Hefnawy, Sally M; Mohammed, Mona M

    2017-08-01

    Hereditary hemochromatosis gene (HFE) mutations have a role in iron overload in pediatric acute lymphoblastic leukemia (ALL) survivors. We aimed to evaluate the genotype frequency and allelic distribution of the two HFE gene mutations (C282Y and H63D) in a sample of Egyptian pediatric ALL survivors and to detect the impact of these two mutations on their iron profile. This study was performed on 35 ALL survivors during their follow-up visits to the Hematology and Oncology Unit, Pediatric Department, Menoufia University Hospitals. Thirty-five healthy children of matched age and sex were chosen as controls. After completing treatment course, ALL survivors were screened for the prevalence of these two mutations by polymerase chain reaction-restriction fragment length polymorphism. Serum ferritin levels were measured by an enzyme-linked immunosorbent assay technique (ELISA). C282Y mutation cannot be detected in any of the 35 survivors or the 35 controls. The H63D heterozygous state (CG) was detected in 28.6% of the survivors group and in 20% of controls, while the H63D homozygous (GG) state was detected in 17.1% of survivors. No compound heterozygosity (C282Y/H63D) was detected at both groups with high G allele frequency (31.4%) in survivors more than controls (10%). There were significant higher levels of iron parameters in homozygote survivors than heterozygotes and the controls. H63D mutation aggravates the iron overload status in pediatric ALL survivors.

  12. A single polymerase (L) mutation in avian metapneumovirus increased virulence and partially maintained virus viability at an elevated temperature.

    Science.gov (United States)

    Brown, Paul A; Lupini, Caterina; Catelli, Elena; Clubbe, Jayne; Ricchizzi, Enrico; Naylor, Clive J

    2011-02-01

    Previously, a virulent avian metapneumovirus, farm isolate Italy 309/04, was shown to have been derived from a live vaccine. Virulence due to the five nucleotide mutations associated with the reversion to virulence was investigated by their addition to the genome of the vaccine strain using reverse genetics. Virulence of these recombinant viruses was determined by infection of 1-day-old turkeys. Disease levels resulting from the combined two matrix mutations was indistinguishable from that produced by the recombinant vaccine, whereas the combined three L gene mutations increased disease to a level (P<0.0001) that was indistinguishable from that caused by the revertant Italy 309/04 virus. Testing of the L mutations individually showed that two mutations did not increase virulence, while the third mutation, corresponding to an asparagine to aspartic acid substitution, produced virulence indistinguishable from that caused by Italy 309/04. In contrast to the vaccine, the virulent mutant also showed increased viability at temperatures typical of turkey core tissues. The notion that increased viral virulence resulted from enhanced ability to replicate in tissues away from the cool respiratory tract, cannot be discounted.

  13. Traumatic stress symptomatology after child maltreatment and single traumatic events: different profiles

    NARCIS (Netherlands)

    Jonkman, Caroline S.; Verlinden, Eva; Bolle, Eva A.; Boer, Frits; Lindauer, Ramón J. L.

    2013-01-01

    The sequelae of child maltreatment tend to extend current posttraumatic stress disorder (PTSD) symptoms. This study examined this assumption, hypothesizing that (a) PTSD and trauma-related symptoms are more severe after single trauma than after child maltreatment; (b) symptoms unrelated to trauma

  14. Single-cell analysis of pyroptosis dynamics reveals conserved GSDMD-mediated subcellular events that precede plasma membrane rupture.

    Science.gov (United States)

    de Vasconcelos, Nathalia M; Van Opdenbosch, Nina; Van Gorp, Hanne; Parthoens, Eef; Lamkanfi, Mohamed

    2018-04-17

    Pyroptosis is rapidly emerging as a mechanism of anti-microbial host defense, and of extracellular release of the inflammasome-dependent cytokines interleukin (IL)-1β and IL-18, which contributes to autoinflammatory pathology. Caspases 1, 4, 5 and 11 trigger this regulated form of necrosis by cleaving the pyroptosis effector gasdermin D (GSDMD), causing its pore-forming amino-terminal domain to oligomerize and perforate the plasma membrane. However, the subcellular events that precede pyroptotic cell lysis are ill defined. In this study, we triggered primary macrophages to undergo pyroptosis from three inflammasome types and recorded their dynamics and morphology using high-resolution live-cell spinning disk confocal laser microscopy. Based on quantitative analysis of single-cell subcellular events, we propose a model of pyroptotic cell disintegration that is initiated by opening of GSDMD-dependent ion channels or pores that are more restrictive than recently proposed GSDMD pores, followed by osmotic cell swelling, commitment of mitochondria and other membrane-bound organelles prior to sudden rupture of the plasma membrane and full permeability to intracellular proteins. This study provides a dynamic framework for understanding cellular changes that occur during pyroptosis, and charts a chronological sequence of GSDMD-mediated subcellular events that define pyroptotic cell death at the single-cell level.

  15. SEARCH FOR DARK MATTER IN EVENTS WITH A SINGLE BOSON AND MISSING TRANSVERSE MOMENTUM WITH ATLAS

    CERN Document Server

    Brandt, Oleg; The ATLAS collaboration

    2017-01-01

    The presence of a non-baryonic dark matter component in the Universe is inferred from the observation of its gravitational interaction. If dark matter interacts weakly with the Standard Model it would be produced at the LHC, escaping the detector and leaving a large missing transverse momentum as their signature. The results of searches for Dark Matter with a single boson and large missing transverse momentum in 13 TeV will be presented.

  16. Automated Detection of Obstructive Sleep Apnea Events from a Single-Lead Electrocardiogram Using a Convolutional Neural Network.

    Science.gov (United States)

    Urtnasan, Erdenebayar; Park, Jong-Uk; Joo, Eun-Yeon; Lee, Kyoung-Joung

    2018-04-23

    In this study, we propose a method for the automated detection of obstructive sleep apnea (OSA) from a single-lead electrocardiogram (ECG) using a convolutional neural network (CNN). A CNN model was designed with six optimized convolution layers including activation, pooling, and dropout layers. One-dimensional (1D) convolution, rectified linear units (ReLU), and max pooling were applied to the convolution, activation, and pooling layers, respectively. For training and evaluation of the CNN model, a single-lead ECG dataset was collected from 82 subjects with OSA and was divided into training (including data from 63 patients with 34,281 events) and testing (including data from 19 patients with 8571 events) datasets. Using this CNN model, a precision of 0.99%, a recall of 0.99%, and an F 1 -score of 0.99% were attained with the training dataset; these values were all 0.96% when the CNN was applied to the testing dataset. These results show that the proposed CNN model can be used to detect OSA accurately on the basis of a single-lead ECG. Ultimately, this CNN model may be used as a screening tool for those suspected to suffer from OSA.

  17. A full-angle Monte-Carlo scattering technique including cumulative and single-event Rutherford scattering in plasmas

    Science.gov (United States)

    Higginson, Drew P.

    2017-11-01

    We describe and justify a full-angle scattering (FAS) method to faithfully reproduce the accumulated differential angular Rutherford scattering probability distribution function (pdf) of particles in a plasma. The FAS method splits the scattering events into two regions. At small angles it is described by cumulative scattering events resulting, via the central limit theorem, in a Gaussian-like pdf; at larger angles it is described by single-event scatters and retains a pdf that follows the form of the Rutherford differential cross-section. The FAS method is verified using discrete Monte-Carlo scattering simulations run at small timesteps to include each individual scattering event. We identify the FAS regime of interest as where the ratio of temporal/spatial scale-of-interest to slowing-down time/length is from 10-3 to 0.3-0.7; the upper limit corresponds to Coulomb logarithm of 20-2, respectively. Two test problems, high-velocity interpenetrating plasma flows and keV-temperature ion equilibration, are used to highlight systems where including FAS is important to capture relevant physics.

  18. Toehold-mediated strand displacement reaction triggered isothermal DNA amplification for highly sensitive and selective fluorescent detection of single-base mutation.

    Science.gov (United States)

    Zhu, Jing; Ding, Yongshun; Liu, Xingti; Wang, Lei; Jiang, Wei

    2014-09-15

    Highly sensitive and selective detection strategy for single-base mutations is essential for risk assessment of malignancy and disease prognosis. In this work, a fluorescent detection method for single-base mutation was proposed based on high selectivity of toehold-mediated strand displacement reaction (TSDR) and powerful signal amplification capability of isothermal DNA amplification. A discrimination probe was specially designed with a stem-loop structure and an overhanging toehold domain. Hybridization between the toehold domain and the perfect matched target initiated the TSDR along with the unfolding of the discrimination probe. Subsequently, the target sequence acted as a primer to initiate the polymerization and nicking reactions, which released a great abundant of short sequences. Finally, the released strands were annealed with the reporter probe, launching another polymerization and nicking reaction to produce lots of G-quadruplex DNA, which could bind the N-methyl mesoporphyrin IX to yield an enhanced fluorescence response. However, when there was even a single base mismatch in the target DNA, the TSDR was suppressed and so subsequent isothermal DNA amplification and fluorescence response process could not occur. The proposed approach has been successfully implemented for the identification of the single-base mutant sequences in the human KRAS gene with a detection limit of 1.8 pM. Furthermore, a recovery of 90% was obtained when detecting the target sequence in spiked HeLa cells lysate, demonstrating the feasibility of this detection strategy for single-base mutations in biological samples. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Single-well monitoring of protein-protein interaction and phosphorylation-dephosphorylation events.

    Science.gov (United States)

    Arcand, Mathieu; Roby, Philippe; Bossé, Roger; Lipari, Francesco; Padrós, Jaime; Beaudet, Lucille; Marcil, Alexandre; Dahan, Sophie

    2010-04-20

    We combined oxygen channeling assays with two distinct chemiluminescent beads to detect simultaneously protein phosphorylation and interaction events that are usually monitored separately. This novel method was tested in the ERK1/2 MAP kinase pathway. It was first used to directly monitor dissociation of MAP kinase ERK2 from MEK1 upon phosphorylation and to evaluate MAP kinase phosphatase (MKP) selectivity and mechanism of action. In addition, MEK1 and ERK2 were probed with an ATP competitor and an allosteric MEK1 inhibitor, which generated distinct phosphorylation-interaction patterns. Simultaneous monitoring of protein-protein interactions and substrate phosphorylation can provide significant mechanistic insight into enzyme activity and small molecule action.

  20. Modeling a Single SEP Event from Multiple Vantage Points Using the iPATH Model

    Science.gov (United States)

    Hu, Junxiang; Li, Gang; Fu, Shuai; Zank, Gary; Ao, Xianzhi

    2018-02-01

    Using the recently extended 2D improved Particle Acceleration and Transport in the Heliosphere (iPATH) model, we model an example gradual solar energetic particle event as observed at multiple locations. Protons and ions that are energized via the diffusive shock acceleration mechanism are followed at a 2D coronal mass ejection-driven shock where the shock geometry varies across the shock front. The subsequent transport of energetic particles, including cross-field diffusion, is modeled by a Monte Carlo code that is based on a stochastic differential equation method. Time intensity profiles and particle spectra at multiple locations and different radial distances, separated in longitudes, are presented. The results shown here are relevant to the upcoming Parker Solar Probe mission.

  1. Quantum theory of single events: Localized de Broglie-wavelets, Schroedinger waves and classical trajectories

    International Nuclear Information System (INIS)

    Barut, A.O.

    1990-06-01

    For an arbitrary potential V with classical trajectories x-vector=g-vector(t) we construct localized oscillating three-dimensional wave lumps ψ(x-vector,t,g-vector) representing a single quantum particle. The crest of the envelope of the ripple follows the classical orbit g-vector(t) slightly modified due to potential V and ψ(x-vector,t;g-vector) satisfies the Schroedinger equation. The field energy, momentum and angular momentum calculated as integrals over all space are equal to particle energy, momentum and angular momentum. The relation to coherent states and to Schroedinger waves are also discussed. (author). 6 refs

  2. It is highly unlikely that the development of an abdominal wall hernia can be attributable to a single strenuous event.

    Science.gov (United States)

    Pathak, Samir; Poston, Graeme J

    2006-03-01

    There is a commonly held belief that the development of a hernia can be attributed to a single strenuous or traumatic event. Hence, many litigants are successful in compensation claims, causing mounting financial burdens on employers, the courts, insurance companies and the tax-payer. However, there is very little scientific evidence to support this assertion. The aim of this study was to ascertain whether there was any causal link in this process. A total of 133 new patients with 135 abdominal herniae of all varieties (115 inguinal, 3 femoral, 9 umbilical, 4 incisional, and 4 ventral or epigastric), of which 25 were recurrent received structured questionnaires on arrival in the surgical clinic. These questionnaires covered all possible aetiological factors for hernia development (type of work, COAD, smoking, pregnancy, obesity, chronic bladder outflow obstruction, previous surgery including appendicectomy), in addition to any possible attribution to a single strenuous or traumatic event. We then reviewed the GP records in the surgery of all patients who answered positively to the latter possible cause. In the study group, 119 (89%) reported a gradual onset of symptoms. Of the 15 (12 male, 3 female; 11%) who believed that their hernia might be related to a single strenuous or traumatic event, 5 had no other aetiological factors. However, not one of the 15 was found to have contemporaneous forensic medical evidence to support their possible claim. We conclude that we are unable to find any clinical evidence to support the hypothesis that a hernia might develop as the result of one single strenuous or traumatic event. While we accept that this mechanism might still possibly occur, we believe that, at best, it is extremely uncommon. If a medical expert is preparing a report on such a case in a claim for personal injury, then they have a duty to the court to examine carefully all the contemporaneous medical records. If no clinical evidence exists to support the claim

  3. A template-free approach for determining the latency of single events of auditory evoked M100

    Energy Technology Data Exchange (ETDEWEB)

    Burghoff, M [Physikalisch-Technische Bundesanstalt (PTB), Berlin (Germany); Link, A [Physikalisch-Technische Bundesanstalt (PTB), Berlin (Germany); Salajegheh, A [Cognitive Neuroscience of Language Laboratory, University of Maryland College Park, MD (United States); Elster, C [Physikalisch-Technische Bundesanstalt (PTB), Berlin (Germany); Poeppel, D [Cognitive Neuroscience of Language Laboratory, University of Maryland College Park, MD (United States); Trahms, L [Physikalisch-Technische Bundesanstalt (PTB), Berlin (Germany)

    2005-02-07

    The phase of the complex output of a narrow band Gaussian filter is taken to define the latency of the auditory evoked response M100 recorded by magnetoencephalography. It is demonstrated that this definition is consistent with the conventional peak latency. Moreover, it provides a tool for reducing the number of averages needed for a reliable estimation of the latency. Single-event latencies obtained by this procedure can be used to improve the signal quality of the conventional average by latency adjusted averaging. (note)

  4. Single-Event Upset and Scaling Trends in New Generation of the Commercial SOI PowerPC Microprocessors

    Science.gov (United States)

    Irom, Farokh; Farmanesh, Farhad; Kouba, Coy K.

    2006-01-01

    Single-event upset effects from heavy ions are measured for Motorola silicon-on-insulator (SOI) microprocessor with 90 nm feature sizes. The results are compared with previous results for SOI microprocessors with feature sizes of 130 and 180 nm. The cross section of the 90 nm SOI processors is smaller than results for 130 and 180 nm counterparts, but the threshold is about the same. The scaling of the cross section with reduction of feature size and core voltage for SOI microprocessors is discussed.

  5. Single event and TREE latchup mitigation for a star tracker sensor: An innovative approach to system level latchup mitigation

    International Nuclear Information System (INIS)

    Kimbrough, J.R.; Colella, N.J.; Davis, R.W.; Bruener, D.B.; Coakley, P.G.; Lutjens, S.W.; Mallon, C.E.

    1994-08-01

    Electronic packages designed for spacecraft should be fault-tolerant and operate without ground control intervention through extremes in the space radiation environment. If designed for military use, the electronics must survive and function in a nuclear radiation environment. This paper presents an innovative ''blink'' approach rather than the typical ''operate through'' approach to achieve system level latchup mitigation on a prototype star tracker camera. Included are circuit designs, flash x-ray test data, and heavy ion data demonstrating latchup mitigation protecting micro-electronics from current latchup and burnout due to Single Event Latchup (SEL) and Transient Radiation Effects on Electronics (TREE)

  6. Nuclear data relevant to single event upsets in semiconductor memories induced by cosmic-ray neutrons and protons

    International Nuclear Information System (INIS)

    Watanabe, Yukinobu

    2008-01-01

    The role of nuclear data is examined in the study of single event upset (SEU) phenomena in semiconductor memories caused by cosmic-ray neutrons and protons. Neutron and proton SEU cross sections are calculated with a simplified semi-empirical model using experimental heavy-ion SEU cross-sections and a dedicated database of neutron and proton induced reactions on 28 Si. Some impacts of the nuclear reaction data on SEU simulation are analyzed by investigating relative contribution of secondary ions and neutron elastic scattering to SEU and influence of simultaneous multiple ions emission on SEU. (author)

  7. Synergistic effects of total ionizing dose on single event upset sensitivity in static random access memory under proton irradiation

    International Nuclear Information System (INIS)

    Xiao Yao; Guo Hong-Xia; Zhang Feng-Qi; Zhao Wen; Wang Yan-Ping; Zhang Ke-Ying; Ding Li-Li; Luo Yin-Hong; Wang Yuan-Ming; Fan Xue

    2014-01-01

    Synergistic effects of the total ionizing dose (TID) on the single event upset (SEU) sensitivity in static random access memories (SRAMs) were studied by using protons. The total dose was cumulated with high flux protons during the TID exposure, and the SEU cross section was tested with low flux protons at several cumulated dose steps. Because of the radiation-induced off-state leakage current increase of the CMOS transistors, the noise margin became asymmetric and the memory imprint effect was observed. (interdisciplinary physics and related areas of science and technology)

  8. Implications of the spatial dependence of the single-event-upset threshold in SRAMs measured with a pulsed laser

    International Nuclear Information System (INIS)

    Buchner, S.; Langworthy, J.B.; Stapor, W.J.; Campbell, A.B.; Rivet, S.

    1994-01-01

    Pulsed laser light was used to measure single event upset (SEU) thresholds for a large number of memory cells in both CMOS and bipolar SRAMs. Results showed that small variations in intercell upset threshold could not explain the gradual rise in the curve of cross section versus linear energy transfer (LET). The memory cells exhibited greater intracell variations implying that the charge collection efficiency within a memory cell varies spatially and contributes substantially to the shape of the curve of cross section versus LET. The results also suggest that the pulsed laser can be used for hardness-assurance measurements on devices with sensitive areas larger than the diameter of the laser beam

  9. Simulation of thermal-neutron-induced single-event upset using particle and heavy-ion transport code system

    International Nuclear Information System (INIS)

    Arita, Yutaka; Kihara, Yuji; Mitsuhasi, Junichi; Niita, Koji; Takai, Mikio; Ogawa, Izumi; Kishimoto, Tadafumi; Yoshihara, Tsutomu

    2007-01-01

    The simulation of a thermal-neutron-induced single-event upset (SEU) was performed on a 0.4-μm-design-rule 4 Mbit static random access memory (SRAM) using particle and heavy-ion transport code system (PHITS): The SEU rates obtained by the simulation were in very good agreement with the result of experiments. PHITS is a useful tool for simulating SEUs in semiconductor devices. To further improve the accuracy of the simulation, additional methods for tallying the energy deposition are required for PHITS. (author)

  10. A single point-mutation within the melanophilin gene causes the lavender plumage colour dilution phenotype in the chicken

    Directory of Open Access Journals (Sweden)

    Tixier-Boichard Michèle

    2008-01-01

    Full Text Available Abstract Background The lavender phenotype in the chicken causes the dilution of both black (eumelanin and red/brown (phaeomelanin pigments. Defects in three genes involved in intracellular melanosomal transport, previously described in mammals, give rise to similar diluted pigmentation phenotypes as those seen in lavender chickens. Results We have used a candidate-gene approach based on an expectation of homology with mammals to isolate a gene involved in pigmentation in chicken. Comparative sequence analysis of candidate genes in the chicken identified a strong association between a mutation in the MLPH gene and the diluted pigmentation phenotype. This mutation results in the amino acid change R35W, at a site also associated with similar phenotypes in mice, humans and cats. Conclusion This is the first time that an avian species with a mutation in the MLPH gene has been reported.

  11. mlh3 mutations in baker's yeast alter meiotic recombination outcomes by increasing noncrossover events genome-wide.

    Directory of Open Access Journals (Sweden)

    Najla Al-Sweel

    2017-08-01

    Full Text Available Mlh1-Mlh3 is an endonuclease hypothesized to act in meiosis to resolve double Holliday junctions into crossovers. It also plays a minor role in eukaryotic DNA mismatch repair (MMR. To understand how Mlh1-Mlh3 functions in both meiosis and MMR, we analyzed in baker's yeast 60 new mlh3 alleles. Five alleles specifically disrupted MMR, whereas one (mlh3-32 specifically disrupted meiotic crossing over. Mlh1-mlh3 representatives for each class were purified and characterized. Both Mlh1-mlh3-32 (MMR+, crossover- and Mlh1-mlh3-45 (MMR-, crossover+ displayed wild-type endonuclease activities in vitro. Msh2-Msh3, an MSH complex that acts with Mlh1-Mlh3 in MMR, stimulated the endonuclease activity of Mlh1-mlh3-32 but not Mlh1-mlh3-45, suggesting that Mlh1-mlh3-45 is defective in MSH interactions. Whole genome recombination maps were constructed for wild-type and MMR+ crossover-, MMR- crossover+, endonuclease defective and null mlh3 mutants in an S288c/YJM789 hybrid background. Compared to wild-type, all of the mlh3 mutants showed increases in the number of noncrossover events, consistent with recombination intermediates being resolved through alternative recombination pathways. Our observations provide a structure-function map for Mlh3 that reveals the importance of protein-protein interactions in regulating Mlh1-Mlh3's enzymatic activity. They also illustrate how defective meiotic components can alter the fate of meiotic recombination intermediates, providing new insights for how meiotic recombination pathways are regulated.

  12. Effects of drain-wall in mitigating N-hit single event transient via 45 nm CMOS process

    International Nuclear Information System (INIS)

    Xu, X Y; Tang, M H; Xiao, Y G; Yan, S A; Zhang, W L; Li, Z; Xiong, Y; Zhao, W; Guo, H X

    2015-01-01

    A three-dimensional (3D) technology computer-aided design (TCAD) simulation in a novel layout technique for N-hit single event transient (SET) mitigation based on drain-wall layout technique is proposed. Numerical simulations of both single-device and mixed-mode show that the proposed layout technique designed with 45 nm CMOS process can efficiently reduce not only charge collection but also SET pulse widths (W SET ). What is more, simulations show that impacts caused by part of ion-incidents can be shielded with this novel layout technique. When compared with conventional layout technique and guard drain layout technique, we find that the proposed novel layout technique can provide the best benefit of SET mitigation with a small sacrifice in effective area. (paper)

  13. Introduction of a point mutation into an HLA class I single-chain trimer induces enhancement of CTL priming and antitumor immunity

    Directory of Open Access Journals (Sweden)

    Masanori Matsui

    2014-01-01

    Full Text Available We previously discovered one particular HLA-A*02:01 mutant that enhanced peptide-specific cytotoxic T lymphocyte (CTL recognition in vitro compared to wild-type HLA-A*02:01. This mutant contains a single amino acid substitution from histidine to leucine at position 74 (H74L that is located in the peptide-binding groove. To investigate the effect of the H74L mutation on the in vivo CTL priming, we took advantage of the technology of the HLA class I single-chain trimer (SCT in which three components involving a peptide, β2 microglobulin and the HLA class I heavy chain are joined together via flexible linkers. We generated recombinant adenovirus expressing SCT comprised influenza A matrix protein (FMP-derived peptide, β2 microglobulin and the H74L heavy chain. HLA-A*02:01 transgenic mice were immunized with the adenovirus, and the induction of peptide-specific CTLs and antitumor immunity was investigated. It was clearly shown that the H74L mutation enabled the HLA-A*02:01 SCT molecule to dramatically enhance both in vivo priming of FMP-specific CTLs and protection against a lethal challenge of tumor cells expressing FMP. These data present the first evidence that a simple point mutation in the HLA class I heavy chain of SCT is beneficial for improving CTL-based immunotherapy and prophylaxis to control tumors.

  14. MMS sensitivity of all amino acid-requiring mutants in aspergillus and its suppression by mutations in a single gene.

    Science.gov (United States)

    Käfer, E

    1987-04-01

    All available amino acid-requiring mutants of Aspergillus nidulans were found to be hypersensitive to MMS (methyl methanesulfonate) to various degrees. On MMS media, secondary mutations could be selected which suppress this MMS sensitivity but do not affect the requirement. Many such mutations were analyzed and found to be alleles of one gene, smsA (= suppressor of MMS sensitivity), which mapped distal on the right arm of chromosome V. This gene is more likely to be involved in general regulation of amino acid biosynthesis than MMS uptake, since a variety of pathway interactions were clearly modified by smsA suppressors in the absence of MMS.

  15. Dramatic Response with Single-Agent Ibrutinib in Multiply Relapsed Marginal Zone Lymphoma with MYD88L265P Mutation

    Directory of Open Access Journals (Sweden)

    Ryan C. Lynch

    2017-09-01

    Full Text Available The B-cell receptor signaling pathway is important in the lymphomagenesis of many lymphomas, including marginal zone lymphoma (MZL. Herein we describe a case of extranodal MZL refractory to multiple lines of therapy. The presence of an IgM paraprotein prompted further evaluation, and the patient was found to have an MYD88L265P mutation. Treatment with ibrutinib led to a dramatic response with prompt resolution of symptoms and significant improvement in measurable sites of disease. The excellent response to ibrutinib in our patient with MYD88L265P-mutated refractory MZL supports a biological rationale for its use.

  16. Reduction of spontaneous somatic mutation frequency by a low-dose X irradiation of Drosophila larvae and possible involvement of DNA single-strand damage repair.

    Science.gov (United States)

    Koana, Takao; Takahashi, Takashi; Tsujimura, Hidenobu

    2012-03-01

    The third instar larvae of Drosophila were irradiated with X rays, and the somatic mutation frequency in their wings was measured after their eclosion. In the flies with normal DNA repair and apoptosis functions, 0.2 Gy irradiation at 0.05 Gy/min reduced the frequency of the so-called small spot (mutant cell clone with reduced reproductive activity) compared with that in the sham-irradiated flies. When apoptosis was suppressed using the baculovirus p35 gene, the small spot frequency increased four times in the sham-irradiated control group, but the reduction by the 0.2-Gy irradiation was still evident. In a non-homologous end joining-deficient mutant, the small spot frequency was also reduced by 0.2 Gy radiation. In a mutant deficient in single-strand break repair, no reduction in the small spot frequency by 0.2 Gy radiation was observed, and the small spot frequency increased with the radiation dose. Large spot (mutant cell clone with normal reproductive activity) frequency was not affected by suppression of apoptosis and increased monotonically with radiation dose in wild-type larvae and in mutants for single- or double-strand break repair. It is hypothesized that some of the small spots resulted from single-strand damage and, in wild-type larvae, 0.2 Gy radiation activated the normal single-strand break repair gene, which reduced the background somatic mutation frequency.

  17. Comparison of analytical models and experimental results for single-event upset in CMOS SRAMs

    International Nuclear Information System (INIS)

    Mnich, T.M.; Diehl, S.E.; Shafer, B.D.

    1983-01-01

    In an effort to design fully radiation-hardened memories for satellite and deep-space applications, a 16K and a 2K CMOS static RAM were modeled for single-particle upset during the design stage. The modeling resulted in the addition of a hardening feedback resistor in the 16K remained tentatively unaltered. Subsequent experiments, using the Lawrence Berkeley Laboratories' 88-inch cyclotron to accelerate krypton and oxygen ions, established an upset threshold for the 2K and the 16K without resistance added, as well as a hardening threshold for the 16K with feedback resistance added. Results for the 16K showed it to be hardenable to the higher level than previously published data for other unhardened 16K RAMs. The data agreed fairly well with the modeling results; however, a close look suggests that modification of the simulation methodology is required to accurately predict the resistance necessary to harden the RAM cell

  18. Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in Thoka sheep

    DEFF Research Database (Denmark)

    Nicel, Linda; Bishop, Stephen; Pong-Wong, Richardo

    2009-01-01

    and infertility in homozygotes. Analysis of homozygote ovarian morphology and a number of genes normally activated in growing follicles showed that GDF9 was not involved in oocyte activation, but in subsequent development of the follicle. This study highlights the importance of oocyte factors in regulating...... ovulation rate, although in some cases homozygous ewes are infertile. In the present study we present a detailed characterisation of a novel mutation in growth differentiation factor 9 (GDF9), found in Icelandic Thoka sheep. This mutation is a single base change (A1279C) resulting in a non-conservative...... fertility and provides new information for structural analysis and investigation of the potentially important sites of dimerization or translational modifications required to produce biologically active GDF9. It also provides the basis for the utilisation of these animals to enhance sheep production...

  19. Does red noise increase or decrease extinction risk? Single extreme events versus series of unfavorable conditions.

    Science.gov (United States)

    Schwager, Monika; Johst, Karin; Jeltsch, Florian

    2006-06-01

    Recent theoretical studies have shown contrasting effects of temporal correlation of environmental fluctuations (red noise) on the risk of population extinction. It is still debated whether and under which conditions red noise increases or decreases extinction risk compared with uncorrelated (white) noise. Here, we explain the opposing effects by introducing two features of red noise time series. On the one hand, positive autocorrelation increases the probability of series of poor environmental conditions, implying increasing extinction risk. On the other hand, for a given time period, the probability of at least one extremely bad year ("catastrophe") is reduced compared with white noise, implying decreasing extinction risk. Which of these two features determines extinction risk depends on the strength of environmental fluctuations and the sensitivity of population dynamics to these fluctuations. If extreme (catastrophic) events can occur (strong noise) or sensitivity is high (overcompensatory density dependence), then temporal correlation decreases extinction risk; otherwise, it increases it. Thus, our results provide a simple explanation for the contrasting previous findings and are a crucial step toward a general understanding of the effect of noise color on extinction risk.

  20. Single-Event Effect Testing of the Vishay Si7414DN n-Type TrenchFET(Registered Trademark) Power MOSFET

    Science.gov (United States)

    Lauenstein, J.-M.; Casey, M. C.; Campola, M. A.; Phan, A. M.; Wilcox, E. P.; Topper, A. D.; Ladbury, R. L.

    2017-01-01

    This study was being undertaken to determine the single event effect susceptibility of the commercial Vishay 60-V TrenchFET power MOSFET. Heavy-ion testing was conducted at the Texas AM University Cyclotron Single Event Effects Test Facility (TAMU) and the Lawrence Berkeley National Laboratory BASE Cyclotron Facility (LBNL). In addition, initial 200-MeV proton testing was conducted at Massachusetts General Hospital (MGH) Francis H. Burr Proton Beam Therapy Center. Testing was performed to evaluate this device for single-event effects from lower-LET, lighter ions relevant to higher risk tolerant space missions.

  1. Hereditary Persistence of Fetal Hemoglobin Caused by Single Nucleotide Promoter Mutations in Sickle Cell Trait and Hb SC Disease.

    Science.gov (United States)

    Akinbami, Anthony O; Campbell, Andrew D; Han, Zeqiu J; Luo, Hong-Yuan; Chui, David H K; Steinberg, Martin H

    2016-01-01

    Hereditary persistence of fetal hemoglobin (HPFH) can be caused by point mutations in the γ-globin gene promoters. We report three rare cases: a child compound heterozygous for Hb S (HBB: c.20A > T) and HPFH with a novel point mutation in the (A)γ-globin gene promoter who had 42.0% Hb S, 17.0% Hb A and 38.0% Hb F; a man with Hb SC (HBB: c.19G > A) disease and a point mutation in the (G)γ-globin gene promoter who had 54.0% Hb S, 18.0% Hb C and 25.0% Hb F; a child heterozygous for Hb S and HPFH due to mutations in both the (A)γ- and (G)γ-globin gene promoters in cis [(G)γ(A)γ(β(+)) HPFH], with 67.0% Hb A, 6.5% Hb S and 25.0% Hb F.

  2. A multiplex single nucleotide polymorphism typing assay for detecting mutations that result in decreased fluoroquinolone susceptibility in Salmonella enterica serovars Typhi and Paratyphi A.

    LENUS (Irish Health Repository)

    Song, Yajun

    2010-08-01

    OBJECTIVES: Decreased susceptibility to fluoroquinolones has become a major problem for the successful therapy of human infections caused by Salmonella enterica, especially the life-threatening typhoid and paratyphoid fevers. METHODS: By using Luminex xTAG beads, we developed a rapid, reliable and cost-effective multiplexed genotyping assay for simultaneously detecting 11 mutations in gyrA, gyrB and parE of S. enterica serovars Typhi and Paratyphi A that result in nalidixic acid resistance (Nal(R)) and\\/or decreased susceptibility to fluoroquinolones. RESULTS: This assay yielded unambiguous single nucleotide polymorphism calls on extracted DNA from 292 isolates of Salmonella Typhi (Nal(R) = 223 and Nal(S) = 69) and 106 isolates of Salmonella Paratyphi A (Nal(R) = 24 and Nal(S) = 82). All of the 247 Nal(R) Salmonella Typhi and Salmonella Paratyphi A isolates were found to harbour at least one of the target mutations, with GyrA Phe-83 as the most common one (143\\/223 for Salmonella Typhi and 18\\/24 for Salmonella Paratyphi A). We also identified three GyrB mutations in eight Nal(S) Salmonella Typhi isolates (six for GyrB Phe-464, one for GyrB Leu-465 and one for GyrB Asp-466), and mutations GyrB Phe-464 and GyrB Asp-466 seem to be related to the decreased ciprofloxacin susceptibility phenotype in Salmonella Typhi. This assay can also be used directly on boiled single colonies. CONCLUSIONS: The assay presented here would be useful for clinical and reference laboratories to rapidly screen quinolone-resistant isolates of Salmonella Typhi and Salmonella Paratyphi A, and decipher the underlying genetic changes for epidemiological purposes.

  3. Single-Event Effects in Power MOSFETs During Heavy Ion Irradiations Performed After Gamma-Ray Degradation

    Science.gov (United States)

    Busatto, G.; De Luca, V.; Iannuzzo, F.; Sanseverino, A.; Velardi, F.

    2013-10-01

    The robustness of commercial power metal-oxide semiconductor field-effect transistors to combined gamma-heavy ion irradiation has been investigated, evidence that the degradation of the gate oxide caused by the γ irradiation can severely corrupt the robustness to single-event effects and drastically modify the physical behavior of the device under test after the impact of a heavy ion. A decrease of the critical voltages at which destructive burnouts and gate ruptures for heavy ion impact appear, has been detected in the devices under test, which were previously irradiated with γ rays. In addition, the amount of critical voltage reduction is strictly related to the amount of the absorbed γ-ray dose. Furthermore, at the failure voltage, the behavior of the device is affected by the conduction of a current through the gate oxide. Moreover, the single-event gate rupture” of the device appears at lower voltages because of the reduction of the Fowler-Nordheim limit in the γ-irradiated devices.

  4. Neutron-induced Single Event Upset on the RPC front-end chips for the CMS experiment

    Energy Technology Data Exchange (ETDEWEB)

    Abbrescia, M.; Colaleo, A.; Iaselli, G.; Loddo, F.; Maggi, M.; Marangelli, B.; Natali, S.; Nuzzo, S.; Pugliese, G.; Ranieri, A.; Romano, F.; Altieri, S.; Belli, G.; Bruno, G.; Guida, R.; Merlo, M.; Ratti, S.P.; Riccardi, C.; Torre, P.; Vitulo, P. E-mail: paolo.vitulo@pv.infn.it; De Bari, A.; Manera, S

    2002-05-21

    Neutrons from a reactor and from a cyclotron have been used to characterise the CMS Resistive Plate Chambers (RPCs) front-end chip to neutron-induced damaging events. Single Event Upset (SEU) cross-sections have been measured up to 60 MeV for different chip thresholds. Tests at a reactor were done with an integrated fast (E{sub n}>3 MeV) neutron fluence of 1.7x10{sup 10} cm{sup -2} and a thermal neutron fluence of 9.5x10{sup 11} cm{sup -2}. High-energy neutrons from a cyclotron were used up to a fluence of 10{sup 12} cm{sup -2}. Data indicate the existence of a chip SEU sensitivity already at thermal energy and a saturated SEU cross-section from 3 to 60 MeV. Values of the SEU cross-sections from the thermal run well agree with those obtained by another CMS group that uses the same technology (0.8 {mu}m BiCMOS) though with different architecture. Cross-sections obtained with fast neutrons (from 3 MeV to about 10 MeV) are consistently higher by one order of magnitude compared to the thermal one. The average time between consecutive SEU events in each chip of the CMS barrel RPCs can be estimated to be 1 h.

  5. Search for anomalous Wtb couplings and top FCNC in t-channel single-top-quark events

    CERN Document Server

    CMS Collaboration

    2014-01-01

    Single-top-quark events in the $t$-channel are used to probe Wtb anomalous couplings and to search for top quark Flavor Changing Neutral Current (FCNC) interactions in proton-proton collisions at $\\sqrt{s}=7$ TeV. The analyzed data correspond to an integrated luminosity of 5~fb$^{-1}$. Events with the top quark decaying into a muon, neutrino and b-quark are selected. A Bayesian neural network is used to discriminate between signal and backgrounds. The observed event yields are consistent with SM prediction, and exclusion limits at 95\\% C.L. are determined. The exclusion limits on anomalous right vector and left tensor couplings of the Wtb vertex are found to be $|f_{V}^{R}|< 0.34$ and $|f_{T}^{L}|<0.09$. In the scenarios with FCNC tcg and tug couplings, limits on the coupling strengths are found to be $\\kappa_{tug}/\\Lambda < 1.8 \\cdot 10^{-2}~ \\mathrm{TeV^{-1}},\\ \\kappa_{tcg}/\\Lambda < 5.6 \\cdot 10^{-2} ~ \\mathrm{TeV^{-1}}$ which corresponds to limits on the branching ratios $Br(t~\\rightarrow~u+g)...

  6. Role of multisensory stimuli in vigilance enhancement- a single trial event related potential study.

    Science.gov (United States)

    Abbasi, Nida Itrat; Bodala, Indu Prasad; Bezerianos, Anastasios; Yu Sun; Al-Nashash, Hasan; Thakor, Nitish V

    2017-07-01

    Development of interventions to prevent vigilance decrement has important applications in sensitive areas like transportation and defence. The objective of this work is to use multisensory (visual and haptic) stimuli for cognitive enhancement during mundane tasks. Two different epoch intervals representing sensory perception and motor response were analysed using minimum variance distortionless response (MVDR) based single trial ERP estimation to understand the performance dependency on both factors. Bereitschaftspotential (BP) latency L3 (r=0.6 in phase 1 (visual) and r=0.71 in phase 2 (visual and haptic)) was significantly correlated with reaction time as compared to that of sensory ERP latency L2 (r=0.1 in both phase 1 and phase 2). This implies that low performance in monotonous tasks is predominantly dependent on the prolonged neural interaction with the muscles to initiate movement. Further, negative relationship was found between the ERP latencies related to sensory perception and Bereitschaftspotential (BP) and occurrence of epochs when multisensory cues are provided. This means that vigilance decrement is reduced with the help of multisensory stimulus presentation in prolonged monotonous tasks.

  7. Study of single-particle correlations in events with the total disintegration of nuclei

    International Nuclear Information System (INIS)

    Abdinov, O.B.; Bagirov, A.M.; Sulejmanov, M.K.; Anoshin, A.I.; Bogdanowicz, J.; Kuznetsov, A.A.

    1997-01-01

    New experimental data on the behaviour of the single-particle two-dimensional correlation functions R versus Q (Q is the number of nucleons emitted from nuclei) and A p (A p is the mass of projectile nuclei) are presented. The interactions of π - -mesons (at a momentum of 40 GeV/c), protons, d, 4 He and 12 C nuclei with carbon nuclei (at a momentum of 4.2 A GeV/c) are considered. The values of R are obtained separately for π - -mesons and protons. In so doing, the values of R are normalised so that -1≤R≤1. The value of R=0 corresponds to the case of the absence of correlations. It has been found that the Q- and A p -dependence of R takes place only for weak correlations (R t and have a nonlinear character, that is the regions with different characters of the Q-dependence of R are separated: there is a change of regimes in the Q-dependences of R. The boundary values of Q=Q*, corresponding to the transitions from one dependence region to another, are determined. The correlations weaken with increasing A p , and they become minimum in 12 CC interactions. Simultaneously with weakening the correlations in the region of large Q≥Q*, the character of the Q-dependence of R changes

  8. Classification of Single-Trial Auditory Events Using Dry-Wireless EEG During Real and Motion Simulated Flight

    Directory of Open Access Journals (Sweden)

    Daniel eCallan

    2015-02-01

    Full Text Available Application of neuro-augmentation technology based on dry-wireless EEG may be considerably beneficial for aviation and space operations because of the inherent dangers involved. In this study we evaluate classification performance of perceptual events using a dry-wireless EEG system during motion platform based flight simulation and actual flight in an open cockpit biplane to determine if the system can be used in the presence of considerable environmental and physiological artifacts. A passive task involving 200 random auditory presentations of a chirp sound was used for evaluation. The advantage of this auditory task is that it does not interfere with the perceptual motor processes involved with piloting the plane. Classification was based on identifying the presentation of a chirp sound versus silent periods. Evaluation of Independent component analysis and Kalman filtering to enhance classification performance by extracting brain activity related to the auditory event from other non-task related brain activity and artifacts was assessed. The results of permutation testing revealed that single trial classification of presence or absence of an auditory event was significantly above chance for all conditions on a novel test set. The best performance could be achieved with both ICA and Kalman filtering relative to no processing: Platform Off (83.4% vs 78.3%, Platform On (73.1% vs 71.6%, Biplane Engine Off (81.1% vs 77.4%, and Biplane Engine On (79.2% vs 66.1%. This experiment demonstrates that dry-wireless EEG can be used in environments with considerable vibration, wind, acoustic noise, and physiological artifacts and achieve good single trial classification performance that is necessary for future successful application of neuro-augmentation technology based on brain-machine interfaces.

  9. Mature Microsatellites: Mechanisms Underlying Dinucleotide Microsatellite Mutational Biases in Human Cells

    OpenAIRE

    Baptiste, Beverly A.; Ananda, Guruprasad; Strubczewski, Noelle; Lutzkanin, Andrew; Khoo, Su Jen; Srikanth, Abhinaya; Kim, Nari; Makova, Kateryna D.; Krasilnikova, Maria M.; Eckert, Kristin A.

    2013-01-01

    Dinucleotide microsatellites are dynamic DNA sequences that affect genome stability. Here, we focused on mature microsatellites, defined as pure repeats of lengths above the threshold and unlikely to mutate below it in a single mutational event. We investigated the prevalence and mutational behavior of these sequences by using human genome sequence data, human cells in culture, and purified DNA polymerases. Mature dinucleotides (?10 units) are present within exonic sequences of >350 genes, re...

  10. 3-D topological signatures and a new discrimination method for single-electron events and 0νββ events in CdZnTe: A Monte Carlo simulation study

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Ming; Li, Teng-Lin; Cang, Ji-Rong [Key Laboratory of Particle & Radiation Imaging (Tsinghua University), Ministry of Education (China); Department of Engineering Physics, Tsinghua University, Beijing 100084 (China); Zeng, Zhi, E-mail: zengzhi@tsinghua.edu.cn [Key Laboratory of Particle & Radiation Imaging (Tsinghua University), Ministry of Education (China); Department of Engineering Physics, Tsinghua University, Beijing 100084 (China); Fu, Jian-Qiang; Zeng, Wei-He; Cheng, Jian-Ping; Ma, Hao; Liu, Yi-Nong [Key Laboratory of Particle & Radiation Imaging (Tsinghua University), Ministry of Education (China); Department of Engineering Physics, Tsinghua University, Beijing 100084 (China)

    2017-06-21

    In neutrinoless double beta (0νββ) decay experiments, the diversity of topological signatures of different particles provides an important tool to distinguish double beta events from background events and reduce background rates. Aiming at suppressing the single-electron backgrounds which are most challenging, several groups have established Monte Carlo simulation packages to study the topological characteristics of single-electron events and 0νββ events and develop methods to differentiate them. In this paper, applying the knowledge of graph theory, a new topological signature called REF track (Refined Energy-Filtered track) is proposed and proven to be an accurate approximation of the real particle trajectory. Based on the analysis of the energy depositions along the REF track of single-electron events and 0νββ events, the REF energy deposition models for both events are proposed to indicate the significant differences between them. With these differences, this paper presents a new discrimination method, which, in the Monte Carlo simulation, achieved a single-electron rejection factor of 93.8±0.3 (stat.)% as well as a 0νββ efficiency of 85.6±0.4 (stat.)% with optimized parameters in CdZnTe.

  11. Analyzing Test-As-You-Fly Single Event Upset (SEU) Responses using SEU Data, Classical Reliability Models, and Space Environment Data

    Science.gov (United States)

    Berg, Melanie; Label, Kenneth; Campola, Michael; Xapsos, Michael

    2017-01-01

    We propose a method for the application of single event upset (SEU) data towards the analysis of complex systems using transformed reliability models (from the time domain to the particle fluence domain) and space environment data.

  12. Compendium of Single Event Effects Test Results for Commercial Off-The-Shelf and Standard Electronics for Low Earth Orbit and Deep Space Applications

    Science.gov (United States)

    Reddell, Brandon D.; Bailey, Charles R.; Nguyen, Kyson V.; O'Neill, Patrick M.; Wheeler, Scott; Gaza, Razvan; Cooper, Jaime; Kalb, Theodore; Patel, Chirag; Beach, Elden R.; hide

    2017-01-01

    We present the results of Single Event Effects (SEE) testing with high energy protons and with low and high energy heavy ions for electrical components considered for Low Earth Orbit (LEO) and for deep space applications.

  13. Characterization of System on a Chip (SoC) Single Event Upset (SEU) Responses Using SEU Data, Classical Reliability Models, and Space Environment Data

    Science.gov (United States)

    Berg, Melanie; Label, Kenneth; Campola, Michael; Xapsos, Michael

    2017-01-01

    We propose a method for the application of single event upset (SEU) data towards the analysis of complex systems using transformed reliability models (from the time domain to the particle fluence domain) and space environment data.

  14. Hearing impairment caused by mutations in two different genes responsible for nonsyndromic and syndromic hearing loss within a single family.

    Science.gov (United States)

    Niepokój, Katarzyna; Rygiel, Agnieszka M; Jurczak, Piotr; Kujko, Aleksandra A; Śniegórska, Dominika; Sawicka, Justyna; Grabarczyk, Alicja; Bal, Jerzy; Wertheim-Tysarowska, Katarzyna

    2018-02-01

    Usher syndrome is rare genetic disorder impairing two human senses, hearing and vision, with the characteristic late onset of vision loss. This syndrome is divided into three types. In all cases, the vision loss is postlingual, while loss of hearing is usually prelingual. The vestibular functions may also be disturbed in Usher type 1 and sometimes in type 3. Vestibular areflexia is helpful in making a proper diagnosis of the syndrome, but, often, the syndrome is misdiagnosed as a nonsyndromic hearing loss. Here, we present a Polish family with hearing loss, which was clinically classified as nonsyndromic. After excluding mutations in the DFNB1 locus, we implemented the next-generation sequencing method and revealed that hearing loss was syndromic and mutations in the USH2A gene indicate Usher syndrome. This research highlights the importance of molecular analysis in establishing a clinical diagnosis of congenital hearing loss.

  15. Translesion DNA synthesis and mutation induced in a plasmid with a single adduct of the environmental contaminant 3-nitrobenzanthrone in SOS-induced Escherichia coli

    International Nuclear Information System (INIS)

    Kawanishi, M.; Kanno, T.; Yagi, T.; Enya-Takamura, T.; Fuchs, R.P.

    2003-01-01

    Full text: 3-Nitrobenzanthrone (NBA) is a powerfully mutagenic nitrated aromatic hydrocarbon found in diesel exhaust and in airborne particulate matters. NBA forms an unusual DNA adduct in vitro that has a C-C bond between the C-8 position of deoxyguanosine and the C-2 position of NBA. We previously found that this adduct is also present in the human cells treated with NBA, and induces mutations in supF shuttle vector system. In this study, we analyzed translesion DNA synthesis (TLS) over a single adduct in lacZ' gene in a plasmid in uvrAmutS Escherichia coli. The result showed that the adduct blocked DNA replication and an observed TLS frequency was 5.4% in non-SOS-induced E. coli. All progenies after the TLS had no mutation. On the other hand, TLS increased to 11.3%, and 4.8% of them had mostly G to T mutations in SOS-induced E. coli. These results suggest that this unusual adduct would be one of causes of lung cancer that is increasing in the urban areas polluted with diesel exhaust. It must be interesting to reveal which DNA polymerase is involved in this TLS

  16. New method for selection and characterization of single-source events in Ni+Ni collisions at 32 A.MeV

    International Nuclear Information System (INIS)

    Maskay-Wallez, Anne-Marie

    1999-01-01

    The study of heavy ion collisions, with the help of such efficient multi-detectors as INDRA, has shown the persistence of reactions leading to single-source events, up to bombarding energies higher than the Fermi one. These events could help characterizing an expected phase transition in nuclear matter. Whatever interesting they may be, the single-source events correspond to a small part of the total cross section, which makes them difficult to isolate and therefore to analyze. That is why different selection means have been tested - thanks to the 'Simon' event generator - on a simulated Ni + Ni at 32 A·MeV sample, before any application to the INDRA experimental data. As the known methods based on global variables did not prove effective, a set of new 4-dimensional quantities has been built, whose main advantage lies in a better description of physical events. From a Discriminant Analysis performed on 625 of these new 'moments' proceeds a highly discriminant variable, called D 625 . The experimental cross section associated with D 625 -selected single-source events amounts to 170 mb at 32 A·MeV. Such quasi-fusion events are shown to disappear at about 60 A·MeV. As regards the deexcitation mode of the 32 A·MeV Ni + Ni single-source events, an extensive experimental study and comparisons of the data with two reference models seem to confirm the hypothesis of a transition between fusion-evaporation and simultaneous multifragmentation mechanisms. (author)

  17. Single-event phenomena on recent semiconductor devices. Charge-type multiple-bit upsets in high integrated memories

    International Nuclear Information System (INIS)

    Makihara, Akiko; Shindou, Hiroyuki; Nemoto, Norio; Kuboyama, Satoshi; Matsuda, Sumio; Ohshima, Takeshi; Hirao, Toshio; Itoh, Hisayoshi

    2001-01-01

    High integrated memories are used in solid state data recorder (SSDR) of the satellite for accumulating observation data. Single event upset phenomena which turn over an accumulated data in the memory cells are caused by heavy ion incidence. Studies on single-bit upset and multiple-bit upset phenomena in the high integrated memory cells are in progress recently. 16 Mbit DRAM (Dynamic Random Access Memories) and 64 Mbit DRAM are irradiated by heavy ion species, such as iodine, bromine and nickel, in comparison with the irradiation damage in the cosmic environment. Data written on the memory devices are read out after the irradiation. The memory cells in three kinds of states, all of charged state, all of discharged state, and an alternative state of charge and discharge, are irradiated for sorting out error modes caused by heavy ion incidence. The soft error in a single memory cells is known as a turn over from charged state to discharged state. Electrons in electron-hole pair generated by heavy ion incidence are captured in a diffusion region between capacitor electrodes of semiconductor. The charged states in the capacitor electrodes before the irradiation are neutralized and changed to the discharged states. According to high integration of the memories, many of the cells are affected by a single ion incidence. The multiple-bit upsets, however, are generated in the memory cells of discharged state before the irradiation, also. The charge-type multiple-bit upsets is considered as that error data are written on the DRAM during refresh cycle of a sense-up circuit and a pre-charge circuit which control the DRAM. (M. Suetake)

  18. Acquired copy-neutral loss of heterozygosity of chromosome 1p as a molecular event associated with marrow fibrosis in MPL-mutated myeloproliferative neoplasms.

    Science.gov (United States)

    Rumi, Elisa; Pietra, Daniela; Guglielmelli, Paola; Bordoni, Roberta; Casetti, Ilaria; Milanesi, Chiara; Sant'Antonio, Emanuela; Ferretti, Virginia; Pancrazzi, Alessandro; Rotunno, Giada; Severgnini, Marco; Pietrelli, Alessandro; Astori, Cesare; Fugazza, Elena; Pascutto, Cristiana; Boveri, Emanuela; Passamonti, Francesco; De Bellis, Gianluca; Vannucchi, Alessandro; Cazzola, Mario

    2013-05-23

    We studied mutations of MPL exon 10 in patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF), first investigating a cohort of 892 consecutive patients. MPL mutation scanning was performed on granulocyte genomic DNA by using a high-resolution melt assay, and the mutant allele burden was evaluated by using deep sequencing. Somatic mutations of MPL, all but one involving codon W515, were detected in 26/661 (4%) patients with ET, 10/187 (5%) with PMF, and 7/44 (16%) patients with post-ET myelofibrosis. Comparison of JAK2 (V617F)-mutated and MPL-mutated patients showed only minor phenotypic differences. In an extended group of 62 MPL-mutated patients, the granulocyte mutant allele burden ranged from 1% to 95% and was significantly higher in patients with PMF or post-ET myelofibrosis compared with those with ET. Patients with higher mutation burdens had evidence of acquired copy-neutral loss of heterozygosity (CN-LOH) of chromosome 1p in granulocytes, consistent with a transition from heterozygosity to homozygosity for the MPL mutation in clonal cells. A significant association was found between MPL-mutant allele burden greater than 50% and marrow fibrosis. These observations suggest that acquired CN-LOH of chromosome 1p involving the MPL location may represent a molecular mechanism of fibrotic transformation in MPL-mutated myeloproliferative neoplasms.

  19. [Incidence rate of adverse reaction/event by Qingkailing injection: a Meta-analysis of single rate].

    Science.gov (United States)

    Ai, Chun-ling; Xie, Yan-ming; Li, Ming-quan; Wang, Lian-xin; Liao, Xing

    2015-12-01

    To systematically review the incidence rate of adverse drug reaction/event by Qingkailing injection. Such databases as the PubMed, EMbase, the Cochrane library, CNKI, VIP WanFang data and CBM were searched by computer from foundation to July 30, 2015. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and cross check data. Then, Meta-analysis was performed by using the R 3.2.0 software, subgroup sensitivity analysis was performed based on age, mode of medicine, observation time and research quality. Sixty-three studies involving 9,793 patients with Qingkailing injection were included, 367 cases of adverse reactions/events were reported in total. The incidence rate of adverse reaction in skin and mucosa group was 2% [95% CI (0.02; 0.03)]; the digestive system adverse reaction was 6% [95% CI(0.05; 0.07); the injection site adverse reaction was 4% [95% CI (0.02; 0.07)]. In the digestive system as the main types of adverse reactions/events, incidence of children and adults were 4.6% [0.021 1; 0.097 7] and 6.9% [0.053 5; 0.089 8], respectively. Adverse reactions to skin and mucous membrane damage as the main performance/event type, the observation time > 7 days and ≤ 7 days incidence of 3% [0.012 9; 0.068 3] and 1.9% [0.007 8; 0.046 1], respectively. Subgroup analysis showed that different types of adverse reactions, combination in the incidence of adverse reactions/events were higher than that of single drug, the difference was statistically significant (P reactions occur, and clinical rational drug use, such as combination, age and other fators, and the influence factors vary in different populations. Therefore, clinical doctors for children and the elderly use special care was required for a clear and open spirit injection, the implementation of individualized medication.

  20. Experimental and simulation studies of neutron-induced single-event burnout in SiC power diodes

    Science.gov (United States)

    Shoji, Tomoyuki; Nishida, Shuichi; Hamada, Kimimori; Tadano, Hiroshi

    2014-01-01

    Neutron-induced single-event burnouts (SEBs) of silicon carbide (SiC) power diodes have been investigated by white neutron irradiation experiments and transient device simulations. It was confirmed that a rapid increase in lattice temperature leads to formation of crown-shaped aluminum and cracks inside the device owing to expansion stress when the maximum lattice temperature reaches the sublimation temperature. SEB device simulation indicated that the peak lattice temperature is located in the vicinity of the n-/n+ interface and anode contact, and that the positions correspond to a hammock-like electric field distribution caused by the space charge effect. Moreover, the locations of the simulated peak lattice temperature agree closely with the positions of the observed destruction traces. Furthermore, it was theoretically demonstrated that the period of temperature increase of a SiC power device is two orders of magnitude less than that of a Si power device, using a thermal diffusion equation.

  1. Monte Carlo calculation of the cross-section of single event upset induced by 14MeV neutrons

    International Nuclear Information System (INIS)

    Li, H.; Deng, J.Y.; Chang, D.M.

    2005-01-01

    High-density static random access memory may experience single event upsets (SEU) in neutron environments. We present a new method to calculate the SEU cross-section. Our method is based on explicit generation and transport of the secondary reaction products and detailed accounting for energy loss by ionization. Instead of simulating the behavior of the circuit, we use the Monte Carlo method to simulate the process of energy deposition in sensitive volumes. Thus, we do not need to know details about the circuit. We only need a reasonable guess for the size of the sensitive volumes. In the Monte Carlo simulation, the cross-section of SEU induced by 14MeV neutrons is calculated. We can see that the Monte Carlo simulation not only can provide a new method to calculate SEU cross-section, but also can give a detailed description about random process of the SEU

  2. Nuclear data relevant to single-event upsets (SEU) in microelectronics and their application to SEU simulation

    International Nuclear Information System (INIS)

    Watanabe, Yukinobu; Tukamoto, Yasuyuki; Kodama, Akihiro; Nakashima, Hideki

    2004-01-01

    A cross-section database for neutron-induced reactions on 28 Si was developed in the energy range between 2 MeV and 3 GeV in order to analyze single-event upsets (SEUs) phenomena induced by cosmic-ray neutrons in microelectronic devices. A simplified spherical device model was proposed for simulation of the initial process of SEUs. The model was applied to SEU cross-section calculations for semiconductor memory devices. The calculated results were compared with measured SEU cross-sections and the other simulation result. The dependence of SEU cross-sections on incident neutron energy and secondary ions having the most important effects on SEUs are discussed. (author)

  3. Comparison Elements on STG DICE cell for Content-Addressable Memory and Simulation of Single-Event Transients

    Directory of Open Access Journals (Sweden)

    V. Ya. Stenin

    2017-06-01

    Full Text Available Comparison elements on base the STG DICE cell and the logical element “Exclusive OR” for a content-addressable memory were designed and simulated. The comparison element contains two identical joint groups of transistors that are spaced on the chip by the distance of four micrometers, so the loss of data in STG DICE cell practically excluded. On the characteristics of the new 65-nm CMOS comparison element, we predict the hardness of these item to single event rate (SER more to hundred times compared to elements on 6-transistors cells and the standard DICE cell with distances 0.5-0.6 μm between mutually sensitive nodes.

  4. Investigation of radial dose effect on single event upset cross-section due to heavy ions using GEANT4

    International Nuclear Information System (INIS)

    Boorboor, S.; Feghhi, S.A.H.; Jafari, H.

    2015-01-01

    The heavy ions are the main cause to produce single event upset (SEU) damage on electronic devices since they are high LET radiations. The dimension of electronic components in new technology, arise a challenge in radiation effect estimations. Accurate investigations require fully considering the ion track in energy deposition as a radial dose distribution. In this work, the distribution of delta rays as well as LET have been calculated to determine ionization structure around ion track by a Monte Carlo code, GEANT4. The radial dose of several heavy ions with different energy in silicon was investigated and compared with the works by other authors in this field. The results showed that heavy ions with identical LET can have different SEU cross-section in silicon transistors. As a demonstrative example, according to our results, the error probability for 4.8 GeV iron was 8 times greater than that for 15 MeV carbon ions, in transistors with new process technology which have small dimension and low critical charges. Our results show that considering radial dose distribution considerably improves the accuracy of the SEU cross-section estimation in electronic devices especially for new technologies. - Highlights: • The single event upset is produced by heavy ions interaction on electronic devices. • The radial dose of several heavy ions in silicon was calculated by GEANT4. • Heavy ions with identical LET had different SEU cross-section in silicon transistors. • Low dimension and critical charge devices were more sensitive to radial dose effect

  5. Induction of lacI- mutations in Escherichia coli cells after single and split-dose irradiation

    International Nuclear Information System (INIS)

    Kozubek, S.; Ryznar, L.

    1992-01-01

    In the lacI system of Escherichia coli, X-ray mutagenesis follows a linear-quadratic curve with suppression; the survival curve is exponential. Dose fractionation leads to nearly complete repair of premutational lesions during an incubation interval of 3.5 h. Repair starts with a delay of 1.5-2 h, suggesting the involvement of an inducible repair/mutation fixation system. The dose-dependence of mutagenesis is described by a simple model assuming two hits being required. A probable explanation might be that the premutagenic lesions consist of two closely spaced lesions on the opposite strands of the DNA molecule. (author)

  6. Effect of vitamin E on cytotoxicity, DNA single strand breaks, chromosomal aberrations, and mutation in Chinese hamster V-79 cells exposed to ultraviolet-B light

    International Nuclear Information System (INIS)

    Sugiyama, M.; Tsuzuki, K.; Matsumoto, K.; Ogura, R.

    1992-01-01

    The effect of pretreatment with vitamin E on cytotoxicity, DNA single strand breaks, and chromosomal aberrations as well as on mutation induced by ultraviolet-B light (UV-B) was investigated in Chinese hamster V-79 cells. Cellular pretreatment with non-toxic levels of 25 μM α-tocopherol succinate (vitamin E) for 24h prior to exposure resulted in a 10-fold increase in cellular levels of α-tocopherol. Using a colony-forming assay, this pretreatment decreased the cytotoxicity of UV-B light. However, alkaline elution assays demonstrated that pretreatment with vitamin E did not affect the number of DNA single strand breaks caused by UV-B light. UV-B exposure produced a dose-dependent induction of chromosomal aberrations and mutations at the HGPRT locus, and neither of these actions of UV-B was influenced by pretreatment with the vitamin. These results suggest that vitamin E protects cells from UV-B-induced cytotoxicity, possibly through its ability to scavenge free radicals. The genotoxicity induced by UV-B light may not correlate directly with the cytotoxic action of this wavelength region in sunlight. (author)

  7. Single event time series analysis in a binary karst catchment evaluated using a groundwater model (Lurbach system, Austria).

    Science.gov (United States)

    Mayaud, C; Wagner, T; Benischke, R; Birk, S

    2014-04-16

    The Lurbach karst system (Styria, Austria) is drained by two major springs and replenished by both autogenic recharge from the karst massif itself and a sinking stream that originates in low permeable schists (allogenic recharge). Detailed data from two events recorded during a tracer experiment in 2008 demonstrate that an overflow from one of the sub-catchments to the other is activated if the discharge of the main spring exceeds a certain threshold. Time series analysis (autocorrelation and cross-correlation) was applied to examine to what extent the various available methods support the identification of the transient inter-catchment flow observed in this binary karst system. As inter-catchment flow is found to be intermittent, the evaluation was focused on single events. In order to support the interpretation of the results from the time series analysis a simplified groundwater flow model was built using MODFLOW. The groundwater model is based on the current conceptual understanding of the karst system and represents a synthetic karst aquifer for which the same methods were applied. Using the wetting capability package of MODFLOW, the model simulated an overflow similar to what has been observed during the tracer experiment. Various intensities of allogenic recharge were employed to generate synthetic discharge data for the time series analysis. In addition, geometric and hydraulic properties of the karst system were varied in several model scenarios. This approach helps to identify effects of allogenic recharge and aquifer properties in the results from the time series analysis. Comparing the results from the time series analysis of the observed data with those of the synthetic data a good agreement was found. For instance, the cross-correlograms show similar patterns with respect to time lags and maximum cross-correlation coefficients if appropriate hydraulic parameters are assigned to the groundwater model. The comparable behaviors of the real and the

  8. Mutations in conserved amino acids in the KCNQ1 channel and risk of cardiac events in type-1 long-QT syndrome

    DEFF Research Database (Denmark)

    Jons, Christian; Moss, Arthur J; Lopes, Coeli M

    2009-01-01

    BACKGROUND: Type-1 long-QT syndrome (LQT1) is caused by mutations in the KCNQ1 gene. The purpose of this study was to investigate whether KCNQ1 mutations in highly conserved amino acid residues within the voltage-gated potassium channel family are associated with an increased risk of cardiac even...

  9. One-by-one single-molecule detection of mutated nucleobases by monitoring tunneling current using a DNA tip.

    Science.gov (United States)

    Bui, Phuc Tan; Nishino, Tomoaki; Shiigi, Hiroshi; Nagaoka, Tsutomu

    2015-01-31

    A DNA molecule was utilized as a probe tip to achieve single-molecule genetic diagnoses. Hybridization of the probe and target DNAs resulted in electron tunneling along the emergent double-stranded DNA. Simple stationary monitoring of the tunneling current leads to single-molecule DNA detection and discovery of base mismatches and methylation.

  10. Delineation of Ehlers-Danlos syndrome phenotype due to the c.934C>T, p.(Arg312Cys) mutation in COL1A1: Report on a three-generation family without cardiovascular events, and literature review.

    Science.gov (United States)

    Colombi, Marina; Dordoni, Chiara; Venturini, Marina; Zanca, Arianna; Calzavara-Pinton, Piergiacomo; Ritelli, Marco

    2017-02-01

    Classical Ehlers-Danlos syndrome (cEDS) is a rare connective tissue disorder primarily characterized by hyperextensible skin, defective wound healing, abnormal scars, easy bruising, and generalized joint hypermobility; arterial dissections are rarely observed. Mutations in COL5A1 and COL5A2 encoding type V collagen account for more than 90% of the patients so far characterized. In addition, cEDS phenotype was reported in a small number of patients carrying the c.934C>T mutation in COL1A1 that results in an uncommon substitution of a non-glycine residue in one Gly-Xaa-Yaa repeat of the pro-α1(I)-chain p.(Arg312Cys), which leads to disturbed collagen fibrillogenesis due to delayed removal of the type I procollagen N-propeptide. This specific mutation has been associated with propensity to arterial rupture in early adulthood; indeed, in literature the individuals harboring this mutation are also referred to as "(classic) vascular-like" EDS patients. Herein, we describe a three-generation cEDS family with six adults carrying the p.(Arg312Cys) substitution, which show a variable and prevalent cutaneous involvement without any major vascular event. These data, together with those available in literature, suggest that vascular events are not a diagnostic handle to differentiate patients with the p.(Arg312Cys) COL1A1 mutation from those with COL5A1 and COL5A2 defects, and highlight that during the diagnostic process the presence of at least the p.(Arg312Cys) substitution in COL1A1 should be investigated in cEDS patients without type V collagen mutations. Nevertheless, for these patients, as well as for those affected with cEDS, a periodical vascular surveillance should be carried out together with cardiovascular risk factors monitoring. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Mutator activity in Schizophyllum commune

    Energy Technology Data Exchange (ETDEWEB)

    Shneyour, Y.; Koltin, Y. (Tel Aviv Univ. (Israel). Dept. of Microbiology)

    1983-01-01

    A strain with an elevated level of spontaneous mutations and an especially high rate of reversion at a specific locus (pab/sup -/) was identified. The mutator trait is recessive. UV sensitivity and the absence of a UV-specific endonucleolytic activity were associated with the enhancement of the mutation rate in mutator strains. The endonuclease associated with the regulation of the mutation rate also acted on single-stranded DNA. The molecular weight of this enzyme is about 38,000 daltons.

  12. Single Mutations in the VP2 300 Loop Region of the Three-Fold Spike of the Carnivore Parvovirus Capsid Can Determine Host Range

    Science.gov (United States)

    Organtini, Lindsey J.; Zhang, Sheng; Hafenstein, Susan L.; Holmes, Edward C.

    2015-01-01

    ABSTRACT Sylvatic carnivores, such as raccoons, have recently been recognized as important hosts in the evolution of canine parvovirus (CPV), a pandemic pathogen of domestic dogs. Although viruses from raccoons do not efficiently bind the dog transferrin receptor (TfR) or infect dog cells, a single mutation changing an aspartic acid to a glycine at capsid (VP2) position 300 in the prototype raccoon CPV allows dog cell infection. Because VP2 position 300 exhibits extensive amino acid variation among the carnivore parvoviruses, we further investigated its role in determining host range by analyzing its diversity and evolution in nature and by creating a comprehensive set of VP2 position 300 mutants in infectious clones. Notably, some position 300 residues rendered CPV noninfectious for dog, but not cat or fox, cells. Changes of adjacent residues (residues 299 and 301) were also observed often after cell culture passage in different hosts, and some of the mutations mimicked changes seen in viruses recovered from natural infections of alternative hosts, suggesting that compensatory mutations were selected to accommodate the new residue at position 300. Analysis of the TfRs of carnivore hosts used in the experimental evolution studies demonstrated that their glycosylation patterns varied, including a glycan present only on the domestic dog TfR that dictates susceptibility to parvoviruses. Overall, there were significant differences in the abilities of viruses with alternative position 300 residues to bind TfRs and infect different carnivore hosts, demonstrating that the process of infection is highly host dependent and that VP2 position 300 is a key determinant of host range. IMPORTANCE Although the emergence and pandemic spread of canine parvovirus (CPV) are well documented, the carnivore hosts and evolutionary pathways involved in its emergence remain enigmatic. We recently demonstrated that a region in the capsid structure of CPV, centered around VP2 position 300

  13. Age-Related Hearing Impairment (ARHI) associated with GJB2 single mutation IVS1+1G>A in the Yakut population isolate in Eastern Siberia.

    Science.gov (United States)

    Barashkov, Nikolay A; Teryutin, Fedor M; Pshennikova, Vera G; Solovyev, Aisen V; Klarov, Leonid A; Solovyeva, Natalya A; Kozhevnikov, Andrei A; Vasilyeva, Lena M; Fedotova, Elvira E; Pak, Maria V; Lekhanova, Sargylana N; Zakharova, Elena V; Savvinova, Kyunney E; Gotovtsev, Nyurgun N; Rafailo, Adyum M; Luginov, Nikolay V; Alexeev, Anatoliy N; Posukh, Olga L; Dzhemileva, Lilya U; Khusnutdinova, Elza K; Fedorova, Sardana A

    2014-01-01

    Age-Related Hearing Impairment (ARHI) is one of the frequent sensory disorders registered in 50% of individuals over 80 years. ARHI is a multifactorial disorder due to environmental and poor-known genetic components. In this study, we present the data on age-related hearing impairment of 48 heterozygous carriers of mutation IVS1+1G>A (GJB2 gene) and 97 subjects with GJB2 genotype wt/wt in the Republic of Sakha/Yakutia (Eastern Siberia, Russia). This subarctic territory was found as the region with the most extensive accumulation of mutation IVS1+1G>A in the world as a result of founder effect in the unique Yakut population isolate. The GJB2 gene resequencing and detailed audiological analysis in the frequency range 0.25, 0.5, 1.0, 2.0, 4.0, 8.0 kHz were performed in all examined subjects that allowed to investigate genotype-phenotype correlations between the presence of single mutation IVS1+1G>A and hearing of subjects from examined groups. We revealed the linear correlation between increase of average hearing thresholds at speech frequencies (PTA0.5,1.0,2.0,4.0 kHz) and age of individuals with GJB2 genotype IVS1+1G>A/wt (rs = 0.499, p = 0.006860 for males and rs = 0.427, p = 0.000277 for females). Moreover, the average hearing thresholds on high frequency (8.0 kHz) in individuals with genotype IVS1+1G>A/wt (both sexes) were significantly worse than in individuals with genotype wt/wt (pA/wt was estimated to be ∼40 years (rs = 0.504, p = 0.003). These findings demonstrate that the single IVS1+1G>A mutation (GJB2) is associated with age-related hearing impairment (ARHI) of the IVS1+1G>A carriers in the Yakuts.

  14. Age-Related Hearing Impairment (ARHI associated with GJB2 single mutation IVS1+1G>A in the Yakut population isolate in Eastern Siberia.

    Directory of Open Access Journals (Sweden)

    Nikolay A Barashkov

    Full Text Available Age-Related Hearing Impairment (ARHI is one of the frequent sensory disorders registered in 50% of individuals over 80 years. ARHI is a multifactorial disorder due to environmental and poor-known genetic components. In this study, we present the data on age-related hearing impairment of 48 heterozygous carriers of mutation IVS1+1G>A (GJB2 gene and 97 subjects with GJB2 genotype wt/wt in the Republic of Sakha/Yakutia (Eastern Siberia, Russia. This subarctic territory was found as the region with the most extensive accumulation of mutation IVS1+1G>A in the world as a result of founder effect in the unique Yakut population isolate. The GJB2 gene resequencing and detailed audiological analysis in the frequency range 0.25, 0.5, 1.0, 2.0, 4.0, 8.0 kHz were performed in all examined subjects that allowed to investigate genotype-phenotype correlations between the presence of single mutation IVS1+1G>A and hearing of subjects from examined groups. We revealed the linear correlation between increase of average hearing thresholds at speech frequencies (PTA0.5,1.0,2.0,4.0 kHz and age of individuals with GJB2 genotype IVS1+1G>A/wt (rs = 0.499, p = 0.006860 for males and rs = 0.427, p = 0.000277 for females. Moreover, the average hearing thresholds on high frequency (8.0 kHz in individuals with genotype IVS1+1G>A/wt (both sexes were significantly worse than in individuals with genotype wt/wt (pA/wt was estimated to be ∼40 years (rs = 0.504, p = 0.003. These findings demonstrate that the single IVS1+1G>A mutation (GJB2 is associated with age-related hearing impairment (ARHI of the IVS1+1G>A carriers in the Yakuts.

  15. Influence of single and combination treatments of physical and chemical mutagen on chlorophyll mutations in Finger Millet

    International Nuclear Information System (INIS)

    Kumar, Binod; Mahto, Jaylal; Haider, Z.A.

    1993-01-01

    Gamma rays, ethyl methane sulfonate (EMS) and their combined treatments influenced differently in producing chlorophyll mutations. A good number of chlorophyll mutants with varied frequencies were recorded in M 2 generation. The frequency of chlorophyll mutants was higher at lower doses of gamma rays, EMS and their combination treatments. The most frequently observed mutant was Albino type. The other chlorophyll mutants isolated were Xantha, Viridis, Striata and Tigrina. The frequency of tigrina and striata was lowest in variety A-404 and Hr-374, respectively. The efficiency and effectiveness was high at the lower doses of mutagens in both the varieties. EMS (0.2%) was more effective than the corresponding lower dose of gamma rays for both the varieties. (author). 10 refs., 4 tabs

  16. Minimalist fault-tolerance techniques for mitigating single-event effects in non-radiation-hardened microcontrollers

    Science.gov (United States)

    Caldwell, Douglas Wyche

    Commercial microcontrollers--monolithic integrated circuits containing microprocessor, memory and various peripheral functions--such as are used in industrial, automotive and military applications, present spacecraft avionics system designers an appealing mix of higher performance and lower power together with faster system-development time and lower unit costs. However, these parts are not radiation-hardened for application in the space environment and Single-Event Effects (SEE) caused by high-energy, ionizing radiation present a significant challenge. Mitigating these effects with techniques which require minimal additional support logic, and thereby preserve the high functional density of these devices, can allow their benefits to be realized. This dissertation uses fault-tolerance to mitigate the transient errors and occasional latchups that non-hardened microcontrollers can experience in the space radiation environment. Space systems requirements and the historical use of fault-tolerant computers in spacecraft provide context. Space radiation and its effects in semiconductors define the fault environment. A reference architecture is presented which uses two or three microcontrollers with a combination of hardware and software voting techniques to mitigate SEE. A prototypical spacecraft function (an inertial measurement unit) is used to illustrate the techniques and to explore how real application requirements impact the fault-tolerance approach. Low-cost approaches which leverage features of existing commercial microcontrollers are analyzed. A high-speed serial bus is used for voting among redundant devices and a novel wire-OR output voting scheme exploits the bidirectional controls of I/O pins. A hardware testbed and prototype software were constructed to evaluate two- and three-processor configurations. Simulated Single-Event Upsets (SEUs) were injected at high rates and the response of the system monitored. The resulting statistics were used to evaluate

  17. SAAFEC: Predicting the Effect of Single Point Mutations on Protein Folding Free Energy Using a Knowledge-Modified MM/PBSA Approach.

    Science.gov (United States)

    Getov, Ivan; Petukh, Marharyta; Alexov, Emil

    2016-04-07

    Folding free energy is an important biophysical characteristic of proteins that reflects the overall stability of the 3D structure of macromolecules. Changes in the amino acid sequence, naturally occurring or made in vitro, may affect the stability of the corresponding protein and thus could be associated with disease. Several approaches that predict the changes of the folding free energy caused by mutations have been proposed, but there is no method that is clearly superior to the others. The optimal goal is not only to accurately predict the folding free energy changes, but also to characterize the structural changes induced by mutations and the physical nature of the predicted folding free energy changes. Here we report a new method to predict the Single Amino Acid Folding free Energy Changes (SAAFEC) based on a knowledge-modified Molecular Mechanics Poisson-Boltzmann (MM/PBSA) approach. The method is comprised of two main components: a MM/PBSA component and a set of knowledge based terms delivered from a statistical study of the biophysical characteristics of proteins. The predictor utilizes a multiple linear regression model with weighted coefficients of various terms optimized against a set of experimental data. The aforementioned approach yields a correlation coefficient of 0.65 when benchmarked against 983 cases from 42 proteins in the ProTherm database. the webserver can be accessed via http://compbio.clemson.edu/SAAFEC/.

  18. The application of a linear algebra to the analysis of mutation rates.

    Science.gov (United States)

    Jones, M E; Thomas, S M; Clarke, K

    1999-07-07

    Cells and bacteria growing in culture are subject to mutation, and as this mutation is the ultimate substrate for selection and evolution, the factors controlling the mutation rate are of some interest. The mutational event is not observed directly, but is inferred from the phenotype of the original mutant or of its descendants; the rate of mutation is inferred from the number of such mutant phenotypes. Such inference presumes a knowledge of the probability distribution for the size of a clone arising from a single mutation. We develop a mathematical formulation that assists in the design and analysis of experiments which investigate mutation rates and mutant clone size distribution, and we use it to analyse data for which the classical Luria-Delbrück clone-size distribution must be rejected. Copyright 1999 Academic Press.

  19. Theoretical and experimental studies of single event effect induced by atmospheric muons on nano-metric technologies

    International Nuclear Information System (INIS)

    Li Cavoli, P.

    2016-01-01

    This study concerns the domain of the microelectronics. It consists in the study of the impact of the 3D morphology of the energy deposit on the Single Event Effect (SEE) modeling, induced by atmospheric muons. Over a first phase, the approach has consisted in the modeling of the energy deposit induced by protons in nano-metric volumes. For that purpose the use of the Monte Carlo code GEANT4 has allowed us to simulate and stock in a database the tracks characteristics of the energy deposit induced by protons. Once the approach validated for the protons, simulations of the energy deposit induced by muons have been realized. A CCD camera has been used in order to measure the radiative atmospheric environment and to constrain the modeling of the energy deposit induced by muons. This study highlights and quantify the contribution of the radial distribution of the energy deposit induced by protons in nano-metric volumes for the SEE prediction. On the other hand, the study shows that the contribution of the radial distribution of the energy deposit induced by muons in nano-metric volumes has a negligible impact on the SEE modeling. It will be interesting to realize measurements of the energy deposit induced by muons in nano-metric technologies under particle accelerator. This will allow to bring experimental data still nonexistent necessary to the development of new physical models more accurate on the modeling of the energy deposit induced by muons. (author)

  20. Feasibility of a neutron detector-dosemeter based on single-event upsets in dynamic random-access memories

    International Nuclear Information System (INIS)

    Phillips, G.W.; August, R.A.; Campbell, A.B.; Nelson, M.E.; Guardala, N.A.; Price, J.L.; Moscovitch, M.

    2002-01-01

    The feasibility was investigated of a solid-state neutron detector/dosemeter based on single-event upset (SEU) effects in dynamic random-access memories (DRAMs), commonly used in computer memories. Such a device, which uses a neutron converter material to produce a charged particle capable of causing an upset, would be light-weight, low-power, and could be read simply by polling the memory for bit flips. It would have significant advantages over standard solid-state neutron dosemeters which require off-line processing for track etching and analysis. Previous efforts at developing an SEU neutron detector/dosemeter have suffered from poor response, which can be greatly enhanced by selecting a modern high-density DRAM chip for SEU sensitivity and by using a thin 10 B film as a converter. Past attempts to use 10 B were not successful because the average alpha particle energy was insufficient to penetrate to the sensitive region of the memory. This can be overcome by removing the surface passivation layer before depositing the 10 B film or by implanting 10B directly into the chip. Previous experimental data show a 10 3 increase in neutron sensitivity by chips containing borosilicate glass, which could be used in an SEU detector. The results are presented of simulations showing that the absolute efficiency of an SEU neutron dosemeter can be increased by at least a factor of 1000 over earlier designs. (author)

  1. Effect of body biasing on single-event induced charge collection in deep N-well technology

    International Nuclear Information System (INIS)

    Ding Yi; Hu Jian-Guo; Tan Hong-Zhou; Qin Jun-Rui

    2015-01-01

    As the device size decreases, the soft error induced by space ions is becoming a great concern for the reliability of integrated circuits (ICs). At present, the body biasing technique is widely used in highly scaled technologies. In the paper, using the three-dimensional technology computer-aided design (TCAD) simulation, we analyze the effect of the body biasing on the single-event charge collection in deep N-well technology. Our simulation results show that the body biasing mainly affects the behavior of the source, and the effect of body biasing on the charge collection for the nMOSFET and pMOSFET is quite different. For the nMOSFET, the RBB will increase the charge collection, while the FBB will reduce the charge collection. For the pMOSFET, the effect of RBB on the SET pulse width is small, while the FBB has an adverse effect. Moreover, the differenceof the effect of body biasing on the charge collection is compared in deep N-well and twin well. (paper)

  2. Search for anomalous Wtb couplings and top FCNC in t-channel single-top-quark events in the CMS experiment

    CERN Document Server

    Tsirova, Natalia

    2015-01-01

    Single-top-quark events in the t-channel are used to probe Wtb anomalous couplings and to search for top-quark Flavor-Changing Neutral Current (FCNC) interactions in proton-proton collisions with the CMS experiment. A Bayesian neural network is used to discriminate between signal and backgrounds. The observed event yields are consistent with SM prediction, and exclusion limits at 95\\% C.L. are determined.

  3. Introducing the event related fixed interval area (ERFIA) multilevel technique: a method to analyze the complete epoch of event-related potentials at single trial level

    NARCIS (Netherlands)

    Vossen, C.J.; Vossen, H.G.M.; Marcus, M.A.E.; van Os, J.; Lousberg, R.

    2013-01-01

    In analyzing time-locked event-related potentials (ERPs), many studies have focused on specific peaks and their differences between experimental conditions. In theory, each latency point after a stimulus contains potentially meaningful information, regardless of whether it is peak-related. Based on

  4. Test Standard Revision Update: JESD57, "Procedures for the Measurement of Single-Event Effects in Semiconductor Devices from Heavy-Ion Irradiation"

    Science.gov (United States)

    Lauenstein, Jean-Marie

    2015-01-01

    The JEDEC JESD57 test standard, Procedures for the Measurement of Single-Event Effects in Semiconductor Devices from Heavy-Ion Irradiation, is undergoing its first revision since 1996. In this talk, we place this test standard into context with other relevant radiation test standards to show its importance for single-event effect radiation testing for space applications. We show the range of industry, government, and end-user party involvement in the revision. Finally, we highlight some of the key changes being made and discuss the trade-space in which setting standards must be made to be both useful and broadly adopted.

  5. Pharmacotherapy for adverse events reduces the length of hospital stay in patients admitted to otolaryngology ward: a single arm intervention study.

    Directory of Open Access Journals (Sweden)

    Akio Suzuki

    Full Text Available To determine whether adverse events extend the duration of hospitalization, and to evaluate the effectiveness of medical intervention in ameliorating adverse events and reducing the prolonged hospital stay associated with adverse events.A single arm intervention study was conducted from October 2012 to March 2014 in the otolaryngology ward of a 614-bed, university-affiliated hospital. Adverse events were monitored daily by physicians, pharmacists and nurses, and recorded in the electronic medical chart for each patient. Appropriate drug management of adverse events was performed by physicians in liaison with pharmacists. The Kaplan-Meier method was used to assess the length of hospitalization of patients who underwent medical intervention for adverse events.Of 571 patients admitted to the otolaryngology ward in a year, 219 patients (38.4% experienced adverse events of grade ≥2. The duration of hospitalization was affected by the grade of adverse events, with a mean duration of hospital stay of 9.2, 17.2, 28.3 and 47.0 days for grades 0, 1, 2, and 3-4, respectively. Medical intervention lowered the incidence of grade ≥2 adverse events to 14.5%. The length of hospitalization was significantly shorter in patients who showed an improvement of adverse events after medical intervention than those who did not (26.4 days vs. 41.6 days, hazard ratio 1.687, 95% confidence interval: 1.260-2.259, P<0.001. A multivariate Cox proportional hazard analysis indicated that insomnia, constipation, nausea/vomiting, infection, non-cancer pain, oral mucositis, odynophagia and neutropenia were significant risk factors for prolongation of hospital stay.Patients who experienced adverse events are at high risk of prolonged hospitalization. Medical intervention for adverse events was found to be effective in reducing the length of hospital stay associated with adverse events.

  6. Application of Single Strand Conformational Polymorphism (PCR-SSCP) in Identification of Some Beta-Globin Gene Mutations in A Group of Egyptian Beta-Thalassemia Patients and Carriers

    International Nuclear Information System (INIS)

    Somaya, E.T.; Soliman, M.D

    2010-01-01

    The present study investigated whether the single-strand conformational polymorphism (SSCP) method could be employed to identify (rather than simply detect) four of the most common beta-globin gene mutations in the Egyptian population: IVS-I-110, IVS-I-6, the IVS-I-1, and Codon 39. Using DNA from 90 beta-thalassemia patients and carriers, by PCR the appropriate 238-bp region of the human beta-globin gene was amplified, the reaction products (Single-stranded DNA) were analyzed by none denaturing polyacrylamide gel electrophoresis, and the bands visualized by silver staining. Single-stranded DNA (ssDNA) fragments showed reproducible pattern of bands that were characteristic of the mutations present. With the use of control samples containing six of the 10 possible combinations of the four beta-globin gene mutations under study, we were able to predict the mutations present in 23 out of 90 (26.4%) of the patients studied. These predictions were confirmed independently by the amplification refractory mutation system (ARMS) method. It is concluded that this non-radioactive PCR-SSCP method can be used to reliably identify mutations in beta-thalassemia patients, provided that suitable controls are available. However, usefulness of this method for determining the genotype of beta-thalassaemic individuals is obviously limited by the great number of controls required. Moreover, the ability to detect mutations by SSCP is in general lower compared to other methods, ARMS, DGGE or DHPLC, which are reported to detect 49.5% to 73% of the mutations present. The SSCP method is nevertheless much easier to employ than other methods and is especially successful for beta-thalassemia carriers. This method would thus be particularly useful for an initial screening of target groups (prenatal diagnosis)

  7. Mixing state of particles with secondary species by single particle aerosol mass spectrometer in an atmospheric pollution event

    Science.gov (United States)

    Xu, Lingling; Chen, Jinsheng

    2016-04-01

    Single particle aerosol mass spectrometer (SPAMS) was used to characterize size distribution, chemical composition, and mixing state of particles in an atmospheric pollution event during 20 Oct. - 5 Nov., 2015 in Xiamen, Southeast China. A total of 533,012 particle mass spectra were obtained and clustered into six groups, comprising of industry metal (4.5%), dust particles (2.6%), carbonaceous species (70.7%), K-Rich particles (20.7%), seasalt (0.6%) and other particles (0.9%). Carbonaceous species were further divided into EC (70.6%), OC (28.5%), and mixed ECOC (0.9%). There were 61.7%, 58.3%, 4.0%, and 14.6% of particles internally mixed with sulfate, nitrate, ammonium and C2H3O, respectively, indicating that these particles had undergone significant aging processing. Sulfate was preferentially mixed with carbonaceous particles, while nitrate tended to mix with metal-containing and dust particles. Compared to clear days, the fractions of EC-, metal- and dust particles remarkably increased, while the fraction of OC-containing particles decreased in pollution days. The mixing state of particles, excepted for OC-containing particles with secondary species was much stronger in pollution days than that in clear days, which revealed the significant influence of secondary particles in atmospheric pollution. The different activity of OC-containing particles might be related to their much smaller aerodynamic diameter. These results could improve our understanding of aerosol characteristics and could be helpful to further investigate the atmospheric process of particles.

  8. Single-cell sequencing analysis characterizes common and cell-lineage-specific mutations in a muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Li, Yingrui; Xu, Xun; Song, Luting

    2012-01-01

    sequencing of 66 individual tumor cells from a muscle-invasive bladder transitional cell carcinoma (TCC). Analyses of the somatic mutant allele frequency spectrum and clonal structure revealed that the tumor cells were derived from a single ancestral cell, but that subsequent evolution occurred, leading...... to two distinct tumor cell subpopulations. By analyzing recurrently mutant genes in an additional cohort of 99 TCC tumors, we identified genes that might play roles in the maintenance of the ancestral clone and in the muscle-invasive capability of subclones of this bladder cancer, respectively...

  9. [Clinical significance of JAK2、CALR and MPL gene mutations in 1 648 Philadelphia chromosome negative myeloproliferative neoplasms patients from a single center].

    Science.gov (United States)

    Li, M Y; Chao, H Y; Sun, A N; Qiu, H Y; Jin, Z M; Tang, X W; Han, Y; Fu, C C; Chen, S N; Wu, D P

    2017-04-14

    Objective: To explore the prevalences of JAK2, CALR and MPL gene mutations and the mutation types in patients with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) , and to compare their clinical characteristics of different mutation types with each other and mutation negative group. Methods: The mutations of JAK2 V617F, JAK2 gene at exon 12, CALR gene at exon 9 and MPL gene at exon 10 in 1 648 Ph negative MPNs patients were detected by direct sequencing. Results: ① The JAK2V617F mutation was found in 471 (92.7%) of 508 PV patients, 819 (78.1%) of 1 049 ET patients and 74 (81.3%) of 91 PMF patients respectively, with the total mutation rate as 82.8% (1 364/1 648) . The JAK2 exon12 mutation was found in 9 (1.7%) of 508 PV patients, none was found in ET or PMF patients, with the total mutation rate as 0.5% (9/1 648) . The CALR mutation was found in 132 (12.6%) of 1 049 ET patients and 11 (12.1%) of 91 PMF patients respectively, with the total mutation rate as 8.7% (143/1 648) ; the MPL mutation was found in 9 (0.9%) of 1 049 ET patients and 1 (1.1%) of 91 PMF patients respectively, with the total mutation rate as 0.6% (10/1 648) . The co-occurrence of any two types of driver gene mutations was not detected by direct sequencing. ②The median onset age of patients with JAK2V617F[61 (15-95) y] was significant higher than of with JAK2 exon12 mutation[49 (33-62) y] or without mutations[42 (3-78) y] ( P MPL mutation[59 (22-71) y] ( P >0.05) . Patients with JAK2V617F had higher white blood cell count and hemoglobin level ( P MPL mutation ( P =0.013) . The platelet count of patients with CALR mutation was significantly higher than of with JAK2V617F[966 (400-2 069) ×10(9)/L vs 800 (198-3 730) ×10(9)/L, P MPL gene mutation revealed normal karyotype. Conclusions: Driver gene mutations detection could ensure the diagnosis and prognosis judgment of MPN more reliable, different subtypes of MPNs had different profiles of driver gene mutations, the latter

  10. Complex Parts, Complex Data: Why You Need to Understand What Radiation Single Event Testing Data Does and Doesn't Show and the Implications Thereof

    Science.gov (United States)

    LaBel, Kenneth A.; Berg, Melanie D.

    2015-01-01

    Electronic parts (integrated circuits) have grown in complexity such that determining all failure modes and risks from single particle event testing is impossible. In this presentation, the authors will present why this is so and provide some realism on what this means. Its all about understanding actual risks and not making assumptions.

  11. Single and multi-photon events with missing energy in $e^+ e^-$ collisions at 161 GeV < $\\sqrt{s}$ < 172 GeV

    CERN Document Server

    Acciarri, M; Aguilar-Benítez, M; Ahlen, S P; Alcaraz, J; Alemanni, G; Allaby, James V; Aloisio, A; Alverson, G; Alviggi, M G; Ambrosi, G; Anderhub, H; Andreev, V P; Angelescu, T; Anselmo, F; Arefev, A; Azemoon, T; Aziz, T; Bagnaia, P; Baksay, L; Banerjee, S; Banerjee, Sw; Banicz, K; Barczyk, A; Barillère, R; Barone, L; Bartalini, P; Baschirotto, A; Basile, M; Battiston, R; Bay, A; Becattini, F; Becker, U; Behner, F; Berdugo, J; Berges, P; Bertucci, B; Betev, B L; Bhattacharya, S; Biasini, M; Biland, A; Bilei, G M; Blaising, J J; Blyth, S C; Bobbink, Gerjan J; Böck, R K; Böhm, A; Boldizsar, L; Borgia, B; Bourilkov, D; Bourquin, Maurice; Braccini, S; Branson, J G; Brigljevic, V; Brock, I C; Buffini, A; Buijs, A; Burger, J D; Burger, W J; Busenitz, J K; Button, A M; Cai, X D; Campanelli, M; Capell, M; Cara Romeo, G; Carlino, G; Cartacci, A M; Casaus, J; Castellini, G; Cavallari, F; Cavallo, N; Cecchi, C; Cerrada-Canales, M; Cesaroni, F; Chamizo-Llatas, M; Chang, Y H; Chaturvedi, U K; Chekanov, S V; Chemarin, M; Chen, A; Chen, G; Chen, G M; Chen, H F; Chen, H S; Chéreau, X J; Chiefari, G; Chien, C Y; Cifarelli, Luisa; Cindolo, F; Civinini, C; Clare, I; Clare, R; Cohn, H O; Coignet, G; Colijn, A P; Colino, N; Commichau, V; Costantini, S; Cotorobai, F; de la Cruz, B; Csilling, Akos; Dai, T S; D'Alessandro, R; De Asmundis, R; Degré, A; Deiters, K; Della Volpe, D; Denes, P; De Notaristefani, F; DiBitonto, Daryl; Diemoz, M; Van Dierendonck, D N; Di Lodovico, F; Dionisi, C; Dittmar, Michael; Dominguez, A; Doria, A; Dova, M T; Duchesneau, D; Duinker, P; Durán, I; Dutta, S; Easo, S; Efremenko, Yu V; El-Mamouni, H; Engler, A; Eppling, F J; Erné, F C; Ernenwein, J P; Extermann, Pierre; Fabre, M; Faccini, R; Falciano, S; Favara, A; Fay, J; Fedin, O; Felcini, Marta; Fenyi, B; Ferguson, T; Ferroni, F; Fesefeldt, H S; Fiandrini, E; Field, J H; Filthaut, Frank; Fisher, P H; Fisk, I; Forconi, G; Fredj, L; Freudenreich, Klaus; Furetta, C; Galaktionov, Yu; Ganguli, S N; García-Abia, P; Gau, S S; Gentile, S; Gheordanescu, N; Giagu, S; Goldfarb, S; Goldstein, J; Gong, Z F; Gougas, Andreas; Gratta, Giorgio; Grünewald, M W; Gupta, V K; Gurtu, A; Gutay, L J; Hartmann, B; Hasan, A; Hatzifotiadou, D; Hebbeker, T; Hervé, A; Van Hoek, W C; Hofer, H; Hong, S J; Hoorani, H; Hou, S R; Hu, G; Innocente, Vincenzo; Jenkes, K; Jin, B N; Jones, L W; de Jong, P; Josa-Mutuberria, I; Kasser, A; Khan, R A; Kamrad, D; Kamyshkov, Yu A; Kapustinsky, J S; Karyotakis, Yu; Kaur, M; Kienzle-Focacci, M N; Kim, D; Kim, D H; Kim, J K; Kim, S C; Kim, Y G; Kinnison, W W; Kirkby, A; Kirkby, D; Kirkby, Jasper; Kiss, D; Kittel, E W; Klimentov, A; König, A C; Kopp, A; Korolko, I; Koutsenko, V F; Krämer, R W; Krenz, W; Kunin, A; Ladrón de Guevara, P; Laktineh, I; Landi, G; Lapoint, C; Lassila-Perini, K M; Laurikainen, P; Lebeau, M; Lebedev, A; Lebrun, P; Lecomte, P; Lecoq, P; Le Coultre, P; Le Goff, J M; Leiste, R; Leonardi, E; Levchenko, P M; Li Chuan; Lin, C H; Lin, W T; Linde, Frank L; Lista, L; Liu, Z A; Lohmann, W; Longo, E; Lu, W; Lü, Y S; Lübelsmeyer, K; Luci, C; Luckey, D; Luminari, L; Lustermann, W; Ma Wen Gan; Maity, M; Majumder, G; Malgeri, L; Malinin, A; Maña, C; Mangeol, D J J; Mangla, S; Marchesini, P A; Marin, A; Martin, J P; Marzano, F; Massaro, G G G; McNally, D; McNeil, R R; Mele, S; Merola, L; Meschini, M; Metzger, W J; Von der Mey, M; Mi, Y; Mihul, A; Van Mil, A J W; Mirabelli, G; Mnich, J; Molnár, P; Monteleoni, B; Moore, R; Morganti, S; Moulik, T; Mount, R; Müller, S; Muheim, F; Muijs, A J M; Nahn, S; Napolitano, M; Nessi-Tedaldi, F; Newman, H; Niessen, T; Nippe, A; Nisati, A; Nowak, H; Oh, Yu D; Opitz, H; Organtini, G; Ostonen, R; Palomares, C; Pandoulas, D; Paoletti, S; Paolucci, P; Park, H K; Park, I H; Pascale, G; Passaleva, G; Patricelli, S; Paul, T; Pauluzzi, M; Paus, C; Pauss, Felicitas; Peach, D; Pei, Y J; Pensotti, S; Perret-Gallix, D; Petersen, B; Petrak, S; Pevsner, A; Piccolo, D; Pieri, M; Pinto, J C; Piroué, P A; Pistolesi, E; Plyaskin, V; Pohl, M; Pozhidaev, V; Postema, H; Produit, N; Prokofev, D; Prokofiev, D O; Rahal-Callot, G; Raja, N; Rancoita, P G; Rattaggi, M; Raven, G; Razis, P A; Read, K; Ren, D; Rescigno, M; Reucroft, S; Van Rhee, T; Riemann, S; Riles, K; Robohm, A; Rodin, J; Roe, B P; Romero, L; Rosier-Lees, S; Rosselet, P; Van Rossum, W; Roth, S; Rubio, Juan Antonio; Ruschmeier, D; Rykaczewski, H; Salicio, J; Sánchez, E; Sanders, M P; Sarakinos, M E; Sarkar, S; Sassowsky, M; Schäfer, C; Shchegelskii, V; Schmidt-Kärst, S; Schmitz, D; Schmitz, P; Scholz, N; Schopper, Herwig Franz; Schotanus, D J; Schwenke, J; Schwering, G; Sciacca, C; Sciarrino, D; Servoli, L; Shevchenko, S; Shivarov, N; Shoutko, V; Shukla, J; Shumilov, E; Shvorob, A V; Siedenburg, T; Son, D; Sopczak, André; Smith, B; Spillantini, P; Steuer, M; Stickland, D P; Stone, A; Stone, H; Stoyanov, B; Strässner, A; Strauch, K; Sudhakar, K; Sultanov, G G; Sun, L Z; Susinno, G F; Suter, H; Swain, J D; Tang, X W; Tauscher, Ludwig; Taylor, L; Ting, Samuel C C; Ting, S M; Tonutti, M; Tonwar, S C; Tóth, J; Tully, C; Tuchscherer, H; Tung, K L; Uchida, Y; Ulbricht, J; Uwer, U; Valente, E; Van de Walle, R T; Vesztergombi, G; Vetlitskii, I; Viertel, Gert M; Vivargent, M; Völkert, R; Vogel, H; Vogt, H; Vorobev, I; Vorobyov, A A; Vorvolakos, A; Wadhwa, M; Wallraff, W; Wang, J C; Wang, X L; Wang, Z M; Weber, A; Wittgenstein, F; Wu, S X; Wynhoff, S; Xu, J; Xu, Z Z; Yang, B Z; Yang, C G; Yao, X Y; Ye, J B; Yeh, S C; You, J M; Zalite, A; Zalite, Yu; Zemp, P; Zeng, Y; Zhang, Z; Zhang, Z P; Zhou, B; Zhu, G Y; Zhu, R Y; Zichichi, Antonino; Ziegler, F

    1997-01-01

    A search for single and multi-photon events with missing energy is performed using data collected at centre-of-mass energies between 161 GeV and 172 GeV for a total of 20.9 pb$^{-1}$ of integrated luminosity. The results obtained are used to derive the value for the $\

  12. [Safety Evaluation of Rare Sugar Syrup: Single-dose Oral Toxicity in Rats, Reverse Mutation Assay, Chromosome Aberration Assay, and Acute Non-Effect Level for Diarrhea of a Single Dose in Humans].

    Science.gov (United States)

    Yamada, Takako; Iida, Tetsuo; Takamine, Satoshi; Hayashi, Noriko; Okuma, Kazuhiro

    2015-01-01

    The safety of rare sugar syrup obtained from high-fructose corn syrup under slightly alkaline conditions was studied. Mutagenicity of rare sugar syrup was assessed by a reverse mutation assay using Salmonella typhimurium and Escherichia coli, and an in vitro chromosomal aberration assay using Chinese hamster lung cell line (CHL/IU). No mutagenicity of rare sugar syrup was detected under these experimental conditions. Oral administration of single dose (15,000 mg/kg) of rare sugar syrup to rats caused no abnormalities, suggesting no adverse effect of rare sugar syrup. In humans, the acute non-effect level of rare sugar syrup for causing diarrhea was estimated as 0.9 g/kg body weight as dry solid base in both males and females.

  13. Towards Better Precision Medicine: PacBio Single-Molecule Long Reads Resolve the Interpretation of HIV Drug Resistant Mutation Profiles at Explicit Quasispecies (Haplotype) Level.

    Science.gov (United States)

    Huang, Da Wei; Raley, Castle; Jiang, Min Kang; Zheng, Xin; Liang, Dun; Rehman, M Tauseef; Highbarger, Helene C; Jiao, Xiaoli; Sherman, Brad; Ma, Liang; Chen, Xiaofeng; Skelly, Thomas; Troyer, Jennifer; Stephens, Robert; Imamichi, Tomozumi; Pau, Alice; Lempicki, Richard A; Tran, Bao; Nissley, Dwight; Lane, H Clifford; Dewar, Robin L

    2016-01-01

    Development of HIV-1 drug resistance mutations (HDRMs) is one of the major reasons for the clinical failure of antiretroviral therapy. Treatment success rates can be improved by applying personalized anti-HIV regimens based on a patient's HDRM profile. However, the sensitivity and specificity of the HDRM profile is limited by the methods used for detection. Sanger-based sequencing technology has traditionally been used for determining HDRM profiles at the single nucleotide variant (SNV) level, but with a sensitivity of only ≥ 20% in the HIV population of a patient. Next Generation Sequencing (NGS) technologies offer greater detection sensitivity (~ 1%) and larger scope (hundreds of samples per run). However, NGS technologies produce reads that are too short to enable the detection of the physical linkages of individual SNVs across the haplotype of each HIV strain present. In this article, we demonstrate that the single-molecule long reads generated using the Third Generation Sequencer (TGS), PacBio RS II, along with the appropriate bioinformatics analysis method, can resolve the HDRM profile at a more advanced quasispecies level. The case studies on patients' HIV samples showed that the quasispecies view produced using the PacBio method offered greater detection sensitivity and was more comprehensive for understanding HDRM situations, which is complement to both Sanger and NGS technologies. In conclusion, the PacBio method, providing a promising new quasispecies level of HDRM profiling, may effect an important change in the field of HIV drug resistance research.

  14. Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS.

    Science.gov (United States)

    Zuidervaart, W; van Nieuwpoort, F; Stark, M; Dijkman, R; Packer, L; Borgstein, A-M; Pavey, S; van der Velden, P; Out, C; Jager, M J; Hayward, N K; Gruis, N A

    2005-06-06

    In contrast to cutaneous melanoma, there is no evidence that BRAF mutations are involved in the activation of the mitogen-activated protein kinase (MAPK) pathway in uveal melanoma, although there is increasing evidence that this pathway is activated frequently in the latter tumours. In this study, we performed mutation analysis of the RAS and BRAF genes in a panel of 11 uveal melanoma cell lines and 19 primary uveal melanoma tumours. In addition, Western blot and immunohistochemical analyses were performed on downstream members of the MAPK pathway in order to assess the contribution of each of these components. No mutations were found in any of the three RAS gene family members and only one cell line carried a BRAF mutation (V599E). Despite this, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), ERK and ELK were constitutively activated in all samples. These data suggest that activation of the MAPK pathway is commonly involved in the development of uveal melanoma, but occurs through a mechanism different to that of cutaneous melanoma.

  15. A single mutation in the castor Δ9-18:0-desaturase changes reaction partitioning from desaturation to oxidase chemistry

    Science.gov (United States)

    Guy, Jodie E.; Abreu, Isabel A.; Moche, Martin; Lindqvist, Ylva; Whittle, Edward; Shanklin, John

    2006-01-01

    Sequence analysis of the diiron cluster-containing soluble desaturases suggests they are unrelated to other diiron enzymes; however, structural alignment of the core four-helix bundle of desaturases to other diiron enzymes reveals a conserved iron binding motif with similar spacing in all enzymes of this structural class, implying a common evolutionary ancestry. Detailed structural comparison of the castor desaturase with that of a peroxidase, rubrerythrin, shows remarkable conservation of both identity and geometry of residues surrounding the diiron center, with the exception of residue 199. Position 199 is occupied by a threonine in the castor desaturase, but the equivalent position in rubrerythrin contains a glutamic acid. We previously hypothesized that a carboxylate in this location facilitates oxidase chemistry in rubrerythrin by the close apposition of a residue capable of facilitating proton transfer to the activated oxygen (in a hydrophobic cavity adjacent to the diiron center based on the crystal structure of the oxygen-binding mimic azide). Here we report that desaturase mutant T199D binds substrate but its desaturase activity decreases by ≈2 × 103-fold. However, it shows a >31-fold increase in peroxide-dependent oxidase activity with respect to WT desaturase, as monitored by single-turnover stopped-flow spectrometry. A 2.65-Å crystal structure of T199D reveals active-site geometry remarkably similar to that of rubrerythrin, consistent with its enhanced function as an oxidase enzyme. That a single amino acid substitution can switch reactivity from desaturation to oxidation provides experimental support for the hypothesis that the desaturase evolved from an ancestral oxidase enzyme. PMID:17088542

  16. Postzygotic single-nucleotide mosaicisms contribute to the etiology of autism spectrum disorder and autistic traits and the origin of mutations.

    Science.gov (United States)

    Dou, Yanmei; Yang, Xiaoxu; Li, Ziyi; Wang, Sheng; Zhang, Zheng; Ye, Adam Yongxin; Yan, Linlin; Yang, Changhong; Wu, Qixi; Li, Jiarui; Zhao, Boxun; Huang, August Yue; Wei, Liping

    2017-08-01

    The roles and characteristics of postzygotic single-nucleotide mosaicisms (pSNMs) in autism spectrum disorders (ASDs) remain unclear. In this study of the whole exomes of 2,361 families in the Simons Simplex Collection, we identified 1,248 putative pSNMs in children and 285 de novo SNPs in children with detectable parental mosaicism. Ultra-deep amplicon resequencing suggested a validation rate of 51%. Analyses of validated pSNMs revealed that missense/loss-of-function (LoF) pSNMs with a high mutant allele fraction (MAF≥ 0.2) contributed to ASD diagnoses (P = 0.022, odds ratio [OR] = 5.25), whereas missense/LoF pSNMs with a low MAF (MAF<0.2) contributed to autistic traits in male non-ASD siblings (P = 0.033). LoF pSNMs in parents were less likely to be transmitted to offspring than neutral pSNMs (P = 0.037), and missense/LoF pSNMs in parents with a low MAF were transmitted more to probands than to siblings (P = 0.016, OR = 1.45). We estimated that pSNMs in probands or de novo mutations inherited from parental pSNMs increased the risk of ASD by approximately 6%. Adding pSNMs into the transmission and de novo association test model revealed 13 new ASD risk genes. These results expand the existing repertoire of genes involved in ASD and shed new light on the contribution of genomic mosaicisms to ASD diagnoses and autistic traits. © 2017 The Authors. Human Mutation published by Wiley Periodicals, Inc.

  17. High success rate and considerable adverse events of pelvic prolapse surgery with Prolift: A single center experience

    Directory of Open Access Journals (Sweden)

    Mun-Kun Hong

    2013-09-01

    Conclusions: Prolapse surgery with Prolift yielded a good anatomical outcome and satisfactory symptom improvement at different periods of follow-up, especially in uterus-sparing prolapse surgery. However, adverse events were not uncommon, and patients should be fully informed of all possible adverse events prior to surgery.

  18. Search for pair production of supersymmetric top-quark partners in events with a single lepton at CMS

    International Nuclear Information System (INIS)

    Costanza, Francesco

    2014-09-01

    The analysis presented in this thesis is a search for direct pair production of supersymmetric top-quark partners at CMS. Supersymmetry is a compelling theory providing possible solutions to several of the Standard Models limitations. However, previous searches for supersymmetric particles came back with empty hands. These results and the discovery of a Higgs boson with a mass of about 125 GeV by the ATLAS and CMS Collaborations strongly constrain the simplest supersymmetric models. Nevertheless, more sophisticated models with light third-generation squarks did not lose their theoretical appeal and are within the reach of the 8 TeV run of the Large Hadron Collider. In this analysis, a search for direct top-squark (t) pair production is performed in a final state consisting of a single isolated lepton, jets, among which at least one is a b-tagged jet, and large missing transverse energy. Six search regions are defined with a semi-automatic procedure to maximize the sensitivity of the analysis. The background estimation is performed using simulated samples validated in control regions with small or no signal contamination. Scale factors are measured in the control regions and used to correct the background in the search regions if needed. The observed event yields in the search regions agree with the predicted backgrounds within the uncertainties, hence no evidence for pair-produced top-squarks can be inferred. The results are used to constrain top-squark pair production in the framework of simplified models. Two possible top-squark decay modes are considered: the decay to top quark and a neutralino (chiz), t→tχ 0 , and the decay to a bottom quark and a chargino (χ + ), t→bχ + , with the subsequent χ + →W + +χ 0 decay. Exclusion limits are set for branching ratios B(t →tχ 0 )=100% and B(t → tχ 0 )=50%. In the former case, for small mass values of the lightest neutralino, the analysis probes top-squark masses up to 600 GeV and up to 500 GeV in the

  19. The p16INK4alpha/p19ARF gene mutations are infrequent and are mutually exclusive to p53 mutations in Indian oral squamous cell carcinomas.

    Science.gov (United States)

    Kannan, K; Munirajan, A K; Krishnamurthy, J; Bhuvarahamurthy, V; Mohanprasad, B K; Panishankar, K H; Tsuchida, N; Shanmugam, G

    2000-03-01

    Eighty-seven untreated primary oral squamous cell carcinomas (SCCs) associated with betel quid and tobacco chewing from Indian patients were analysed for the presence of mutations in the commonly shared exon 2 of p16INK4alpha/p19ARF genes. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing analysis were used to detect mutations. SSCP analysis indicated that only 9% (8/87) of the tumours had mutation in p16INK4alpha/p19ARF genes. Seventy-two tumours studied here were previously analysed for p53 mutations and 21% (15/72) of them were found to have mutations in p53 gene. Only one tumour was found to have mutation at both p53 and p16INK4alpha/p19ARF genes. Thus, the mutation rates observed were 21% for p53, 9% for p16INK4alpha/p19ARF, and 1% for both. Sequencing analysis revealed two types of mutations; i) G to C (GCAG to CCAG) transversion type mutation at intron 1-exon 2 splice junction and ii) another C to T transition type mutation resulting in CGA to TGA changing arginine to a termination codon at p16INK4alpha gene codon 80 and the same mutation will alter codon 94 of p19ARF gene from CCG to CTG (proline to leucine). These results suggest that p16INK4alpha/p19ARF mutations are less frequent than p53 mutations in Indian oral SCCs. The p53 and p16INK4alpha/p19ARF mutational events are independent and are mutually exclusive suggesting that mutational inactivation of either p53 or p16INK4alpha/p19ARF may alleviate the need for the inactivation of the other gene.

  20. One small step for a yeast--microevolution within macrophages renders Candida glabrata hypervirulent due to a single point mutation.

    Directory of Open Access Journals (Sweden)

    Sascha Brunke

    2014-10-01

    Full Text Available Candida glabrata is one of the most common causes of candidemia, a life-threatening, systemic fungal infection, and is surpassed in frequency only by Candida albicans. Major factors contributing to the success of this opportunistic pathogen include its ability to readily acquire resistance to antifungals and to colonize and adapt to many different niches in the human body. Here we addressed the flexibility and adaptability of C. glabrata during interaction with macrophages with a serial passage approach. Continuous co-incubation of C. glabrata with a murine macrophage cell line for over six months resulted in a striking alteration in fungal morphology: The growth form changed from typical spherical yeasts to pseudohyphae-like structures - a phenotype which was stable over several generations without any selective pressure. Transmission electron microscopy and FACS analyses showed that the filamentous-like morphology was accompanied by changes in cell wall architecture. This altered growth form permitted faster escape from macrophages and increased damage of macrophages. In addition, the evolved strain (Evo showed transiently increased virulence in a systemic mouse infection model, which correlated with increased organ-specific fungal burden and inflammatory response (TNFα and IL-6 in the brain. Similarly, the Evo mutant significantly increased TNFα production in the brain on day 2, which is mirrored in macrophages confronted with the Evo mutant, but not with the parental wild type. Whole genome sequencing of the Evo strain, genetic analyses, targeted gene disruption and a reverse microevolution experiment revealed a single nucleotide exchange in the chitin synthase-encoding CHS2 gene as the sole basis for this phenotypic alteration. A targeted CHS2 mutant with the same SNP showed similar phenotypes as the Evo strain under all experimental conditions tested. These results indicate that microevolutionary processes in host-simulative conditions

  1. Single point mutations distributed in 10 soluble and membrane regions of the Nicotiana plumbaginifolia plasma membrane PMA2 H+-ATPase activate the enzyme and modify the structure of the C-terminal region.

    Science.gov (United States)

    Morsomme, P; Dambly, S; Maudoux, O; Boutry, M

    1998-12-25

    The Nicotiana plumbaginifolia pma2 (plasma membrane H+-ATPase) gene is capable of functionally replacing the H+-ATPase genes of the yeast Saccharomyces cerevisiae, provided that the external pH is kept above 5.0. Single point mutations within the pma2 gene were previously identified that improved H+-ATPase activity and allowed yeast growth at pH 4.0. The aim of the present study was to identify most of the PMA2 positions, the mutation of which would lead to improved growth and to determine whether all these mutations result in similar enzymatic and structural modifications. We selected additional mutants in total 42 distinct point mutations localized in 30 codons. They were distributed in 10 soluble and membrane regions of the enzyme. Most mutant PMA2 H+-ATPases were characterized by a higher specific activity, lower inhibition by ADP, and lower stimulation by lysophosphatidylcholine than wild-type PMA2. The mutants thus seem to be constitutively activated. Partial tryptic digestion and immunodetection showed that the PMA2 mutants had a conformational change making the C-terminal region more accessible. These data therefore support the hypothesis that point mutations in various H+-ATPase parts displace the inhibitory C-terminal region, resulting in enzyme activation. The high density of mutations within the first half of the C-terminal region suggests that this part is involved in the interaction between the inhibitory C-terminal region and the rest of the enzyme.

  2. Standardized reporting of adverse events after microvascular decompression of cranial nerves; a population-based single-institution consecutive series

    DEFF Research Database (Denmark)

    Bartek, Jiri; Gulati, Sasha; Unsgård, Geirmund

    2016-01-01

    and 1 June 2013. Adverse events occurring within 30 days were classified according to the Landriel Ibanez classification for neurosurgical complications: grade I represents any non-life threatening complication treated without invasive procedures; grade II is complications requiring invasive management......OBJECTIVE: To investigate frequencies of adverse events occurring within 30 days after microvascular decompression (MVD) surgery using a standardized report form of adverse events. METHODS: We conducted a retrospective review of 98 adult patients (≥16 years) treated with MVD between 1 January 1994......; grade III is life-threatening adverse events requiring treatment in an intensive care unit (ICU); grade IV is death as a result of complications. We sought to compare our results with reports from the literature. RESULTS: Patients' median age was 61 years (range 26-83), and 64 (65 %) were females...

  3. Comparison of single-word and adjective-noun phrase production using event-related brain potentials

    DEFF Research Database (Denmark)

    Lange, Violaine Michel

    2015-01-01

    stimuli varying in complexity -black and white line drawings, coloured line drawings, and arrays of drawings-in participants producing single nouns. Whilst naming latencies were similar for single noun production between visual stimuli conditions, ERPs differed between drawing arrays and single drawings...... in a time-window extending beyond early visual analysis. In a second experiment, different participants were asked to produce either single noun or adjective-noun dual-word phrases to black-and-white and coloured line drawings, respectively. Adjective-noun phrase production (2W) resulted in naming latencies...

  4. Comparing Monte Carlo acceptance/efficiency for tt-bar single lepton events with central and plug electrons

    International Nuclear Information System (INIS)

    Rotaru, M.

    2005-01-01

    The tt-bar production using MC events with one charged lepton (electron), neutrino and jets from pp-bar collisions at a center-of-mass energy of 1.96 TeV was investigated. The aim of this work was to compare the rate of events in central (|η|<1.1) and plug (1.1<|η|<2.8) region. (author)

  5. A Single Base Pair Mutation Encoding a Premature Stop Codon in the MIS type II receptor is Responsible for Canine Persistent Müllerian Duct Syndrome

    Science.gov (United States)

    Wu, Xiufeng; Wan, Shengqin; Pujar, Shashikant; Haskins, Mark E.; Schlafer, Donald H.; Lee, Mary M.; Meyers-Wallen, Vicki N.

    2008-01-01

    Müllerian Inhibiting Substance (MIS), a secreted glycoprotein in the Transforming Growth Factor-beta (TGF-beta) family of growth factors, mediates regression of the Müllerian ducts during embryonic sex differentiation in males. In Persistent Müllerian Duct Syndrome (PMDS), rather than undergoing involution, the Müllerian ducts persist in males, giving rise to the uterus, Fallopian tubes, and upper vagina. Genetic defects in MIS or its receptor (MISRII) have been identified in patients with PMDS. The phenotype in the canine model of PMDS derived from the miniature schnauzer breed is strikingly similar to that of human patients. In this model, PMDS is inherited as a sex-limited autosomal recessive trait. Previous studies indicated that a defect in the MIS receptor or its downstream signaling pathway was likely to be causative of the canine syndrome. In this study the canine PMDS phenotype and clinical sequelae are described in detail. Affected and unaffected members of this pedigree are genotyped, identifying a single base pair substitution in MISRII that introduces a stop codon in exon 3. The homozygous mutation terminates translation at 80 amino acids, eliminating much of the extracellular domain and the entire transmembrane and intracellular signaling domains. Findings in this model may enable insights to be garnered from correlation of detailed clinical descriptions with molecular defects, which are not otherwise possible in the human syndrome. PMID:18723470

  6. Safety, pharmacokinetics, and pharmacodynamics of TV-1380, a novel mutated butyrylcholinesterase treatment for cocaine addiction, after single and multiple intramuscular injections in healthy subjects.

    Science.gov (United States)

    Cohen-Barak, Orit; Wildeman, Jacqueline; van de Wetering, Jeroen; Hettinga, Judith; Schuilenga-Hut, Petra; Gross, Aviva; Clark, Shane; Bassan, Merav; Gilgun-Sherki, Yossi; Mendzelevski, Boaz; Spiegelstein, Ofer

    2015-05-01

    Human plasma butyrylcholinesterase (BChE) contributes to cocaine metabolism and has been considered for use in treating cocaine addiction and cocaine overdose. TV-1380 is a recombinant protein composed of the mature form of human serum albumin fused at its amino terminus to the carboxy-terminus of a truncated and mutated BChE. In preclinical studies, TV-1380 has been shown to rapidly eliminate cocaine in the plasma thus forestalling entry of cocaine into the brain and heart. Two randomized, blinded phase I studies were conducted to evaluate the safety, pharmacokinetics, and pharmacodynamics of TV-1380, following single and multiple administration in healthy subjects. TV-1380 was found to be safe and well tolerated with a long half-life (43-77 hours) and showed a dose-proportional increase in systemic exposure. Consistent with preclinical results, the ex vivo cocaine hydrolysis, TV-1380 activity clearly increased upon treatment in a dose-dependent manner. In addition, there was a direct relationship between ex vivo cocaine hydrolysis (kel ) and TV-1380 serum concentrations. There was no evidence that TV-1380 affected heart rate, the uncorrected QT interval, or the heart-rate-corrected QTcF interval. TV-1380, therefore, offers a safe once-weekly therapy to increase cocaine hydrolysis. © 2015 The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  7. Single residue AAV capsid mutation improves transduction of photoreceptors in the Abca4-/- mouse and bipolar cells in the rd1 mouse and human retina ex vivo.

    Science.gov (United States)

    De Silva, Samantha R; Charbel Issa, Peter; Singh, Mandeep S; Lipinski, Daniel M; Barnea-Cramer, Alona O; Walker, Nathan J; Barnard, Alun R; Hankins, Mark W; MacLaren, Robert E

    2016-11-01

    Gene therapy using adeno-associated viral (AAV) vectors for the treatment of retinal degenerations has shown safety and efficacy in clinical trials. However, very high levels of vector expression may be necessary for the treatment of conditions such as Stargardt disease where a dual vector approach is potentially needed, or in optogenetic strategies for end-stage degeneration in order to achieve maximal light sensitivity. In this study, we assessed two vectors with single capsid mutations, rAAV2/2(Y444F) and rAAV2/8(Y733F) in their ability to transduce retina in the Abca4 -/- and rd1 mouse models of retinal degeneration. We noted significantly increased photoreceptor transduction using rAAV2/8(Y733F) in the Abca4 -/- mouse, in contrast to previous work where vectors tested in this model have shown low levels of photoreceptor transduction. Bipolar cell transduction was achieved following subretinal delivery of both vectors in the rd1 mouse, and via intravitreal delivery of rAAV2/2(Y444F). The successful use of rAAV2/8(Y733F) to target bipolar cells was further validated on human tissue using an ex vivo culture system of retinal explants. Capsid mutant AAV vectors transduce human retinal cells and may be particularly suited to treat retinal degenerations in which high levels of transgene expression are required.

  8. Single-strand conformation polymorphism (SSCP)-based mutation scanning approaches to fingerprint sequence variation in ribosomal DNA of ascaridoid nematodes.

    Science.gov (United States)

    Zhu, X Q; Gasser, R B

    1998-06-01

    In this study, we assessed single-strand conformation polymorphism (SSCP)-based approaches for their capacity to fingerprint sequence variation in ribosomal DNA (rDNA) of ascaridoid nematodes of veterinary and/or human health significance. The second internal transcribed spacer region (ITS-2) of rDNA was utilised as the target region because it is known to provide species-specific markers for this group of parasites. ITS-2 was amplified by PCR from genomic DNA derived from individual parasites and subjected to analysis. Direct SSCP analysis of amplicons from seven taxa (Toxocara vitulorum, Toxocara cati, Toxocara canis, Toxascaris leonina, Baylisascaris procyonis, Ascaris suum and Parascaris equorum) showed that the single-strand (ss) ITS-2 patterns produced allowed their unequivocal identification to species. While no variation in SSCP patterns was detected in the ITS-2 within four species for which multiple samples were available, the method allowed the direct display of four distinct sequence types of ITS-2 among individual worms of T. cati. Comparison of SSCP/sequencing with the methods of dideoxy fingerprinting (ddF) and restriction endonuclease fingerprinting (REF) revealed that also ddF allowed the definition of the four sequence types, whereas REF displayed three of four. The findings indicate the usefulness of the SSCP-based approaches for the identification of ascaridoid nematodes to species, the direct display of sequence variation in rDNA and the detection of population variation. The ability to fingerprint microheterogeneity in ITS-2 rDNA using such approaches also has implications for studying fundamental aspects relating to mutational change in rDNA.

  9. Extending Jak2V617F and MplW515 mutation analysis to single hematopoietic colonies and B and T lymphocytes.

    Science.gov (United States)

    Pardanani, Animesh; Lasho, Terra L; Finke, Christy; Mesa, Ruben A; Hogan, William J; Ketterling, Rhett P; Gilliland, Dwight Gary; Tefferi, Ayalew

    2007-09-01

    JAK2V617F and MPLW515L/K are myeloproliferative disorder (MPD)-associated mutations. We genotyped 552 individual hematopoietic colonies obtained by CD34+ cell culture from 16 affected patients (13 JAK2V617F and 3 MPLW515L/K) to determine (a) the proportion of colonies harboring a particular mutation in the presence or absence of cytokines, (b) the lineage distribution of endogenous colonies for each mutation, and (c) the differences (if any) in the pattern of mutation among the various MPDs, as established by genotyping of individual colonies. Genotyping analysis revealed cohabitation of mutation-negative and mutation-positive endogenous colonies in polycythemia vera as well as other MPDs. Culture of progenitor cells harboring MPLW515L/K yielded virtually no endogenous erythroid colonies in contrast to JAK2V617F-harboring progenitor cells. The mutation pattern (i.e., relative distribution of homozygous, heterozygous, or wild-type colonies) was not a distinguishing feature among the MPDs, and MPLW515 mutations were detected in B and/or T lymphocytes in all three patients tested. These observations suggest that clonal myelopoiesis antedates acquisition of JAK2V617F or MPLW515L/K mutations and that the latter is acquired in a lympho-myeloid progenitor cell.

  10. Comparison of circadian, weekly, and seasonal variations of electrical storms and single events of ventricular fibrillation in patients with Brugada syndrome

    Directory of Open Access Journals (Sweden)

    Yoshiyasu Aizawa

    2016-06-01

    Full Text Available In patients with Brugada syndrome (BS, VF occurred predominantly during the nocturnal period. Some patients also developed ESs. In addition to the circadian rhythm, patients showed weekly and seasonal patterns. The patients with ESs had peak episodes of VF on Saturday and in the winter and spring, while episodes of VF in patients with single VF events occurred most often on Monday with smaller seasonal variation. Except for age, there was no difference in the clinical or ECG characteristics between the patients with ESs and those with single VF episodes.

  11. Diverse growth hormone receptor gene mutations in Laron syndrome.

    Science.gov (United States)

    Berg, M A; Argente, J; Chernausek, S; Gracia, R; Guevara-Aguirre, J; Hopp, M; Pérez-Jurado, L; Rosenbloom, A; Toledo, S P; Francke, U

    1993-01-01

    To better understand the molecular genetic basis and genetic epidemiology of Laron syndrome (growth-hormone insensitivity syndrome), we analyzed the growth-hormone receptor (GHR) genes of seven unrelated affected individuals from the United States, South America, Europe, and Africa. We amplified all nine GHR gene exons and splice junctions from these individuals by PCR and screened the products for mutations by using denaturing gradient gel electrophoresis (DGGE). We identified a single GHR gene fragment with abnormal DGGE results for each affected individual, sequenced this fragment, and, in each case, identified a mutation likely to cause Laron syndrome, including two nonsense mutations (R43X and R217X), two splice-junction mutations, (189-1 G to T and 71 + 1 G to A), and two frameshift mutations (46 del TT and 230 del TA or AT). Only one of these mutations, R43X, has been previously reported. Using haplotype analysis, we determined that this mutation, which involves a CpG dinucleotide hot spot, likely arose as a separate event in this case, relative to the two prior reports of R43X. Aside from R43X, the mutations we identified are unique to patients from particular geographic regions. Ten GHR gene mutations have now been described in this disorder. We conclude that Laron syndrome is caused by diverse GHR gene mutations, including deletions, RNA processing defects, translational stop codons, and missense codons. All the identified mutations involve the extracellular domain of the receptor, and most are unique to particular families or geographic areas. Images Figure 1 Figure 2 PMID:8488849

  12. Kinetic modelling of hydrocracking catalytic reactions by the single events theory; Modelisation cinetique des reactions catalytiques d`hydrocraquage par la theorie des evenements constitutifs

    Energy Technology Data Exchange (ETDEWEB)

    Schweitzer, J.M.

    1998-11-23

    Kinetic modelling of petroleum hydrocracking is particularly difficult given the complexity of the feedstocks. There are two distinct classes of kinetics models: lumped empirical models and detailed molecular models. The productivity of lumped empirical models is generally not very accurate, and the number of kinetic parameters increases rapidly with the number of lumps. A promising new methodology is the use of kinetic modelling based on the single events theory. Due to the molecular approach, a finite and limited number of kinetic parameters can describe the kinetic behaviour of the hydrocracking of heavy feedstock. The parameters are independent of the feedstock. However, the available analytical methods are not able to identify the products on the molecular level. This can be accounted for by means of an posteriori lamping technique, which incorporates the detailed knowledge of the elementary step network. Thus, the lumped kinetic parameters are directly calculated from the fundamental kinetic coefficients and the single event model is reduced to a re-lumped molecular model. Until now, the ability of the method to extrapolate to higher carbon numbers had not been demonstrated. In addition, no study had been published for three phase (gas-liquid-solid) systems and a complex feedstock. The objective of this work is to validate the `single events` method using a paraffinic feedstock. First of all, a series of experiments was conducted on a model compound (hexadecane) in order to estimate the fundamental kinetic parameters for acyclic molecules. To validate the single event approach, these estimated kinetic coefficients were used to simulate hydrocracking of a paraffinic mixture ranging from C11 to C18. The simulation results were then compared to the results obtained from the hydrocracking experiments. The comparison allowed to validate the model for acyclic molecules and to demonstrate that the model is applicable to compounds with higher carbon numbers. (author

  13. Search for supersymmetry in pp collisions at sqrt(s)=7 TeV in events with a single lepton, jets, and missing transverse momentum

    Energy Technology Data Exchange (ETDEWEB)

    Chatrchyan, Serguei [Yerevan Physics Inst. (Armenia); et al.

    2011-08-01

    Results are reported from a search for physics beyond the standard model in proton-proton collisions at a center-of-mass energy of 7 TeV, focusing on the signature with a single, isolated, high-transverse-momentum lepton (electron or muon), energetic jets, and large missing transverse momentum. The data sample comprises an integrated luminosity of 36 inverse picobarns, recorded by the CMS experiment at the LHC. The search is motivated by models of new physics, including supersymmetry. The observed event yields are consistent with standard model backgrounds predicted using control samples obtained from the data. The characteristics of the event sample are consistent with those expected for the production of t t-bar and W +jets events. The results are interpreted in terms of limits on the parameter space for the constrained minimal supersymmetric extension of the standard model.

  14. Single Event Upset Analysis: On-orbit performance of the Alpha Magnetic Spectrometer Digital Signal Processor Memory aboard the International Space Station

    Science.gov (United States)

    Li, Jiaqiang; Choutko, Vitaly; Xiao, Liyi

    2018-03-01

    Based on the collection of error data from the Alpha Magnetic Spectrometer (AMS) Digital Signal Processors (DSP), on-orbit Single Event Upsets (SEUs) of the DSP program memory are analyzed. The daily error distribution and time intervals between errors are calculated to evaluate the reliability of the system. The particle density distribution of International Space Station (ISS) orbit is presented and the effects from the South Atlantic Anomaly (SAA) and the geomagnetic poles are analyzed. The impact of solar events on the DSP program memory is carried out combining data analysis and Monte Carlo simulation (MC). From the analysis and simulation results, it is concluded that the area corresponding to the SAA is the main source of errors on the ISS orbit. Solar events can also cause errors on DSP program memory, but the effect depends on the on-orbit particle density.

  15. Simultaneous Determination of Structure and Event Location Using Body and Surface Wave Measurements at a Single Station: Preparation for Mars Data from the InSight Mission

    Science.gov (United States)

    Panning, M. P.; Banerdt, W. B.; Beucler, E.; Blanchette-Guertin, J. F.; Boese, M.; Clinton, J. F.; Drilleau, M.; James, S. R.; Kawamura, T.; Khan, A.; Lognonne, P. H.; Mocquet, A.; van Driel, M.

    2015-12-01

    An important challenge for the upcoming InSight mission to Mars, which will deliver a broadband seismic station to Mars along with other geophysical instruments in 2016, is to accurately determine event locations with the use of a single station. Locations are critical for the primary objective of the mission, determining the internal structure of Mars, as well as a secondary objective of measuring the activity of distribution of seismic events. As part of the mission planning process, a variety of techniques have been explored for location of marsquakes and inversion of structure, and preliminary procedures and software are already under development as part of the InSight Mars Quake and Mars Structure Services. One proposed method, involving the use of recordings of multiple-orbit surface waves, has already been tested with synthetic data and Earth recordings. This method has the strength of not requiring an a priori velocity model of Mars for quake location, but will only be practical for larger events. For smaller events where only first orbit surface waves and body waves are observable, other methods are required. In this study, we implement a transdimensional Bayesian inversion approach to simultaneously invert for basic velocity structure and location parameters (epicentral distance and origin time) using only measurements of body wave arrival times and dispersion of first orbit surface waves. The method is tested with synthetic data with expected Mars noise and Earth data for single events and groups of events and evaluated for errors in both location and structural determination, as well as tradeoffs between resolvable parameters and the effect of 3D crustal variations.

  16. The ABCA4 2588G>C Stargardt mutation: single origin and increasing frequency from South-West to North-East Europe.

    NARCIS (Netherlands)

    Maugeri, A.; Flothmann, K.; Hemmrich, N.; Ingvast, S.; Jorge, P.; Paloma, E.; Patel, R.; Rozet, J.M.; Tammur, J.; Testa, F.; Balcells, S.; Bird, A.C.; Brunner, H.G.; Hoyng, C.B.; Metspalu, A.; Simonelli, F.; Allikmets, R.; Bhattacharya, S.S.; Urso, M. D'; Gonzalez-Duarte, R.; Kaplan, J.; Meerman, G.J. te; Santos, R.L.; Schwartz, M.; Camp, G. van; Wadelius, C.; Weber, B.; Cremers, F.P.M.

    2002-01-01

    Inherited retinal dystrophies represent the most important cause of vision impairment in adolescence, affecting approximately 1 out of 3000 individuals. Mutations of the photoreceptor-specific gene ABCA4 (ABCR) are a common cause of retinal dystrophy. A number of mutations have been repeatedly

  17. The ABCA4 2588G > C Stargardt mutation : Single origin and increasing frequency from South-West to North-East Europe

    NARCIS (Netherlands)

    Maugeri, A; Flothmann, K; Hemmrich, N; Ingvast, S; Jorge, P; Paloma, E; Patel, R; Rozet, JM; Tammur, J; Testa, F; Balcells, S; Bird, AC; Brunner, HG; Hoyng, CB; Metspalu, A; Simonelli, F; Allikmets, R; Bhattacharya, SS; D'Urso, M; Gonzalez-Duarte, R; Kaplan, J; Meerman, GJT; Santoss, R; Schwartz, M; Van Camp, G; Wadelius, C; Weber, BHF; Cremers, FPM

    Inherited retinal dystrophies represent the most important cause of vision impairment in adolescence, affecting approximately 1 out of 3000 individuals. Mutations of the photoreceptor-specific gene ABCA4 (ABCR) are a common cause of retinal dystrophy. A number of mutations have been repeatedly

  18. Identification of the timing-of-events model with multiple competing exit risks from single-spell data

    DEFF Research Database (Denmark)

    Drepper, Bettina; Effraimidis, G.

    2016-01-01

    The identification result of the timing-of-events model (Abbring and Van den Berg, 2003b) is extended to a model with several competing exit risk equations. This extension allows e.g. to simultaneously identify the different effects a benefit sanction has on the rate of finding work and leaving t...

  19. A Novel Heterozygous Intronic Mutation in the FBN1 Gene Contributes to FBN1 RNA Missplicing Events in the Marfan Syndrome

    Directory of Open Access Journals (Sweden)

    Mario Torrado

    2018-01-01

    Full Text Available Marfan syndrome (MFS is an autosomal dominantly inherited connective tissue disorder, mostly caused by mutations in the fibrillin-1 (FBN1 gene. We, by using targeted next-generation sequence analysis, identified a novel intronic FBN1 mutation (the c.2678-15C>A variant in a MFS patient with aortic dilatation. The computational predictions showed that the heterozygous c.2678-15C>A intronic variant might influence the splicing process by differentially affecting canonical versus cryptic splice site utilization within intron 22 of the FBN1 gene. RT-PCR and Western blot analyses, using FBN1 minigenes transfected into HeLa and COS-7 cells, revealed that the c.2678-15C>A variant disrupts normal splicing of intron 22 leading to aberrant 13-nt intron 22 inclusion, frameshift, and premature termination codon. Collectively, the results strongly suggest that the c.2678-15C>A variant could lead to haploinsufficiency of the FBN1 functional protein and structural connective tissue fragility in MFS complicated by aorta dilation, a finding that further expands on the genetic basis of aortic pathology.

  20. CL-imaging and ion microprobe dating of single zircons from a high-grade rock from the Central Zone, Limpopo Belt, South Africa: Evidence for a single metamorphic event at ˜2.0 Ga

    Science.gov (United States)

    Mouri, H.; Brandl, G.; Whitehouse, M.; de Waal, S.; Guiraud, M.

    2008-02-01

    The combination of ion microprobe dating and cathodoluminescence (CL) imaging of zircons from a high-grade rock from the Central Zone of the Limpopo Belt were used to constrain the age of metamorphic events in the area. Zircon grains extracted from an orthopyroxene-gedrite-bearing granulite were prepared for single crystal CL-imaging and ion microprobe dating. The grains display complex zoning when using SEM-based CL-imaging. A common feature in most grains is the presence of a distinct core with a broken oscillatory zoned structure, which clearly appears to be the remnant of an original grain of igneous origin. This core is overgrown by an unzoned thin rim measuring about 10-30 μm in diameter, which is considered as new zircon growth during a single metamorphic event. Selected domains of the zircon grains were analysed for U, Pb and Th isotopic composition using a CAMECA IMS 1270 ion microprobe (Nordsim facility). Most of the grains define a near-concordant cluster with some evidence of Pb loss. The most concordant ages of the cores yielded a weighted mean 207Pb/ 206Pb age of 2689 ± 15 (2 σ) Ma, interpreted as the age of the protolith of an igneous origin. The unzoned overgrowths of the zircon grains yielded a considerably younger weighted mean 207Pb/ 206Pb age of ˜2006.5 ± 8.0 Ma (2 σ), and these data are interpreted to reflect closely the age of the ubiquitous high-grade metamorphic event in the Central Zone. This study shows clearly, based on both the internal structure of the zircons and the data obtained by ion microprobe dating, that only a single metamorphic event is recorded by the studied 2.69 Ga old rocks, and we found no evidence of an earlier metamorphic event at ˜2.5 Ga as postulated earlier by some workers.

  1. Deep sequencing of natural and experimental populations of Drosophila melanogaster reveals biases in the spectrum of new mutations.

    Science.gov (United States)

    Assaf, Zoe June; Tilk, Susanne; Park, Jane; Siegal, Mark L; Petrov, Dmitri A

    2017-12-01

    Mutations provide the raw material of evolution, and thus our ability to study evolution depends fundamentally on having precise measurements of mutational rates and patterns. We generate a data set for this purpose using (1) de novo mutations from mutation accumulation experiments and (2) extremely rare polymorphisms from natural populations. The first, mutation accumulation (MA) lines are the product of maintaining flies in tiny populations for many generations, therefore rendering natural selection ineffective and allowing new mutations to accrue in the genome. The second, rare genetic variation from natural populations allows the study of mutation because extremely rare polymorphisms are relatively unaffected by the filter of natural selection. We use both methods in Drosophila melanogaster , first generating our own novel data set of sequenced MA lines and performing a meta-analysis of all published MA mutations (∼2000 events) and then identifying a high quality set of ∼70,000 extremely rare (≤0.1%) polymorphisms that are fully validated with resequencing. We use these data sets to precisely measure mutational rates and patterns. Highlights of our results include: a high rate of multinucleotide mutation events at both short (∼5 bp) and long (∼1 kb) genomic distances, showing that mutation drives GC content lower in already GC-poor regions, and using our precise context-dependent mutation rates to predict long-term evolutionary patterns at synonymous sites. We also show that de novo mutations from independent MA experiments display similar patterns of single nucleotide mutation and well match the patterns of mutation found in natural populations. © 2017 Assaf et al.; Published by Cold Spring Harbor Laboratory Press.

  2. Effects of DNA double-strand and single-strand breaks on intrachromosomal recombination events in cell-cycle-arrested yeast cells

    International Nuclear Information System (INIS)

    Galli, A.; Schiestl, R.H.

    1998-01-01

    Intrachromosomal recombination between repeated elements can result in deletion (DEL recombination) events. We investigated the inducibility of such intrachromosomal recombination events at different stages of the cell cycle and the nature of the primary DNA lesions capable of initiating these events. Two genetic systems were constructed in Saccharomyces cerevisiae that select for DEL recombination events between duplicated alleles of CDC28 and TUB2. We determined effects of double-strand breaks (DSBs) and single-strand breaks (SSBs) between the duplicated alleles on DEL recombination when induced in dividing cells or cells arrested in G1 or G2. Site-specific DSBs and SSBs were produced by overexpression of the I-Sce I endonuclease and the gene II protein (gIIp), respectively. I-Sce I-induced DSBs caused an increase in DEL recombination frequencies in both dividing and cell-cycle-arrested cells, indicating that G1- and G2-arrested cells are capable of completing DSB repair. In contrast, gIIp-induced SSBs caused an increase in DEL recombination frequency only in dividing cells. To further examine these phenomena we used both γ-irradiation, inducing DSBs as its most relevant lesion, and UV, inducing other forms of DNA damage. UV irradiation did not increase DEL recombination frequencies in G1 or G2, whereas γ-rays increased DEL recombination frequencies in both phases. Both forms of radiation, however, induced DEL recombination in dividing cells. The results suggest that DSBsbut not SSBs induce DEL recombination, probably via the single-strand annealing pathway. Further, DSBs in dividing cells may result from the replication of a UV or SSB-damaged template. Alternatively, UV induced events may occur by replication slippage after DNA polymerase pausing in front of the damage. (author)

  3. Thromboembolic events associated with single balloon-, double balloon-, and stent-assisted coil embolization of asymptomatic unruptured cerebral aneurysms: evaluation with diffusion-weighted MR imaging

    International Nuclear Information System (INIS)

    Takigawa, Tomoji; Suzuki, Kensuke; Sugiura, Yoshiki; Suzuki, Ryotaro; Takano, Issei; Shimizu, Nobuyuki; Tanaka, Yoshihiro; Hyodo, Akio

    2014-01-01

    The introduction of the balloon remodeling and stent-assisted technique has revolutionized the approach to coil embolization for wide-neck aneurysms. The purpose of this study was to determine the frequency of thromboembolic events associated with single balloon-assisted, double balloon-assisted, and stent-assisted coil embolization for asymptomatic unruptured aneurysms. A retrospective review was undertaken by 119 patients undergoing coiling with an adjunctive technique for unruptured saccular aneurysms (64 single balloon, 12 double balloon, 43 stent assisted). All underwent diffusion-weighted imaging (DWI) within 24 h after the procedure. DWI showed hyperintense lesions in 48 (40 %) patients, and ten (21 %) of these patients incurred neurological deterioration (permanent, two; transient, eight). Hyperintense lesions were detected significantly more often in procedures with the double balloon-assisted technique (7/12, 58 %) than with the single balloon-assisted technique (16/64, 25 %, p = 0.05). Occurrence of new lesions was significantly higher with the use of stent-assisted technique (25/43, 58 %) than with the single balloon-assisted technique (p = 0.001). Symptomatic ischemic rates were similar between the three groups. The increased number of microcatheters was significantly related to the DWI abnormalities (two microcatheters, 15/63 (23.8 %); three microcatheters, 20/41 (48.8 %) (p = 0.008); four microcatheters, 12/15 (80 %) (p = 0.001)). Thromboembolic events detected on DWI related to coil embolization for unruptured aneurysms are relatively common, especially in association with the double balloon-assisted and stent-assisted techniques. Furthermore, the number of microcatheters is highly correlated with DWI abnormalities. The high rate of thromboembolic events suggests the need for evaluation of platelet reactivity and the addition or change of antiplatelet agents. (orig.)

  4. Measurement of top quark and W boson polarisation observables with t-channel single-top-quark events in the ATLAS experiment.

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00288626

    This thesis presents two studies, one related with the alignment of the ATLAS Inner Detector tracking system and other with the measurement of top quark and W boson polarisation observables using t-channel single-top-quark events. The first topic describes the implementation of a monitoring tool, which is used to monitor the Level 1 alignment corrections obtained in the calibration loop, as well as the use of constraints on the momentum and impact parameters biases using $Z \\rightarrow\\mu\\mu$ events on the alignment algorithms. These techniques were developed during 2012 data taking campaign and provide the most accurate description of the ATLAS Inner Detector. The second topic presents a detailed measurement of top quark and W boson polarisation observables using the 20.3 $fb^{-1}$ of data collected by the ATLAS detector at $\\sqrt{s}$ = 8 TeV. The measurement is performed using $t$-channel single top quark events and exploits the feature that the produced top quark is highly polarised along the direction of ...

  5. Measurement of the top quark mass using single top quark events in proton-proton collisions at √(s) = 8 TeV

    Energy Technology Data Exchange (ETDEWEB)

    Sirunyan, A.M.; Tumasyan, A. [Yerevan Physics Institute, Yerevan (Armenia); Adam, W. [Institut fuer Hochenergiephysik, Vienna (Austria); Collaboration: CMS Collaboration; and others

    2017-05-15

    A measurement of the top quark mass is reported in events containing a single top quark produced via the electroweak t channel. The analysis is performed using data from proton-proton collisions collected with the CMS detector at the LHC at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.7 fb{sup -1}. Top quark candidates are reconstructed from their decay to a W boson decaying leptonically to a muon and a neutrino. The final state signature and kinematic properties of single top quark events in the t channel are used to enhance the purity of the sample, suppressing the contribution from top quark pair production. A fit to the invariant mass distribution of reconstructed top quark candidates yields a value of the top quark mass of 172.95 ± 0.77(stat){sup +0.97}{sub -0.93}(syst) GeV. This result is in agreement with the current world average, and represents the first measurement of the top quark mass in event topologies not dominated by top quark pair production, therefore contributing to future averages with partially uncorrelated systematic uncertainties and a largely uncorrelated statistical uncertainty. (orig.)

  6. Measurement of the top quark mass using single top quark events in proton-proton collisions at $\\sqrt{s}= $ 8 TeV

    CERN Document Server

    Sirunyan, Albert M; Adam, Wolfgang; Aşılar, Ece; Bergauer, Thomas; Brandstetter, Johannes; Brondolin, Erica; Dragicevic, Marko; Erö, Janos; Flechl, Martin; Friedl, Markus; Fruehwirth, Rudolf; Ghete, Vasile Mihai; Hartl, Christian; Hörmann, Natascha; Hrubec, Josef; Jeitler, Manfred; König, Axel; Krätschmer, Ilse; Liko, Dietrich; Matsushita, Takashi; Mikulec, Ivan; Rabady, Dinyar; Rad, Navid; Rahbaran, Babak; Rohringer, Herbert; Schieck, Jochen; Strauss, Josef; Waltenberger, Wolfgang; Wulz, Claudia-Elisabeth; Dvornikov, Oleg; Makarenko, Vladimir; Mossolov, Vladimir; Suarez Gonzalez, Juan; Zykunov, Vladimir; Shumeiko, Nikolai; Alderweireldt, Sara; De Wolf, Eddi A; Janssen, Xavier; Lauwers, Jasper; Van De Klundert, Merijn; Van Haevermaet, Hans; Van Mechelen, Pierre; Van Remortel, Nick; Van Spilbeeck, Alex; Abu Zeid, Shimaa; Blekman, Freya; D'Hondt, Jorgen; Daci, Nadir; De Bruyn, Isabelle; Deroover, Kevin; Lowette, Steven; Moortgat, Seth; Moreels, Lieselotte; Olbrechts, Annik; Python, Quentin; Skovpen, Kirill; Tavernier, Stefaan; Van Doninck, Walter; Van Mulders, Petra; Van Parijs, Isis; Brun, Hugues; Clerbaux, Barbara; De Lentdecker, Gilles; Delannoy, Hugo; Fasanella, Giuseppe; Favart, Laurent; Goldouzian, Reza; Grebenyuk, Anastasia; Karapostoli, Georgia; Lenzi, Thomas; Léonard, Alexandre; Luetic, Jelena; Maerschalk, Thierry; Marinov, Andrey; Randle-conde, Aidan; Seva, Tomislav; Vander Velde, Catherine; Vanlaer, Pascal; Vannerom, David; Yonamine, Ryo; Zenoni, Florian; Zhang, Fengwangdong; Cimmino, Anna; Cornelis, Tom; Dobur, Didar; Fagot, Alexis; Gul, Muhammad; Khvastunov, Illia; Poyraz, Deniz; Salva Diblen, Sinem; Schöfbeck, Robert; Tytgat, Michael; Van Driessche, Ward; Yazgan, Efe; Zaganidis, Nicolas; Bakhshiansohi, Hamed; Beluffi, Camille; Bondu, Olivier; Brochet, Sébastien; Bruno, Giacomo; Caudron, Adrien; De Visscher, Simon; Delaere, Christophe; Delcourt, Martin; Francois, Brieuc; Giammanco, Andrea; Jafari, Abideh; Komm, Matthias; Krintiras, Georgios; Lemaitre, Vincent; Magitteri, Alessio; Mertens, Alexandre; Musich, Marco; Piotrzkowski, Krzysztof; Quertenmont, Loic; Selvaggi, Michele; Vidal Marono, Miguel; Wertz, Sébastien; Beliy, Nikita; Aldá Júnior, Walter Luiz; Alves, Fábio Lúcio; Alves, Gilvan; Brito, Lucas; Hensel, Carsten; Moraes, Arthur; Pol, Maria Elena; Rebello Teles, Patricia; Belchior Batista Das Chagas, Ewerton; Carvalho, Wagner; Chinellato, Jose; Custódio, Analu; Melo Da Costa, Eliza; Da Silveira, Gustavo Gil; De Jesus Damiao, Dilson; De Oliveira Martins, Carley; Fonseca De Souza, Sandro; Huertas Guativa, Lina Milena; Malbouisson, Helena; Matos Figueiredo, Diego; Mora Herrera, Clemencia; Mundim, Luiz; Nogima, Helio; Prado Da Silva, Wanda Lucia; Santoro, Alberto; Sznajder, Andre; Tonelli Manganote, Edmilson José; Torres Da Silva De Araujo, Felipe; Vilela Pereira, Antonio; Ahuja, Sudha; Bernardes, Cesar Augusto; Dogra, Sunil; Tomei, Thiago; De Moraes Gregores, Eduardo; Mercadante, Pedro G; Moon, Chang-Seong; Novaes, Sergio F; Padula, Sandra; Romero Abad, David; Ruiz Vargas, José Cupertino; Aleksandrov, Aleksandar; Hadjiiska, Roumyana; Iaydjiev, Plamen; Rodozov, Mircho; Stoykova, Stefka; Sultanov, Georgi; Vutova, Mariana; Dimitrov, Anton; Glushkov, Ivan; Litov, Leander; Pavlov, Borislav; Petkov, Peicho; Fang, Wenxing; Ahmad, Muhammad; Bian, Jian-Guo; Chen, Guo-Ming; Chen, He-Sheng; Chen, Mingshui; Chen, Ye; Cheng, Tongguang; Jiang, Chun-Hua; Leggat, Duncan; Liu, Zhenan; Romeo, Francesco; Ruan, Manqi; Shaheen, Sarmad Masood; Spiezia, Aniello; Tao, Junquan; Wang, Chunjie; Wang, Zheng; Zhang, Huaqiao; Zhao, Jingzhou; Ban, Yong; Chen, Geng; Li, Qiang; Liu, Shuai; Mao, Yajun; Qian, Si-Jin; Wang, Dayong; Xu, Zijun; Avila, Carlos; Cabrera, Andrés; Chaparro Sierra, Luisa Fernanda; Florez, Carlos; Gomez, Juan Pablo; González Hernández, Carlos Felipe; Ruiz Alvarez, José David; Sanabria, Juan Carlos; Godinovic, Nikola; Lelas, Damir; Puljak, Ivica; Ribeiro Cipriano, Pedro M; Sculac, Toni; Antunovic, Zeljko; Kovac, Marko; Brigljevic, Vuko; Ferencek, Dinko; Kadija, Kreso; Mesic, Benjamin; Susa, Tatjana; Attikis, Alexandros; Mavromanolakis, Georgios; Mousa, Jehad; Nicolaou, Charalambos; Ptochos, Fotios; Razis, Panos A; Rykaczewski, Hans; Tsiakkouri, Demetra; Finger, Miroslav; Finger Jr, Michael; Carrera Jarrin, Edgar; El-khateeb, Esraa; Elgammal, Sherif; Mohamed, Amr; Kadastik, Mario; Perrini, Lucia; Raidal, Martti; Tiko, Andres; Veelken, Christian; Eerola, Paula; Pekkanen, Juska; Voutilainen, Mikko; Härkönen, Jaakko; Jarvinen, Terhi; Karimäki, Veikko; Kinnunen, Ritva; Lampén, Tapio; Lassila-Perini, Kati; Lehti, Sami; Lindén, Tomas; Luukka, Panja-Riina; Tuominiemi, Jorma; Tuovinen, Esa; Wendland, Lauri; Talvitie, Joonas; Tuuva, Tuure; Besancon, Marc; Couderc, Fabrice; Dejardin, Marc; Denegri, Daniel; Fabbro, Bernard; Faure, Jean-Louis; Favaro, Carlotta; Ferri, Federico; Ganjour, Serguei; Ghosh, Saranya; Givernaud, Alain; Gras, Philippe; Hamel de Monchenault, Gautier; Jarry, Patrick; Kucher, Inna; Locci, Elizabeth; Machet, Martina; Malcles, Julie; Rander, John; Rosowsky, André; Titov, Maksym; Abdulsalam, Abdulla; Antropov, Iurii; Baffioni, Stephanie; Beaudette, Florian; Busson, Philippe; Cadamuro, Luca; Chapon, Emilien; Charlot, Claude; Davignon, Olivier; Granier de Cassagnac, Raphael; Jo, Mihee; Lisniak, Stanislav; Miné, Philippe; Nguyen, Matthew; Ochando, Christophe; Ortona, Giacomo; Paganini, Pascal; Pigard, Philipp; Regnard, Simon; Salerno, Roberto; Sirois, Yves; Stahl Leiton, Andre Govinda; Strebler, Thomas; Yilmaz, Yetkin; Zabi, Alexandre; Zghiche, Amina; Agram, Jean-Laurent; Andrea, Jeremy; Aubin, Alexandre; Bloch, Daniel; Brom, Jean-Marie; Buttignol, Michael; Chabert, Eric Christian; Chanon, Nicolas; Collard, Caroline; Conte, Eric; Coubez, Xavier; Fontaine, Jean-Charles; Gelé, Denis; Goerlach, Ulrich; Le Bihan, Anne-Catherine; Van Hove, Pierre; Gadrat, Sébastien; Beauceron, Stephanie; Bernet, Colin; Boudoul, Gaelle; Carrillo Montoya, Camilo Andres; Chierici, Roberto; Contardo, Didier; Courbon, Benoit; Depasse, Pierre; El Mamouni, Houmani; Fay, Jean; Gascon, Susan; Gouzevitch, Maxime; Grenier, Gérald; Ille, Bernard; Lagarde, Francois; Laktineh, Imad Baptiste; Lethuillier, Morgan; Mirabito, Laurent; Pequegnot, Anne-Laure; Perries, Stephane; Popov, Andrey; Sabes, David; Sordini, Viola; Vander Donckt, Muriel; Verdier, Patrice; Viret, Sébastien; Khvedelidze, Arsen; Tsamalaidze, Zviad; Autermann, Christian; Beranek, Sarah; Feld, Lutz; Kiesel, Maximilian Knut; Klein, Katja; Lipinski, Martin; Preuten, Marius; Schomakers, Christian; Schulz, Johannes; Verlage, Tobias; Albert, Andreas; Brodski, Michael; Dietz-Laursonn, Erik; Duchardt, Deborah; Endres, Matthias; Erdmann, Martin; Erdweg, Sören; Esch, Thomas; Fischer, Robert; Güth, Andreas; Hamer, Matthias; Hebbeker, Thomas; Heidemann, Carsten; Hoepfner, Kerstin; Knutzen, Simon; Merschmeyer, Markus; Meyer, Arnd; Millet, Philipp; Mukherjee, Swagata; Olschewski, Mark; Padeken, Klaas; Pook, Tobias; Radziej, Markus; Reithler, Hans; Rieger, Marcel; Scheuch, Florian; Sonnenschein, Lars; Teyssier, Daniel; Thüer, Sebastian; Cherepanov, Vladimir; Flügge, Günter; Kargoll, Bastian; Kress, Thomas; Künsken, Andreas; Lingemann, Joschka; Müller, Thomas; Nehrkorn, Alexander; Nowack, Andreas; Pistone, Claudia; Pooth, Oliver; Stahl, Achim; Aldaya Martin, Maria; Arndt, Till; Asawatangtrakuldee, Chayanit; Beernaert, Kelly; Behnke, Olaf; Behrens, Ulf; Bin Anuar, Afiq Aizuddin; Borras, Kerstin; Campbell, Alan; Connor, Patrick; Contreras-Campana, Christian; Costanza, Francesco; Diez Pardos, Carmen; Dolinska, Ganna; Eckerlin, Guenter; Eckstein, Doris; Eichhorn, Thomas; Eren, Engin; Gallo, Elisabetta; Garay Garcia, Jasone; Geiser, Achim; Gizhko, Andrii; Grados Luyando, Juan Manuel; Grohsjean, Alexander; Gunnellini, Paolo; Harb, Ali; Hauk, Johannes; Hempel, Maria; Jung, Hannes; Kalogeropoulos, Alexis; Karacheban, Olena; Kasemann, Matthias; Keaveney, James; Kleinwort, Claus; Korol, Ievgen; Krücker, Dirk; Lange, Wolfgang; Lelek, Aleksandra; Lenz, Teresa; Leonard, Jessica; Lipka, Katerina; Lobanov, Artur; Lohmann, Wolfgang; Mankel, Rainer; Melzer-Pellmann, Isabell-Alissandra; Meyer, Andreas Bernhard; Mittag, Gregor; Mnich, Joachim; Mussgiller, Andreas; Pitzl, Daniel; Placakyte, Ringaile; Raspereza, Alexei; Roland, Benoit; Sahin, Mehmet Özgür; Saxena, Pooja; Schoerner-Sadenius, Thomas; Spannagel, Simon; Stefaniuk, Nazar; Van Onsem, Gerrit Patrick; Walsh, Roberval; Wissing, Christoph; Blobel, Volker; Centis Vignali, Matteo; Draeger, Arne-Rasmus; Dreyer, Torben; Garutti, Erika; Gonzalez, Daniel; Haller, Johannes; Hoffmann, Malte; Junkes, Alexandra; Klanner, Robert; Kogler, Roman; Kovalchuk, Nataliia; Lapsien, Tobias; Marchesini, Ivan; Marconi, Daniele; Meyer, Mareike; Niedziela, Marek; Nowatschin, Dominik; Pantaleo, Felice; Peiffer, Thomas; Perieanu, Adrian; Scharf, Christian; Schleper, Peter; Schmidt, Alexander; Schumann, Svenja; Schwandt, Joern; Stadie, Hartmut; Steinbrück, Georg; Stober, Fred-Markus Helmut; Stöver, Marc; Tholen, Heiner; Troendle, Daniel; Usai, Emanuele; Vanelderen, Lukas; Vanhoefer, Annika; Vormwald, Benedikt; Akbiyik, Melike; Barth, Christian; Baur, Sebastian; Baus, Colin; Berger, Joram; Butz, Erik; Caspart, René; Chwalek, Thorsten; Colombo, Fabio; De Boer, Wim; Dierlamm, Alexander; Fink, Simon; Freund, Benedikt; Friese, Raphael; Giffels, Manuel; Gilbert, Andrew; Goldenzweig, Pablo; Haitz, Dominik; Hartmann, Frank; Heindl, Stefan Michael; Husemann, Ulrich; Katkov, Igor; Kudella, Simon; Mildner, Hannes; Mozer, Matthias Ulrich; Müller, Thomas; Plagge, Michael; Quast, Gunter; Rabbertz, Klaus; Röcker, Steffen; Roscher, Frank; Schröder, Matthias; Shvetsov, Ivan; Sieber, Georg; Simonis, Hans-Jürgen; Ulrich, Ralf; Wayand, Stefan; Weber, Marc; Weiler, Thomas; Williamson, Shawn; Wöhrmann, Clemens; Wolf, Roger; Anagnostou, Georgios; Daskalakis, Georgios; Geralis, Theodoros; Giakoumopoulou, Viktoria Athina; Kyriakis, Aristotelis; Loukas, Demetrios; Topsis-Giotis, Iasonas; Kesisoglou, Stilianos; Panagiotou, Apostolos; Saoulidou, Niki; Tziaferi, Eirini; Evangelou, Ioannis; Flouris, Giannis; Foudas, Costas; Kokkas, Panagiotis; Loukas, Nikitas; Manthos, Nikolaos; Papadopoulos, Ioannis; Paradas, Evangelos; Filipovic, Nicolas; Pasztor, Gabriella; Bencze, Gyorgy; Hajdu, Csaba; Horvath, Dezso; Sikler, Ferenc; Veszpremi, Viktor; Vesztergombi, Gyorgy; Zsigmond, Anna Julia; Beni, Noemi; Czellar, Sandor; Karancsi, János; Makovec, Alajos; Molnar, Jozsef; Szillasi, Zoltan; Bartók, Márton; Raics, Peter; Trocsanyi, Zoltan Laszlo; Ujvari, Balazs; Komaragiri, Jyothsna Rani; Bahinipati, Seema; Bhowmik, Sandeep; Choudhury, Somnath; Mal, Prolay; Mandal, Koushik; Nayak, Aruna; Sahoo, Deepak Kumar; Sahoo, Niladribihari; Swain, Sanjay Kumar; Bansal, Sunil; Beri, Suman Bala; Bhatnagar, Vipin; Chawla, Ridhi; Bhawandeep, Bhawandeep; Kalsi, Amandeep Kaur; Kaur, Anterpreet; Kaur, Manjit; Kumar, Ramandeep; Kumari, Priyanka; Mehta, Ankita; Mittal, Monika; Singh, Jasbir; Walia, Genius; Kumar, Ashok; Bhardwaj, Ashutosh; Choudhary, Brajesh C; Garg, Rocky Bala; Keshri, Sumit; Malhotra, Shivali; Naimuddin, Md; Ranjan, Kirti; Sharma, Ramkrishna; Sharma, Varun; Bhattacharya, Rajarshi; Bhattacharya, Satyaki; Chatterjee, Kalyanmoy; Dey, Sourav; Dutt, Suneel; Dutta, Suchandra; Ghosh, Shamik; Majumdar, Nayana; Modak, Atanu; Mondal, Kuntal; Mukhopadhyay, Supratik; Nandan, Saswati; Purohit, Arnab; Roy, Ashim; Roy, Debarati; Roy Chowdhury, Suvankar; Sarkar, Subir; Sharan, Manoj; Thakur, Shalini; Behera, Prafulla Kumar; Chudasama, Ruchi; Dutta, Dipanwita; Jha, Vishwajeet; Kumar, Vineet; Mohanty, Ajit Kumar; Netrakanti, Pawan Kumar; Pant, Lalit Mohan; Shukla, Prashant; Topkar, Anita; Aziz, Tariq; Dugad, Shashikant; Kole, Gouranga; Mahakud, Bibhuprasad; Mitra, Soureek; Mohanty, Gagan Bihari; Parida, Bibhuti; Sur, Nairit; Sutar, Bajrang; Banerjee, Sudeshna; Dewanjee, Ram Krishna; Ganguly, Sanmay; Guchait, Monoranjan; Jain, Sandhya; Kumar, Sanjeev; Maity, Manas; Majumder, Gobinda; Mazumdar, Kajari; Sarkar, Tanmay; Wickramage, Nadeesha; Chauhan, Shubhanshu; Dube, Sourabh; Hegde, Vinay; Kapoor, Anshul; Kothekar, Kunal; Pandey, Shubham; Rane, Aditee; Sharma, Seema; Chenarani, Shirin; Eskandari Tadavani, Esmaeel; Etesami, Seyed Mohsen; Khakzad, Mohsen; Mohammadi Najafabadi, Mojtaba; Naseri, Mohsen; Paktinat Mehdiabadi, Saeid; Rezaei Hosseinabadi, Ferdos; Safarzadeh, Batool; Zeinali, Maryam; Felcini, Marta; Grunewald, Martin; Abbrescia, Marcello; Calabria, Cesare; Caputo, Claudio; Colaleo, Anna; Creanza, Donato; Cristella, Leonardo; De Filippis, Nicola; De Palma, Mauro; Fiore, Luigi; Iaselli, Giuseppe; Maggi, Giorgio; Maggi, Marcello; Miniello, Giorgia; My, Salvatore; Nuzzo, Salvatore; Pompili, Alexis; Pugliese, Gabriella; Radogna, Raffaella; Ranieri, Antonio; Selvaggi, Giovanna; Sharma, Archana; Silvestris, Lucia; Venditti, Rosamaria; Verwilligen, Piet; Abbiendi, Giovanni; Battilana, Carlo; Bonacorsi, Daniele; Braibant-Giacomelli, Sylvie; Brigliadori, Luca; Campanini, Renato; Capiluppi, Paolo; Castro, Andrea; Cavallo, Francesca Romana; Chhibra, Simranjit Singh; Codispoti, Giuseppe; Cuffiani, Marco; Dallavalle, Gaetano-Marco; Fabbri, Fabrizio; Fanfani, Alessandra; Fasanella, Daniele; Giacomelli, Paolo; Grandi, Claudio; Guiducci, Luigi; Marcellini, Stefano; Masetti, Gianni; Montanari, Alessandro; Navarria, Francesco; Perrotta, Andrea; Rossi, Antonio; Rovelli, Tiziano; Siroli, Gian Piero; Tosi, Nicolò; Albergo, Sebastiano; Costa, Salvatore; Di Mattia, Alessandro; Giordano, Ferdinando; Potenza, Renato; Tricomi, Alessia; Tuve, Cristina; Barbagli, Giuseppe; Ciulli, Vitaliano; Civinini, Carlo; D'Alessandro, Raffaello; Focardi, Ettore; Lenzi, Piergiulio; Meschini, Marco; Paoletti, Simone; Russo, Lorenzo; Sguazzoni, Giacomo; Strom, Derek; Viliani, Lorenzo; Benussi, Luigi; Bianco, Stefano; Fabbri, Franco; Piccolo, Davide; Primavera, Federica; Calvelli, Valerio; Ferro, Fabrizio; Monge, Maria Roberta; Robutti, Enrico; Tosi, Silvano; Brianza, Luca; Brivio, Francesco; Ciriolo, Vincenzo; Dinardo, Mauro Emanuele; Fiorendi, Sara; Gennai, Simone; Ghezzi, Alessio; Govoni, Pietro; Malberti, Martina; Malvezzi, Sandra; Manzoni, Riccardo Andrea; Menasce, Dario; Moroni, Luigi; Paganoni, Marco; Pedrini, Daniele; Pigazzini, Simone; Ragazzi, Stefano; Tabarelli de Fatis, Tommaso; Buontempo, Salvatore; Cavallo, Nicola; De Nardo, Guglielmo; Di Guida, Salvatore; Esposito, Marco; Fabozzi, Francesco; Fienga, Francesco; Iorio, Alberto Orso Maria; Lanza, Giuseppe; Lista, Luca; Meola, Sabino; Paolucci, Pierluigi; Sciacca, Crisostomo; Thyssen, Filip; Azzi, Patrizia; Bacchetta, Nicola; Benato, Lisa; Bisello, Dario; Boletti, Alessio; Carlin, Roberto; Carvalho Antunes De Oliveira, Alexandra; Checchia, Paolo; Dall'Osso, Martino; De Castro Manzano, Pablo; Dorigo, Tommaso; Dosselli, Umberto; Gasparini, Fabrizio; Gasparini, Ugo; Gozzelino, Andrea; Lacaprara, Stefano; Margoni, Martino; Meneguzzo, Anna Teresa; Pazzini, Jacopo; Pozzobon, Nicola; Ronchese, Paolo; Simonetto, Franco; Torassa, Ezio; Zanetti, Marco; Zotto, Pierluigi; Zumerle, Gianni; Braghieri, Alessandro; Fallavollita, Francesco; Magnani, Alice; Montagna, Paolo; Ratti, Sergio P; Re, Valerio; Riccardi, Cristina; Salvini, Paola; Vai, Ilaria; Vitulo, Paolo; Alunni Solestizi, Luisa; Bilei, Gian Mario; Ciangottini, Diego; Fanò, Livio; Lariccia, Paolo; Leonardi, Roberto; Mantovani, Giancarlo; Menichelli, Mauro; Saha, Anirban; Santocchia, Attilio; Androsov, Konstantin; Azzurri, Paolo; Bagliesi, Giuseppe; Bernardini, Jacopo; Boccali, Tommaso; Castaldi, Rino; Ciocci, Maria Agnese; Dell'Orso, Roberto; Donato, Silvio; Fedi, Giacomo; Giassi, Alessandro; Grippo, Maria Teresa; Ligabue, Franco; Lomtadze, Teimuraz; Martini, Luca; Messineo, Alberto; Palla, Fabrizio; Rizzi, Andrea; Savoy-Navarro, Aurore; Spagnolo, Paolo; Tenchini, Roberto; Tonelli, Guido; Venturi, Andrea; Verdini, Piero Giorgio; Barone, Luciano; Cavallari, Francesca; Cipriani, Marco; Del Re, Daniele; Diemoz, Marcella; Gelli, Simone; Longo, Egidio; Margaroli, Fabrizio; Marzocchi, Badder; Meridiani, Paolo; Organtini, Giovanni; Paramatti, Riccardo; Preiato, Federico; Rahatlou, Shahram; Rovelli, Chiara; Santanastasio, Francesco; Amapane, Nicola; Arcidiacono, Roberta; Argiro, Stefano; Arneodo, Michele; Bartosik, Nazar; Bellan, Riccardo; Biino, Cristina; Cartiglia, Nicolo; Cenna, Francesca; Costa, Marco; Covarelli, Roberto; Degano, Alessandro; Demaria, Natale; Finco, Linda; Kiani, Bilal; Mariotti, Chiara; Maselli, Silvia; Migliore, Ernesto; Monaco, Vincenzo; Monteil, Ennio; Monteno, Marco; Obertino, Maria Margherita; Pacher, Luca; Pastrone, Nadia; Pelliccioni, Mario; Pinna Angioni, Gian Luca; Ravera, Fabio; Romero, Alessandra; Ruspa, Marta; Sacchi, Roberto; Shchelina, Ksenia; Sola, Valentina; Solano, Ada; Staiano, Amedeo; Traczyk, Piotr; Belforte, Stefano; Casarsa, Massimo; Cossutti, Fabio; Della Ricca, Giuseppe; Zanetti, Anna; Kim, Dong Hee; Kim, Gui Nyun; Kim, Min Suk; Lee, Sangeun; Lee, Seh Wook; Oh, Young Do; Sekmen, Sezen; Son, Dong-Chul; Yang, Yu Chul; Lee, Ari; Kim, Hyunchul; Brochero Cifuentes, Javier Andres; Kim, Tae Jeong; Cho, Sungwoong; Choi, Suyong; Go, Yeonju; Gyun, Dooyeon; Ha, Seungkyu; Hong, Byung-Sik; Jo, Youngkwon; Kim, Yongsun; Lee, Kisoo; Lee, Kyong Sei; Lee, Songkyo; Lim, Jaehoon; Park, Sung Keun; Roh, Youn; Almond, John; Kim, Junho; Lee, Haneol; Oh, Sung Bin; Radburn-Smith, Benjamin Charles; Seo, Seon-hee; Yang, Unki; Yoo, Hwi Dong; Yu, Geum Bong; Choi, Minkyoo; Kim, Hyunyong; Kim, Ji Hyun; Lee, Jason Sang Hun; Park, Inkyu; Ryu, Geonmo; Ryu, Min Sang; Choi, Young-Il; Goh, Junghwan; Hwang, Chanwook; Lee, Jongseok; Yu, Intae; Dudenas, Vytautas; Juodagalvis, Andrius; Vaitkus, Juozas; Ahmed, Ijaz; Ibrahim, Zainol Abidin; Md Ali, Mohd Adli Bin; Mohamad Idris, Faridah; Wan Abdullah, Wan Ahmad Tajuddin; Yusli, Mohd Nizam; Zolkapli, Zukhaimira; Castilla-Valdez, Heriberto; De La Cruz-Burelo, Eduard; Heredia-De La Cruz, Ivan; Hernandez-Almada, Alberto; Lopez-Fernandez, Ricardo; Magaña Villalba, Ricardo; Mejia Guisao, Jhovanny; Sánchez Hernández, Alberto; Carrillo Moreno, Salvador; Oropeza Barrera, Cristina; Vazquez Valencia, Fabiola; Carpinteyro, Severiano; Pedraza, Isabel; Salazar Ibarguen, Humberto Antonio; Uribe Estrada, Cecilia; Morelos Pineda, Antonio; Krofcheck, David; Butler, Philip H; Ahmad, Ashfaq; Ahmad, Muhammad; Hassan, Qamar; Hoorani, Hafeez R; Khan, Wajid Ali; Saddique, Asif; Shah, Mehar Ali; Shoaib, Muhammad; Waqas, Muhammad; Bialkowska, Helena; Bluj, Michal; Boimska, Bożena; Frueboes, Tomasz; Górski, Maciej; Kazana, Malgorzata; Nawrocki, Krzysztof; Romanowska-Rybinska, Katarzyna; Szleper, Michal; Zalewski, Piotr; Bunkowski, Karol; Byszuk, Adrian; Doroba, Krzysztof; Kalinowski, Artur; Konecki, Marcin; Krolikowski, Jan; Misiura, Maciej; Olszewski, Michal; Walczak, Marek; Bargassa, Pedrame; Beirão Da Cruz E Silva, Cristóvão; Calpas, Betty; Di Francesco, Agostino; Faccioli, Pietro; Ferreira Parracho, Pedro Guilherme; Gallinaro, Michele; Hollar, Jonathan; Leonardo, Nuno; Lloret Iglesias, Lara; Nemallapudi, Mythra Varun; Rodrigues Antunes, Joao; Seixas, Joao; Toldaiev, Oleksii; Vadruccio, Daniele; Varela, Joao; Afanasiev, Serguei; Bunin, Pavel; Gavrilenko, Mikhail; Golutvin, Igor; Gorbunov, Ilya; Kamenev, Alexey; Karjavin, Vladimir; Lanev, Alexander; Malakhov, Alexander; Matveev, Viktor; Palichik, Vladimir; Perelygin, Victor; Shmatov, Sergey; Shulha, Siarhei; Skatchkov, Nikolai; Smirnov, Vitaly; Voytishin, Nikolay; Zarubin, Anatoli; Chtchipounov, Leonid; Golovtsov, Victor; Ivanov, Yury; Kim, Victor; Kuznetsova, Ekaterina; Murzin, Victor; Oreshkin, Vadim; Sulimov, Valentin; Vorobyev, Alexey; Andreev, Yuri; Dermenev, Alexander; Gninenko, Sergei; Golubev, Nikolai; Karneyeu, Anton; Kirsanov, Mikhail; Krasnikov, Nikolai; Pashenkov, Anatoli; Tlisov, Danila; Toropin, Alexander; Epshteyn, Vladimir; Gavrilov, Vladimir; Lychkovskaya, Natalia; Popov, Vladimir; Pozdnyakov, Ivan; Safronov, Grigory; Spiridonov, Alexander; Toms, Maria; Vlasov, Evgueni; Zhokin, Alexander; Aushev, Tagir; Bylinkin, Alexander; Danilov, Mikhail; Popova, Elena; Rusinov, Vladimir; Andreev, Vladimir; Azarkin, Maksim; Dremin, Igor; Kirakosyan, Martin; Leonidov, Andrey; Terkulov, Adel; Baskakov, Alexey; Belyaev, Andrey; Boos, Edouard; Bunichev, Viacheslav; Dubinin, Mikhail; Dudko, Lev; Klyukhin, Vyacheslav; Kodolova, Olga; Korneeva, Natalia; Lokhtin, Igor; Miagkov, Igor; Obraztsov, Stepan; Perfilov, Maxim; Savrin, Viktor; Volkov, Petr; Blinov, Vladimir; Skovpen, Yuri; Shtol, Dmitry; Azhgirey, Igor; Bayshev, Igor; Bitioukov, Sergei; Elumakhov, Dmitry; Kachanov, Vassili; Kalinin, Alexey; Konstantinov, Dmitri; Krychkine, Victor; Petrov, Vladimir; Ryutin, Roman; Sobol, Andrei; Troshin, Sergey; Tyurin, Nikolay; Uzunian, Andrey; Volkov, Alexey; Adzic, Petar; Cirkovic, Predrag; Devetak, Damir; Dordevic, Milos; Milosevic, Jovan; Rekovic, Vladimir; Alcaraz Maestre, Juan; Barrio Luna, Mar; Calvo, Enrique; Cerrada, Marcos; Chamizo Llatas, Maria; Colino, Nicanor; De La Cruz, Begona; Delgado Peris, Antonio; Escalante Del Valle, Alberto; Fernandez Bedoya, Cristina; Fernández Ramos, Juan Pablo; Flix, Jose; Fouz, Maria Cruz; Garcia-Abia, Pablo; Gonzalez Lopez, Oscar; Goy Lopez, Silvia; Hernandez, Jose M; Josa, Maria Isabel; Navarro De Martino, Eduardo; Pérez-Calero Yzquierdo, Antonio María; Puerta Pelayo, Jesus; Quintario Olmeda, Adrián; Redondo, Ignacio; Romero, Luciano; Senghi Soares, Mara; de Trocóniz, Jorge F; Missiroli, Marino; Moran, Dermot; Cuevas, Javier; Fernandez Menendez, Javier; Gonzalez Caballero, Isidro; González Fernández, Juan Rodrigo; Palencia Cortezon, Enrique; Sanchez Cruz, Sergio; Suárez Andrés, Ignacio; Vischia, Pietro; Vizan Garcia, Jesus Manuel; Cabrillo, Iban Jose; Calderon, Alicia; Curras, Esteban; Fernandez, Marcos; Garcia-Ferrero, Juan; Gomez, Gervasio; Lopez Virto, Amparo; Marco, Jesus; Martinez Rivero, Celso; Matorras, Francisco; Piedra Gomez, Jonatan; Rodrigo, Teresa; Ruiz-Jimeno, Alberto; Scodellaro, Luca; Trevisani, Nicolò; Vila, Ivan; Vilar Cortabitarte, Rocio; Abbaneo, Duccio; Auffray, Etiennette; Auzinger, Georg; Baillon, Paul; Ball, Austin; Barney, David; Bloch, Philippe; Bocci, Andrea; Botta, Cristina; Camporesi, Tiziano; Castello, Roberto; Cepeda, Maria; Cerminara, Gianluca; Chen, Yi; D'Enterria, David; Dabrowski, Anne; Daponte, Vincenzo; David Tinoco Mendes, Andre; De Gruttola, Michele; De Roeck, Albert; Di Marco, Emanuele; Dobson, Marc; Dorney, Brian; Du Pree, Tristan; Duggan, Daniel; Dünser, Marc; Dupont, Niels; Elliott-Peisert, Anna; Everaerts, Pieter; Fartoukh, Stephane; Franzoni, Giovanni; Fulcher, Jonathan; Funk, Wolfgang; Gigi, Dominique; Gill, Karl; Girone, Maria; Glege, Frank; Gulhan, Doga; Gundacker, Stefan; Guthoff, Moritz; Harris, Philip; Hegeman, Jeroen; Innocente, Vincenzo; Janot, Patrick; Kieseler, Jan; Kirschenmann, Henning; Knünz, Valentin; Kornmayer, Andreas; Kortelainen, Matti J; Kousouris, Konstantinos; Krammer, Manfred; Lange, Clemens; Lecoq, Paul; Lourenco, Carlos; Lucchini, Marco Toliman; Malgeri, Luca; Mannelli, Marcello; Martelli, Arabella; Meijers, Frans; Merlin, Jeremie Alexandre; Mersi, Stefano; Meschi, Emilio; Milenovic, Predrag; Moortgat, Filip; Morovic, Srecko; Mulders, Martijn; Neugebauer, Hannes; Orfanelli, Styliani; Orsini, Luciano; Pape, Luc; Perez, Emmanuel; Peruzzi, Marco; Petrilli, Achille; Petrucciani, Giovanni; Pfeiffer, Andreas; Pierini, Maurizio; Racz, Attila; Reis, Thomas; Rolandi, Gigi; Rovere, Marco; Sakulin, Hannes; Sauvan, Jean-Baptiste; Schäfer, Christoph; Schwick, Christoph; Seidel, Markus; Sharma, Archana; Silva, Pedro; Sphicas, Paraskevas; Steggemann, Jan; Stoye, Markus; Takahashi, Yuta; Tosi, Mia; Treille, Daniel; Triossi, Andrea; Tsirou, Andromachi; Veckalns, Viesturs; Veres, Gabor Istvan; Verweij, Marta; Wardle, Nicholas; Wöhri, Hermine Katharina; Zagoździńska, Agnieszka; Zeuner, Wolfram Dietrich; Bertl, Willi; Deiters, Konrad; Erdmann, Wolfram; Horisberger, Roland; Ingram, Quentin; Kaestli, Hans-Christian; Kotlinski, Danek; Langenegger, Urs; Rohe, Tilman; Wiederkehr, Stephan Albert; Bachmair, Felix; Bäni, Lukas; Bianchini, Lorenzo; Casal, Bruno; Dissertori, Günther; Dittmar, Michael; Donegà, Mauro; Grab, Christoph; Heidegger, Constantin; Hits, Dmitry; Hoss, Jan; Kasieczka, Gregor; Lustermann, Werner; Mangano, Boris; Marionneau, Matthieu; Martinez Ruiz del Arbol, Pablo; Masciovecchio, Mario; Meinhard, Maren Tabea; Meister, Daniel; Micheli, Francesco; Musella, Pasquale; Nessi-Tedaldi, Francesca; Pandolfi, Francesco; Pata, Joosep; Pauss, Felicitas; Perrin, Gaël; Perrozzi, Luca; Quittnat, Milena; Rossini, Marco; Schönenberger, Myriam; Starodumov, Andrei; Tavolaro, Vittorio Raoul; Theofilatos, Konstantinos; Wallny, Rainer; Aarrestad, Thea Klaeboe; Amsler, Claude; Caminada, Lea; Canelli, Maria Florencia; De Cosa, Annapaola; Galloni, Camilla; Hinzmann, Andreas; Hreus, Tomas; Kilminster, Benjamin; Ngadiuba, Jennifer; Pinna, Deborah; Rauco, Giorgia; Robmann, Peter; Salerno, Daniel; Seitz, Claudia; Yang, Yong; Zucchetta, Alberto; Candelise, Vieri; Doan, Thi Hien; Jain, Shilpi; Khurana, Raman; Konyushikhin, Maxim; Kuo, Chia-Ming; Lin, Willis; Pozdnyakov, Andrey; Yu, Shin-Shan; Kumar, Arun; Chang, Paoti; Chang, You-Hao; Chao, Yuan; Chen, Kai-Feng; Chen, Po-Hsun; Fiori, Francesco; Hou, George Wei-Shu; Hsiung, Yee; Liu, Yueh-Feng; Lu, Rong-Shyang; Miñano Moya, Mercedes; Paganis, Efstathios; Psallidas, Andreas; Tsai, Jui-fa; Asavapibhop, Burin; Singh, Gurpreet; Srimanobhas, Norraphat; Suwonjandee, Narumon; Adiguzel, Aytul; Damarseckin, Serdal; Demiroglu, Zuhal Seyma; Dozen, Candan; Eskut, Eda; Girgis, Semiray; Gokbulut, Gul; Guler, Yalcin; Hos, Ilknur; Kangal, Evrim Ersin; Kara, Ozgun; Kayis Topaksu, Aysel; Kiminsu, Ugur; Oglakci, Mehmet; Onengut, Gulsen; Ozdemir, Kadri; Ozturk, Sertac; Polatoz, Ayse; Tali, Bayram; Turkcapar, Semra; Zorbakir, Ibrahim Soner; Zorbilmez, Caglar; Bilin, Bugra; Bilmis, Selcuk; Isildak, Bora; Karapinar, Guler; Yalvac, Metin; Zeyrek, Mehmet; Gülmez, Erhan; Kaya, Mithat; Kaya, Ozlem; Yetkin, Elif Asli; Yetkin, Taylan; Cakir, Altan; Cankocak, Kerem; Sen, Sercan; Grynyov, Boris; Levchuk, Leonid; Sorokin, Pavel; Aggleton, Robin; Ball, Fionn; Beck, Lana; Brooke, James John; Burns, Douglas; Clement, Emyr; Cussans, David; Flacher, Henning; Goldstein, Joel; Grimes, Mark; Heath, Greg P; Heath, Helen F; Jacob, Jeson; Kreczko, Lukasz; Lucas, Chris; Newbold, Dave M; Paramesvaran, Sudarshan; Poll, Anthony; Sakuma, Tai; Seif El Nasr-storey, Sarah; Smith, Dominic; Smith, Vincent J; Bell, Ken W; Belyaev, Alexander; Brew, Christopher; Brown, Robert M; Calligaris, Luigi; Cieri, Davide; Cockerill, David JA; Coughlan, John A; Harder, Kristian; Harper, Sam; Olaiya, Emmanuel; Petyt, David; Shepherd-Themistocleous, Claire; Thea, Alessandro; Tomalin, Ian R; Williams, Thomas; Baber, Mark; Bainbridge, Robert; Buchmuller, Oliver; Bundock, Aaron; Burton, Darren; Casasso, Stefano; Citron, Matthew; Colling, David; Corpe, Louie; Dauncey, Paul; Davies, Gavin; De Wit, Adinda; Della Negra, Michel; Di Maria, Riccardo; Dunne, Patrick; Elwood, Adam; Futyan, David; Haddad, Yacine; Hall, Geoffrey; Iles, Gregory; James, Thomas; Lane, Rebecca; Laner, Christian; Lucas, Robyn; Lyons, Louis; Magnan, Anne-Marie; Malik, Sarah; Mastrolorenzo, Luca; Nash, Jordan; Nikitenko, Alexander; Pela, Joao; Penning, Bjoern; Pesaresi, Mark; Raymond, David Mark; Richards, Alexander; Rose, Andrew; Scott, Edward; Seez, Christopher; Summers, Sioni; Tapper, Alexander; Uchida, Kirika; Vazquez Acosta, Monica; Virdee, Tejinder; Wright, Jack; Zenz, Seth Conrad; Cole, Joanne; Hobson, Peter R; Khan, Akram; Kyberd, Paul; Reid, Ivan; Symonds, Philip; Teodorescu, Liliana; Turner, Mark; Borzou, Ahmad; Call, Kenneth; Dittmann, Jay; Hatakeyama, Kenichi; Liu, Hongxuan; Pastika, Nathaniel; Bartek, Rachel; Dominguez, Aaron; Buccilli, Andrew; Cooper, Seth; Henderson, Conor; Rumerio, Paolo; West, Christopher; Arcaro, Daniel; Avetisyan, Aram; Bose, Tulika; Gastler, Daniel; Rankin, Dylan; Richardson, Clint; Rohlf, James; Sulak, Lawrence; Zou, David; Benelli, Gabriele; Cutts, David; Garabedian, Alex; Hakala, John; Heintz, Ulrich; Hogan, Julie Managan; Jesus, Orduna; Kwok, Ka Hei Martin; Laird, Edward; Landsberg, Greg; Mao, Zaixing; Narain, Meenakshi; Piperov, Stefan; Sagir, Sinan; Spencer, Eric; Syarif, Rizki; Breedon, Richard; Burns, Dustin; Calderon De La Barca Sanchez, Manuel; Chauhan, Sushil; Chertok, Maxwell; Conway, John; Conway, Rylan; Cox, Peter Timothy; Erbacher, Robin; Flores, Chad; Funk, Garrett; Gardner, Michael; Ko, Winston; Lander, Richard; Mclean, Christine; Mulhearn, Michael; Pellett, Dave; Pilot, Justin; Shalhout, Shalhout; Shi, Mengyao; Smith, John; Squires, Michael; Stolp, Dustin; Tos, Kyle; Tripathi, Mani; Bachtis, Michail; Bravo, Cameron; Cousins, Robert; Dasgupta, Abhigyan; Florent, Alice; Hauser, Jay; Ignatenko, Mikhail; Mccoll, Nickolas; Saltzberg, David; Schnaible, Christian; Valuev, Vyacheslav; Weber, Matthias; Bouvier, Elvire; Burt, Kira; Clare, Robert; Ellison, John Anthony; Gary, J William; Ghiasi Shirazi, Seyyed Mohammad Amin; Hanson, Gail; Heilman, Jesse; Jandir, Pawandeep; Kennedy, Elizabeth; Lacroix, Florent; Long, Owen Rosser; Olmedo Negrete, Manuel; Paneva, Mirena Ivova; Shrinivas, Amithabh; Si, Weinan; Wei, Hua; Wimpenny, Stephen; Yates, Brent; Branson, James G; Cerati, Giuseppe Benedetto; Cittolin, Sergio; Derdzinski, Mark; Gerosa, Raffaele; Holzner, André; Klein, Daniel; Krutelyov, Vyacheslav; Letts, James; Macneill, Ian; Olivito, Dominick; Padhi, Sanjay; Pieri, Marco; Sani, Matteo; Sharma, Vivek; Simon, Sean; Tadel, Matevz; Vartak, Adish; Wasserbaech, Steven; Welke, Charles; Wood, John; Würthwein, Frank; Yagil, Avraham; Zevi Della Porta, Giovanni; Amin, Nick; Bhandari, Rohan; Bradmiller-Feld, John; Campagnari, Claudio; Dishaw, Adam; Dutta, Valentina; Franco Sevilla, Manuel; George, Christopher; Golf, Frank; Gouskos, Loukas; Gran, Jason; Heller, Ryan; Incandela, Joe; Mullin, Sam Daniel; Ovcharova, Ana; Qu, Huilin; Richman, Jeffrey; Stuart, David; Suarez, Indara; Yoo, Jaehyeok; Anderson, Dustin; Bendavid, Joshua; Bornheim, Adolf; Bunn, Julian; Duarte, Javier; Lawhorn, Jay Mathew; Mott, Alexander; Newman, Harvey B; Pena, Cristian; Spiropulu, Maria; Vlimant, Jean-Roch; Xie, Si; Zhu, Ren-Yuan; Andrews, Michael Benjamin; Ferguson, Thomas; Paulini, Manfred; Russ, James; Sun, Menglei; Vogel, Helmut; Vorobiev, Igor; Weinberg, Marc; Cumalat, John Perry; Ford, William T; Jensen, Frank; Johnson, Andrew; Krohn, Michael; Leontsinis, Stefanos; Mulholland, Troy; Stenson, Kevin; Wagner, Stephen Robert; Alexander, James; Chaves, Jorge; Chu, Jennifer; Dittmer, Susan; Mcdermott, Kevin; Mirman, Nathan; Nicolas Kaufman, Gala; Patterson, Juliet Ritchie; Rinkevicius, Aurelijus; Ryd, Anders; Skinnari, Louise; Soffi, Livia; Tan, Shao Min; Tao, Zhengcheng; Thom, Julia; Tucker, Jordan; Wittich, Peter; Zientek, Margaret; Winn, Dave; Abdullin, Salavat; Albrow, Michael; Apollinari, Giorgio; Apresyan, Artur; Banerjee, Sunanda; Bauerdick, Lothar AT; Beretvas, Andrew; Berryhill, Jeffrey; Bhat, Pushpalatha C; Bolla, Gino; Burkett, Kevin; Butler, Joel Nathan; Cheung, Harry; Chlebana, Frank; Cihangir, Selcuk; Cremonesi, Matteo; Elvira, Victor Daniel; Fisk, Ian; Freeman, Jim; Gottschalk, Erik; Gray, Lindsey; Green, Dan; Grünendahl, Stefan; Gutsche, Oliver; Hare, Daryl; Harris, Robert M; Hasegawa, Satoshi; Hirschauer, James; Hu, Zhen; Jayatilaka, Bodhitha; Jindariani, Sergo; Johnson, Marvin; Joshi, Umesh; Klima, Boaz; Kreis, Benjamin; Lammel, Stephan; Linacre, Jacob; Lincoln, Don; Lipton, Ron; Liu, Miaoyuan; Liu, Tiehui; Lopes De Sá, Rafael; Lykken, Joseph; Maeshima, Kaori; Magini, Nicolo; Marraffino, John Michael; Maruyama, Sho; Mason, David; McBride, Patricia; Merkel, Petra; Mrenna, Stephen; Nahn, Steve; O'Dell, Vivian; Pedro, Kevin; Prokofyev, Oleg; Rakness, Gregory; Ristori, Luciano; Sexton-Kennedy, Elizabeth; Soha, Aron; Spalding, William J; Spiegel, Leonard; Stoynev, Stoyan; Strait, James; Strobbe, Nadja; Taylor, Lucas; Tkaczyk, Slawek; Tran, Nhan Viet; Uplegger, Lorenzo; Vaandering, Eric Wayne; Vernieri, Caterina; Verzocchi, Marco; Vidal, Richard; Wang, Michael; Weber, Hannsjoerg Artur; Whitbeck, Andrew; Wu, Yujun; Acosta, Darin; Avery, Paul; Bortignon, Pierluigi; Bourilkov, Dimitri; Brinkerhoff, Andrew; Carnes, Andrew; Carver, Matthew; Curry, David; Das, Souvik; Field, Richard D; Furic, Ivan-Kresimir; Konigsberg, Jacobo; Korytov, Andrey; Low, Jia Fu; Ma, Peisen; Matchev, Konstantin; Mei, Hualin; Mitselmakher, Guenakh; Rank, Douglas; Shchutska, Lesya; Sperka, David; Thomas, Laurent; Wang, Jian; Wang, Sean-Jiun; Yelton, John; Linn, Stephan; Markowitz, Pete; Martinez, German; Rodriguez, Jorge Luis; Ackert, Andrew; Adams, Todd; Askew, Andrew; Bein, Samuel; Hagopian, Sharon; Hagopian, Vasken; Johnson, Kurtis F; Kolberg, Ted; Prosper, Harrison; Santra, Arka; Yohay, Rachel; Baarmand, Marc M; Bhopatkar, Vallary; Colafranceschi, Stefano; Hohlmann, Marcus; Noonan, Daniel; Roy, Titas; Yumiceva, Francisco; Adams, Mark Raymond; Apanasevich, Leonard; Berry, Douglas; Betts, Russell Richard; Bucinskaite, Inga; Cavanaugh, Richard; Evdokimov, Olga; Gauthier, Lucie; Gerber, Cecilia Elena; Hofman, David Jonathan; Jung, Kurt; Sandoval Gonzalez, Irving Daniel; Varelas, Nikos; Wang, Hui; Wu, Zhenbin; Zakaria, Mohammed; Zhang, Jingyu; Bilki, Burak; Clarida, Warren; Dilsiz, Kamuran; Durgut, Süleyman; Gandrajula, Reddy Pratap; Haytmyradov, Maksat; Khristenko, Viktor; Merlo, Jean-Pierre; Mermerkaya, Hamit; Mestvirishvili, Alexi; Moeller, Anthony; Nachtman, Jane; Ogul, Hasan; Onel, Yasar; Ozok, Ferhat; Penzo, Aldo; Snyder, Christina; Tiras, Emrah; Wetzel, James; Yi, Kai; Blumenfeld, Barry; Cocoros, Alice; Eminizer, Nicholas; Fehling, David; Feng, Lei; Gritsan, Andrei; Maksimovic, Petar; Roskes, Jeffrey; Sarica, Ulascan; Swartz, Morris; Xiao, Meng; You, Can; Al-bataineh, Ayman; Baringer, Philip; Bean, Alice; Boren, Samuel; Bowen, James; Castle, James; Forthomme, Laurent; Kenny III, Raymond Patrick; Khalil, Sadia; Kropivnitskaya, Anna; Majumder, Devdatta; Mcbrayer, William; Murray, Michael; Sanders, Stephen; Stringer, Robert; Tapia Takaki, Daniel; Wang, Quan; Ivanov, Andrew; Kaadze, Ketino; Maravin, Yurii; Mohammadi, Abdollah; Saini, Lovedeep Kaur; Skhirtladze, Nikoloz; Toda, Sachiko; Rebassoo, Finn; Wright, Douglas; Anelli, Christopher; Baden, Drew; Baron, Owen; Belloni, Alberto; Calvert, Brian; Eno, Sarah Catherine; Ferraioli, Charles; Gomez, Jaime; Hadley, Nicholas John; Jabeen, Shabnam; Jeng, Geng-Yuan; Kellogg, Richard G; Kunkle, Joshua; Mignerey, Alice; Ricci-Tam, Francesca; Shin, Young Ho; Skuja, Andris; Tonjes, Marguerite; Tonwar, Suresh C; Abercrombie, Daniel; Allen, Brandon; Apyan, Aram; Azzolini, Virginia; Barbieri, Richard; Baty, Austin; Bi, Ran; Bierwagen, Katharina; Brandt, Stephanie; Busza, Wit; Cali, Ivan Amos; D'Alfonso, Mariarosaria; Demiragli, Zeynep; Gomez Ceballos, Guillelmo; Goncharov, Maxim; Hsu, Dylan; Iiyama, Yutaro; Innocenti, Gian Michele; Klute, Markus; Kovalskyi, Dmytro; Krajczar, Krisztian; Lai, Yue Shi; Lee, Yen-Jie; Levin, Andrew; Luckey, Paul David; Maier, Benedikt; Marini, Andrea Carlo; Mcginn, Christopher; Mironov, Camelia; Narayanan, Siddharth; Niu, Xinmei; Paus, Christoph; Roland, Christof; Roland, Gunther; Salfeld-Nebgen, Jakob; Stephans, George; Tatar, Kaya; Velicanu, Dragos; Wang, Jing; Wang, Ta-Wei; Wyslouch, Bolek; Benvenuti, Alberto; Chatterjee, Rajdeep Mohan; Evans, Andrew; Hansen, Peter; Kalafut, Sean; Kao, Shih-Chuan; Kubota, Yuichi; Lesko, Zachary; Mans, Jeremy; Nourbakhsh, Shervin; Ruckstuhl, Nicole; Rusack, Roger; Tambe, Norbert; Turkewitz, Jared; Acosta, John Gabriel; Oliveros, Sandra; Avdeeva, Ekaterina; Bloom, Kenneth; Claes, Daniel R; Fangmeier, Caleb; Gonzalez Suarez, Rebeca; Kamalieddin, Rami; Kravchenko, Ilya; Malta Rodrigues, Alan; Monroy, Jose; Siado, Joaquin Emilo; Snow, Gregory R; Stieger, Benjamin; Alyari, Maral; Dolen, James; Godshalk, Andrew; Harrington, Charles; Iashvili, Ia; Kaisen, Josh; Nguyen, Duong; Parker, Ashley; Rappoccio, Salvatore; Roozbahani, Bahareh; Alverson, George; Barberis, Emanuela; Hortiangtham, Apichart; Massironi, Andrea; Morse, David Michael; Nash, David; Orimoto, Toyoko; Teixeira De Lima, Rafael; Trocino, Daniele; Wang, Ren-Jie; Wood, Darien; Bhattacharya, Saptaparna; Charaf, Otman; Hahn, Kristan Allan; Kumar, Ajay; Mucia, Nicholas; Odell, Nathaniel; Pollack, Brian; Schmitt, Michael Henry; Sung, Kevin; Trovato, Marco; Velasco, Mayda; Dev, Nabarun; Hildreth, Michael; Hurtado Anampa, Kenyi; Jessop, Colin; Karmgard, Daniel John; Kellams, Nathan; Lannon, Kevin; Marinelli, Nancy; Meng, Fanbo; Mueller, Charles; Musienko, Yuri; Planer, Michael; Reinsvold, Allison; Ruchti, Randy; Rupprecht, Nathaniel; Smith, Geoffrey; Taroni, Silvia; Wayne, Mitchell; Wolf, Matthias; Woodard, Anna; Alimena, Juliette; Antonelli, Louis; Bylsma, Ben; Durkin, Lloyd Stanley; Flowers, Sean; Francis, Brian; Hart, Andrew; Hill, Christopher; Hughes, Richard; Ji, Weifeng; Liu, Bingxuan; Luo, Wuming; Puigh, Darren; Winer, Brian L; Wulsin, Howard Wells; Cooperstein, Stephane; Driga, Olga; Elmer, Peter; Hardenbrook, Joshua; Hebda, Philip; Lange, David; Luo, Jingyu; Marlow, Daniel; Medvedeva, Tatiana; Mei, Kelvin; Ojalvo, Isabel; Olsen, James; Palmer, Christopher; Piroué, Pierre; Stickland, David; Svyatkovskiy, Alexey; Tully, Christopher; Malik, Sudhir; Barker, Anthony; Barnes, Virgil E; Folgueras, Santiago; Gutay, Laszlo; Jha, Manoj; Jones, Matthew; Jung, Andreas Werner; Khatiwada, Ajeeta; Miller, David Harry; Neumeister, Norbert; Schulte, Jan-Frederik; Shi, Xin; Sun, Jian; Wang, Fuqiang; Xie, Wei; Parashar, Neeti; Stupak, John; Adair, Antony; Akgun, Bora; Chen, Zhenyu; Ecklund, Karl Matthew; Geurts, Frank JM; Guilbaud, Maxime; Li, Wei; Michlin, Benjamin; Northup, Michael; Padley, Brian Paul; Roberts, Jay; Rorie, Jamal; Tu, Zhoudunming; Zabel, James; Betchart, Burton; Bodek, Arie; de Barbaro, Pawel; Demina, Regina; Duh, Yi-ting; Ferbel, Thomas; Galanti, Mario; Garcia-Bellido, Aran; Han, Jiyeon; Hindrichs, Otto; Khukhunaishvili, Aleko; Lo, Kin Ho; Tan, Ping; Verzetti, Mauro; Agapitos, Antonis; Chou, John Paul; Gershtein, Yuri; Gómez Espinosa, Tirso Alejandro; Halkiadakis, Eva; Heindl, Maximilian; Hughes, Elliot; Kaplan, Steven; Kunnawalkam Elayavalli, Raghav; Kyriacou, Savvas; Lath, Amitabh; Nash, Kevin; Osherson, Marc; Saka, Halil; Salur, Sevil; Schnetzer, Steve; Sheffield, David; Somalwar, Sunil; Stone, Robert; Thomas, Scott; Thomassen, Peter; Walker, Matthew; Delannoy, Andrés G; Foerster, Mark; Heideman, Joseph; Riley, Grant; Rose, Keith; Spanier, Stefan; Thapa, Krishna; Bouhali, Othmane; Celik, Ali; Dalchenko, Mykhailo; De Mattia, Marco; Delgado, Andrea; Dildick, Sven; Eusebi, Ricardo; Gilmore, Jason; Huang, Tao; Juska, Evaldas; Kamon, Teruki; Mueller, Ryan; Pakhotin, Yuriy; Patel, Rishi; Perloff, Alexx; Perniè, Luca; Rathjens, Denis; Safonov, Alexei; Tatarinov, Aysen; Ulmer, Keith; Akchurin, Nural; Cowden, Christopher; Damgov, Jordan; De Guio, Federico; Dragoiu, Cosmin; Dudero, Phillip Russell; Faulkner, James; Gurpinar, Emine; Kunori, Shuichi; Lamichhane, Kamal; Lee, Sung Won; Libeiro, Terence; Peltola, Timo; Undleeb, Sonaina; Volobouev, Igor; Wang, Zhixing; Greene, Senta; Gurrola, Alfredo; Janjam, Ravi; Johns, Willard; Maguire, Charles; Melo, Andrew; Ni, Hong; Sheldon, Paul; Tuo, Shengquan; Velkovska, Julia; Xu, Qiao; Arenton, Michael Wayne; Barria, Patrizia; Cox, Bradley; Goodell, Joseph; Hirosky, Robert; Ledovskoy, Alexander; Li, Hengne; Neu, Christopher; Sinthuprasith, Tutanon; Sun, Xin; Wang, Yanchu; Wolfe, Evan; Xia, Fan; Clarke, Christopher; Harr, Robert; Karchin, Paul Edmund; Sturdy, Jared; Belknap, Donald; Buchanan, James; Caillol, Cécile; Dasu, Sridhara; Dodd, Laura; Duric, Senka; Gomber, Bhawna; Grothe, Monika; Herndon, Matthew; Hervé, Alain; Klabbers, Pamela; Lanaro, Armando; Levine, Aaron; Long, Kenneth; Loveless, Richard; Perry, Thomas; Pierro, Giuseppe Antonio; Polese, Giovanni; Ruggles, Tyler; Savin, Alexander; Smith, Nicholas; Smith, Wesley H; Taylor, Devin; Woods, Nathaniel

    2017-05-29

    A measurement of the top quark mass is reported in events containing a single top quark produced via the electroweak $t$ channel. The analysis is performed using data from proton-proton collisions collected with the CMS detector at the LHC at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.7 fb$^{-1}$. The top quark is reconstructed from its decay to a W boson and a b quark, with the W boson decaying leptonically to a muon and a neutrino. The specific topology and kinematic properties of single top quark events in the $t$ channel are used to enhance the purity of the sample, suppressing the contribution from top quark pair production. A fit to the invariant mass distribution of reconstructed top quark candidates yields a value of the top quark mass of 172.95 $\\pm$ 0.77 (stat) $^{+0.97}_{-0.93}$ (syst) GeV. This result is in agreement with the current world average, and represents the first measurement of the top quark mass in event topologies not dominated by top quark pair p...

  7. Measurement of the top quark mass using single top quark events in proton-proton collisions at [Formula: see text] TeV.

    Science.gov (United States)

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    2017-01-01

    A measurement of the top quark mass is reported in events containing a single top quark produced via the electroweak t channel. The analysis is performed using data from proton-proton collisions collected with the CMS detector at the LHC at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.7 fb[Formula: see text]. Top quark candidates are reconstructed from their decay to a [Formula: see text] boson and a b quark, with the [Formula: see text] boson decaying leptonically to a muon and a neutrino. The final state signature and kinematic properties of single top quark events in the t channel are used to enhance the purity of the sample, suppressing the contribution from top quark pair production. A fit to the invariant mass distribution of reconstructed top quark candidates yields a value of the top quark mass of [Formula: see text]. This result is in agreement with the current world average, and represents the first measurement of the top quark mass in event topologies not dominated by top quark pair production, therefore contributing to future averages with partially uncorrelated systematic uncertainties and a largely uncorrelated statistical uncertainty.

  8. Haplotype analysis suggest that the MLH1 c.2059C > T mutation is a Swedish founder mutation.

    Science.gov (United States)

    von Salomé, Jenny; Liu, Tao; Keihäs, Markku; Morak, Moni; Holinski-Feder, Elke; Berry, Ian R; Moilanen, Jukka S; Baert-Desurmont, Stéphanie; Lindblom, Annika; Lagerstedt-Robinson, Kristina

    2017-12-29

    Lynch syndrome (LS) predisposes to a spectrum of cancers and increases the lifetime risk of developing colorectal- or endometrial cancer to over 50%. Lynch syndrome is dominantly inherited and is caused by defects in DNA mismatch-repair genes MLH1, MSH2, MSH6 or PMS2, with the vast majority detected in MLH1 and MSH2. Recurrent LS-associated variants observed in apparently unrelated individuals, have either arisen de novo in different families due to mutation hotspots, or are inherited from a founder (a common ancestor) that lived several generations back. There are variants that recur in some populations while also acting as founders in other ethnic groups. Testing for founder mutations can facilitate molecular diagnosis of Lynch Syndrome more efficiently and more cost effective than screening for all possible mutations. Here we report a study of the missense mutation MLH1 c.2059C > T (p.Arg687Trp), a potential founder mutation identified in eight Swedish families and one Finnish family with Swedish ancestors. Haplotype analysis confirmed that the Finnish and Swedish families shared a haplotype of between 0.9 and 2.8 Mb. While MLH1 c.2059C > T exists worldwide, the Swedish haplotype was not found among mutation carriers from Germany or France, which indicates a common founder in the Swedish population. The geographic distribution of MLH1 c.2059C > T in Sweden suggests a single, ancient mutational event in the northern part of Sweden.

  9. Recurrent LDL-receptor mutation causes familial ...

    African Journals Online (AJOL)

    1995-05-05

    May 5, 1995 ... 3. eaudet . New. Recurrent LDL-receptor mutation causes familial hypercholesterolaemia in ... amplification refractory mutation system (ARMS)" and single- strand conformation .... Location. Afrikaner. Mixed race. ApaLl.

  10. Search for Dark Matter in Events with a Single Boson and Missing Transverse Momentum using the ATLAS Detector

    CERN Document Server

    Okawa, Hideki; The ATLAS collaboration

    2017-01-01

    The presence of a non-baryonic dark matter component in the Universe is inferred from the observation of its gravitational interaction. If dark matter interacts weakly with the Standard Model it would be produced at the LHC, escaping the detector and leaving a large missing transverse momentum as their signature. The results of searches with a single boson and large missing transverse momentum in 13 TeV will be presented.

  11. Assessment of long-term knowledge retention following single-day simulation training for uncommon but critical obstetrical events

    Science.gov (United States)

    Vadnais, Mary A.; Dodge, Laura E.; Awtrey, Christopher S.; Ricciotti, Hope A.; Golen, Toni H.; Hacker, Michele R.

    2013-01-01

    Objective The objectives were to determine (i) whether simulation training results in short-term and long-term improvement in the management of uncommon but critical obstetrical events and (ii) to determine whether there was additional benefit from annual exposure to the workshop. Methods Physicians completed a pretest to measure knowledge and confidence in the management of eclampsia, shoulder dystocia, postpartum hemorrhage and vacuum-assisted vaginal delivery. They then attended a simulation workshop and immediately completed a posttest. Residents completed the same posttests 4 and 12 months later, and attending physicians completed the posttest at 12 months. Physicians participated in the same simulation workshop 1 year later and then completed a final posttest. Scores were compared using paired t-tests. Results Physicians demonstrated improved knowledge and comfort immediately after simulation. Residents maintained this improvement at 1 year. Attending physicians remained more comfortable managing these scenarios up to 1 year later; however, knowledge retention diminished with time. Repeating the simulation after 1 year brought additional improvement to physicians. Conclusion Simulation training can result in short-term and contribute to long-term improvement in objective measures of knowledge and comfort level in managing uncommon but critical obstetrical events. Repeat exposure to simulation training after 1 year can yield additional benefits. PMID:22191668

  12. A single mutation in the 15S rRNA gene confers nonsense suppressor activity and interacts with mRF1 the release factor in yeast mitochondria

    Directory of Open Access Journals (Sweden)

    Ali Gargouri

    2015-08-01

    Full Text Available We have determined the nucleotide sequence of the mim3-1 mitochondrial ribosomal suppressor, acting on ochre mitochondrial mutations and one frameshift mutation in Saccharomyces cerevisiae. The 15s rRNA suppressor gene contains a G633 to C transversion. Yeast mitochondrial G633 corresponds to G517 of the E.coli 15S rRNA, which is occupied by an invariant G in all known small rRNA sequences. Interestingly, this mutation has occurred at the same position as the known MSU1 mitochondrial suppressor which changes G633 to A. The suppressor mutation lies in a highly conserved region of the rRNA, known in E.coli as the 530-loop, interacting with the S4, S5 and S12 ribosomal proteins. We also show an interesting interaction between the mitochondrial mim3-1 and the nuclear nam3-1 suppressors, both of which have the same action spectrum on mitochondrial mutations: nam3-1 abolishes the suppressor effect when present with mim3-1 in the same haploid cell. We discuss these results in the light of the nature of Nam3, identified by [1] as the yeast mitochondrial translation release factor. A hypothetical mechanism of suppression by "ribosome shifting" is also discussed in view of the nature of mutations suppressed and not suppressed.

  13. submitter Preparatory studies on the determination of the top-quark mass in single top-quark events with the ATLAS detector at the LHC

    CERN Document Server

    Wahdan, Shayma'; Wagner, Wolfgang

    In this thesis, a measurement of the single top quark mass produced in the t -channel is presented, using the data sample recorded recently in 2015 with the ATLAS detector at the LHC, at a centre of mass energy of √ s = 13 TeV and corresponding to an integrated luminosity of 3.2 f b−1 . The selected events contain one charged lepton (electron or muon), missing transverse energy, and two jets with high transverse momentum with one of them being b-tagged. The template method is used to extract the top quark mass from the distribution of the invariant mass of the lepton and the b-jet (m(`b)) in the selected events. The result of the measured top quark mass is: mtop = [174.56 ± 3.11(syst.) ± 1.02(stat.)] GeV.

  14. Dipyridamole thallium-201 single-photon emission computed tomography for prediction of perioperative cardiac events in patients with arteriosclerosis obliterans undergoing vascular surgery

    International Nuclear Information System (INIS)

    Ziyang, Huang; Komori, Sadayoshi; Sawanobori, Takao

    1998-01-01

    The aim of the study was to determine whether or not dipyridamole thallium-201 single-photon emission computed tomography ( 201 Tl-SPECT) has significant additive value for predicting perioperative cardiac events in patients with arteriosclerosis obliterans (ASO) undergoing vascular surgery. Routine preoperative 201 Tl-SPECT was performed in 106 consecutive patients with ASO (age 68±8.9 years; 91 men and 15 women). The frequency of reversible defects in a clinical high-risk group (n=44) was significantly higher than in a low-risk group (n=62; 55% vs 24%, p 201 Tl-SPECT data to clinical risk-stratified patients with ASO allows better prediction of perioperative cardiac events. (author)

  15. Deep Sequence Analysis of Non-Small Cell Lung Cancer: Integrated Analysis of Gene Expression, Alternative Splicing, and Single Nucleotide Variations in Lung Adenocarcinomas with and without Oncogenic KRAS Mutations

    International Nuclear Information System (INIS)

    Kalari, Krishna R.; Rossell, David; Necela, Brian M.; Asmann, Yan W.; Nair, Asha

    2012-01-01

    KRAS mutations are highly prevalent in non-small cell lung cancer (NSCLC), and tumors harboring these mutations tend to be aggressive and resistant to chemotherapy. We used next-generation sequencing technology to identify pathways that are specifically altered in lung tumors harboring a KRAS mutation. Paired-end RNA-sequencing of 15 primary lung adenocarcinoma tumors (8 harboring mutant KRAS and 7 with wild-type KRAS) were performed. Sequences were mapped to the human genome, and genomic features, including differentially expressed genes, alternate splicing isoforms and single nucleotide variants, were determined for tumors with and without KRAS mutation using a variety of computational methods. Network analysis was carried out on genes showing differential expression (374 genes), alternate splicing (259 genes), and SNV-related changes (65 genes) in NSCLC tumors harboring a KRAS mutation. Genes exhibiting two or more connections from the lung adenocarcinoma network were used to carry out integrated pathway analysis. The most significant signaling pathways identified through this analysis were the NFκB, ERK1/2, and AKT pathways. A 27 gene mutant KRAS-specific sub network was extracted based on gene–gene connections from the integrated network, and interrogated for druggable targets. Our results confirm previous evidence that mutant KRAS tumors exhibit activated NFκB, ERK1/2, and AKT pathways and may be preferentially sensitive to target therapeutics toward these pathways. In addition, our analysis indicates novel, previously unappreciated links between mutant KRAS and the TNFR and PPARγ signaling pathways, suggesting that targeted PPARγ antagonists and TNFR inhibitors may be useful therapeutic strategies for treatment of mutant KRAS lung tumors. Our study is the first to integrate genomic features from RNA-Seq data from NSCLC and to define a first draft genomic landscape model that is unique to tumors with oncogenic KRAS mutations.

  16. Single base mutation in the proα2(I) collagen gene that causes efficient splicing of RNA from exon 27 to exon 29 and synthesis of a shortened but in-frame proα2(I) chain

    International Nuclear Information System (INIS)

    Tromp, G.; Prockop, D.J.

    1988-01-01

    Previous observations demonstrated that a lethal variant of osteogenesis imperfecta had two altered alleles for proα2(I) chains of type I procollagen. One mutation produced a nonfunctioning allele in that there was synthesis of mRNA but no detectable synthesis of proα2(I) chains from the allele. The mutation in the other allele caused synthesis of shortened proα2(I) chains that lacked most or all of the 18 amino acids encoded by exon 28. Subclones of the proα2(I) gene were prepared from the proband's DNA and the DNA sequence was determined for a 582-base-pair (bp) region that extended from the last 30 bp of intervening sequence 26 to the first 26 bp of intervening sequence 29. Data from six independent subclones demonstrated that all had the same sequence as a previously isolated normal clone for the proα2(I) gene except that four subclones had a single base mutation at the 3' end of intervening sequence 27. The mutation was a substitution of guanine for adenine that changed the universal consensus sequence for the 3' splicing site of RNA from -AG- to -GG-. S1 nuclease experiments demonstrated that about half the proα2(I) mRNA in the proband's fibroblasts was abnormally spliced and that the major species of abnormal proα2(I) mRNA was completely spliced from the last codon of exon 27 to the first codon of exon 29. The mutation is apparently unique among RNA splicing mutations of mammalian systems in producing a shortened polypeptide chain that is in-frame in terms of coding sequences, that is used in the subunit assembly of a protein, and that contributes to a lethal phenotype

  17. Embryo genome profiling by single-cell sequencing for successful preimplantation genetic diagnosis in a family harboring COL4A1 c.1537G>A; p.G513S mutation

    Directory of Open Access Journals (Sweden)

    Nayana H Patel

    2016-01-01

    Full Text Available CONTEXT: Genetic profiling of embryos (also known as preimplantation genetic diagnosis before implantation has dramatically enhanced the success quotient of in vitro fertilization (IVF in recent times. The technology helps in avoiding selective pregnancy termination since the baby is likely to be free of the disease under consideration. AIM: Screening of embryos free from c.1537G>A; p.G513S mutation within the COL4A1 gene for which the father was known in before be in heterozygous condition. SUBJECTS AND METHODS: Processing of trophectoderm biopsies was done from twelve embryos for c.1537G>A; p.G513S mutation within the COL4A1 gene. DNA extracted from isolated cells were subjected to whole genome amplification using an isothermal amplification and strand displacement technology. Oligonucleotide primers bracketing the mutation were synthesized and used to amplify 162 base pairs (bp polymerase chain reaction amplicons originating from each embryo which were subsequently sequenced to detect the presence or absence of the single base polymorphism. RESULTS: Three out of 12 embryos interrogated in this study were found to be normal while 9 were found to harbor the mutation in heterozygous condition. Implantation of one of the normal embryos following by chorionic villus sampling at 11 th week of pregnancy indicated that the baby was free from c.1537G>A; p.G513S mutation within the COL4A1 gene. CONCLUSIONS: Single-cell sequencing is a helpful tool for preimplantation embryo profiling. This is the first report from India describing the birth of a normal child through IVF procedure where a potential pathogenic COL4A1 allele was avoided using this technology.

  18. Increased reaction time variability in attention-deficit hyperactivity disorder as a response-related phenomenon: evidence from single-trial event-related potentials.

    Science.gov (United States)

    Saville, Christopher W N; Feige, Bernd; Kluckert, Christian; Bender, Stephan; Biscaldi, Monica; Berger, Andrea; Fleischhaker, Christian; Henighausen, Klaus; Klein, Christoph

    2015-07-01

    Increased intra-subject variability (ISV) in reaction times (RTs) is a promising endophenotype for attention-deficit hyperactivity disorder (ADHD) and among the most robust hallmarks of the disorder. ISV has been assumed to represent an attentional deficit, either reflecting lapses in attention or increased neural noise. Here, we use an innovative single-trial event-related potential approach to assess whether the increased ISV associated with ADHD is indeed attributable to attention, or whether it is related to response-related processing. We measured electroencephalographic responses to working memory oddball tasks in patients with ADHD (N = 20, aged 11.3 ± 1.1) and healthy controls (N = 25, aged 11.7 ± 1.1), and analysed these data with a recently developed method of single-trial event-related potential analysis. Estimates of component latency variability were computed for the stimulus-locked and response-locked forms of the P3b and the lateralised readiness potential (LRP). ADHD patients showed significantly increased ISV in behavioural ISV. This increased ISV was paralleled by an increase in variability in response-locked event-related potential latencies, while variability in stimulus-locked latencies was equivalent between groups. This result held across the P3b and LRP. Latency of all components predicted RTs on a single-trial basis, confirming that all were relevant for speed of processing. These data suggest that the increased ISV found in ADHD could be associated with response-end, rather than stimulus-end processes, in contrast to prevailing conceptions about the endophenotype. This mental chronometric approach may also be useful for exploring whether the existing lack of specificity of ISV to particular psychiatric conditions can be improved upon. © 2014 Association for Child and Adolescent Mental Health.

  19. Atomic-scale nanoindentation: detection and identification of single glide events in three dimensions by force microscopy

    International Nuclear Information System (INIS)

    Egberts, P; Bennewitz, R

    2011-01-01

    Indentation experiments on the nanometre scale have been performed by means of atomic force microscopy in ultra-high vacuum on KBr(100) surfaces. The surfaces yield in the form of discrete surface displacements with a typical length scale of 1 A. These surface displacements are detected in both normal and lateral directions. Measurement of the lateral tip displacement requires a load-dependent calibration due to the load dependence of the effective lateral compliance. Correlation of the lateral and normal displacements for each glide event allow identification of the activated slip system. The results are discussed in terms of the resolved shear stress in indentation experiments and of typical results in atomistic simulations of nanometre-scale indentation.

  20. The supply voltage scaled dependency of the recovery of single event upset in advanced complementary metal—oxide—semiconductor static random-access memory cells

    International Nuclear Information System (INIS)

    Li Da-Wei; Qin Jun-Rui; Chen Shu-Ming

    2013-01-01

    Using computer-aided design three-dimensional simulation technology, the supply voltage scaled dependency of the recovery of single event upset and charge collection in static random-access memory cells are investigated. It reveals that the recovery linear energy transfer threshold decreases with the supply voltage reducing, which is quite attractive for dynamic voltage scaling and subthreshold circuit radiation-hardened design. Additionally, the effect of supply voltage on charge collection is also investigated. It is concluded that the supply voltage mainly affects the bipolar gain of the parasitical bipolar junction transistor (BJT) and the existence of the source plays an important role in supply voltage variation. (geophysics, astronomy, and astrophysics)

  1. The usefulness of dipyridamole thallium-201 single photon emission computed tomography for predicting perioperative cardiac events in patients undergoing non-cardiac vascular surgery

    International Nuclear Information System (INIS)

    Chen Tao; Huang Gang

    2004-01-01

    The aim of this study was to evaluate the usefulness of dipyridamole Tl-201 myocardium single photon emission computed tomography (201Tl-SPECT) for predicting perioperative cardiac events in patients with arteriosclerosis obliterans (ASO) and abdominal aortic aneurysm (AAA) undergoing non-cardiac vascular surgery. Methods: Preoperative dipyridamole 201Tl-SPECT imaging in association with clinical risk assessment was performed in 224 consecutive patients (97 ASO and 127 AAA). Results: The patients were classified into three groups, including low-risk (n=173, 77%), intermediate-risk (n=39, 18%), and high-risk (n=12, 5%) groups according to the clinical risk stratification. The prevalence of reversible Tl-201 defect was significantly higher in the high-risk group than that in the low-risk group (83% vs. 14%, p<0.001). In 180 patients who underwent vascular surgery, 9 patients (5.0%) had perioperative cardiac events, including heart failure (n=l), unstable angina (n=2), and other cardiac events such as arrhythmias (n=6). The clinical variables including the clinical risk stratification did not significantly correlate with the perioperative cardiac events. In contrast, the reversible defect on 201Tl-SPECT was the only variable to predict perioperative cardiac events by a stepwise logistic regression analysis (odds ratio 7.0, 95% confidence interval l.7-28.0, p=0.007). It was also a significant predictor of perioperative cardiac events in a subgroup of low risk patients (odds ratio 11.6, 95% confidence interval 2.3-57.4, p=0.004). The sensitivity and specificity of the reversible defect for predicting perioperative cardiac events were 55.6% and 84.8% in all operated patients, and 57.1% and 89.7% in low risk patients, respectively. Conclusions: The preoperative dipyridamole 201Tl-SPECT was useful for predicting perioperative cardiac events in patients with vascular diseases, even in patients identified as having a low risk based on the clinical risk assessment. (authors)

  2. Identification and functional analysis of three distinct mutations in the human galactose-1-phosphate uridyltransferase gene associated with galactosemia in a single family

    Energy Technology Data Exchange (ETDEWEB)

    Fridovich-Keil, J.L.; Langley, S.D.; Mazur, L.A.; Lennon, J.C.; Dembure, P.O.; Elsas, L.J. II [Emory Univ. School of Medicine, Atlanta, GA (United States)

    1995-03-01

    We have identified three mutations associated with transferase-deficiency galactosemia in a three-generation family including affected members in two generations and have modeled all three mutations in a yeast-expression system. A sequence of pedigree, biochemical, and molecular analyses of the galactose-1-phosphate uridyltransferase (GALT) enzyme and genetic locus in both affected and carrier individuals revealed three distinct base substitutions in this family, two (Q188R and S135L) that had been reported previously and one (V151A) that was novel. Biochemical analyses of red-blood-cell lysates from the relevant family members suggested that each of these mutations was associated with dramatic impairment of GALT activity in these cells. While this observation was consistent with our previous findings concerning the Q188R mutation expressed both in humans and in a yeast-model system, it was at odds with a report by Reichardt and colleagues, indicating that in their COS cell-expression system the S135L substitution behaved as a neutral polymorphism. To address this apparent paradox, as well as to investigate the functional significance of the newly identified V151A substitution, all three mutations were recreated by site-directed mutagenesis of the otherwise wild-type human GALT sequence and were expressed both individually and in the appropriate allelic combinations in a GALT-deficient strain of the yeast Saccharomyces cerevisiae. The results of these yeast-modeling studies were fully consistent with the patient data, leading us to conclude that, at least within the context of the cell types studied, in the homozygous state Q188R is a mutation that eliminates GALT activity, and S135L and V151A are both mutations that impair GALT activity to <6% of wild-type values. 22 refs., 5 figs.

  3. Splice junction mutation in some Ashkenazi Jews with Tay-Sachs disease: Evidence against a single defect within this ethnic group

    Energy Technology Data Exchange (ETDEWEB)

    Myerowitz, R. (National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD (USA))

    1988-06-01

    Tay-Sachs disease is an inherited disorder in which the {alpha} chain of the lysosomal enzyme {beta}-N-acetylhexosaminidase A bears the mutation. Ashkenazi Jews are found to be carriers for a severe type of Tay-Sachs disease, the classic form, 10 times more frequently than the general population. Ashkenazi Jewish patients with classic Tay-Sachs disease have appeared to be clinically and biochemically identical, and the usual assumption has been that they harbor the same {alpha}-chain mutation. The author has isolated the {alpha}-chain gene from an Ashkenazi Jewish patient, GM2968, with classic Tay-Sachs disease and compared its nucleotide sequences with that of the normal {alpha}-chain gene in the promoter region, exon and splice junction regions, and polyadenylylation signal area. Only one difference was observed between these sequences. The alteration is presumed to be functionally significant and to result in aberrant mRNA splicing. Utilizing the polymerase chain reaction to amplify the region encompassing the mutation, the author developed an assay to screen patients and heterozygote carriers for this mutation. Surprisingly, in each of two Ashkenazi patients, only one {alpha}-chain allele harbored the splice junction mutation. Only one parent of each of these patients was positive for the defect. Another Ashkenazi patient did not bear this mutation at all nor did either of the subject's parents. The data are consistent with the presence of more than one mutation underlying the classic form of Tay-Sachs disease in the Ashkenazi Jewish population.

  4. Splice junction mutation in some Ashkenazi Jews with Tay-Sachs disease: Evidence against a single defect within this ethnic group

    International Nuclear Information System (INIS)

    Myerowitz, R.

    1988-01-01

    Tay-Sachs disease is an inherited disorder in which the α chain of the lysosomal enzyme β-N-acetylhexosaminidase A bears the mutation. Ashkenazi Jews are found to be carriers for a severe type of Tay-Sachs disease, the classic form, 10 times more frequently than the general population. Ashkenazi Jewish patients with classic Tay-Sachs disease have appeared to be clinically and biochemically identical, and the usual assumption has been that they harbor the same α-chain mutation. The author has isolated the α-chain gene from an Ashkenazi Jewish patient, GM2968, with classic Tay-Sachs disease and compared its nucleotide sequences with that of the normal α-chain gene in the promoter region, exon and splice junction regions, and polyadenylylation signal area. Only one difference was observed between these sequences. The alteration is presumed to be functionally significant and to result in aberrant mRNA splicing. Utilizing the polymerase chain reaction to amplify the region encompassing the mutation, the author developed an assay to screen patients and heterozygote carriers for this mutation. Surprisingly, in each of two Ashkenazi patients, only one α-chain allele harbored the splice junction mutation. Only one parent of each of these patients was positive for the defect. Another Ashkenazi patient did not bear this mutation at all nor did either of the subject's parents. The data are consistent with the presence of more than one mutation underlying the classic form of Tay-Sachs disease in the Ashkenazi Jewish population

  5. Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors

    DEFF Research Database (Denmark)

    Goriely, Anne; Hansen, Ruth M S; Taylor, Indira B

    2009-01-01

    Genes mutated in congenital malformation syndromes are frequently implicated in oncogenesis, but the causative germline and somatic mutations occur in separate cells at different times of an organism's life. Here we unify these processes to a single cellular event for mutations arising in male germ...... cells that show a paternal age effect. Screening of 30 spermatocytic seminomas for oncogenic mutations in 17 genes identified 2 mutations in FGFR3 (both 1948A>G, encoding K650E, which causes thanatophoric dysplasia in the germline) and 5 mutations in HRAS. Massively parallel sequencing of sperm DNA...... a common 'selfish' pathway supporting proliferation in the testis, leading to diverse phenotypes in the next generation including fetal lethality, congenital syndromes and cancer predisposition....

  6. The usefulness of dipyridamole thallium-201 single photon emission computed tomography for predicting perioperative cardiac events in patients undergoing non-cardiac vascular surgery

    International Nuclear Information System (INIS)

    Chen, Tao; Kuwabara, Yasuo; Tsutsui, Hiroyuki; Sasaki, Masayuki; Nakagawa, Makoto; Koga, Hirofumi; Kaneko, Kouichirou; Komori, Kimihiro; Masuda, Kouji

    2002-01-01

    The aim of this study was to evaluate the usefulness of dipyridamole Tl-201 myocardium single photon emission computed tomography ( 201 Tl-SPECT) for predicting perioperative cardiac events in patients with arteriosclerosis obliterans (ASO) and abdominal aortic aneurysm (AAA) undergoing non-cardiac vascular surgery. Preoperative dipyridamole 201 Tl-SPECT imaging in association with clinical risk assessment was performed in 224 consecutive patients (97 ASO and 127 AAA). The patients were classified into three groups, including low-risk (n=173, 77%), intermediate-risk (n=39, 18%), and high-risk (n=12, 5%) groups according to the clinical risk stratification. The prevalence of reversible Tl-201 defect was significantly higher in the high-risk group than that in the low-risk group (83% vs. 14%, p 201 Tl-SPECT was the only variable to predict perioperative cardiac events by a stepwise logistic regression analysis (odds ratio 7.0, 95% confidence interval 1.7-28.0, p=0.007). It was also a significant predictor of perioperative cardiac events in a subgroup of low risk patients (odds ratio 11.6, 95% confidence interval 2.3-57.4, p=0.004). The sensitivity and specificity of the reversible defect for predicting perioperative cardiac events were 55.6% and 84.8% in all operated patients, and 57.1% and 89.7% in low risk patients, respectively. The preoperative dipyridamole 201 Tl-SPECT was useful for predicting perioperative cardiac events in patients with vascular diseases, even in patients identified as having a low risk based on the clinical risk assessment. (author)

  7. CHARACTERIZING LENSES AND LENSED STARS OF HIGH-MAGNIFICATION SINGLE-LENS GRAVITATIONAL MICROLENSING EVENTS WITH LENSES PASSING OVER SOURCE STARS

    International Nuclear Information System (INIS)

    Choi, J.-Y.; Shin, I.-G.; Park, S.-Y.; Han, C.; Gould, A.; Gaudi, B. S.; Henderson, C. B.; Sumi, T.; Udalski, A.; Beaulieu, J.-P.; Street, R.; Dominik, M.; Allen, W.; Almeida, L. A.; Bos, M.; Christie, G. W.; Depoy, D. L.; Dong, S.; Drummond, J.; Gal-Yam, A.

    2012-01-01

    We present the analysis of the light curves of nine high-magnification single-lens gravitational microlensing events with lenses passing over source stars, including OGLE-2004-BLG-254, MOA-2007-BLG-176, MOA-2007-BLG-233/OGLE-2007-BLG-302, MOA-2009-BLG-174, MOA-2010-BLG-436, MOA-2011-BLG-093, MOA-2011-BLG-274, OGLE-2011-BLG-0990/MOA-2011-BLG-300, and OGLE-2011-BLG-1101/MOA-2011-BLG-325. For all of the events, we measure the linear limb-darkening coefficients of the surface brightness profile of source stars by measuring the deviation of the light curves near the peak affected by the finite-source effect. For seven events, we measure the Einstein radii and the lens-source relative proper motions. Among them, five events are found to have Einstein radii of less than 0.2 mas, making the lenses very low mass star or brown dwarf candidates. For MOA-2011-BLG-274, especially, the small Einstein radius of θ E ∼ 0.08 mas combined with the short timescale of t E ∼ 2.7 days suggests the possibility that the lens is a free-floating planet. For MOA-2009-BLG-174, we measure the lens parallax and thus uniquely determine the physical parameters of the lens. We also find that the measured lens mass of ∼0.84 M ☉ is consistent with that of a star blended with the source, suggesting that the blend is likely to be the lens. Although we did not find planetary signals for any of the events, we provide exclusion diagrams showing the confidence levels excluding the existence of a planet as a function of the separation and mass ratio.

  8. CHARACTERIZING LENSES AND LENSED STARS OF HIGH-MAGNIFICATION SINGLE-LENS GRAVITATIONAL MICROLENSING EVENTS WITH LENSES PASSING OVER SOURCE STARS

    Energy Technology Data Exchange (ETDEWEB)

    Choi, J.-Y.; Shin, I.-G.; Park, S.-Y.; Han, C. [Department of Physics, Institute for Astrophysics, Chungbuk National University, Cheongju 371-763 (Korea, Republic of); Gould, A.; Gaudi, B. S.; Henderson, C. B. [Department of Astronomy, Ohio State University, 140 W. 18th Ave., Columbus, OH 43210 (United States); Sumi, T. [Department of Earth and Space Science, Osaka University, Osaka 560-0043 (Japan); Udalski, A. [Warsaw University Observatory, Al. Ujazdowskie 4, 00-478 Warszawa (Poland); Beaulieu, J.-P. [Institut d' Astrophysique de Paris, UMR7095 CNRS-Universite Pierre and Marie Curie, 98 bis boulevard Arago, 75014 Paris (France); Street, R. [Las Cumbres Observatory Global Telescope Network, 6740B Cortona Dr, Suite 102, Goleta, CA 93117 (United States); Dominik, M. [School of Physics and Astronomy, SUPA, University of St. Andrews, North Haugh, St. Andrews, KY16 9SS (United Kingdom); Allen, W. [Vintage Lane Observatory, Blenheim (New Zealand); Almeida, L. A. [Instituto Nacional de Pesquisas Espaciais/MCTI, Sao Jose dos Campos, Sao Paulo (Brazil); Bos, M. [Molehill Astronomical Observatory, North Shore (New Zealand); Christie, G. W. [Auckland Observatory, P.O. Box 24-180, Auckland (New Zealand); Depoy, D. L. [Department of Physics, Texas A and M University, College Station, TX (United States); Dong, S. [Institute for Advanced Study, Einstein Drive, Princeton, NJ 08540 (United States); Drummond, J. [Possum Observatory, Patutahi (New Zealand); Gal-Yam, A. [Benoziyo Center for Astrophysics, Weizmann Institute (Israel); Collaboration: muFUN Collaboration; MOA Collaboration; OGLE Collaboration; PLANET Collaboration; RoboNet Collaboration; MiNDSTEp Consortium; and others

    2012-05-20

    We present the analysis of the light curves of nine high-magnification single-lens gravitational microlensing events with lenses passing over source stars, including OGLE-2004-BLG-254, MOA-2007-BLG-176, MOA-2007-BLG-233/OGLE-2007-BLG-302, MOA-2009-BLG-174, MOA-2010-BLG-436, MOA-2011-BLG-093, MOA-2011-BLG-274, OGLE-2011-BLG-0990/MOA-2011-BLG-300, and OGLE-2011-BLG-1101/MOA-2011-BLG-325. For all of the events, we measure the linear limb-darkening coefficients of the surface brightness profile of source stars by measuring the deviation of the light curves near the peak affected by the finite-source effect. For seven events, we measure the Einstein radii and the lens-source relative proper motions. Among them, five events are found to have Einstein radii of less than 0.2 mas, making the lenses very low mass star or brown dwarf candidates. For MOA-2011-BLG-274, especially, the small Einstein radius of {theta}{sub E} {approx} 0.08 mas combined with the short timescale of t{sub E} {approx} 2.7 days suggests the possibility that the lens is a free-floating planet. For MOA-2009-BLG-174, we measure the lens parallax and thus uniquely determine the physical parameters of the lens. We also find that the measured lens mass of {approx}0.84 M{sub Sun} is consistent with that of a star blended with the source, suggesting that the blend is likely to be the lens. Although we did not find planetary signals for any of the events, we provide exclusion diagrams showing the confidence levels excluding the existence of a planet as a function of the separation and mass ratio.

  9. L1014F-kdr Mutation in Indian Anopheles subpictus (Diptera: Culicidae) Arising From Two Alternative Transversions in the Voltage-Gated Sodium Channel and a Single PIRA-PCR for Their Detection.

    Science.gov (United States)

    Singh, O P; Dykes, C L; Sharma, G; Das, M K

    2015-01-01

    Leucine-to-phenylalanine substitution at residue L1014 in the voltage-gated sodium channel, target site of action for dichlorodiphenyltrichloroethane (DDT) and pyrethroids, is the most common knockdown resistance (kdr) mutation reported in several insects conferring resistance against DDT and pyrethroids. Here, we report presence of two coexisting alternative transversions, A>T and A>C, on the third codon position of L1014 residue in malaria vector Anopheles subpictus Grassi (species A) from Jamshedpur (India), both leading to the same amino acid substitution of Leu-to-Phe with allelic frequencies of 19 and 67%, respectively. A single primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) was devised for the identification of L1014F-kdr mutation in An. subpictus resulting from either type of point mutation. Genotyping of samples with PIRA-PCR revealed high frequency (82%) of L1014F-kdr mutation in the study area. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Detecting single-electron events in TEM using low-cost electronics and a silicon strip sensor.

    Science.gov (United States)

    Gontard, Lionel C; Moldovan, Grigore; Carmona-Galán, Ricardo; Lin, Chao; Kirkland, Angus I

    2014-04-01

    There is great interest in developing novel p