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. 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)

  4. A single natural nucleotide mutation alters bacterial pathogen host tropism.

    Science.gov (United States)

    Viana, David; Comos, María; McAdam, Paul R; Ward, Melissa J; Selva, Laura; Guinane, Caitriona M; González-Muñoz, Beatriz M; Tristan, Anne; Foster, Simon J; Fitzgerald, J Ross; Penadés, José R

    2015-04-01

    The capacity of microbial pathogens to alter their host tropism leading to epidemics in distinct host species populations is a global public and veterinary health concern. To investigate the molecular basis of a bacterial host-switching event in a tractable host species, we traced the evolutionary trajectory of the common rabbit clone of Staphylococcus aureus. We report that it evolved through a likely human-to-rabbit host jump over 40 years ago and that only a single naturally occurring nucleotide mutation was required and sufficient to convert a human-specific S. aureus strain into one that could infect rabbits. Related mutations were identified at the same locus in other rabbit strains of distinct clonal origin, consistent with convergent evolution. This first report of a single mutation that was sufficient to alter the host tropism of a microorganism during its evolution highlights the capacity of some pathogens to readily expand into new host species populations.

  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. 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...... of the effect of a recombination event is the genealogical type of the event and whether SNP variation is present that can reveal the genealogical consequences of the recombination event. Recombination events that only change some branch lengths in the genealogy have a very small, but detectable, effect....... The more lineages left when the recombination event occurs, the larger effect it has, implying that it is mainly young recombination events that we detect when estimating the rate. If the population is growing, though, more lineages are present back in time and relatively more ancient recombination events...

  7. 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.

  8. Comparison of uncommon EGFR exon 21 L858R compound mutations with single mutation.

    Science.gov (United States)

    Peng, Liang; Song, Zhigang; Jiao, Shunchang

    2015-01-01

    Non-small-cell lung cancer with epidermal growth factor receptor (EGFR) mutation is sensitive to EGFR tyrosine kinase inhibitors (TKIs). But little is known about the response to EGFR TKIs and the prognostic role of compound mutations. This study compared the uncommon EGFR exon 21 L858R compound mutations with single mutation to characterize EGFR compound mutations and investigated their response to EGFR TKI treatment. We retrospectively screened 799 non-small-cell lung cancer patients from August 1, 2009 to June 1, 2012 by EGFR mutation testing. EGFR mutations were detected in 443 patients, with 22 (4.97%) compound mutations. Subsequently, six patients with EGFR exon 21 L858R compound mutations and 18 paired patients with single L858R mutation were well characterized. Finally, we also analyzed the EGFR TKI treatment response and patients' outcomes of compound or single L858R mutations. There was no differential treatment effect on the disease control rate and objective response rate between the L858R compound mutations and single mutation groups. No significant difference in overall survival or progression-free survival of these two groups was found by log-rank test. In conclusion, we demonstrated that no significant difference was detected in the response to EGFR TKIs and patients' outcomes in the compound and single mutation groups.

  9. Are Prothrombotic Mutations a Time-to-Event Risk Factor?

    Science.gov (United States)

    Tomic, Branko V; Gvozdenov, Maja Z; Pruner, Iva B; Simic, Jelena M; Kovac, Mirjana K; Radojkovic, Dragica P; Djordjevic, Valentina J

    2017-11-08

    Deep vein thrombosis (DVT) represents a common disorder involving genetic and acquired risk factors. It has been proposed that acquired risk factors are more important with aging than genetic factors, indicating different prevalence of prothrombotic mutations throughout the lifespan. To determine the role of the most frequent prothrombotic genetic risk factors (Factor V [FV] Leiden and Factor II [FII] G20210A mutations) in first-time DVT etiology in patients of different ages. This retrospective study included 701 patients living in Serbia with diagnosed DVT as a first-time thrombotic event. Risk assessment for mutations as age-related markers showed no statistical difference (FV Leiden mutation-OR, 1.027; 95% confidence interval [CI], .87-1.22; P = .76 and FII G20210A mutation-OR, 0.940, 95% CI, .74-1.19; P = .61). Our results show similar mutation prevalence regardless of how old the patients were at the time of the first DVT occurrence. Our results indicate that these 2 mutations cannot be used as prognostic marker for time-to-event first DVT in the Serbian population; however, further studies are required. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  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. 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.

  12. Heterogeneity within AML with CEBPA mutations; only CEBPA double mutations, but not single CEBPA mutations are associated with favourable prognosis

    OpenAIRE

    Pabst, T; Eyholzer, M; Fos, J; Mueller, B U

    2009-01-01

    CCAAT/enhancer binding protein alpha (CEBPA) mutations in AML are associated with favourable prognosis and are divided into N- and C-terminal mutations. The majority of AML patients have both types of mutations. We assessed the prognostic significance of single (n=7) and double (n=12) CEBPA mutations among 224 AML patients. Double CEBPA mutations conferred a decisively favourable overall (P=0.006) and disease-free survival (P=0.013). However, clinical outcome of patients with single CEBPA mut...

  13. 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

  14. 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...

  15. Dual Interlocked Logic for Single-Event Transient Mitigation

    Science.gov (United States)

    2017-03-01

    Dual Interlocked Logic for Single -Event Transient Mitigation Jeffrey Maharrey, Jeffrey Kauppila, Dennis Ball, Timothy Holman, Lloyd Massengill...is shown to be robust to single event transients. Keywords: SET; CVSL; DIL; single event transient; hardened logic; cascode voltage switch; dual...interlocked Introduction Single event transients (SETs) generated in combinational logic are a major, often dominant, contributor to soft errors in

  16. 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.

  17. 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

  18. Single event upsets in spacecraft digital systems

    Science.gov (United States)

    Leukowicz, P. E.; Richter, L. J.

    This paper describes the physical environments that can result in random bit changes in spaceborne memory systems. The impact of bit flips in digital telemetry systems is emphasized, with special attention paid to software requirements for protection from single event upset (SEU) effects. Some observations on incidence rates are presented along with an outline of hardware and software methods that can be taken to prevent future SEU problems. Several conclusions are drawn about strategies for preventing data corruption on the next generation of satellites in the presence of SEU-inducing particles.

  19. Generalized quiver mutations and single-centered indices

    CERN Document Server

    Manschot, Jan; Sen, Ashoke

    2014-01-01

    Quiver quantum mechanics is invariant under Seiberg duality. A mathematical consequence is that the cohomology of the Higgs branch moduli space is invariant under mutations of the quiver. The Coulomb branch formula, on the other hand, conjecturally expresses the Poincar\\'e / Dolbeault polynomial of the Higgs branch moduli space in terms of certain quantities known as single-centered indices. In this work we determine the transformations of these single-centered indices under mutations. Moreover, we generalize these mutations to quivers whose nodes carry single-centered indices different from unity. Although the Higgs branch description of these generalized quivers is currently unknown, the Coulomb branch formula is conjectured to be invariant under generalized mutations.

  20. Laboratory tests for single-event effects

    International Nuclear Information System (INIS)

    Buchner, S.; McMorrow, D.; Melinger, J.; Campbell, A.B.

    1996-01-01

    Integrated circuits are currently tested at accelerators for their susceptibility to single-event effects (SEE's). However, because of the cost and limited accessibility associated with accelerator testing, there is considerable interest in developing alternate testing methods. Two laboratory techniques for measuring SEE, one involving a pulsed laser and the other 252 Cf, are described in detail in this paper. The pulsed laser provides information on the spatial and temporal dependence of SEE, information that has proven invaluable in understanding and mitigating SEE in spite of the differences in the physical mechanisms responsible for SEE induced by light and by ions. Considerable effort has been expended on developing 252 Cf as a laboratory test for SEE, but the technique has not found wide use because it is severely limited by the low energy and short range of the emitted ions that are unable to reach junctions either covered with dielectric layers or deep below the surface. In fact, there are documented cases where single-event latchup (SEL) testing with 252 Cf gave significantly different results from accelerator testing. A detailed comparison of laboratory and accelerator SEE data is presented in this review in order to establish the limits of each technique

  1. Improving Single Event Effects Testing Through Software

    Science.gov (United States)

    Banker, M. W.

    2011-01-01

    Radiation encountered in space environments can be damaging to microelectronics and potentially cause spacecraft failure. Single event effects (SEE) are a type of radiation effect that occur when an ion strikes a device. Single event gate rupture (SEGR) is a type of SEE that can cause failure in power transistors. Unlike other SEE rates in which a constant linear energy transfer (LET) can be used, SEGR rates sometimes require a non-uniform LET to be used to be accurate. A recent analysis shows that SEGR rates are most easily calculated when the environment is described as a stopping rate per unit volume for each ion species. Stopping rates in silicon for pertinent ions were calculated using the Stopping and Range of Ions in Matter (SRIM) software and CREME-MC software. A reference table was generated and can be used by others to calculate SEGR rates for a candidate device. Additionally, lasers can be used to simulate SEEs, providing more control and information at lower cost than heavy ion testing. The electron/hole pair generation rate from a laser pulse in a semiconductor can be related to the LET of an ion. MATLAB was used to generate a plot to easily make this comparison.

  2. 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

  3. Single Event Effect (SEE) Test Planning 101

    Science.gov (United States)

    LaBel, Kenneth A.; Pellish, Jonathan; Berg, Melanie D.

    2011-01-01

    This is a course on SEE Test Plan development. It is an introductory discussion of the items that go into planning an SEE test that should complement the SEE test methodology used. Material will only cover heavy ion SEE testing and not proton, LASER, or other though many of the discussed items may be applicable. While standards and guidelines for how-to perform single event effects (SEE) testing have existed almost since the first cyclotron testing, guidance on the development of SEE test plans has not been as easy to find. In this section of the short course, we attempt to rectify this lack. We consider the approach outlined here as a "living" document: mission specific constraints and new technology related issues always need to be taken into account. We note that we will use the term "test planning" in the context of those items being included in a test plan.

  4. Trunk mutational events present minimal intra- and inter-tumoral heterogeneity in hepatocellular carcinoma.

    Science.gov (United States)

    Torrecilla, Sara; Sia, Daniela; Harrington, Andrew N; Zhang, Zhongyang; Cabellos, Laia; Cornella, Helena; Moeini, Agrin; Camprecios, Genis; Leow, Wei-Qiang; Fiel, Maria Isabel; Hao, Ke; Bassaganyas, Laia; Mahajan, Milind; Thung, Swan N; Villanueva, Augusto; Florman, Sander; Schwartz, Myron E; Llovet, Josep M

    2017-12-01

    According to the clonal model of tumor evolution, trunk alterations arise at early stages and are ubiquitous. Through the characterization of early stages of hepatocarcinogenesis, we aimed to identify trunk alterations in hepatocellular carcinoma (HCC) and study their intra- and inter-tumor distribution in advanced lesions. A total of 151 samples representing the multistep process of hepatocarcinogenesis were analyzed by targeted-sequencing and a single nucleotide polymorphism array. Genes altered in early lesions (31 dysplastic nodules [DNs] and 38 small HCCs [sHCC]) were defined as trunk. Their distribution was explored in: a) different regions of large tumors (43 regions, 21 tumors), and b) different nodules of the same patient (39 tumors, 17 patients). Multinodular lesions were classified as intrahepatic metastases (IMs) or synchronous tumors based on chromosomal aberrations. TERT promoter mutations (10.5%) and broad copy-number aberrations in chromosomes 1 and 8 (3-7%) were identified as trunk gatekeepers in DNs and were maintained in sHCCs. Trunk drivers identified in sHCCs included TP53 (23%) and CTNNB1 (11%) mutations, and focal amplifications or deletions in known drivers (6%). Overall, TERT, TP53 and CTNNB1 mutations were the most frequent trunk events and at least one was present in 51% of sHCCs. Around 90% of mutations in these genes were ubiquitous among different regions of large tumors. In multinodular HCCs, 35% of patients harbored IMs; 85% of mutations in TERT, TP53 and/or CTNNB1 were retained in primary and metastatic tumors. Trunk events in early stages (TERT, TP53, CTNNB1 mutations) were ubiquitous across different regions of the same tumor and between primary and metastatic nodules in >85% of cases. This concept supports the knowledge that single biopsies would suffice to capture trunk mutations in HCC. Trunk alterations arise at early stages of cancer and are shared among all malignant cells of the tumor. In order to identify trunk alterations

  5. 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.

  6. Single-Molecule Counting of Point Mutations by Transient DNA Binding

    Science.gov (United States)

    Su, Xin; Li, Lidan; Wang, Shanshan; Hao, Dandan; Wang, Lei; Yu, Changyuan

    2017-03-01

    High-confidence detection of point mutations is important for disease diagnosis and clinical practice. Hybridization probes are extensively used, but are hindered by their poor single-nucleotide selectivity. Shortening the length of DNA hybridization probes weakens the stability of the probe-target duplex, leading to transient binding between complementary sequences. The kinetics of probe-target binding events are highly dependent on the number of complementary base pairs. Here, we present a single-molecule assay for point mutation detection based on transient DNA binding and use of total internal reflection fluorescence microscopy. Statistical analysis of single-molecule kinetics enabled us to effectively discriminate between wild type DNA sequences and single-nucleotide variants at the single-molecule level. A higher single-nucleotide discrimination is achieved than in our previous work by optimizing the assay conditions, which is guided by statistical modeling of kinetics with a gamma distribution. The KRAS c.34 A mutation can be clearly differentiated from the wild type sequence (KRAS c.34 G) at a relative abundance as low as 0.01% mutant to WT. To demonstrate the feasibility of this method for analysis of clinically relevant biological samples, we used this technology to detect mutations in single-stranded DNA generated from asymmetric RT-PCR of mRNA from two cancer cell lines.

  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...

  8. 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)

  9. Familial Mediterranean fever with a single MEFV mutation: comparison of rare and common mutations in a Turkish paediatric cohort.

    Science.gov (United States)

    Soylemezoglu, Oguz; Kandur, Yasar; Duzova, Ali; Ozkaya, Ozan; Kasapcopur, Ozgür; Baskin, Esra; Fidan, Kibriya; Yalcinkaya, Fatos

    2015-01-01

    Presence of common MEFV gene mutations strengthened the diagnosis of FMF in addition to the typical clinical characteristics of FMF. However, there are also rare mutations. P369S, A744S, R761H, K695R, F479L are the main rare mutations in Turkish population. We aimed to evaluate FMF patients with a single allele MEFV mutation and to compare patients with common and rare mutations. We retrospectively reviewed the medical records of FMF patients with a single allele mutation who were followed up between 2008 and 2013 in six centres. We compared the patients with rare and common mutations for disease severity score, frequent exacerbations ( >1 attack per month), long attack period (>3 day), symptoms, age at the onset of symptoms, gender, consanguinity, and family history. Two hundred and seventeen patients (M/F=101/116) with the diagnosis of FMF and single mutation were included. Heterozygote mutations were defined as common (M694V, V726A, M68OI) and rare mutations (A744S, P369S, K695R, R761H, F479L). Sixty-seven patients (27 males, 40 females) had one single rare mutation and 150 (74 males, 76 females) had one single common mutation. No difference was found between the rare and common mutations with respect to the disease severity score. There was no significant difference between common and rare heterozygote form of mutations in terms of disease severity. Patients with typical characteristics of FMF, with some rare mutations (A744S, P369S) should be treated in the same manner as patients with a common mutation.

  10. 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.

  11. 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.

  12. Single Event Effect Hardware Trojans with Remote Activation

    Science.gov (United States)

    2017-03-01

    Interrupt SEFI Corruption of a data path leading to loss of normal operation Complex devices with built-in cpu/state machine or control...Acronym Description Devices Affected Single Event Upset SEU Corruption of the information stored in a memory element Memories, latches in logic...devices Multiple Bit Upset MBU Several memory elements corrupted by a single strike Memories, latches in logic devices Single Event Functional

  13. 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...... and used to derive information on the possible effects of the mutations. The substitution of residue Phe114, situated on the opposite side of Cu relative to the disulfide, by Ala resulted in a rate increase by a factor of almost 2. By assuming that this effect is only due to an increase in driving force......Single-site mutants of the blue, single-copper protein, azurin, from Pseudomonas aeruginosa were reduced by CO2- radicals in pulse radiolysis experiments. The single disulfide group was reduced directly by CO2- with rates similar to those of the native protein [Farver, O., & Pecht, I. (1989) Proc...

  14. Mutation of NRAS is a rare genetic event in ovarian low-grade serous carcinoma.

    Science.gov (United States)

    Xing, Deyin; Suryo Rahmanto, Yohan; Zeppernick, Felix; Hannibal, Charlotte G; Kjaer, Susanne K; Vang, Russell; Shih, Ie-Ming; Wang, Tian-Li

    2017-10-01

    Activating mutations involving the members of the RAS signaling pathway, including KRAS, NRAS, and BRAF, have been reported in ovarian low-grade serous carcinoma and its precursor lesion, serous borderline tumor (SBT). Whether additional genetic alterations in the RAS oncogene family accumulate during the progression of SBT to invasive low-grade serous carcinoma (LGSC) remains largely unknown. Although mutations of KRAS and BRAF occur at a very early stage of progression, even preceding the development of SBT, additional driving events, such as NRAS mutations, have been postulated to facilitate progression. In this study, we analyzed NRAS exon 3 mutational status in 98 cases that were diagnosed with SBT/atypical proliferative serous tumor, noninvasive LGSC, or invasive LGSC. Of the latter, NRAS Q61R (CAA to CGA) mutations were detected in only 2 of 56 (3.6%) cases. The same mutation was not detected in any of the SBTs (atypical proliferative serous tumors) or noninvasive LGSCs. Mutational analysis for hotspots in KRAS and BRAF demonstrated a wild-type pattern of KRAS and BRAF in one of the NRAS-mutated cases. Interestingly, another LGSC case with NRAS mutation harbored a concurrent BRAF V600L mutation. These findings indicate that, although recurrent NRAS mutations are present, their low prevalence indicates that NRAS plays a limited role in the development of LGSC. Further studies to identify other oncogenic events that drive LGSC progression are warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Analysis of Single Event Evoked Potentials.

    Science.gov (United States)

    1979-11-01

    stimuli is available in the literature, and since this study deals with single responses, an assumption had to be made before the information in the...Figue 4 Repon e mocekroadpten.trp atrsadt ln 0m10 4 4 22 A S10 2D 3 40 5 64 10 i 13 10 II0 Visul wo (miautes) of side of dck Figure 5. The effect of unit...differences in their average evoked responses. These responses will also lend themselves to detection based on information from multiple electrodes because

  16. Clonal status of actionable driver events and the timing of mutational processes in cancer evolution

    DEFF Research Database (Denmark)

    McGranahan, Nicholas; Favero, Francesco; de Bruin, Elza C.

    2015-01-01

    Deciphering whether actionable driver mutations are found in all or a subset of tumor cells will likely be required to improve drug development and precision medicine strategies. We analyzed nine cancer types to determine the subclonal frequencies of driver events, to time mutational processes...... during cancer evolution, and to identify drivers of subclonal expansions. Although mutations in known driver genes typically occurred early in cancer evolution, we also identified later subclonal “actionable” mutations, including BRAF (V600E), IDH1 (R132H), PIK3CA (E545K), EGFR (L858R), and KRAS (G12D......), which may compromise the efficacy of targeted therapy approaches. More than 20% of IDH1 mutations in glioblastomas, and 15% of mutations in genes in the PI3K (phosphatidylinositol 3-kinase)–AKT–mTOR (mammalian target of rapamycin) signaling axis across all tumor types were subclonal. Mutations...

  17. 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)

  18. 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...

  19. Angiomyolipoma have common mutations in TSC2 but no other common genetic events.

    Directory of Open Access Journals (Sweden)

    Wei Qin

    Full Text Available Renal angiomyolipoma are part of the PEComa family of neoplasms, and occur both in association with Tuberous Sclerosis Complex (TSC and independent of that disorder. Previous studies on the molecular genetic alterations that occur in angiomyolipoma are very limited. We evaluated 9 angiomyolipoma for which frozen tissue was available from a consecutive surgical series. Seven of 8 samples subjected to RT-PCR-cDNA sequencing showed mutations in TSC2; none showed mutations in TSC1 or RHEB. Six of the seven mutations were deletions. We searched for 983 activating and inactivating mutations in 115 genes, and found none in these tumors. Similarly analysis for genomic regions of loss or gain, assessed by Affymetrix SNP6.0 analysis, showed no abnormalities. Loss of heterozygosity in the TSC2 region was commonly seen, except in patients with low frequency TSC2 mutations. We conclude that sporadic renal angiomyolipoma usually have mutations in TSC2, but not TSC1 or RHEB, and have no other common genomic events, among those we searched for. However, chromosomal translocations and gene fusion events were not assessed here. TSC2 inactivation by mutation is a consistent and likely necessary genetic event in the pathogenesis of most angiomyolipoma.

  20. 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

  1. 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.)

  2. Mutation of NRAS is a Rare Genetic Event in Ovarian Low-Grade Serous Carcinoma

    DEFF Research Database (Denmark)

    Xing, Deyin; Rahmanto, Yohan Suryo; Zeppernick, Felix

    2017-01-01

    Activating mutations involving the members of the RAS signaling pathway, including KRAS, NRAS, and BRAF, have been reported in ovarian low-grade serous carcinoma and its precursor lesion, serous borderline tumor (SBT). Whether additional genetic alterations in the RAS oncogene family accumulate...... during the progression of serous borderline tumor (SBT) to invasive low grade serous carcinoma (LGSC) remains largely unknown. While mutations of KRAS and BRAF occur at a very early stage of progression, even preceding the development of SBT, additional driving events, such as NRAS mutations, have been...

  3. 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.

  4. 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.

  5. Planning Single-Event Nutrition Education: A New Model

    Science.gov (United States)

    Brown, Lora Beth

    2011-01-01

    A theoretical model for planning single-event nutrition education contrasts a Practical, Foods, and Positive (PFP) emphasis to an Abstract, Nutrient, and Negative (ANN) focus on nutrition topics. Use of this model makes messages more appealing to consumers and may increase the likelihood that people will apply the nutrition information in their…

  6. 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

  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. Inferring clonal evolution of tumors from single nucleotide somatic mutations.

    Science.gov (United States)

    Jiao, Wei; Vembu, Shankar; Deshwar, Amit G; Stein, Lincoln; Morris, Quaid

    2014-02-01

    High-throughput sequencing allows the detection and quantification of frequencies of somatic single nucleotide variants (SNV) in heterogeneous tumor cell populations. In some cases, the evolutionary history and population frequency of the subclonal lineages of tumor cells present in the sample can be reconstructed from these SNV frequency measurements. But automated methods to do this reconstruction are not available and the conditions under which reconstruction is possible have not been described. We describe the conditions under which the evolutionary history can be uniquely reconstructed from SNV frequencies from single or multiple samples from the tumor population and we introduce a new statistical model, PhyloSub, that infers the phylogeny and genotype of the major subclonal lineages represented in the population of cancer cells. It uses a Bayesian nonparametric prior over trees that groups SNVs into major subclonal lineages and automatically estimates the number of lineages and their ancestry. We sample from the joint posterior distribution over trees to identify evolutionary histories and cell population frequencies that have the highest probability of generating the observed SNV frequency data. When multiple phylogenies are consistent with a given set of SNV frequencies, PhyloSub represents the uncertainty in the tumor phylogeny using a "partial order plot". Experiments on a simulated dataset and two real datasets comprising tumor samples from acute myeloid leukemia and chronic lymphocytic leukemia patients demonstrate that PhyloSub can infer both linear (or chain) and branching lineages and its inferences are in good agreement with ground truth, where it is available. PhyloSub can be applied to frequencies of any "binary" somatic mutation, including SNVs as well as small insertions and deletions. The PhyloSub and partial order plot software is available from https://github.com/morrislab/phylosub/.

  9. Do multiple health events reduce resilience when compared with single events?

    Science.gov (United States)

    Morin, Ruth T; Galatzer-Levy, Isaac R; Maccallum, Fiona; Bonanno, George A

    2017-08-01

    The impact of multiple major life stressors is hypothesized to reduce the probability of resilience and increase rates of mortality. However, this hypothesis lacks strong empirical support because of the lack of prospective evidence. This study investigated whether experiencing multiple major health events diminishes rates of resilience and increases rates of mortality using a large population-based prospective cohort. There were n = 1,395 individuals sampled from the Health and Retirement Study (HRS) and examined prospectively from 2 years before 4 years after either single or multiple health events (lung disease, heart disease, stroke, or cancer). Distinct depression and resilience trajectories were identified using latent growth mixture modeling (LGMM). These trajectories were compared on rates of mortality 4 years after the health events. Findings indicated that 4 trajectories best fit the data including resilience, emergent postevent depression, chronic pre-to-post depression, and depressed prior followed by improvement. Analyses demonstrate that multiple health events do not decrease rates of resilience but do increase the severity of symptoms among those on the emergent depression trajectory. Emergent depression increased mortality compared with all others but among those in this class, rates were not different in response to single versus multiple health events. Multiple major stressors do not reduce rates of resilience. The emergence of depression after health events does significantly increase risk for mortality regardless of the number of events. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  10. Single Event Rates for Devices Sensitive to Particle Energy

    Science.gov (United States)

    Edmonds, L. D.; Scheick, L. Z.; Banker, M. W.

    2012-01-01

    Single event rates (SER) can include contributions from low-energy particles such that the linear energy transfer (LET) is not constant. Previous work found that the environmental description that is most relevant to the low-energy contribution to the rate is a "stopping rate per unit volume" even when the physical mechanisms for a single-event effect do not require an ion to stop in some device region. Stopping rate tables are presented for four heavy-ion environments that are commonly used to assess device suitability for space applications. A conservative rate estimate utilizing limited test data is derived, and the example of SEGR rate in a power MOSFET is presented.

  11. 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.

  12. 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

  13. A Search for Single Photon Events in Neutrino Interactions

    CERN Document Server

    Kullenberg, C.T.; Dimmery, D.; Tian, X.C.; Autiero, D.; Gninenko, S.; Rubbia, A.; Alekhin, S.; Astier, P.; Baldisseri, A.; Baldo-Ceolin, M.; Banner, M.; Bassompierre, G.; Benslama, K.; Besson, N.; Bird, I.; Blumenfeld, B.; Bobisut, F.; Bouchez, J.; Boyd, S.; Bueno, A.; Bunyatov, S.; Camilleri, L.; Cardini, A.; Cattaneo, P.W.; Cavasinni, V.; Cervera-Villanueva, A.; Challis, R.; Chukanov, A.; Collazuol, G.; Conforto, G.; Conta, C.; Contalbrigo, M.; Cousins, R.; Degaudenzi, H.; De Santo, A.; Del Prete, T.; Di Lella, L.; do Couto e Silva, E.; Dumarchez, J.; Ellis, M.; Feldman, G.J.; Ferrari, R.; Ferrère, D.; Flaminio, V.; Fraternali, M.; Gaillard, J.-M.; Gangler, E.; Geiser, A.; Geppert, D.; Gibin, D.; Godley, A.; Gomez-Cadenas, J.-J.; Gosset, J.; Gößling, C.; Gouanère, M.; Grant, A.; Graziani, G.; Guglielmi, A.; Hagner, C.; Hernando, J.; Hurst, P.; Hyett, N.; Iacopini, E.; Joseph, C.; Juget, F.; Kent, N.; Klimov, O.; Kokkonen, J.; Kovzelev, A.; Krasnoperov, A.; Kim, J.J.; Kirsanov, M.; Kulagin, S.; Lacaprara, S.; Lachaud, C.; Lakić, B.; Lanza, A.; La Rotonda, L.; Laveder, M.; Letessier-Selvon, A.; Levy, J.M.; Ling, J.; Linssen, L.; Ljubičic, A.; Long, J.; Lupi, A.; Lyubushkin, V.; Marchionni, A.; Martelli, F.; Méchain, X.; Mendiburu, J.-P.; Meyer, J.-P.; Mezzetto, M.; Moorhead, G.F.; Naumov, D.; Nédélec, P.; Nefedov, Yu.; Nguyen-Mau, C.; Orestano, D.; Pastore, F.; Peak, L.S.; Pennacchio, E.; Pessard, H.; Petti, R.; Placci, A.; Polesello, G.; Pollmann, D.; Polyarush, A.; Poulsen, C.; Popov, B.; Rebuffi, L.; Rico, J.; Riemann, P.; Roda, C.; Salvatore, F.; Samoylov, O.; Schahmaneche, K.; Schmidt, B.; Schmidt, T.; Sconza, A.; Scott, A.M.; Seaton, M.B.; Sevior, M.; Sillou, D.; Soler, F.J.P.; Sozzi, G.; Steele, D.; Stiegler, U.; Stipčević, M.; Stolarczyk, Th.; Tareb-Reyes, M.; Taylor, G.N.; Tereshchenko, V.; Toropin, A.; Touchard, A.-M.; Tovey, S.N.; Tran, M.-T.; Tsesmelis, E.; Ulrichs, J.; Vacavant, L.; Valdata-Nappi, M.; Valuev, V.; Vannucci, F.; Varvell, K.E.; Veltri, M.; Vercesi, V.; Vidal-Sitjes, G.; Vieira, J.-M.; Vinogradova, T.; Weber, F.V.; Weisse, T.; Wilson, F.F.; Winton, L.J.; Wu, Q.; Yabsley, B.D.; Zaccone, H.; Zuber, K.; Zuccon, P.

    2012-01-01

    We present a search for neutrino-induced events containing a single, exclusive photon using data from the NOMAD experiment at the CERN SPS where the average energy of the neutrino flux is $\\simeq 25$ GeV. The search is motivated by an excess of electron-like events in the 200--475 MeV energy region as reported by the MiniBOONE experiment. In NOMAD, photons are identified via their conversion to $e^+e^-$ in an active target embedded in a magnetic field. The background to the single photon signal is dominated by the asymmetric decay of neutral pions produced either in a coherent neutrino-nucleus interaction, or in a neutrino-nucleon neutral current deep inelastic scattering, or in an interaction occurring outside the fiducial volume. All three backgrounds are determined {\\it in situ} using control data samples prior to opening the `signal-box'. In the signal region, we observe {\\bf 155} events with a predicted background of {\\bf 129.2 $\\pm$ 8.5 $\\pm$ 3.3}. We interpret this as null evidence for excess of single...

  14. 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)

  15. Single event upsets caused by solar energetic heavy ions

    International Nuclear Information System (INIS)

    Tylka, A.J.; Adams, J.H. Jr.; Boberg, P.R.; Smith, E.C.

    1996-01-01

    The authors calculate single event upset (SEU) rates due to protons, alphas, and heavier ions in two satellite systems for the major solar particle events of 1989--92, using a new and complete analysis of GOES proton data and high-energy heavy-ion fluences from the University of Chicago Cosmic Ray Telescope on IMP-8. These measurements cover the entire range of energies relevant to SEU studies and therefore overcome shortcomings of previous studies, which relied upon theoretical or semi-empirical estimates of high-energy heavy-ion spectra. They compare the results to the observed SEU rates in these events. The SEU rates in one device were overwhelmingly dominated by protons. However, even after taking into account uncertainties in the ground-test cross-section data, the authors find that at least ∼45% of the SEUs in the other device must have been caused by heavy ions. The results demonstrate that both protons and heavy ions must be considered in order to make a reliable assessment of SEU vulnerabilities. Furthermore, the GOES/Chicago database of solar particle events provides a basis for making accurate solar particle SEU calculations and credible worst-case estimates. In particular, measurements of the historic solar particle events of October 1989 are used in worst week and worst day environment models in CREME96, a revision of NRL's Cosmic Ray Effects on MicroElectronics code

  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. Analysis of experiment testing technology for single event effects in China

    International Nuclear Information System (INIS)

    He Chaohui

    2001-01-01

    The merit and demerit of simulation source were analyzed for Single Event Effects (SEE) experiment testing in China. Laboratory experiment systems for SEE were brief introduced and requests for SEE test system were emphasize analyzed. Test systems were presented for Single Event Upset, Single Event Latch-up, Single Event Burnout and Single Event Gate-Rupture. The attention should be in mind in SEE experiments were discussed

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

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    provides an excellent prototype system to elucidate the different mechanisms underlying the loss in DNA binding affinity and specificity upon single point mutation because over 50% of all human cancers involve p53 mutations, which occur mostly in the sequence–specific DNA–binding central domain (residues 102–292, ...

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

    DEFF Research Database (Denmark)

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

    1993-01-01

    and used to derive information on the possible effects of the mutations. The substitution of residue Phe114, situated on the opposite side of Cu relative to the disulfide, by Ala resulted in a rate increase by a factor of almost 2. By assuming that this effect is only due to an increase in driving force...... 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...

  20. Origins and Spread of Machado-Joseph Disease Ancestral Mutations Events.

    Science.gov (United States)

    Martins, Sandra; Sequeiros, Jorge

    2018-01-01

    Machado-Joseph disease (MJD) is the most common autosomal dominant spinocerebellar ataxia reported worldwide, but it shows marked geographic differences in prevalence. The study of ancestral origins and spreading routes of MJD mutational events has contributed to explain such differences. During human evolution, at least two independent de novo MJD expansions occurred in distinct haplotype backgrounds: TTACAC and GTGGCA (named Joseph and Machado lineages). The most ancient Joseph lineage, probably of Asian origin, has been introduced recently in Europe, where founder effects are responsible for the high MJD prevalence, as occurs in the Portuguese/Azorean island of Flores and Northeastern mainland. The Machado lineage is geographically more restricted, with most known families in Portugal (island of São Miguel and along the Tagus valley). The hypothesis of other mutational origins has been raised, namely to explain the disease among Australian aborigines; however, a comprehensive haplotype study suggested the introduction of the Joseph lineage in that community via Asia. Also, additional SNP-based haplotypes (TTAGAC, TTGGAC and GTGCCA) were observed in other MJD families, but phylogenetic analysis with more polymorphic flanking markers did not point to independent mutational events, reinforcing the hypothesis of a very low mutation rate underlying this repeat expansion locus.

  1. Time-resolved gamma spectroscopy of single events

    Science.gov (United States)

    Wolszczak, W.; Dorenbos, P.

    2018-04-01

    In this article we present a method of characterizing scintillating materials by digitization of each individual scintillation pulse followed by digital signal processing. With this technique it is possible to measure the pulse shape and the energy of an absorbed gamma photon on an event-by-event basis. In contrast to time-correlated single photon counting technique, the digital approach provides a faster measurement, an active noise suppression, and enables characterization of scintillation pulses simultaneously in two domains: time and energy. We applied this method to study the pulse shape change of a CsI(Tl) scintillator with energy of gamma excitation. We confirmed previously published results and revealed new details of the phenomenon.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. Translocation events in a single-walled carbon nanotube

    Energy Technology Data Exchange (ETDEWEB)

    He Jin; Lindsay, Stuart [Biodesign Institute, Arizona State University, Tempe, AZ 85287 (United States); Liu Hao [Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287 (United States); Pang Pei; Cao Di, E-mail: jinhe@asu.ed [Department of Physics, Arizona State University, Tempe, AZ 85287 (United States)

    2010-11-17

    Translocation of DNA oligomers through a single-walled carbon nanotube was demonstrated recently. Translocation events are accompanied by giant current pulses, the origin of which remains obscure. Here, we show that the introduction of a nucleotide, guanosine triphosphate, alone into the input reservoir of a carbon nanotube nanofluidic device also gives giant current pulses. Taken together with data on oligomer translocation, these new results suggest that the pulse width has a nonlinear, power-law dependence on the number of nucleotides in a DNA molecule. We have also measured the time for the onset of DNA translocation pulses after bias reversal, finding that the time for the onset of translocation is directly proportional to the period of the bias reversal.

  8. Translocation events in a single-walled carbon nanotube

    International Nuclear Information System (INIS)

    He Jin; Lindsay, Stuart; Liu Hao; Pang Pei; Cao Di

    2010-01-01

    Translocation of DNA oligomers through a single-walled carbon nanotube was demonstrated recently. Translocation events are accompanied by giant current pulses, the origin of which remains obscure. Here, we show that the introduction of a nucleotide, guanosine triphosphate, alone into the input reservoir of a carbon nanotube nanofluidic device also gives giant current pulses. Taken together with data on oligomer translocation, these new results suggest that the pulse width has a nonlinear, power-law dependence on the number of nucleotides in a DNA molecule. We have also measured the time for the onset of DNA translocation pulses after bias reversal, finding that the time for the onset of translocation is directly proportional to the period of the bias reversal.

  9. Single event upset immunity of strontium bismuth tantalate ferroelectric memories

    International Nuclear Information System (INIS)

    Benedetto, J.M.; Derbenwick, G.F.; Cuchiaro, J.D.

    1999-01-01

    An embedded 1Kbit non-volatile (NV) serial memory manufactured with strontium bismuth tantalate (SBT) ferroelectric (FE) technology was shown to be immune to effects of heavy ion irradiation. The memories did not lose any data in the non-volatile mode when exposed to xenon (maximum effective LET of 128 MeV-cm 2 /mg and a total fluence of 1.5 x 10 7 ions/cm 2 ). The ferroelectric memories also did not exhibit any loss in the ability to rewrite new data into the memory bits, indicating that no significant degradation of the FE dipoles occurred as a result of the heavy ion exposure. The fast read/write times of FE memories also means that single event gate rupture is unlikely to occur in this technology

  10. 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

  11. 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.

  12. Single ABCA3 Mutations Increase Risk for Neonatal Respiratory Distress Syndrome

    Science.gov (United States)

    Wegner, Daniel J.; DePass, Kelcey; Heins, Hillary; Druley, Todd E.; Mitra, Robi D.; An, Ping; Zhang, Qunyuan; Nogee, Lawrence M.; Cole, F. Sessions; Hamvas, Aaron

    2012-01-01

    BACKGROUND AND OBJECTIVE: Neonatal respiratory distress syndrome (RDS) due to pulmonary surfactant deficiency is heritable, but common variants do not fully explain disease heritability. METHODS: Using next-generation, pooled sequencing of race-stratified DNA samples from infants ≥34 weeks’ gestation with and without RDS (n = 513) and from a Missouri population-based cohort (n = 1066), we scanned all exons of 5 surfactant-associated genes and used in silico algorithms to identify functional mutations. We validated each mutation with an independent genotyping platform and compared race-stratified, collapsed frequencies of rare mutations by gene to investigate disease associations and estimate attributable risk. RESULTS: Single ABCA3 mutations were overrepresented among European-descent RDS infants (14.3% of RDS vs 3.7% of non-RDS; P = .002) but were not statistically overrepresented among African-descent RDS infants (4.5% of RDS vs 1.5% of non-RDS; P = .23). In the Missouri population-based cohort, 3.6% of European-descent and 1.5% of African-descent infants carried a single ABCA3 mutation. We found no mutations among the RDS infants and no evidence of contribution to population-based disease burden for SFTPC, CHPT1, LPCAT1, or PCYT1B. CONCLUSIONS: In contrast to lethal neonatal RDS resulting from homozygous or compound heterozygous ABCA3 mutations, single ABCA3 mutations are overrepresented among European-descent infants ≥34 weeks’ gestation with RDS and account for ∼10.9% of the attributable risk among term and late preterm infants. Although ABCA3 mutations are individually rare, they are collectively common among European- and African-descent individuals in the general population. PMID:23166334

  13. 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.

  14. Complex Dynamic Scene Perception: Effects of Attentional Set on Perceiving Single and Multiple Event Types

    Science.gov (United States)

    Sanocki, Thomas; Sulman, Noah

    2013-01-01

    Three experiments measured the efficiency of monitoring complex scenes composed of changing objects, or events. All events lasted about 4 s, but in a given block of trials, could be of a single type (single task) or of multiple types (multitask, with a total of four event types). Overall accuracy of detecting target events amid distractors was…

  15. Primer system for single cell detection of double mutation for Tay-Sachs disease.

    Science.gov (United States)

    Liu, M C; Drury, K C; Kipersztok, S; Zheng, W; Williams, R S

    2000-02-01

    Nearly 100% of infantile Tay-Sachs disease is produced by two mutations occurring in the alpha chain of the lysosomal enzyme beta-N-acetylhexosaminidase (HEXA) in the Ashkenazi Jewish population. Although others have described primer systems used to amplify both sites simultaneously, few discuss the allele dropout problems inherent in this test. Our goal was to construct a more robust test enabling stronger signal generation for single cell preimplantation genetic diagnosis and to investigate the occurrence of allele dropout. New nested primers were designed to optimize detection of both major Tay-Sachs mutations. Four hundred fifty-seven single cells, including normal cells and those carrying mutations of either the 4bp insertion exon 11 or splice-site intron 12 defects, were used to screen a new primer system. Based on PCR amplified product analysis, total efficiency of amplification was 85.3%, (390/457). The allele dropout rate for the 4bp insertion mutation in exon 11 and splice-site mutation in intron 12 was 4.8% and 5.8%, respectively. Multiple mutation detection and analysis within the Tay-Sachs disease gene (HEXA) is possible using single cells for clinical preimplantation genetic diagnosis. Alternative PCR primers and conditions offer various methods for developing systems compatible to specific program requirements.

  16. Comparison of single event upset rates for microelectronic memory devices during interplanetary solar particle events

    Science.gov (United States)

    Mckerracher, P. L.; Kinnison, J. D.; Maurer, R. H.

    1993-01-01

    Variability in the methods and models used for single event upset calculations in microelectronic memory devices can lead to a range of possible upset rates. Using heavy ion and proton data for selected DRAM and SRAM memories, we have calculated an array of upset rates in order to compare the Adams worst case interplanetary solar flare model to a model proposed by scientists at the Jet Propulsion Laboratory. In addition, methods of upset rate calculation are compared: the Cosmic Ray Effects on Microelectronics CREME code and a Monte Carlo algorithm developed at the Applied Physics Laboratory. The results show that use of a more realistic, although still conservative, model of the space environment can have significant cost saving benefits.

  17. An improved system of detecting single event effect in SRAM

    International Nuclear Information System (INIS)

    Tong Teng; Wang Xiaohui; Zhang Zhangang; Liu Tianqi; Gu Song; Yang Zhenlei; Su Hong; Liu Jie

    2014-01-01

    The material research center in Institute of Modern Physics, Chinese Academy of Sciences (IMP, CAS) have made a fruitful achievements in the research of single event effects (SEEs) occurring in static random access memory (SRAM). However, there are some drawbacks exist in the two systems of detecting SEE owning by the material research center. Therefore, an improved method of detecting SEE is proposed, and the method functionality is implemented in a circuit. Further, a sequence of experiments are carried out in the beam radiation terminal of the Heavy Ion Facility in Lanzhou (HIRFL), and a bunch of experimental data are collected. The irradiation tests were carried out using 129 Xe for the SEE research of 65 nm SRAMs; Using 12 C for the SEE research of the 65, 130 and 150 nm SRAMs with ECC module; Using 129 Xe for the SEL research of the common commercial SRAMs and so on. These experiments provide a statistical evidence of the effectiveness and robustness of the improved system. It is believed that the proposed system will be beneficial for detecting SEE in diverse settings, and it could be taken advantage of as a platform for future research on SEE tests in more intricate devices. (authors)

  18. MAP: Mutation Arranger for Defining Phenotype-Related Single-Nucleotide Variant

    Directory of Open Access Journals (Sweden)

    In-Pyo Baek

    2014-12-01

    Full Text Available Next-generation sequencing (NGS is widely used to identify the causative mutations underlying diverse human diseases, including cancers, which can be useful for discovering the diagnostic and therapeutic targets. Currently, a number of single-nucleotide variant (SNV-calling algorithms are available; however, there is no tool for visualizing the recurrent and phenotype-specific mutations for general researchers. In this study, in order to support defining the recurrent mutations or phenotype-specific mutations from NGS data of a group of cancers with diverse phenotypes, we aimed to develop a user-friendly tool, named mutation arranger for defining phenotype-related SNV (MAP. MAP is a user-friendly program with multiple functions that supports the determination of recurrent or phenotype-specific mutations and provides graphic illustration images to the users. Its operation environment, the Microsoft Windows environment, enables more researchers who cannot operate Linux to define clinically meaningful mutations with NGS data from cancer cohorts.

  19. 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)

  20. 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.

  1. 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.

  2. 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...

  3. Highly sensitive, non-invasive detection of colorectal cancer mutations using single molecule, third generation sequencing

    Directory of Open Access Journals (Sweden)

    Giancarlo Russo

    2015-12-01

    We present the first study that applies the high read accuracy and depth of single molecule, real time, circular consensus sequencing (SMRT-CCS to the detection of mutations in stool DNA in order to provide a non-invasive, sensitive and accurate test for CRC. In stool DNA isolated from patients diagnosed with adenocarcinoma, we are able to detect mutations at frequencies below 0.5% with no false positives. This approach establishes a foundation for a non-invasive, highly sensitive assay to screen the population for CRC and the early stage adenomas that lead to CRC.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-03-01

    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 /sup 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.

  5. 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

  6. Mutations in Exons 9 and 13 of KIT Gene Are Rare Events in Gastrointestinal Stromal Tumors

    Science.gov (United States)

    Lasota, Jerzy; Wozniak, Agnieszka; Sarlomo-Rikala, Maarit; Rys, Janusz; Kordek, Radzislaw; Nassar, Aziza; Sobin, Leslie H.; Miettinen, Markku

    2000-01-01

    Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, typically express the KIT protein. Activating mutations in the juxtamembrane domain (exon 11) of the c-kit gene have been shown in a subset of GISTs. These mutations lead into ligand-independent activation of the tyrosine kinase of c-kit, and have a transforming effect in vitro. Several groups have studied the clinical implication of the c-kit mutation status of exon 11 in GISTs and a possible relationship between c-kit mutations and malignant behavior has been established. Recently, a 1530ins6 mutation in exon 9 and missense mutations, 1945A>G in exon 13 of the c-kit gene were reported. The frequency and clinical importance of these findings are unknown. In this study we evaluated 200 GISTs for the presence of mutations in exons 9 and 13 of c-kit. Six cases revealed 1530ins6 mutation in exon 9 and two cases 1945A>G mutation in exon 13. All tumors with mutations in exon 9 and 13 lacked mutations in exon 11 of c-kit. None of the analyzed tumors had more than one type of c-kit mutation. All but one of the eight tumors with mutations in exon 9 or 13 of the c-kit gene were histologically and clinically malignant. All four of six cases with exon 9 mutation of which location of primary tumor was known, were small intestinal, suggesting that this type of mutation could preferentially occur in small intestinal tumors. Exon 9 and 13 mutations seem to be rare, and they cover only a small portion (8%) of the balance of GISTs that do not have mutations in exon 11 of c-kit. This finding indicates that other genetic alterations may activate c-kit in GISTs, or that KIT is not activated by mutations in all cases. PMID:11021812

  7. 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.

  8. 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.

  9. Detection of Janus Kinase 2 gene single point mutation in real samples with electrochemical DNA biosensor.

    Science.gov (United States)

    Topkaya, Seda Nur; Kosova, Buket; Ozsoz, Mehmet

    2014-02-15

    Janus Kinase 2 (JAK2) gene single point mutations, which have been reported to be associated with myeloproliferative disorders, are usually detected through conventional methods such as melting curve assays, allele-specific and quantitative Polymerase Chain Reactions (PCRs). Herein, an electrochemical biosensor for the detection of a Guanine (G) to Thymine (T) transversion at nucleotide position 1849 of the JAK2 gene was reported. Due to clinical importance of this mutation, easy and sensitive tests are needed to be developed. Our aim was to design a biosensor system that is capable of detecting the mutation within less than 1h with high sensitivity. For these purposes, an electrochemical sensing system was developed based on detecting hybridization. Hybridization between probe and its target and discrimination of single point mutation was investigated by monitoring guanine oxidation signals observed at +1.0 V with Differential Pulse Voltammetry (DPV) by using synthetic oligonucleotides and Polymerase Chain Reaction (PCR) amplicons. Hybridization between probe and PCR amplicons was also determined with Electrochemical Impedance Spectroscopy (EIS). We successfully detect hybridization first in synthetic samples, and ultimately in real samples involving blood samples from patients as well as additional healthy controls. The limit of detection (S/N=3) was calculated as 44 pmol of target sequence in a 40-μl reaction volume in real samples. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Familial Ehlers-Danlos syndrome with lethal arterial events caused by a mutation in COL5A1.

    Science.gov (United States)

    Monroe, Glen R; Harakalova, Magdalena; van der Crabben, Saskia N; Majoor-Krakauer, Danielle; Bertoli-Avella, Aida M; Moll, Frans L; Oranen, Björn I; Dooijes, Dennis; Vink, Aryan; Knoers, Nine V; Maugeri, Alessandra; Pals, Gerard; Nijman, Isaac J; van Haaften, Gijs; Baas, Annette F

    2015-06-01

    Different forms of Ehlers-Danlos syndrome (EDS) exist, with specific phenotypes and associated genes. Vascular EDS, caused by heterozygous mutations in the COL3A1 gene, is characterized by fragile vasculature with a high risk of catastrophic vascular events at a young age. Classic EDS, caused by heterozygous mutations in the COL5A1 or COL5A2 genes, is characterized by fragile, hyperextensible skin and joint laxity. To date, vessel rupture in four unrelated classic EDS patients with a confirmed COL5A1 mutation has been reported. We describe familial occurrence of a phenotype resembling vascular EDS in a mother and her two sons, who all died at an early age from arterial ruptures. Diagnostic Sanger sequencing in the proband failed to detect aberrations in COL3A1, COL1A1, COL1A2, TGFBR1, TGFBR2, SMAD3, and ACTA2. Next, the proband's DNA was analyzed using a next-generation sequencing approach targeting 554 genes linked to vascular disease (VASCULOME project). A novel heterozygous mutation in COL5A1 was detected, resulting in an essential glycine substitution at the C-terminal end of the triple helix domain (NM_000093.4:c.4610G>T; p.Gly1537Val). This mutation was also present in DNA isolated from autopsy material of the index's brother. No material was available from the mother, but the mutation was excluded in her parents, siblings and in the father of her sons, suggesting that the COL5A1 mutation occurred in the mother's genome de novo. In conclusion, we report familial occurrence of lethal arterial events caused by a COL5A1 mutation. © 2015 Wiley Periodicals, Inc.

  11. 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.

  12. Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life-threatening events

    DEFF Research Database (Denmark)

    Barsheshet, Alon; Goldenberg, Ilan; O-Uchi, Jin

    2012-01-01

    β-Adrenergic stimulation is the main trigger for cardiac events in type 1 long-QT syndrome (LQT1). We evaluated a possible association between ion channel response to β-adrenergic stimulation and clinical response to β-blocker therapy according to mutation location....

  13. Primer System for Single Cell Detection of Double Mutation for Tay-Sachs Disease

    OpenAIRE

    Liu, Ming Cheng; Drury, Kenneth C.; Kipersztok, Simon; Zheng, Wenrong; Williams, R. Stan

    2000-01-01

    Purpose: Nearly 100% of infantile Tay-Sachs disease isproduced by two mutations occurring in the alpha chain ofthe lysosomal enzyme beta-N-acetylhexosaminidase (HEXA)in the Ashkenazi Jewish population. Although others havedescribed primer systems used to amplify both sitessimultaneously, few discuss the allele dropout problems inherent inthis test. Our goal was to construct a more robust testenabling stronger signal generation for single cellpreimplantation genetic diagnosis and to investigat...

  14. 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

  15. 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

  16. Single mutations in the transmembrane envelope protein abrogate the immunosuppressive property of HIV-1

    Directory of Open Access Journals (Sweden)

    Morozov Vladimir A

    2012-08-01

    Full Text Available Abstract Background The mechanism by which HIV-1 induces AIDS is still unknown. Previously, synthetic peptides corresponding to the conserved immunosuppressive (isu domain in gp41 of HIV-1 had been shown to inhibit proliferation and to modulate cytokine expression of immune cells. The question is, whether the viral gp41 can do the same. Results We show for the first time that two trimeric forms of glycosylated gp41 released from transfected human cells modulated expression of cytokines and other genes in human PBMCs in the same manner, but at least seven hundred-fold stronger compared to that induced by the isu peptide. Single amino acid substitutions in the isu domain of gp41 introduced by site-directed mutagenesis abrogated this property. Furthermore, replication-competent HIV-1 with a mutation in the isu domain of gp41 did not modulate the cytokine expression, while wild-type virus did. Interestingly, most of the abrogating mutations were not reported in viral sequences derived from infected individuals, suggesting that mutated non-immunosuppressive viruses were eliminated by immune responses. Finally, immunisation of rats with gp41 mutated in the isu domain resulted in increased antibody responses compared with the non-mutated gp41. These results show that non-mutated gp41 is immunosuppressive in immunisation experiments, i.e. in vivo, and this has implications for the vaccine development. Conclusions These findings indicate that the isu domain of gp41 modulates cytokine expression in vitro and suppresses antibody response in vivo and therefore may contribute to the virus induced immunodeficiency.

  17. Single item inventory models : A time- and event- averages approach

    NARCIS (Netherlands)

    E.M. Bazsa-Oldenkamp; P. den Iseger

    2003-01-01

    textabstractThis paper extends a fundamental result about single-item inventory systems. This approach allows more general performance measures, demand processes and order policies, and leads to easier analysis and implementation, than prior research. We obtain closed form expressions for the

  18. Single mutation induced H3N2 hemagglutinin antibody neutralization: a free energy perturbation study.

    Science.gov (United States)

    Zhou, Ruhong; Das, Payel; Royyuru, Ajay K

    2008-12-11

    The single mutation effect on the binding affinity of H3N2 viral protein hemagglutinin (HA) with the monoclonical antibody fragment (Fab) is studied in this paper using the free energy perturbation (FEP) simulations. An all-atom protein model with explicit solvents is used to perform an aggregate of several microsecond FEP molecular dynamics simulations. A recent experiment shows that a single mutation in H3N2 HA, T131I, increases the antibody-antigen dissociation constant Kd by a factor of approximately 4000 (equivalent to a binding affinity decrease of approximately 5 kcal/mol), thus introducing an escape of the antibody (Ab) neutralization. Our FEP result confirms this experimental finding by estimating the HA-Ab binding affinity decrease of 5.2 +/- 0.9 kcal/mol but with a somewhat different molecular mechanism from the experimental findings. Detailed analysis reveals that this large binding affinity decrease in the T131I mutant is mainly due to the displacement of two bridge water molecules otherwise present in the wild-type HA/Ab interface. The decomposition of the binding free energy supports this observation, as the major contribution to the binding affinity is from the electrostatic interactions. In addition, we find that the loss of the binding affinity is also related to the large conformational distortion of one loop (loop 155-161) in the unbound state of the mutant. We then simulate all other possible mutations for this specific mutation site T131, and predict a few more mutations with even larger decreases in the binding affinity (i.e., better candidates for antibody neutralization), such as T131W, T131Y, and T131F. As for further validation, we have also modeled another mutation, S157L, with experimental binding affinity available (Kd increasing approximately 500 times), and found a binding affinity decrease of 4.1 +/- 1.0 kcal/mol, which is again in excellent agreement with experiment. These large scale simulations might provide new insights into the

  19. Detection and quantitation of single nucleotide polymorphisms, DNA sequence variations, DNA mutations, DNA damage and DNA mismatches

    Science.gov (United States)

    McCutchen-Maloney, Sandra L.

    2002-01-01

    DNA mutation binding proteins alone and as chimeric proteins with nucleases are used with solid supports to detect DNA sequence variations, DNA mutations and single nucleotide polymorphisms. The solid supports may be flow cytometry beads, DNA chips, glass slides or DNA dips sticks. DNA molecules are coupled to solid supports to form DNA-support complexes. Labeled DNA is used with unlabeled DNA mutation binding proteins such at TthMutS to detect DNA sequence variations, DNA mutations and single nucleotide length polymorphisms by binding which gives an increase in signal. Unlabeled DNA is utilized with labeled chimeras to detect DNA sequence variations, DNA mutations and single nucleotide length polymorphisms by nuclease activity of the chimera which gives a decrease in signal.

  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. Two single mutations commonly cause qualitative change of nonspecific carboxylesterases in insects.

    Science.gov (United States)

    Cui, Feng; Lin, Zhe; Wang, Hongsheng; Liu, Silu; Chang, Haijing; Reeck, Gerald; Qiao, Chuanling; Raymond, Michel; Kang, Le

    2011-01-01

    Carboxylesterases provide key mechanisms of resistance to insecticides, particularly organophosphates (OPs), in insects. One resistance mechanism is a qualitative change in the properties of a carboxylesterase. Two mutant forms, G151D and W271L, have been observed, mostly in dipteran species, to affect substrate specificity of enzymes. But whether these two single mutations can commonly change character of insect carboxylesterases is unknown. In our study carboxylesterase genes from seven insects distributed among four orders were cloned, mutated at position 151 or 271 and expressed in Escherichia coli. The kinetics of the purified recombinant proteins was examined towards an artificial carboxylester and two OP insecticides. The G/A151D and W271L mutation significantly reduced carboxylesterase activity in 87.5% and 100% cases, respectively, and at the same time conferred OP hydrolase activities in 62.5% and 87.5% cases, respectively. Thus, the change at position 271 is more effective to influence substrate specificity than that at position 151. These results may suggest that these two mutations have the potential to cause insecticide resistance broadly in insects. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. 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

  3. 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...... the wild-type RGI lyase in Bacillus subtilis as opposed to in Pichia pastoris; this effect is suggested to be a negative result of glycosylation of the P. pastoris expressed enzyme. A ~ twofold improvement in thermal stability at 60 °C, accompanied by less significant increases in Tm of the enzyme mutants......, 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...

  4. 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.

  5. 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.

  6. SCHEMA recombination of a fungal cellulase uncovers a single mutation that contributes markedly to stability.

    Science.gov (United States)

    Heinzelman, Pete; Snow, Christopher D; Smith, Matthew A; Yu, Xinlin; Kannan, Arvind; Boulware, Kevin; Villalobos, Alan; Govindarajan, Sridhar; Minshull, Jeremy; Arnold, Frances H

    2009-09-25

    A quantitative linear model accurately (R(2) = 0.88) describes the thermostabilities of 54 characterized members of a family of fungal cellobiohydrolase class II (CBH II) cellulase chimeras made by SCHEMA recombination of three fungal enzymes, demonstrating that the contributions of SCHEMA sequence blocks to stability are predominantly additive. Thirty-one of 31 predicted thermostable CBH II chimeras have thermal inactivation temperatures higher than the most thermostable parent CBH II, from Humicola insolens, and the model predicts that hundreds more CBH II chimeras share this superior thermostability. Eight of eight thermostable chimeras assayed hydrolyze the solid cellulosic substrate Avicel at temperatures at least 5 degrees C above the most stable parent, and seven of these showed superior activity in 16-h Avicel hydrolysis assays. The sequence-stability model identified a single block of sequence that adds 8.5 degrees C to chimera thermostability. Mutating individual residues in this block identified the C313S substitution as responsible for the entire thermostabilizing effect. Introducing this mutation into the two recombination parent CBH IIs not featuring it (Hypocrea jecorina and H. insolens) decreased inactivation, increased maximum Avicel hydrolysis temperature, and improved long time hydrolysis performance. This mutation also stabilized and improved Avicel hydrolysis by Phanerochaete chrysosporium CBH II, which is only 55-56% identical to recombination parent CBH IIs. Furthermore, the C313S mutation increased total H. jecorina CBH II activity secreted by the Saccharomyces cerevisiae expression host more than 10-fold. Our results show that SCHEMA structure-guided recombination enables quantitative prediction of cellulase chimera thermostability and efficient identification of stabilizing mutations.

  7. High risk of severe cardiac adverse events in patients with mitochondrial m.3243A>G mutation.

    Science.gov (United States)

    Malfatti, Edoardo; Laforêt, Pascal; Jardel, Claude; Stojkovic, Tanya; Behin, Anthony; Eymard, Bruno; Lombès, Anne; Benmalek, Amria; Bécane, Henri-Marc; Berber, Nawal; Meune, Christophe; Duboc, Denis; Wahbi, Karim

    2013-01-01

    To determine the long-term incidence of cardiac life-threatening complications and death in patients with the m.3243A>G mutation, and to identify cardiac prognostic factors. We retrospectively included patients carrying the m.3243A>G mutation who were admitted to the Neuromuscular Disease Clinic of Pitié Salpêtrière Hospital between January 1992 and December 2010. We collected information relative to their yearly neurologic and cardiac investigations, their mutation load in blood, urine, and muscle at initial admission, and the occurrence of cardiac life-threatening adverse events and death during follow-up. Forty-one patients (median age = 47 years [36-55 years], men = 13) were included, of whom 38 had clinical manifestations of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and 3 were asymptomatic. One patient had a personal history of cardiac transplantation. Cardiac investigations displayed left ventricular hypertrophy, left ventricular dysfunction, or both abnormalities in 18 patients, along with Wolff-Parkinson-White syndrome in 7, conduction system disease in 4, and atrial fibrillation in 1. Over a median 5-year (3-9 years) follow-up period, 11 patients died, including 3 due to heart failure; 7 had life-threatening adverse events, including 6 hospitalizations for severe heart failure and 1 resuscitated cardiac arrest. By multivariate analysis, left ventricular hypertrophy was the only parameter independently associated with occurrence of cardiac adverse events. Patients with the m.3243A>G mutation have a high incidence of cardiac death and life-threatening adverse events. Left ventricular hypertrophy was the only parameter independently associated with occurrence of these events.

  8. Intercalation events visualized in single microcrystals of graphite.

    Science.gov (United States)

    White, Edward R; Lodico, Jared J; Regan, B C

    2017-12-06

    The electrochemical intercalation of layered materials, particularly graphite, is fundamental to the operation of rechargeable energy-storage devices such as the lithium-ion battery and the carbon-enhanced lead-acid battery. Intercalation is thought to proceed in discrete stages, where each stage represents a specific structure and stoichiometry of the intercalant relative to the host. However, the three-dimensional structures of the stages between unintercalated and fully intercalated are not known, and the dynamics of the transitions between stages are not understood. Using optical and scanning transmission electron microscopy, we video the intercalation of single microcrystals of graphite in concentrated sulfuric acid. Here we find that intercalation charge transfer proceeds through highly variable current pulses that, although directly associated with structural changes, do not match the expectations of the classical theories. Evidently random nanoscopic defects dominate the dynamics of intercalation.

  9. 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.

  10. 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.

  11. 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.

  12. Development of Cost-Effective Screening Techniques to Assess Single-Event Latchup Susceptibility

    Data.gov (United States)

    National Aeronautics and Space Administration — Although Single-Event Latchup (SEL) has proven to be one of the most significant radiation threats for low-cost missions, conventional SEL hardness assurance...

  13. Single-event upset and snapback in silicon-on-insulator devices

    International Nuclear Information System (INIS)

    Dodd, Paul E.; Shaneyfelt, Marty R.; Schwank, James R.; Hash, Gerald L.; Draper, Bruce L.; Winokur, Peter S.

    2000-01-01

    SEU is studied in SOI transistors and circuits with various body tie structures. The importance of impact ionization effects, including single-event snapback, is explored. Implications for hardness assurance testing of SOI integrated circuits are discussed

  14. 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)

  15. Pulsed laser simulation of VLSI single-event effect testing study

    International Nuclear Information System (INIS)

    Xue Yuxiong; Cao Zhou Yang Shiyu; Tian Kai; Liu Shufen; Chu Nan; Cao Haining; Shang Zhi

    2008-01-01

    This paper describes a study aimed at investigating the pulsed laser simulation of Single-Event Effect (SEE) testing for VLSI Intel386EX CPU, using our laboratory LSS (laser simulation system). We have detailed SEE testing principle, testing method, testing system constituting, testing result. It validates that our laser pulses simulate may use SEE testing in VLSI, and Intel 386Ex have a large locking resistance to single event. (authors)

  16. 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.

  17. 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.

  18. CSF1R mutations link POLD and HDLS as a single disease entity.

    Science.gov (United States)

    Nicholson, Alexandra M; Baker, Matt C; Finch, Nicole A; Rutherford, Nicola J; Wider, Christian; Graff-Radford, Neill R; Nelson, Peter T; Clark, H Brent; Wszolek, Zbigniew K; Dickson, Dennis W; Knopman, David S; Rademakers, Rosa

    2013-03-12

    Pigmented orthochromatic leukodystrophy (POLD) and hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) are rare neurodegenerative disorders characterized by cerebral white matter abnormalities, myelin loss, and axonal swellings. The striking overlap of clinical and pathologic features of these disorders suggested a common pathogenesis; however, no genetic or mechanistic link between POLD and HDLS has been established. Recently, we reported that mutations in the colony-stimulating factor 1 receptor (CSF1R) gene cause HDLS. In this study, we determined whether CSF1R mutations are also a cause of POLD. We performed sequencing of CSF1R in 2 pathologically confirmed POLD families. For the largest family (FTD368), a detailed case report was provided and brain samples from 2 affected family members previously diagnosed with POLD were re-evaluated to determine whether they had HDLS features. In vitro functional characterization of wild-type and mutant CSF1R was also performed. We identified CSF1R mutations in both POLD families: in family 5901, we found c.2297T>C (p.M766T), previously reported by us in HDLS family CA1, and in family FTD368, we identified c.2345G>A (p.R782H), recently reported in a biopsy-proven HDLS case. Immunohistochemical examination in family FTD368 showed the typical neuronal and glial findings of HDLS. Functional analyses of CSF1R mutant p.R782H (identified in this study) and p.M875T (previously observed in HDLS), showed a similar loss of CSF1R autophosphorylation of selected tyrosine residues in the kinase domain for both mutations when compared with wild-type CSF1R. We provide the first genetic and mechanistic evidence that POLD and HDLS are a single clinicopathologic entity.

  19. Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events.

    Science.gov (United States)

    Liu, Jinfeng; Lee, William; Jiang, Zhaoshi; Chen, Zhongqiang; Jhunjhunwala, Suchit; Haverty, Peter M; Gnad, Florian; Guan, Yinghui; Gilbert, Houston N; Stinson, Jeremy; Klijn, Christiaan; Guillory, Joseph; Bhatt, Deepali; Vartanian, Steffan; Walter, Kimberly; Chan, Jocelyn; Holcomb, Thomas; Dijkgraaf, Peter; Johnson, Stephanie; Koeman, Julie; Minna, John D; Gazdar, Adi F; Stern, Howard M; Hoeflich, Klaus P; Wu, Thomas D; Settleman, Jeff; de Sauvage, Frederic J; Gentleman, Robert C; Neve, Richard M; Stokoe, David; Modrusan, Zora; Seshagiri, Somasekar; Shames, David S; Zhang, Zemin

    2012-12-01

    Lung cancer is a highly heterogeneous disease in terms of both underlying genetic lesions and response to therapeutic treatments. We performed deep whole-genome sequencing and transcriptome sequencing on 19 lung cancer cell lines and three lung tumor/normal pairs. Overall, our data show that cell line models exhibit similar mutation spectra to human tumor samples. Smoker and never-smoker cancer samples exhibit distinguishable patterns of mutations. A number of epigenetic regulators, including KDM6A, ASH1L, SMARCA4, and ATAD2, are frequently altered by mutations or copy number changes. A systematic survey of splice-site mutations identified 106 splice site mutations associated with cancer specific aberrant splicing, including mutations in several known cancer-related genes. RAC1b, an isoform of the RAC1 GTPase that includes one additional exon, was found to be preferentially up-regulated in lung cancer. We further show that its expression is significantly associated with sensitivity to a MAP2K (MEK) inhibitor PD-0325901. Taken together, these data present a comprehensive genomic landscape of a large number of lung cancer samples and further demonstrate that cancer-specific alternative splicing is a widespread phenomenon that has potential utility as therapeutic biomarkers. The detailed characterizations of the lung cancer cell lines also provide genomic context to the vast amount of experimental data gathered for these lines over the decades, and represent highly valuable resources for cancer biology.

  20. DNA biosensor based on hybridization refractory mutation system approach for single mismatch detection.

    Science.gov (United States)

    Joda, Hamdi; Beni, Valerio; Katakis, Ioanis; O'Sullivan, Ciara K

    2015-04-01

    We report on a simple approach to enhance solid-phase hybridization-based single base mismatch discrimination at high ionic strength based on the deliberate insertion of a natural DNA base mismatch in the surface-tethered probe. A large drop in hybridization signal of single base mismatched alleles using the designed probe as compared with the conventional probe, from 80% to less than 25% of the signal obtained with the fully complementary, non-mutation-containing sequence, when using colorimetric detection was further improved to 20% when using electrochemical detection, attributable to a difference of spacing of immobilized probes. Finally, the designed probe was used for the electrochemical detection of the DQA1*05:05 allele amplified from real human blood samples. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. 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.

  2. 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.

  3. 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.

  4. Dominance effects of deleterious and beneficial mutations in a single gene of the RNA virus ϕ6.

    Directory of Open Access Journals (Sweden)

    Sarah B Joseph

    Full Text Available Most of our knowledge of dominance stems from studies of deleterious mutations. From these studies we know that most deleterious mutations are recessive, and that this recessivity arises from a hyperbolic relationship between protein function (i.e., protein concentration or activity and fitness. Here we investigate whether this knowledge can be used to make predictions about the dominance of beneficial and deleterious mutations in a single gene. We employed a model system--the bacteriophage φ6--that allowed us to generate a collection of mutations in haploid conditions so that it was not biased toward either dominant beneficial or recessive deleterious mutations. Screening for the ability to infect a bacterial host that does not permit infection by the wildtype φ6, we generated a collection of mutations in P3, a gene involved in attachment to the host and in phage particle assembly. The resulting collection contained mutations with both deleterious and beneficial effects on fitness. The deleterious mutations in our collection had additive effects on fitness and the beneficial mutations were recessive. Neither of these observations were predicted from previous studies of dominance. This pattern is not consistent with the hyperbolic (diminishing returns relationship between protein function and fitness that is characteristic of enzymatic genes, but could have resulted from a curve of increasing returns.

  5. Quartz crystal microbalance detection of DNA single-base mutation based on monobase-coded cadmium tellurium nanoprobe.

    Science.gov (United States)

    Zhang, Yuqin; Lin, Fanbo; Zhang, Youyu; Li, Haitao; Zeng, Yue; Tang, Hao; Yao, Shouzhuo

    2011-01-01

    A new method for the detection of point mutation in DNA based on the monobase-coded cadmium tellurium nanoprobes and the quartz crystal microbalance (QCM) technique was reported. A point mutation (single-base, adenine, thymine, cytosine, and guanine, namely, A, T, C and G, mutation in DNA strand, respectively) DNA QCM sensor was fabricated by immobilizing single-base mutation DNA modified magnetic beads onto the electrode surface with an external magnetic field near the electrode. The DNA-modified magnetic beads were obtained from the biotin-avidin affinity reaction of biotinylated DNA and streptavidin-functionalized core/shell Fe(3)O(4)/Au magnetic nanoparticles, followed by a DNA hybridization reaction. Single-base coded CdTe nanoprobes (A-CdTe, T-CdTe, C-CdTe and G-CdTe, respectively) were used as the detection probes. The mutation site in DNA was distinguished by detecting the decreases of the resonance frequency of the piezoelectric quartz crystal when the coded nanoprobe was added to the test system. This proposed detection strategy for point mutation in DNA is proved to be sensitive, simple, repeatable and low-cost, consequently, it has a great potential for single nucleotide polymorphism (SNP) detection. 2011 © The Japan Society for Analytical Chemistry

  6. Measurement of the top quark mass from single-top production events

    CERN Document Server

    CMS Collaboration

    2016-01-01

    We measure the mass of the top quark from events where a single top quark is produced. The analysis is performed on data from $\\mathrm{pp}$ collisions collected by the CMS detector at a center of mass energy of 8 TeV. The top quark is reconstructed from its decay $\\mathrm{t} \\rightarrow \\mathrm{W}^+ \\mathrm{b}$, with the $\\mathrm{W}$ boson decaying leptonically in the muon channel. Specific event topology and kinematic properties are used in order to enrich the sample in single-top-quark events in the t-channel, at the expense of top-quark pair production events. For the single-top quark component, a fit to the reconstructed top invariant mass distribution yields $m_{\\mathrm{t}}=172.60 \\pm 0.77~\\mathrm{(stat)}~^{+0.97}_{-0.93}~\\mathrm{(syst)}$ GeV.

  7. Method and apparatus for single-stepping coherence events in a multiprocessor system under software control

    Science.gov (United States)

    Blumrich, Matthias A.; Salapura, Valentina

    2010-11-02

    An apparatus and method are disclosed for single-stepping coherence events in a multiprocessor system under software control in order to monitor the behavior of a memory coherence mechanism. Single-stepping coherence events in a multiprocessor system is made possible by adding one or more step registers. By accessing these step registers, one or more coherence requests are processed by the multiprocessor system. The step registers determine if the snoop unit will operate by proceeding in a normal execution mode, or operate in a single-step mode.

  8. 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.

  9. 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.

  10. Mutations in Conserved Amino Acids in the KCNQ1 Channel and Risk of Cardiac Events in Type-1 Long-QT Syndrome

    NARCIS (Netherlands)

    Jons, Christian; Moss, Arthur J.; Lopes, Coeli M.; McNitt, Scott; Zareba, Wojciech; Goldenberg, Ilan; Qi, Ming; Wilde, Arthur A. M.; Shimizu, Wataru; Kanters, Jorgen K.; Towbin, Jeffrey A.; Ackerman, Michael J.; Robinson, Jennifer L.

    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 events.

  11. 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.

  12. 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.

  13. 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)

  14. A single quantum dot-based biosensor for DNA point mutation assay.

    Science.gov (United States)

    Tang, Wei; Zhu, Guichi; Liang, Li; Zhang, Chun-Yang

    2015-09-07

    Sensitive and selective detection of point mutation is essential to molecular biology research and early clinical diagnosis. Here, we demonstrate a single quantum dot (QD)-based biosensor for DNA point mutation assay. In this assay, a mutant target (G/C) remains unchanged after the endonuclease treatment, and the polymerase chain reaction (PCR) may be initiated with the assistance of primers and polymerase, generating a large number of mutant targets. The amplified mutant targets can be captured by biotinylated probes during the process of denaturation and annealing, and Cy5-dGTP may be assembled into the biotinylated probe with the catalysis of polymerase, leading to the formation of Cy5-labeled biotinylated probes. The Cy5-labeled biotinylated probes can be further assembled onto the QD surface to obtain a Cy5-DNA-QD complex, resulting in the generation of fluorescence resonance energy transfer (FRET) between the QD donor and the Cy5 receptor. The mutant targets can be quantitatively evaluated by the measurement of Cy5 counts by total internal reflection fluorescence (TIRF) microscopy. While in the presence of wild-type targets (T/A), no Cy5-dGTP can be assembled into the biotinylated probe due to the presence of a mismatch and consequently no FRET is observed. This single QD-based biosensor exhibits high sensitivity with a detection limit of 5.3 aM (or 32 copies) and can even discriminate as low as 0.01% variant frequency from the mixture of mutant targets and wild-type ones. Importantly, this biosensor can be used for genomic analysis in human lung cancer cells, and may be further applied for an early clinical diagnosis and personalized medicine.

  15. Single tagged 2γ events with BGO, ALR, and VSAT of L3

    Science.gov (United States)

    Baksay, Laszlo; Dehmelt, Klaus; Hohlmann, Marcus

    2003-11-01

    In order to extend the investigation of the Q^2 evolution of the hadronic structure function F_2^γ with L3, to Q^2 as low as 0.5GeV^2 and as high as 3850GeV^2, we will include the electromagnetic calorimeters (BGO), active lead rings (ALR), and the very small angle tagging detectors (VSAT) as tagging devices for single tagged 2γ events. Strategies for selecting events with these detector components will be presented.

  16. Overview of software tools for modeling single event upsets in microelectronic devices

    Directory of Open Access Journals (Sweden)

    Anatoly Alexandrovich Smolin

    2016-10-01

    Full Text Available The paper presents the results of the analysis of existing simulation tools for evaluation of single event upset susceptibility of microelectronic devices with deep sub-micron feature sizes. This simulation tools are meant to replace obsolete approach to single event rate estimation based on integral rectangular parallelepiped model. Three main approaches implemented in simulation tools are considered: combined use of particle transport codes and rectangular parallelepiped model, combined use of particle transport codes and analytical models of charge collection and circuit simulators, and combined use of particle transport codes and TCAD simulators.

  17. 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\\%.

  18. A single residue mutation of 5-enoylpyruvylshikimate-3-phosphate synthase in Pseudomonas stutzeri enhances resistance to the herbicide glyphosate.

    Science.gov (United States)

    Liang, Aimin; Sha, Jiying; Lu, Wei; Chen, Ming; Li, Liang; Jin, Dan; Yan, Yongliang; Wang, Jin; Ping, Shuzhen; Zhang, Wei; Wang, Yiding; Lin, Min

    2008-08-01

    A novel class II 5-enoylpyruvylshikimate-3-phosphate synthase (EPSPS) was identified from Pseudomonas stutzeri A1501 by complementation of an Escherichia coli auxotrophic aroA mutant. The single amino acid substitution of serine (Ser) for asparagine (Asn)-130 of the A1501 EPSPS enhanced resistance to 200 mM glyphosate. The mutated EPSPS had a 2.5-fold increase for IC(50) [glyphosate] value, a 2-fold increase for K (i) [glyphosate] value, but a K (m) [PEP] value similar to that of wild type. The effect of the single residue mutation on glyphosate resistance was also analyzed using a computer-based three-dimensional model.

  19. Selection of Single Top Events with the CMS Detector at LHC

    CERN Document Server

    Abramov, Victor; Slabospitsky, Sergey; Najafabadi, M Mohammadi; Giammanco, Andrea; Tenchini, Roberto; Boos, Edouard; Dudko, Lev; Savrin, Viktor; Sherstnev, Alexander; Kalinin, Sergey; Drozdetsky, A A

    2006-01-01

    The detection of single-top events with CMS is discussed. Two selections are proposed, aimed to measure single top production in the Standard Model t- and s-channel, respectively. The perspectives of the measurements for an integrated luminosity of 10 fb-1 are described. The results are based on detailed detector simulations, either based on GEANT4, or on faster techniques. The reconstruction procedures developed by the CMS Collaboration are utilized.

  20. 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.

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

    International Nuclear Information System (INIS)

    Argaw, Takele; Wilson, Carolyn A.

    2015-01-01

    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

  2. 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

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

    Indian Academy of Sciences (India)

    Unknown

    Single event upset is defined by NASA as 'radiation- induced errors in microelectronic circuits caused when charged particles (usually from the radiation belts or from cosmic rays) lose energy by ionizing the medium through which they pass, leaving behind a wake of elec- tron-hole pairs'. SEU are transient soft errors and ...

  4. Single Event Testing on Complex Devices: Test Like You Fly versus Test-Specific Design Structures

    Science.gov (United States)

    Berg, Melanie; LaBel, Kenneth A.

    2014-01-01

    We present a framework for evaluating complex digital systems targeted for harsh radiation environments such as space. Focus is limited to analyzing the single event upset (SEU) susceptibility of designs implemented inside Field Programmable Gate Array (FPGA) devices. Tradeoffs are provided between application-specific versus test-specific test structures.

  5. 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.

  6. Simulation aided hardening of N-channel power MOSFETs to prevent single event burnout

    International Nuclear Information System (INIS)

    Dachs, C.; Palau, J.M.; Bruguier, G.; Gasiot, J.; Roubaud, F.; Tastet, P.; Calvet, M.C.; Calvel, P.

    1995-01-01

    2D MEDICI simulator is used to investigate hardening solutions to single-event burnout (SEB). SEB parametric dependencies such as carrier lifetime reduction, base enlargement, and emitter doping decrease have been verified and a p + plug modification approach for SEB hardening of power MOSFETs is validated with simulations on actual device structures

  7. 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)

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. Electrochemical Dynamics of a Single Platinum Nanoparticle Collision Event for the Hydrogen Evolution Reaction.

    Science.gov (United States)

    Xiang, Zhi-Peng; Deng, Hai-Qiang; Peljo, Pekka; Fu, Zhi-Yong; Wang, Su-Li; Mandler, Daniel; Sun, Gong-Quan; Liang, Zhen-Xing

    2018-03-19

    Chronoamperometry was used to study the dynamics of Pt nanoparticle (NP) collision with an inert ultramicroelectrode via electrocatalytic amplification (ECA) in the hydrogen evolution reaction. ECA and dynamic light scattering (DLS) results reveal that the NP colloid remains stable only at low proton concentrations (1.0 mm) under a helium (He) atmosphere, ensuring that the collision events occur at genuinely single NP level. Amperometry of single NP collisions under a He atmosphere shows that each discrete current profile of the collision event evolves from spike to staircase at more negative potentials, while a staircase response is observed at all of the applied potentials under hydrogen-containing atmospheres. The particle size distribution estimated from the diffusion-controlled current in He agrees well with electron microscopy and DLS observations. These results shed light on the interfacial dynamics of the single nanoparticle collision electrochemistry. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. The nematocyst extract of Hydra attenuata causes single channel events in lipid bilayers.

    Science.gov (United States)

    Weber, J; Schürholz, T; Neumann, E

    1990-01-01

    The nematocyst extract of Hydra attenuata causes single conductance events in reconstituted planar lipid membranes as well as in inside-out patches derived from liposomes. The smallest single channel conductance level of the toxins is 110 pS. The conductance levels increase stepwise with time up to 2000 pS. These large conductance jumps indicate channel cooperativity. If the membrane-voltage is changed from positive to negative values, the single channel events become undefined and noisy, indicating major reorganizations of the proteins which form the channels. The molecular properties of the ionophoric component(s) of the nematocyst extract may help explain the observed macroscopic effects, such as hemolysis of human erythrocytes, after addition of the nematocyst extract.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kimbrough, J.R.; Colella, N.J.; Denton, S.M.; Shaeffer, D.L.; Shih, D.; Wilburn, J.W. (Lawrence Livermore National Lab., CA (United States)); Coakley, P.G. (JAYCOR, San Diego, CA (United States)); Casteneda, C. (Crocker Nuclar Lab., Davis, CA (United States)); Koga, R. (Aerospace Corp., El Segundo, CA (United States)); Clark, D.A.; Ullmann, J.L. (Los Alamos National Lab., NM (United States))

    1994-12-01

    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.

  15. Single-trial normalization for event-related spectral decomposition reduces sensitivity to noisy trials

    Directory of Open Access Journals (Sweden)

    Romain eGrandchamp

    2011-09-01

    Full Text Available In EEG research, the classical Event-Related Potential (ERP model often proves to be a limited method when studying complex brain dynamics. For this reason, spectral techniques adapted from signal processing such as Event-Related Spectral Perturbation (ERSP – and its variant ERS (Event-Related Synchronization and ERD (Event-Related Desynchronization – have been used over the past 20-years. They represent average spectral changes in response to a stimulus.These spectral methods do not have strong consensus for comparing pre and post-stimulus activity. When computing ERSP, pre-stimulus baseline removal is usually performed after averaging the spectral estimate of multiple trials. Correcting the baseline of each single-trial prior to averaging spectral estimates is an alternative baseline correction method. However, we show that this method leads to positively skewed post-stimulus ERSP values. We eventually present new single-trial based ERSP baseline correction methods that perform trial normalization or centering prior to applying classical baseline correction methods. We show that single-trial correction methods minimize the contribution of artifactual data trials with high-amplitude spectral estimates and are robust to outliers when performing statistical inference testing. We then characterize these methods in terms of their time-frequency responses and behavior when performing statistical inference testing compared to classical ERSP methods.

  16. Single-Event Effect Testing of the Linear Technology LTC6103HMS8#PBF Current Sense Amplifier

    Science.gov (United States)

    Yau, Ka-Yen; Campola, Michael J.; Wilcox, Edward

    2016-01-01

    The LTC6103HMS8#PBF (henceforth abbreviated as LTC6103) current sense amplifier from Linear Technology was tested for both destructive and non-destructive single-event effects (SEE) using the heavy-ion cyclotron accelerator beam at Lawrence Berkeley National Laboratory (LBNL) Berkeley Accelerator Effects (BASE) facility. During testing, the input voltages and output currents were monitored to detect single event latch-up (SEL) and single-event transients (SETs).

  17. Morphological evolution through multiple cis-regulatory mutations at a single gene.

    Science.gov (United States)

    McGregor, Alistair P; Orgogozo, Virginie; Delon, Isabelle; Zanet, Jennifer; Srinivasan, Dayalan G; Payre, François; Stern, David L

    2007-08-02

    One central, and yet unsolved, question in evolutionary biology is the relationship between the genetic variants segregating within species and the causes of morphological differences between species. The classic neo-darwinian view postulates that species differences result from the accumulation of small-effect changes at multiple loci. However, many examples support the possible role of larger abrupt changes in the expression of developmental genes in morphological evolution. Although this evidence might be considered a challenge to a neo-darwinian micromutationist view of evolution, there are currently few examples of the actual genes causing morphological differences between species. Here we examine the genetic basis of a trichome pattern difference between Drosophila species, previously shown to result from the evolution of a single gene, shavenbaby (svb), probably through cis-regulatory changes. We first identified three distinct svb enhancers from D. melanogaster driving reporter gene expression in partly overlapping patterns that together recapitulate endogenous svb expression. All three homologous enhancers from D. sechellia drive expression in modified patterns, in a direction consistent with the evolved svb expression pattern. To test the influence of these enhancers on the actual phenotypic difference, we conducted interspecific genetic mapping at a resolution sufficient to recover multiple intragenic recombinants. This functional analysis revealed that independent genetic regions upstream of svb that overlap the three identified enhancers are collectively required to generate the D. sechellia trichome pattern. Our results demonstrate that the accumulation of multiple small-effect changes at a single locus underlies the evolution of a morphological difference between species. These data support the view that alleles of large effect that distinguish species may sometimes reflect the accumulation of multiple mutations of small effect at select genes.

  18. 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)

  19. A Stochastic Single-Molecule Event Triggers Phenotype Switching of a Bacterial Cell

    Science.gov (United States)

    Xie, Sunney; Choi, Paul; Cai, Long

    2009-03-01

    By monitoring fluorescently labeled lactose permease with single-molecule sensitivity, we investigated the molecular mechanism of how an Escherichia coli cell with the lac operon switches from one phenotype to another. At intermediate inducer concentrations, a population of genetically identical cells exhibits two phenotypes: induced cells with highly fluorescent membranes and uninduced cells with a small number of membrane-bound permeases. We found that this basal-level expression results from partial dissociation of the tetrameric lactose repressor from one of its operators on looped DNA. In contrast, infrequent events of complete dissociation of the repressor from DNA result in large bursts of permease expression that trigger induction of the lac operon. Hence, a stochastic single-molecule event determines a cell's phenotype.

  20. 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

  1. 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)

  2. 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.

  3. 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)

  4. 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

  5. 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)

  6. 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.

  7. 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.

  8. Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer and activating EGFR mutations (BELIEF): an international, multicentre, single-arm, phase 2 trial.

    Science.gov (United States)

    Rosell, Rafael; Dafni, Urania; Felip, Enriqueta; Curioni-Fontecedro, Alessandra; Gautschi, Oliver; Peters, Solange; Massutí, Bartomeu; Palmero, Ramon; Aix, Santiago Ponce; Carcereny, Enric; Früh, Martin; Pless, Miklos; Popat, Sanjay; Kotsakis, Athanasios; Cuffe, Sinead; Bidoli, Paolo; Favaretto, Adolfo; Froesch, Patrizia; Reguart, Noemí; Puente, Javier; Coate, Linda; Barlesi, Fabrice; Rauch, Daniel; Thomas, Michael; Camps, Carlos; Gómez-Codina, Jose; Majem, Margarita; Porta, Rut; Shah, Riyaz; Hanrahan, Emer; Kammler, Roswitha; Ruepp, Barbara; Rabaglio, Manuela; Kassapian, Marie; Karachaliou, Niki; Tam, Rachel; Shames, David S; Molina-Vila, Miguel A; Stahel, Rolf A

    2017-05-01

    The tyrosine kinase inhibitor erlotinib improves the outcomes of patients with advanced non-small-cell lung carcinoma (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations. The coexistence of the T790M resistance mutation with another EGFR mutation in treatment-naive patients has been associated with a shorter progression-free survival to EGFR inhibition than in the absence of the T790M mutation. To test this hypothesis clinically, we developed a proof-of-concept study, in which patients with EGFR-mutant NSCLC were treated with the combination of erlotinib and bevacizumab, stratified by the presence of the pretreatment T790M mutation. BELIEF was an international, multicentre, single-arm, phase 2 trial done at 29 centres in eight European countries. Eligible patients were aged 18 years or older and had treatment-naive, pathologically confirmed stage IIIB or stage IV lung adenocarcinoma with a confirmed, activating EGFR mutation (exon 19 deletion or L858R mutation). Patients received oral erlotinib 150 mg per day and intravenous bevacizumab 15 mg/kg every 21 days and were tested centrally for the pretreatment T790M resistance mutation with a peptide nucleic acid probe-based real-time PCR. The primary endpoint was progression-free survival. The primary efficacy analysis was done in the intention-to-treat population and was stratified into two parallel substudies according to the centrally confirmed pretreatment T790M mutation status of enrolled patients (T790M positive or negative). The safety analysis was done in all patients that have received at least one dose of trial treatment. This trial was registered with ClinicalTrials.gov, number NCT01562028. Between June 11, 2012, and Oct 28, 2014, 109 patients were enrolled and included in the efficacy analysis. 37 patients were T790M mutation positive and 72 negative. The overall median progression-free survival was 13·2 months (95% CI 10·3-15·5), with a 12 month progression-free survival of 55% (95% CI

  9. 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.

  10. Single mutation in the matrix gene of seasonal influenza A viruses critically affects the performance of diagnostic molecular assay.

    Science.gov (United States)

    Duh, Darja; Blažič, Barbara

    2018-01-01

    Reduced intensity of the fluorescence signal in the amplification curve was observed when using a WHO recommended real time RT-PCR for influenza virus detection. A single mutation, G189T, in the conserved region of influenza virus matrix gene was detected by Sanger sequencing. The mutation is located in the probe binding region, hence we speculated it could be the reason for the atypical shape of amplification curve. The mutation was first noted in Slovenia in 2011 and 2013 for seasonal influenza A virus types A(H1N1)pdm09 and A(H3N2), respectively. In the following years, 2014 and 2015, the majority of influenza A(H3N2) viruses alone carried the mutation. The amplification of matrix gene for these influenza A(H3N2) viruses continuously resulted in the atypically shaped amplification curves. The performance of the particular assay was critically affected; therefore, the assay was no longer usable as diagnostic tool for influenza virus detection. Mutations in the conserved region of influenza virus genome are more common than expected and this would need to be considered when targeting matrix gene. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. 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 events...... acid residue was calculated ranging from 0 (no conservation) to 1.0 (full conservation). Cox analysis was used to identify independent factors associated with the first cardiac event (syncope, aborted cardiac arrest, or death). Patients were subcategorized into tertiles by their adjusted Shannon...

  12. Accuracy of the detection of binding events using 3D single particle tracking.

    Science.gov (United States)

    Carozza, Sara; Culkin, Jamie; van Noort, John

    2017-01-01

    Nanoparticles can be used as markers to track the position of biomolecules, such as single proteins, inside living cells. The activity of a protein can sometimes be inferred from changes in the mobility of the attached particle. Mean Square Displacement analysis is the most common method to obtain mobility information from trajectories of tracked particles, such as the diffusion coefficient D . However, the precision of D sets a limit to discriminate changes in mobility caused by biological events from changes that reflect the stochasticity inherent to diffusion. This issue is of particular importance in an experiment aiming to quantify dynamic processes. Here, we present simulations and 3D tracking experiments with Gold Nanorods freely diffusing in glycerol solution to establish the best analysis parameters to extract the diffusion coefficient. We applied this knowledge to the detection of a temporary change in diffusion, as it can occur due to the transient binding of a particle to an immobile structure within the cell, and tested its dependence on the magnitude of the change in diffusion and duration of this event. The simulations show that the spatial accuracy of particle tracking generally does not limit the detection of short binding events. Careful analysis of the magnitude of the change in diffusion and the number of frames per binding event is required for accurate quantification of such events.

  13. Autonomous Gait Event Detection with Portable Single-Camera Gait Kinematics Analysis System

    Directory of Open Access Journals (Sweden)

    Cheng Yang

    2016-01-01

    Full Text Available Laboratory-based nonwearable motion analysis systems have significantly advanced with robust objective measurement of the limb motion, resulting in quantified, standardized, and reliable outcome measures compared with traditional, semisubjective, observational gait analysis. However, the requirement for large laboratory space and operational expertise makes these systems impractical for gait analysis at local clinics and homes. In this paper, we focus on autonomous gait event detection with our bespoke, relatively inexpensive, and portable, single-camera gait kinematics analysis system. Our proposed system includes video acquisition with camera calibration, Kalman filter + Structural-Similarity-based marker tracking, autonomous knee angle calculation, video-frame-identification-based autonomous gait event detection, and result visualization. The only operational effort required is the marker-template selection for tracking initialization, aided by an easy-to-use graphic user interface. The knee angle validation on 10 stroke patients and 5 healthy volunteers against a gold standard optical motion analysis system indicates very good agreement. The autonomous gait event detection shows high detection rates for all gait events. Experimental results demonstrate that the proposed system can automatically measure the knee angle and detect gait events with good accuracy and thus offer an alternative, cost-effective, and convenient solution for clinical gait kinematics analysis.

  14. 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

  15. Identifying and calling insertions, deletions, and single-base mutations efficiently from sequence data

    Science.gov (United States)

    Whole genome sequencing studies can directly identify causative mutations for subsequent use in genomic evaluations, but sequence variant identification is a lengthy and sometimes inaccurate process. The speed and accuracy of identifying small insertions and deletions of sequence, collectively terme...

  16. 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.

  17. Mechanistic Studies of the Spore Photoproduct Lyase (SPL) via a Single Cysteine Mutation

    Science.gov (United States)

    Yang, Linlin; Lin, Gengjie; Nelson, Renae S.; Jian, Yajun; Telser, Joshua; Li, Lei

    2012-01-01

    disrupted by this single mutation. PMID:22906093

  18. Critical evaluation of the pulsed laser method for single event effects testing and fundamental studies

    International Nuclear Information System (INIS)

    Melinger, J.S.; Buchner, S.; McMorrow, D.; Stapor, W.J.; Weatherford, T.R.; Campbell, A.B.; Eisen, H.

    1994-01-01

    In this paper the authors present an evaluation of the pulsed laser as a technique for single events effects (SEE) testing. They explore in detail the important optical effects, such as laser beam propagation, surface reflection, and linear and nonlinear absorption, which determine the nature of laser-generated charge tracks in semiconductor materials. While there are differences in the structure of laser- and ion-generated charge tracks, they show that in many cases the pulsed laser remains an invaluable tool for SEE testing. Indeed, for several SEE applications, they show that the pulsed laser method represents a more practical approach than conventional accelerator-based methods

  19. 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.

  20. 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_\

  1. 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

  2. The associated charged particle multiplicity of high-p/sub T/ pi /sup 0/ and single-photon events

    CERN Document Server

    Diakonou, M; Albrow, M G; Almehed, S; Benary, O; Bøggild, H; Botner, O; Cnops, A M; Cockerill, D J A; Dagan, S; Dahl-Jensen, Erik; Dahl-Jensen, I; Damgaard, G; Fabjan, Christian Wolfgang; Filippas-Tassos, A; Fokitis, E; Fowler, E C; Hallgren, A; Hansen, K H; Henning, S; Hood, D M; Hooper, J; Jarlskog, G; Karpathopoulos, S; Killian, T; Kourkoumelis, C; Kreisler, M; Lissauer, D; Lörstad, B; Ludlam, T; Mannelli, I; McCubbin, N A; Melin, A; Mjörnmark, U; Møller, R; Molzon, W; Mouzourakis, P; Nielsen, B S; Nielsen, S O; Nilsson, A; Oren, Y; Palmer, R B; Rahm, David Charles; Rehak, P; Resvanis, L K; Rosselt, L; Schistad, B; Stumer, I; Svensson, L; von Dardel, Guy F; Willis, W J

    1980-01-01

    The associated charged particle multiplicities of high-p/sub T/ pi /sup 0/ and single-photon events were measured at the CERN intersecting storage rings using lead/liquid-argon calorimeters and a scintillation counter array placed around the intersection region. The average multiplicity on the trigger side for the single-photon events was found to be significantly lower than that for the pi /sup 0/ events. The away-side multiplicity for both pi /sup 0/ and single- photon events increases with the trigger particle p/sub T/, but, at a fixed p/sub T/, the direct photon sample was found to have a slightly lower average multiplicity. The differences in the event structure can be explained if a large fraction of the single photons are produced via qg to gamma q constituent scattering. (16 refs).

  3. CDKN2A mutations and MC1R variants in Italian patients with single or multiple primary melanoma.

    Science.gov (United States)

    Pastorino, L; Bonelli, L; Ghiorzo, P; Queirolo, P; Battistuzzi, L; Balleari, E; Nasti, S; Gargiulo, S; Gliori, S; Savoia, P; Abate Osella, S; Bernengo, M G; Bianchi Scarrà, G

    2008-12-01

    We evaluated the contribution of germline CDKN2A mutations and MC1R variants to the development of melanoma in a hospital-based study of single (SPM, n = 398) and multiple primary melanoma (MPM, n = 95). The overall frequency of CDKN2A mutations was 15.2%, and four-fold higher in MPM than in SPM cases (OR = 4.27; 95% CI 2.43-7.53). The likelihood of identifying a CDKN2A mutation increased with family history of melanoma and younger age at diagnosis in MPM cases. Compared to SPM patients, the risk of harboring a CDKN2A mutation rose as the number of primary melanomas increased and was not influenced by family history. The G101W and E27X founder mutations were the most common. Several other mutations (W15X, Q50X, R58X, A68L, A127P and H142R) were detected for the first time in Italian patients. One novel mutation, T77A, was identified. Several non-coding variants with unknown functional significance were also found (5'UTR -25C > T, -21C > T, -67G > C, IVS1 +37G > C); the novel 5'UTR -21C > T variant was not detected in controls. The CDKN2A A148T polymorphism was more frequent in MPM patients than in the control population (15.7% versus 6.6%). Compared to the SPM patients, MPM cases had a 2-fold increased probability of being MC1R variant carriers and a higher probability of carrying two or more variants. No specific association was observed between the type of variant and the number of melanomas, suggesting that the number rather than the type of MC1R variant increases the risk of MPM. We observed no interaction between CDKN2A status and the presence of MC1R variants. The high frequency of CDKN2A mutations in our MPM cases, independent of their family history, is of relevance to genetic counseling and testing in our population.

  4. Patients with single ventricle physiology undergoing noncardiac surgery are at high risk for adverse events.

    Science.gov (United States)

    Brown, Morgan L; DiNardo, James A; Odegard, Kirsten C

    2015-08-01

    intraoperative adverse events (9.8%) including: arrhythmias requiring treatment (n = 4), conversion from sedation to a general anesthetic (n = 2), difficult airway (n = 1), inadvertent extubation with desaturation and bradycardia (n = 1), hypotension and desaturation (n = 1), and cardiac arrest (n = 1). Postoperative events (surgery in a high-risk subgroup of palliated cardiac patients with single ventricle physiology. However, 11.8% of patients had an adverse event associated with their anesthetic. © 2015 John Wiley & Sons Ltd.

  5. CScape: a tool for predicting oncogenic single-point mutations in the cancer genome.

    Science.gov (United States)

    Rogers, Mark F; Shihab, Hashem A; Gaunt, Tom R; Campbell, Colin

    2017-09-14

    For somatic point mutations in coding and non-coding regions of the genome, we propose CScape, an integrative classifier for predicting the likelihood that mutations are cancer drivers. Tested on somatic mutations, CScape tends to outperform alternative methods, reaching 91% balanced accuracy in coding regions and 70% in non-coding regions, while even higher accuracy may be achieved using thresholds to isolate high-confidence predictions. Positive predictions tend to cluster in genomic regions, so we apply a statistical approach to isolate coding and non-coding regions of the cancer genome that appear enriched for high-confidence predicted disease-drivers. Predictions and software are available at http://CScape.biocompute.org.uk/ .

  6. 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.

  7. Adverse events in a newborn on valproate therapy due to loss-of-function mutations in CYP2C9

    Directory of Open Access Journals (Sweden)

    Andrea Nagy

    2015-01-01

    Full Text Available An increased risk of valproate-induced toxicity has been reported in children, particularly in those younger than 2 years of age. Significant variations in valproate pharmacokinetics and shifts in the metabolic pathways towards CYP2C9-dependent metabolism seem to play some role in the age-related differences in the incidence of adverse events. We present the case of a premature patient with moderate hemorrhage in the subependymal region (grade II — intraventricular hemorrhage without ventricular dilatation, several myoclonic episodes in her right upper arm (series of jerks lasting milliseconds, and epileptiform abnormalities on the EEG (localized spike-and-wave in the left frontal region with preserved background activity who was treated with valproate. Serious side effects, consisting of bone marrow depression, hyperammonemia, and serum alkaline phosphatase elevation, were observed seventeen days after the beginning of valproate therapy. The toxic symptoms were likely the consequence of a reduced ability to metabolize valproate. The patient was demonstrated to carry two loss-of-function mutations in CYP2C9 (CYP2C9*3/*3 resulting in exaggerated blood concentrations of valproate. The present case highlights the importance of assaying inborn errors in CYP2C9 gene in pediatric patients to avoid valproate-evoked serious side effects.

  8. 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

  9. Primary single event effect studies on Xilinx 28-nm System-on-Chip (SoC)

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yao [Xi’an Jiaotong University, Xi’an, Shaanxi 710049 (China); Liu, Shuhuan, E-mail: shuhuanliu@126.com [Xi’an Jiaotong University, Xi’an, Shaanxi 710049 (China); Du, Xuecheng; Yuan, Yuan; He, Chaohui [Xi’an Jiaotong University, Xi’an, Shaanxi 710049 (China); Ren, Xiaotang [Peking University, Beijing 100000 (China); Du, Xiaozhi; Li, Yonghong [Xi’an Jiaotong University, Xi’an, Shaanxi 710049 (China)

    2016-09-21

    Single Event Effect (SEE) on Xilinx 28-nm System-on-Chip (SoC) was investigated by both simulation and experiments in this study. In the simulation process, typical structure of NAND gate and flip-flop in SoC were designed using Cadence tool. Various kinds of radiation were simulated as pulsed current source in consideration of multilayer wiring and energy loss before reaching the sensitive area. The circuit modules were simulated as SEE occurred and malfunctioned when pulsed current source existed. The changes of the circuit modules output were observed when pulsed current signals were placed at different sensitive nodes or the circuit operated under different conditions. The sensitive nodes in typical modules and the possible reasons of test program malfunction were primarily studied. In the experimental process, SoC chip was irradiated with α particles, protons and laser respectively. The irradiation test results showed that Single Event Upset (SEU) occurred in typical modules of SoC, in accordance with the simulation results.

  10. 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.

  11. A single prolific r-process event preserved in an ultra-faint dwarf galaxy

    Science.gov (United States)

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

    2016-03-01

    The heaviest elements in the periodic table are synthesized through the r-process, but the astrophysical site for r-process nucleosynthesis is still unknown. Ultra-faint dwarf galaxies contain a simple fossil record of early chemical enrichment that may determine this site. Previous measurements found very low levels of neutron-capture elements in ultra-faint dwarfs, preferring supernovae as the r-process site. I present high-resolution chemical abundances of nine stars in the recently discovered ultra-faint dwarf Reticulum II, which display extremely enhanced r-process abundances 2-3 orders of magnitude higher than the other ultra-faint dwarfs. Stars with such extreme r-process enhancements are only rarely found in the Milky Way halo. The r-process abundances imply that the neutron-capture material in Reticulum II was synthesized in a single prolific event that is incompatible with r-process yields from ordinary core-collapse supernovae. Reticulum II provides an opportunity to discriminate whether the source of this pure r-process signature is a neutron star merger or magnetorotationally driven supernova. The single event is also a uniquely stringent constraint on the metal mixing and star formation history of this ultra-faint dwarf galaxy.

  12. 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.

  13. Single institute study of FLT3 mutation in acute myeloid leukemia ...

    Indian Academy of Sciences (India)

    inc(cp5)/46, XY(15). 85–93, XXYY, inc(cp5)/46, XY(15). Negative result (no mutation detected). stomach cramps and melenae of one month's duration. At presentation, he was pale with moderate organomegaly. His clinical and cytogenetic analyses are presented in tables 1&2. The immunophenotype of bone marrow blasts ...

  14. Single institute study of FLT3 mutation in acute myeloid leukemia ...

    Indian Academy of Sciences (India)

    FLT3/ITD mutation; p53 tumor suppressor gene; NRAS gene; acute myeloid leukemia (AML); tetraploidy/near-tetraploidy; human genetics. ... Institute of Hematology, Medical School, 11000 Belgrade, Serbia; Institute of Molecular Genetics and Genetic Engineering, Medical School, 11000 Belgrade, Serbia; Institute of ...

  15. 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

  16. Estimation of pea (Pisum sativum L.) microsatellite mutation rate based on pedigree and single-seed descent analyses.

    Science.gov (United States)

    Cieslarová, Jaroslava; Hanáček, Pavel; Fialová, Eva; Hýbl, Miroslav; Smýkal, Petr

    2011-11-01

    Microsatellites, or simple sequence repeats (SSRs) are widespread class of repetitive DNA sequences, used in population genetics, genetic diversity and mapping studies. In spite of the SSR utility, the genetic and evolutionary mechanisms are not fully understood. We have investigated three microsatellite loci with different position in the pea (Pisum sativum L.) genome, the A9 locus residing in LTR region of abundant retrotransposon, AD270 as intergenic and AF016458 located in 5'untranslated region of expressed gene. Comparative analysis of a 35 pair samples from seven pea varieties propagated by single-seed descent for ten generations, revealed single 4 bp mutation in 10th generation sample at AD270 locus corresponding to stepwise increase in one additional ATCT repeat unit. The estimated mutation rate was 4.76 × 10(-3) per locus per generation, with a 95% confidence interval of 1.2 × 10(-4) to 2.7 × 10(-2). The comparison of cv. Bohatýr accessions retrieved from different collections, showed intra-, inter-accession variation and differences in flanking and repeat sequences. Fragment size and sequence alternations were also found in long term in vitro organogenic culture, established at 1983, indicative of somatic mutation process. The evidence of homoplasy was detected across of unrelated pea genotypes, which adversaly affects the reliability of diversity estimates not only for diverse germplasm but also highly bred material. The findings of this study have important implications for Pisum phylogeny studies, variety identification and registration process in pea breeding where mutation rate influences the genetic diversity and the effective population size estimates.

  17. 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.

  18. Compendium of Single-Event Latchup and Total Ionizing Dose Test Results of Commercial Analog to Digital Converters

    Science.gov (United States)

    Irom, Farokh; Agarwal, Shri G.

    2012-01-01

    This paper reports single-event latchup and total dose results for a variety of analog to digital converters targeted for possible use in NASA spacecraft's. The compendium covers devices tested over the last 15 years.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chadwick, M.B. [Los Alamos National Lab., NM (United States). Theoretical Div.; Normand, E. [Boeing Military Aircraft and Missile Systems, Seattle, WA (United States)

    1999-06-01

    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.

  20. 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.

  1. Decreased necrotizing fasciitis capacity caused by a single nucleotide mutation that alters a multiple gene virulence axis.

    Science.gov (United States)

    Olsen, Randall J; Sitkiewicz, Izabela; Ayeras, Ara A; Gonulal, Vedia E; Cantu, Concepcion; Beres, Stephen B; Green, Nicole M; Lei, Benfang; Humbird, Tammy; Greaver, Jamieson; Chang, Ellen; Ragasa, Willie P; Montgomery, Charles A; Cartwright, Joiner; McGeer, Allison; Low, Donald E; Whitney, Adeline R; Cagle, Philip T; Blasdel, Terry L; DeLeo, Frank R; Musser, James M

    2010-01-12

    Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species, but there is remarkably little information bearing on how they alter bacterial virulence. We recently discovered a single-nucleotide mutation in the group A Streptococcus genome that is epidemiologically associated with decreased human necrotizing fasciitis ("flesh-eating disease"). Working from this clinical observation, we find that wild-type mtsR function is required for group A Streptococcus to cause necrotizing fasciitis in mice and nonhuman primates. Expression microarray analysis revealed that mtsR inactivation results in overexpression of PrsA, a chaperonin involved in posttranslational maturation of SpeB, an extracellular cysteine protease. Isogenic mutant strains that overexpress prsA or lack speB had decreased secreted protease activity in vivo and recapitulated the necrotizing fasciitis-negative phenotype of the DeltamtsR mutant strain in mice and monkeys. mtsR inactivation results in increased PrsA expression, which in turn causes decreased SpeB secreted protease activity and reduced necrotizing fasciitis capacity. Thus, a naturally occurring single-nucleotide mutation dramatically alters virulence by dysregulating a multiple gene virulence axis. Our discovery has broad implications for the confluence of population genomics and molecular pathogenesis research.

  2. 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.

  3. Single-event multilevel surgery in children with spastic diplegia: a pilot randomized controlled trial.

    Science.gov (United States)

    Thomason, Pamela; Baker, Richard; Dodd, Karen; Taylor, Nicholas; Selber, Paulo; Wolfe, Rory; Graham, H Kerr

    2011-03-02

    Single-event multilevel surgery is considered the standard of care to improve gait and functioning of children with spastic diplegic cerebral palsy. However, the evidence base is limited. This pilot study is the first randomized controlled trial of single-event multilevel surgery, to our knowledge. Nineteen children (twelve boys and seven girls with a mean age of nine years and eight months) with spastic diplegia were enrolled. Eleven children were randomized to the surgical group and eight, to the control group. The control group underwent a program of progressive resistance strength training. The randomized phase of the trial concluded at twelve months. The control group then exited the study and progressed to surgery, whereas the surgical group continued to be followed in a prospective cohort study. The primary outcome measures were the Gait Profile Score (GPS) and the Gillette Gait Index (GGI). Secondary outcome measures were gross motor function (Gross Motor Function Measure-66 [GMFM-66]), functional mobility (Functional Mobility Scale [FMS]), time spent in the upright position, and health-related quality of life (Child Health Questionnaire [CHQ]). A total of eighty-five surgical procedures were performed, with a mean of eight procedures per child (standard deviation, four). The surgical group had a 34% improvement in the GPS and a 57% improvement in the GGI at twelve months. The control group had a small nonsignificant deterioration in both indices. The between-group differences for the change in the GPS (-5.5; 95% confidence interval, -7.6 to -3.4) and the GGI (-218; 95% confidence interval, -299 to -136) were highly significant. The differences between the groups with regard to the secondary outcome measures were not significant at twelve months. At twenty-four months after surgery, there was a 4.9% increase in the GMFM-66 score and improvements in the FMS score, time spent in the upright position, and the physical functioning domain of the CHQ in the

  4. 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...

  5. Insight into a Novel p53 Single Point Mutation (G389E by Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Maria Cristina De Rosa

    2010-12-01

    Full Text Available The majority of inactivating mutations of p53 reside in the central core DNA binding domain of the protein. In this computational study, we investigated the structural effects of a novel p53 mutation (G389E, identified in a patient with congenital adrenal hyperplasia, which is located within the extreme C-terminal domain (CTD of p53, an unstructured, flexible region (residues 367–393 of major importance for the regulation of the protein. Based on the three-dimensional structure of a carboxyl-terminal peptide of p53 in complex with the S100B protein, which is involved in regulation of the tumor suppressor activity, a model of wild type (WT and mutant extreme CTD was developed by molecular modeling and molecular dynamics simulation. It was found that the G389E amino acid replacement has negligible effects on free p53 in solution whereas it significantly affects the interactions of p53 with the S100B protein. The results suggest that the observed mutation may interfere with p53 transcription activation and provide useful information for site-directed mutagenesis experiments.

  6. Mixed response and time-to-event endpoints for multistage single-arm phase II design.

    Science.gov (United States)

    Lai, Xin; Zee, Benny Chung-Ying

    2015-06-04

    The objective of phase II cancer clinical trials is to determine if a treatment has sufficient activity to warrant further study. The efficiency of a conventional phase II trial design has been the object of considerable debate, particularly when the study regimen is characteristically cytostatic. At the time of development of a phase II cancer trial, we accumulated clinical experience regarding the time to progression (TTP) for similar classes of drugs and for standard therapy. By considering the time to event (TTE) in addition to the tumor response endpoint, a mixed-endpoint phase II design may increase the efficiency and ability of selecting promising cytotoxic and cytostatic agents for further development. We proposed a single-arm phase II trial design by extending the Zee multinomial method to fully use mixed endpoints with tumor response and the TTE. In this design, the dependence between the probability of response and the TTE outcome is modeled through a Gaussian copula. Given the type I and type II errors and the hypothesis as defined by the response rate (RR) and median TTE, such as median TTP, the decision rules for a two-stage phase II trial design can be generated. We demonstrated through simulation that the proposed design has a smaller expected sample size and higher early stopping probability under the null hypothesis than designs based on a single-response endpoint or a single TTE endpoint. The proposed design is more efficient for screening new cytotoxic or cytostatic agents and less likely to miss an effective agent than the alternative single-arm design.

  7. Accurate mitochondrial DNA sequencing using off-target reads provides a single test to identify pathogenic point mutations.

    Science.gov (United States)

    Griffin, Helen R; Pyle, Angela; Blakely, Emma L; Alston, Charlotte L; Duff, Jennifer; Hudson, Gavin; Horvath, Rita; Wilson, Ian J; Santibanez-Koref, Mauro; Taylor, Robert W; Chinnery, Patrick F

    2014-12-01

    Mitochondrial disorders are a common cause of inherited metabolic disease and can be due to mutations affecting mitochondrial DNA or nuclear DNA. The current diagnostic approach involves the targeted resequencing of mitochondrial DNA and candidate nuclear genes, usually proceeds step by step, and is time consuming and costly. Recent evidence suggests that variations in mitochondrial DNA sequence can be obtained from whole-exome sequence data, raising the possibility of a comprehensive single diagnostic test to detect pathogenic point mutations. We compared the mitochondrial DNA sequence derived from off-target exome reads with conventional mitochondrial DNA Sanger sequencing in 46 subjects. Mitochondrial DNA sequences can be reliably obtained using three different whole-exome sequence capture kits. Coverage correlates with the relative amount of mitochondrial DNA in the original genomic DNA sample, heteroplasmy levels can be determined using variant and total read depths, and-providing there is a minimum read depth of 20-fold-rare sequencing errors occur at a rate similar to that observed with conventional Sanger sequencing. This offers the prospect of using whole-exome sequence in a diagnostic setting to screen not only all protein coding nuclear genes but also all mitochondrial DNA genes for pathogenic mutations. Off-target mitochondrial DNA reads can also be used to assess quality control and maternal ancestry, inform on ethnic origin, and allow genetic disease association studies not previously anticipated with existing whole-exome data sets.

  8. MGMT promoter hypermethylation is a frequent, early, and consistent event in astrocytoma progression, and not correlated with TP53 mutation

    NARCIS (Netherlands)

    F.H. Groenendijk (Floris); W. Taal (Walter); H.J. Dubbink (Erik Jan); C.R. Haarloo (Cathleen); M.C.M. Kouwenhoven (Mathilde); M.J. van den Bent (Martin); J.M. Kros (Johan); W.N.M. Dinjens (Winand)

    2011-01-01

    textabstractHypermethylation of the MGMT gene promoter and mutation of the TP53 tumor-suppressor gene are frequently present in diffuse astrocytomas. However, there is only anecdotal information about MGMT methylation status and TP53 mutations during progression of low-grade diffuse astrocytoma

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

    CERN Document Server

    Noah, E; Bisello, D; Faccio, F; Friedl, M; Fulcher, J R; Hall, G; Huhtinen, M; Kaminski, A; Pernicka, Manfred; 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.

  10. 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.

  11. Screening of nanosatellite microprocessors using californium single-event latch-up test results

    Science.gov (United States)

    Tomioka, Takahiro; Okumura, Yuta; Masui, Hirokazu; Takamiya, Koichi; Cho, Mengu

    2016-09-01

    A single-event latch-up (SEL) test using a 252Cf radioisotope was carried out. The results were compared with those of a proton test and from observation in orbit. A radioisotope can reproduce phenomena observed in orbit that are caused by protons. Considering the inexpensive nature of the 252Cf test, it is more suitable for nanosatellites that require low cost and fast delivery. A SEL occurrence rate of a commercial-off-the-shelf microprocessor was derived from the ground test results. The 252Cf test provided a SEL rate approximately 1×106 times greater than that in orbit. This data can be used to derive the minimum SEL occurrence rate in orbit and help satellite designers to evaluate the risk of SEL and take measures if necessary.

  12. Experimental study on the single event effects in pulse width modulators by laser testing

    International Nuclear Information System (INIS)

    Zhao Wen; Guo Xiaoqiang; Chen Wei; Guo Hongxia; Lin Dongsheng; Luo Yinhong; Ding Lili; Wang Yuanming; Wang Hanning

    2015-01-01

    This paper presents single event effect (SEE) characteristics of UC1845AJ pulse width modulators (PWMs) by laser testing. In combination with analysis to map PWM circuitry in the microchip dies, the typical SEE response waveforms for laser pulses located in different circuit blocks of UC1845AJ are obtained and the SEE mechanisms are analyzed. The laser SEE test results show that there are some differences in the SEE mechanisms of different circuit blocks, and phase shifts or changes in the duty cycles of few output pulses are the main SEE behaviors for UC1845AJ. In addition, a new SEE behavior which manifests as changes in the duty cycles of many output pulses is revealed. This means that an SEE hardened design should be considered. (paper)

  13. 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...

  14. Single Event Effect cross section calibration and application to quasi-monoenergetic and spallation facilities

    Directory of Open Access Journals (Sweden)

    Alía Rubén García

    2018-01-01

    Full Text Available We describe an approach to calibrate Single Event Effect (SEE-based detectors in monoenergetic fields and apply the resulting semi-empiric responses to more general mixed-field cases in which a broad variety of particle species and energy spectra are present. The calibration of the response functions is based both on experimental proton (30–200 MeV and neutron (5–300 MeV data and considerations derived from Monte Carlo simulations using the FLUKA Monte Carlo code. The application environments include the quasi-monoenergetic neutrons at RCNP, the atmospheric-like VESUVIO spallation spectrum and the CHARM high-energy accelerator test facility. The agreement between the mixed-field response and that predicted through the mono-energetic calibration is within ±30% for the broad variety of cases considered and thus regarded as highly successful for mixed-field monitoring applications.

  15. 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)

  16. 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)

  17. 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.

  18. 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.

  19. 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)

  20. Neutron-induced single event upsets in static RAMs observed at 10 KM flight altitude

    Science.gov (United States)

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

    1993-04-01

    Neutron induced single event upsets (SEUs) in static memory devices (SRAMs) have so far been seen only in laboratory environments. We report observations of 14 neutron induced SEUs at commercial aircraft flight altitudes. The observed SEU rate at 10 km flight altitude based on exposure of 160 standard 256 Kbit CMOS SRAMs is 4.8 x 10 exp -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.

  1. Spatial-Temporal Feature Analysis on Single-Trial Event Related Potential for Rapid Face Identification

    Directory of Open Access Journals (Sweden)

    Lei Jiang

    2017-11-01

    Full Text Available The event-related potential (ERP is the brain response measured in electroencephalography (EEG, which reflects the process of human cognitive activity. ERP has been introduced into brain computer interfaces (BCIs to communicate the computer with the subject's intention. Due to the low signal-to-noise ratio of EEG, most ERP studies are based on grand-averaging over many trials. Recently single-trial ERP detection attracts more attention, which enables real time processing tasks as rapid face identification. All the targets needed to be retrieved may appear only once, and there is no knowledge of target label for averaging. More interestingly, how the features contribute temporally and spatially to single-trial ERP detection has not been fully investigated. In this paper, we propose to implement a local-learning-based (LLB feature extraction method to investigate the importance of spatial-temporal components of ERP in a task of rapid face identification using single-trial detection. Comparing to previous methods, LLB method preserves the nonlinear structure of EEG signal distribution, and analyze the importance of original spatial-temporal components via optimization in feature space. As a data-driven methods, the weighting of the spatial-temporal component does not depend on the ERP detection method. The importance weights are optimized by making the targets more different from non-targets in feature space, and regularization penalty is introduced in optimization for sparse weights. This spatial-temporal feature extraction method is evaluated on the EEG data of 15 participants in performing a face identification task using rapid serial visual presentation paradigm. Comparing with other methods, the proposed spatial-temporal analysis method uses sparser (only 10% of the total features, and could achieve comparable performance (98% of single-trial ERP detection as the whole features across different detection methods. The interesting finding is

  2. 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.

  3. The impact of a single-nucleotide mutation of bgl2 on cellulase induction in a Trichoderma reesei mutant.

    Science.gov (United States)

    Shida, Yosuke; Yamaguchi, Kaori; Nitta, Mikiko; Nakamura, Ayana; Takahashi, Machiko; Kidokoro, Shun-Ichi; Mori, Kazuki; Tashiro, Kosuke; Kuhara, Satoru; Matsuzawa, Tomohiko; Yaoi, Katsuro; Sakamoto, Yasumitsu; Tanaka, Nobutada; Morikawa, Yasushi; Ogasawara, Wataru

    2015-01-01

    The filamentous fungus Trichoderma reesei (anamorph of Hypocrea jecorina) produces increased cellulase expression when grown on cellulose or its derivatives as a sole carbon source. It has been believed that β-glucosidases of T. reesei not only metabolize cellobiose but also contribute in the production of inducers of cellulase gene expression by their transglycosylation activity. The cellulase hyper-producing mutant PC-3-7 developed in Japan has enhanced cellulase production ability when cellobiose is used as the inducer. The comparative genomics analysis of PC-3-7 and its parent revealed a single-nucleotide mutation within the bgl2 gene encoding intracellular β-glucosidase II (BGLII/Cel1a), giving rise to an amino acid substitution in PC-3-7, which could potentially account for the enhanced cellulase expression when these strains are cultivated on cellulose and cellobiose. To analyze the effects of the BGLII mutation in cellulase induction, we constructed both a bgl2 revertant and a disruptant. Enzymatic analysis of the transformant lysates showed that the strain expressing mutant BGLII exhibited weakened cellobiose hydrolytic activity, but produced some transglycosylation products, suggesting that the SNP in bgl2 strongly diminished cellobiase activity, but did not result in complete loss of function of BGLII. The analysis of the recombinant BGLII revealed that transglycosylation products might be oligosaccharides, composed probably of glucose linked β-1,4, β-1,3, or a mixture of both. PC-3-7 revertants of bgl2 exhibited reduced expression and inducibility of cellulase during growth on cellulose and cellobiose substrates. Furthermore, the effect of this bgl2 mutation was reproduced in the common strain QM9414 in which the transformants showed cellulase production comparable to that of PC-3-7. We conclude that BGLII plays an important role in cellulase induction in T. reesei and that the bgl2 mutation in PC-3-7 brought about enhanced cellulase expression on

  4. Long term outcome of single event multilevel surgery in spastic diplegia with flexed knee gait.

    Science.gov (United States)

    Sung, Ki Hyuk; Chung, Chin Youb; Lee, Kyoung Min; Akhmedov, Bekhzad; Lee, Seung Yeol; Choi, In Ho; Cho, Tae-Joon; Yoo, Won Joon; Park, Moon Seok

    2013-04-01

    Distal hamstring lengthening (DHL) is a commonly performed procedure in flexed knee gait. However, the necessity of this procedure has been challenged due to the concerns on adverse effects in long-term follow-up. This retrospective study was undertaken to investigate the long-term outcome of single event multilevel surgery (SEMLS), including bilateral DHL, in ambulatory patients with cerebral palsy using 3D gait analysis. Twenty-nine ambulatory patients with spastic diplegic cerebral palsy who had undergone SEMLS including bilateral DHL were included. 3D gait analysis was performed preoperatively, 1 year postoperatively and over 10 years postoperatively. Preoperative temporal parameters, kinematics and GDI were compared with values obtained 1 and 10 year follow-up visits. The mean age of patients at time of first surgery was 8.3 years (range, 5.4-16.3 years), and mean time from first surgery to last 3D gait analysis was 11.8 years (range, 10.0-13.3 years). Mean pelvic tilt was not changed significantly after SEMLS including DHL. Mean knee flexion at initial contact decreased from 31.1° preoperatively to 26.0° at 1 year postoperatively (p=0.065), and then decreased significantly to 23.6° at 10 years postoperatively (p=0.038) versus the preoperative value. Mean GDI score significantly improved from 69.4 preoperatively to 77.9 at 1 year postoperatively (p=0.003) and continuously improved to 82.2 at 10 years postoperatively (p=0.017). Single event multilevel surgery including DHL provides a favorable outcome 10 years postoperatively in patients with spastic diplegic cerebral palsy. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. A detector system for studying nuclear reactions relevant to Single Event Effects

    Energy Technology Data Exchange (ETDEWEB)

    Murin, Yu. [V.G. Khlopin Radium Institute, 2nd Murinski 28, 194021 St. Petersburg (Russian Federation)]. E-mail: murin@jinr.ru; Babain, Yu. [V.G. Khlopin Radium Institute, 2nd Murinski 28, 194021 St. Petersburg (Russian Federation); Chubarov, M. [V.G. Khlopin Radium Institute, 2nd Murinski 28, 194021 St. Petersburg (Russian Federation); Tuboltsev, Yu. [V.G. Khlopin Radium Institute, 2nd Murinski 28, 194021 St. Petersburg (Russian Federation); Pljuschev, V. [V.G. Khlopin Radium Institute, 2nd Murinski 28, 194021 St. Petersburg (Russian Federation); Zubkov, M. [V.G. Khlopin Radium Institute, 2nd Murinski 28, 194021 St. Petersburg (Russian Federation); Nomokonov, P. [High Energy Laboratory, Joint Institute for Nuclear Research, 141980 Moscow Region (Russian Federation); Voronin, A. [Moscow State University, 119992 Moscow (Russian Federation); Merkin, M. [Moscow State University, 119992 Moscow (Russian Federation); Kondratiev, V. [St. Petersburg State University, 198504 St. Petersburg (Russian Federation); Olsson, N.; Blomgren, J. [Department of Neutron Research, Uppsala University, Box 525, SE 751 20 Uppsala (Sweden); Westerberg, L. [Department of Physics, Uppsala University, Box 530, SE 751 21 Uppsala (Sweden); Ekstroem, C.; Kolozhvari, A. [The Svedberg Laboratory, Uppsala University, Box 533, SE 751 21 Uppsala (Sweden); Jaederstroem, H. [Department of Nuclear and Particle Physics, Uppsala University, Box 531, SE 751 21 Uppsala (Sweden); Jakobsson, B.; Golubev, P. [Department of Physics, Lund University, Box 118, SE 221 00 Lund (Sweden); Bargholz, Chr.; Geren, L.; Tegner, P.-E.; Zartova, I. [Department of Physics, Stockholm University, AlbaNova, SE 10691 Stockholm (Sweden); Budzanowski, A.; Czech, B.; Skwirczynska, I. [H. Niewodniczanski Institute of Nuclear Physics, PL 31 342 Cracow (Poland); Tang, H.H.K. [IBM, T.J. Watson Research Center, Yorktown Heights, NY 10598 (United States)

    2007-08-01

    We describe a device to study reactions relevant for the Single Event Effect (SEE) in microelectronics by means of 200A and 300AMeV, inverse kinematics, Si+H and Si+D reactions. The work is focused on the possibility to measure Z=2-14 projectile fragments as efficiently as possible. During commissioning and first experiments the fourth quadrant of the CELSIUS storage ring acted as a spectrometer to register fragments in two planes of Si strip detectors in the angular region 0{sup a}t -0.6{sup a}t. A combination of ring-structured and sector-structured Si strip detector planes operated at angles 0.6{sup a}t-1.1{sup a}t. For specific event tagging a Si+ phoswich scintillator wall operated in the range 3.9{sup a}t-11.7{sup a}t and Si {delta}E-E telescopes of CHICSi type operated at large angles.

  6. 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.

  7. 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

  8. Molecular-genetic diagnostics of von Hippel-Lindau syndrome (VHL) in Bulgaria: first complex mutation event in the VHL gene.

    Science.gov (United States)

    Glushkova, Maria; Dimova, Petia; Yordanova, Iglika; Todorov, Tihomir; Tourtourikov, Ivan; Mitev, Vanyo; Todorova, Albena

    2018-02-01

    Von Hippel-Lindau syndrome is an autosomal-dominant disease characterized by the formation of various tumours and cysts in many different parts of the body. Von Hippel-Lindau syndrome is caused by VHL gene mutations leading to production of impaired tumor suppressor Von Hippel-Lindau syndrome protein or its complete absence. To study five patients with clinically suspected Von Hippel-Lindau syndrome, who were referred for molecular genetic testing. Sanger sequencing of the coding regions of the VHL gene. Five clinically relevant germline mutations were detected. One of the pathogenic variants has not been previously reported. This novel mutation is a complex mutation event combining a duplication and an indel, rearranging exon 3 of the VHL gene - c. [516_517dupGTCAAGCCT; 532_542delCTGGACATCGTinsATTA], p. (Glu173Serfs*4). Overall, our results showed that the diagnosis of Von Hippel-Lindau syndrome in our country is difficult most probably because of its heterogeneous clinical manifestation and insufficient knowledge on the diagnostic criteria for the disease. From genetic point of view our results add some novel data on the mutation profile of the VHL gene. In order to prove or revise the diagnosis, early genetic testing is strongly recommended in affected patients and their family members to ensure appropriate follow-up and treatment of the malignancies.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Structural and dynamic changes associated with beneficial engineered single-amino-acid deletion mutations in enhanced green fluorescent protein.

    Science.gov (United States)

    Arpino, James A J; Rizkallah, Pierre J; Jones, D Dafydd

    2014-08-01

    Single-amino-acid deletions are a common part of the natural evolutionary landscape but are rarely sampled during protein engineering owing to limited and prejudiced molecular understanding of mutations that shorten the protein backbone. Single-amino-acid deletion variants of enhanced green fluorescent protein (EGFP) have been identified by directed evolution with the beneficial effect of imparting increased cellular fluorescence. Biophysical characterization revealed that increased functional protein production and not changes to the fluorescence parameters was the mechanism that was likely to be responsible. The structure EGFP(D190Δ) containing a deletion within a loop revealed propagated changes only after the deleted residue. The structure of EGFP(A227Δ) revealed that a `flipping' mechanism was used to adjust for residue deletion at the end of a β-strand, with amino acids C-terminal to the deletion site repositioning to take the place of the deleted amino acid. In both variants new networks of short-range and long-range interactions are generated while maintaining the integrity of the hydrophobic core. Both deletion variants also displayed significant local and long-range changes in dynamics, as evident by changes in B factors compared with EGFP. Rather than being detrimental, deletion mutations can introduce beneficial structural effects through altering core protein properties, folding and dynamics, as well as function.

  14. Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers.

    Science.gov (United States)

    Hirawat, Samit; Welch, Ellen M; Elfring, Gary L; Northcutt, Valerie J; Paushkin, Sergey; Hwang, Seongwoo; Leonard, Eileen M; Almstead, Neil G; Ju, William; Peltz, Stuart W; Miller, Langdon L

    2007-04-01

    Nonsense (premature stop codon) mutations are causative in 5% to 15% of patients with monogenetic inherited disorders. PTC124, a 284-Dalton 1,2,4-oxadiazole, promotes ribosomal readthrough of premature stop codons in mRNA and offers therapeutic potential for multiple genetic diseases. The authors conducted 2 phase I studies of PTC124 in 62 healthy adult volunteers. The initial, single-dose study evaluated doses of 3 to 200 mg/kg and assessed fed-fasting status on pharmacokinetics following a dose of 50 mg/kg. The subsequent multiple-dose study evaluated doses from 10 to 50 mg/kg/dose twice per day (bid) for up to 14 days. PTC124 administered orally as a liquid suspension was palatable and well tolerated through single doses of 100 mg/kg. At 150 and 200 mg/kg, PTC124 induced mild headache, dizziness, and gastrointestinal events. With repeated doses through 50 mg/kg/dose bid, reversible transaminase elevations Duchenne muscular dystrophy.

  15. 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.

  16. Detection of p53 mutations by single-strand conformation polymorphisms (SSCP) gel electrophoresis. A comparative study of radioactive and nonradioactive silver-stained SSCP analysis.

    Science.gov (United States)

    Bosari, S; Marchetti, A; Buttitta, F; Graziani, D; Borsani, G; Loda, M; Bevilacqua, G; Coggi, G

    1995-12-01

    p53 mutations are the most common genetic abnormality in humans tumors, but their clinical significance remains to be precisely elucidated. Conventional single-strand conformation polymorphism (SSCP) analysis, a well-established technique for detecting p53 mutations, uses radioactively labeled polymerase chain reaction (PCR) products, which migrate abnormally in the presence of mutations. We performed radioactive PCR-SSCP analysis in a series of 30 formalin-fixed, paraffin-embedded ovarian carcinomas and two cell lines (SW480 and Caov4) harboring known homozygous p53 mutations and compared the results with nonradioactive silver-stained SSCP. The purpose was to assess whether nonradioactive SSCP is suitable for detecting p53 mutations in a rapid, sensitive, cost-effective fashion, without the need of radioactive isotopes. We accomplished PCR amplification of p53 exons 5 through 8 in 26 carcinomas, and radioactive SSCP detected p53 mutations in 13 tumors; three mutations were localized in exon 5, six in exon 6, two in exon 7, and two in exon 8. All mutations were correctly identified with nonradioactive SSCP, except for one exon 8 mutation. To establish the sensitivity of nonradioactive SSCP, DNA samples of SW480 and Caov4 were mixed with increasing amounts (0-90%) of normal DNA and subjected to PCR-SSCP analysis. Mutations were detected until the concentration of SW480 and Caov4 was 15% and 10%, respectively, of the total sample. The results of our investigation demonstrate that nonradioactive silver-stained SSCP is a sensitive, rapid, and simple technique to detect p53 mutations, even in formalin-fixed tissues, and could be easily used to investigate large series of patients to assess the clinical significance of p53 mutations in human tumors.

  17. Single Amino Acid Mutation Controls Hole Transfer Dynamics in DNA-Methyltransferase HhaI Complexes.

    Science.gov (United States)

    Corbella, Marina; Voityuk, Alexander A; Curutchet, Carles

    2015-09-17

    Different mutagenic effects are generated by DNA oxidation that implies the formation of radical cation states (so-called holes) on purine nucleobases. The interaction of DNA with proteins may protect DNA from oxidative damage owing to hole transfer (HT) from the stack to aromatic amino acids. However, how protein binding affects HT dynamics in DNA is still poorly understood. Here, we report a computational study of HT in DNA complexes with methyltransferase HhaI with the aim of elucidating the molecular factors that explain why long-range DNA HT is inhibited when the glutamine residue inserted in the double helix is mutated into a tryptophan. We combine molecular dynamics, quantum chemistry, and kinetic Monte Carlo simulations and find that protein binding stabilizes the energies of the guanine radical cation states and significantly impacts the corresponding electronic couplings, thus determining the observed behavior, whereas the formation of a tryptophan radical leads to less efficient HT.

  18. 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

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

    Indian Academy of Sciences (India)

    Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniqueswere employed to clarify the changes in charge transfer during the fabrication and utilization of the DNA biosensor. The DNA hybridization event was monitored by differential pulse voltammetry (DPV). Under optimal conditions, the ...

  20. Single-Trial Event-Related Potential Correlates of Belief Updating

    Science.gov (United States)

    Murawski, Carsten; Bode, Stefan

    2015-01-01

    Abstract Belief updating—the process by which an agent alters an internal model of its environment—is a core function of the CNS. Recent theory has proposed broad principles by which belief updating might operate, but more precise details of its implementation in the human brain remain unclear. In order to address this question, we studied how two components of the human event-related potential encoded different aspects of belief updating. Participants completed a novel perceptual learning task while electroencephalography was recorded. Participants learned the mapping between the contrast of a dynamic visual stimulus and a monetary reward and updated their beliefs about a target contrast on each trial. A Bayesian computational model was formulated to estimate belief states at each trial and was used to quantify the following two variables: belief update size and belief uncertainty. Robust single-trial regression was used to assess how these model-derived variables were related to the amplitudes of the P3 and the stimulus-preceding negativity (SPN), respectively. Results showed a positive relationship between belief update size and P3 amplitude at one fronto-central electrode, and a negative relationship between SPN amplitude and belief uncertainty at a left central and a right parietal electrode. These results provide evidence that belief update size and belief uncertainty have distinct neural signatures that can be tracked in single trials in specific ERP components. This, in turn, provides evidence that the cognitive mechanisms underlying belief updating in humans can be described well within a Bayesian framework. PMID:26473170

  1. 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

  2. A single mutation in the GSTe2 gene allows tracking of metabolically based insecticide resistance in a major malaria vector.

    Science.gov (United States)

    Riveron, Jacob M; Yunta, Cristina; Ibrahim, Sulaiman S; Djouaka, Rousseau; Irving, Helen; Menze, Benjamin D; Ismail, Hanafy M; Hemingway, Janet; Ranson, Hilary; Albert, Armando; Wondji, Charles S

    2014-02-25

    Metabolic resistance to insecticides is the biggest threat to the continued effectiveness of malaria vector control. However, its underlying molecular basis, crucial for successful resistance management, remains poorly characterized. Here, we demonstrate that the single amino acid change L119F in an upregulated glutathione S-transferase gene, GSTe2, confers high levels of metabolic resistance to DDT in the malaria vector Anopheles funestus. Genome-wide transcription analysis revealed that GSTe2 was the most over-expressed detoxification gene in DDT and permethrin-resistant mosquitoes from Benin. Transgenic expression of GSTe2 in Drosophila melanogaster demonstrated that over-transcription of this gene alone confers DDT resistance and cross-resistance to pyrethroids. Analysis of GSTe2 polymorphism established that the point mutation is tightly associated with metabolic resistance to DDT and its geographical distribution strongly correlates with DDT resistance patterns across Africa. Functional characterization of recombinant GSTe2 further supports the role of the L119F mutation, with the resistant allele being more efficient at metabolizing DDT than the susceptible one. Importantly, we also show that GSTe2 directly metabolizes the pyrethroid permethrin. Structural analysis reveals that the mutation confers resistance by enlarging the GSTe2 DDT-binding cavity, leading to increased DDT access and metabolism. Furthermore, we show that GSTe2 is under strong directional selection in resistant populations, and a restriction of gene flow is observed between African regions, enabling the prediction of the future spread of this resistance. This first DNA-based metabolic resistance marker in mosquitoes provides an essential tool to track the evolution of resistance and to design suitable resistance management strategies.

  3. A single mutation in the GSTe2 gene allows tracking of metabolically based insecticide resistance in a major malaria vector

    Science.gov (United States)

    2014-01-01

    Background Metabolic resistance to insecticides is the biggest threat to the continued effectiveness of malaria vector control. However, its underlying molecular basis, crucial for successful resistance management, remains poorly characterized. Results Here, we demonstrate that the single amino acid change L119F in an upregulated glutathione S-transferase gene, GSTe2, confers high levels of metabolic resistance to DDT in the malaria vector Anopheles funestus. Genome-wide transcription analysis revealed that GSTe2 was the most over-expressed detoxification gene in DDT and permethrin-resistant mosquitoes from Benin. Transgenic expression of GSTe2 in Drosophila melanogaster demonstrated that over-transcription of this gene alone confers DDT resistance and cross-resistance to pyrethroids. Analysis of GSTe2 polymorphism established that the point mutation is tightly associated with metabolic resistance to DDT and its geographical distribution strongly correlates with DDT resistance patterns across Africa. Functional characterization of recombinant GSTe2 further supports the role of the L119F mutation, with the resistant allele being more efficient at metabolizing DDT than the susceptible one. Importantly, we also show that GSTe2 directly metabolizes the pyrethroid permethrin. Structural analysis reveals that the mutation confers resistance by enlarging the GSTe2 DDT-binding cavity, leading to increased DDT access and metabolism. Furthermore, we show that GSTe2 is under strong directional selection in resistant populations, and a restriction of gene flow is observed between African regions, enabling the prediction of the future spread of this resistance. Conclusions This first DNA-based metabolic resistance marker in mosquitoes provides an essential tool to track the evolution of resistance and to design suitable resistance management strategies. PMID:24565444

  4. [Single event multilevel surgery to improve gait in diplegic cerebral palsy - a prospective controlled trial].

    Science.gov (United States)

    Zwick, E B; Saraph, V; Strobl, W; Steinwender, G

    2001-01-01

    To evaluate prospectively the outcome of gait-improvement surgery in children with spastic diplegia. Three-dimensional gait analysis was performed in twenty children with spastic diplegia. Ten children underwent single event multilevel surgery for gait improvement. Indications for individual procedures followed a fixed set of selection criteria. The other ten children continued with their physiotherapy programme and served as a control group. A second gait analysis was performed in all children after 1.5 years. Time-distance parameters and kinematics of the pelvis, hip, knee and ankle joints in the sagittal plane served as main outcome measures The patients walked faster with an increased stride length after surgery in comparison to the conservatively treated controls. The average pelvic tilt increased slightly and the range of motion of the knee joint increased considerably after multilevel surgery. The motion at the ankle remained unchanged over the study period in both the groups. An improved knee extension during the stance phase of gait served to improve stance limb stability and facilitated an unhindered swing phase of the opposite limb. This prospective trial showed favourable changes in gait function after multilevel surgery in spastic diplegic children.

  5. Monitoring single event upsets in SRAM-based FPGAs at the SuperKEKB interaction point

    Science.gov (United States)

    Giordano, R.; Tortone, G.; Perrella, S.; Izzo, V.; Aloisio, A.

    2017-07-01

    In February 2016, the SuperKEKB positron-electron high-luminosity collider of the KEK laboratory (Tsukuba, Japan) started being commissioned. A dedicated commissioning detector, named BEAST2, has been used to characterize beam backgrounds before the Belle2 detector was rolled into the beams and to provide tuning parameters for Monte Carlo simulations. BEAST2 consists of a fiberglass support structure and several sub-detectors mounted onto it, including time projection chambers (TPCs) and He-3 tubes. In this work, we present direct measurements of radiation-induced single event upsets in a SRAM-based FPGA device installed in BEAST2 at a distance of ~ 1 m from the beam interaction point. Our goal was to provide experimental results of the expected radiation-induced configuration upset rate and power consumption variation at Belle2 and at other experiments operating in similar radiation environments. Beam currents for both electron and positron rings spanned a range between 50 and 500 mA, therefore providing data about the FPGA operation in different radiation conditions. Even if the machine has not been providing collisions yet, as the beams were not focused to the interaction point, our results show a rate of 0.15 upsets/day averaged over the whole commissioning time frame. We had neither evidence of total dose effects on the FPGA power consumption nor of permanent damage to the device.

  6. 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.)

  7. 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)

  8. Single-trial event-related potential extraction through one-unit ICA-with-reference

    Science.gov (United States)

    Lih Lee, Wee; Tan, Tele; Falkmer, Torbjörn; Leung, Yee Hong

    2016-12-01

    Objective. In recent years, ICA has been one of the more popular methods for extracting event-related potential (ERP) at the single-trial level. It is a blind source separation technique that allows the extraction of an ERP without making strong assumptions on the temporal and spatial characteristics of an ERP. However, the problem with traditional ICA is that the extraction is not direct and is time-consuming due to the need for source selection processing. In this paper, the application of an one-unit ICA-with-Reference (ICA-R), a constrained ICA method, is proposed. Approach. In cases where the time-region of the desired ERP is known a priori, this time information is utilized to generate a reference signal, which is then used for guiding the one-unit ICA-R to extract the source signal of the desired ERP directly. Main results. Our results showed that, as compared to traditional ICA, ICA-R is a more effective method for analysing ERP because it avoids manual source selection and it requires less computation thus resulting in faster ERP extraction. Significance. In addition to that, since the method is automated, it reduces the risks of any subjective bias in the ERP analysis. It is also a potential tool for extracting the ERP in online application.

  9. 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

  10. Low energy proton induced single event upset in 65 nm DDR and QDR commercial SRAMs

    Science.gov (United States)

    Ye, B.; Liu, J.; Wang, T. S.; Liu, T. Q.; Maaz, K.; Luo, J.; Wang, B.; Yin, Y. N.; Ji, Q. G.; Sun, Y. M.; Hou, M. D.

    2017-09-01

    The single event upset (SEU) response of 65 nm commercial double data rate static random access memory (SRAM) and quad data rate SRAM was investigated by using proton beams with energies in the range of 0.15 MeV to 8.0 MeV. Experimental results show that a significant number of SEU occurrences can be triggered when the energy of incident proton is below 1 MeV. For the low energy protons, the SEU cross section measured in these SRAMs was found to increase with increasing proton energy, attaining a peak value, and then decreases as the proton energy was further increased. While in case of quad data rate SRAMs, it seems that they are more sensitive to SEU occurrences as compared with double data rate SRAMs. The bias voltage and data pattern dependence on SEU cross section induced by the low energy protons were also investigated in this work. In addition, the over-layer thickness of the SRAMs and the impact of degrader use in proton induced SEU test were also analyzed in detail. Monte Carlo simulations results indicate that the use of degrader in case of low energy proton induced SEU test results in a significant reduction of the SEU cross section.

  11. 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).

  12. 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.

  13. Calibration of a neutron detector based on single event upset of SRAM memories

    Energy Technology Data Exchange (ETDEWEB)

    Domingo, C., E-mail: carles.domingo@uab.ca [Departament de Fisica, Univ. Autonoma de Barcelona, E-08193 Bellaterra (Spain); Gomez, F. [Dpto. de Particulas, Univ. de Santiago, 15782 Santiago de Compostela (Spain); Sanchez-Doblado, F. [Dpto. de Fisiologia Medica y Biofisica, Univ. de Sevilla, 41009 Sevilla (Spain); Servicio de Radiofisica, Hospital Univ. Virgen Macarena, 41009 Sevilla (Spain); Hartmann, G.H. [DKFZ E0400, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Amgarou, K.; Garcia-Fuste, M.J. [Departament de Fisica, Univ. Autonoma de Barcelona, E-08193 Bellaterra (Spain); Romero, M.T. [Dpto. de Fisiologia Medica y Biofisica, Univ. de Sevilla, 41009 Sevilla (Spain); Boettger, R.; Nolte, R.; Wissmann, F.; Zimbal, A.; Schuhmacher, H. [PTB, Bundesallee 100, 38116 Braunschweig (Germany)

    2010-12-15

    One of the challenges of measuring neutron fluences around medical linacs is the fact that the scattered photon fluence is important and higher than the surrounding neutron leakage fluence. Additionally most electron accelerators are pulsed, with repetition rates of the order of hundreds of Hertz, while the pulse duration is in the microsecond range. For this reason, neutron fluence around RT linacs is usually measured through passive methods, with the inconvenience of their time consuming analysis. A new neutron detector, based on the relation between Single Event Upsets (SEU) in digital SRAM memories and the existing thermal neutron fluence, has been developed. This work reports the calibration results of prototypes of this detector, obtained from exposures to the Physikalisch-Technische Bundesanstalt in Braunschweig (PTB) moderated {sup 252}Cf source, to PTB quasi-monoenergetic neutron beams of 0.565 MeV, 1.2 MeV, 5 MeV, 8 MeV and 14.8 MeV, and to the GKSS thermal neutron beam.

  14. SRAM single event upset calculation and test using protons in the secondary beam in the BEPC

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yuanming; Guo Hongxia; Zhang Fengqi; Zhang Keying; Chen Wei; Luo Yinhong; Guo Xiaoqiang, E-mail: wangym2007@gmail.com [Northwest Institute of Nuclear Technology, Xi' an 710024 (China)

    2011-09-15

    The protons in the secondary beam in the Beijing Electron Positron Collider (BEPC) are first analyzed and a large proportion at the energy of 50-100 MeV supply a source gap of high energy protons. In this study, the proton energy spectrum of the secondary beam was obtained and a model for calculating the proton single event upset (SEU) cross section of a static random access memory (SRAM) cell has been presented in the BEPC secondary beam proton radiation environment. The proton SEU cross section for different characteristic dimensions has been calculated. The test of SRAM SEU cross sections has been designed, and a good linear relation between SEUs in SRAM and the fluence was found, which is evidence that an SEU has taken place in the SRAM. The SEU cross sections were measured in SRAM with different dimensions. The test result shows that the SEU cross section per bit will decrease with the decrease of the characteristic dimensions of the device, while the total SEU cross section still increases upon the increase of device capacity. The test data accords with the calculation results, so the high-energy proton SEU test on the proton beam in the BEPC secondary beam could be conducted. (semiconductor physics)

  15. 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)

  16. 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...

  17. A Single Residue Mutation in the Gαq Subunit of the G Protein Complex Causes Blindness in Drosophila

    Directory of Open Access Journals (Sweden)

    Jinguo Cao

    2018-01-01

    Full Text Available Heterotrimeric G proteins play central roles in many signaling pathways, including the phototransduction cascade in animals. However, the degree of involvement of the G protein subunit Gαq is not clear since animals with previously reported strong loss-of-function mutations remain responsive to light stimuli. We recovered a new allele of Gαq in Drosophila that abolishes light response in a conventional electroretinogram assay, and reduces sensitivity in whole-cell recordings of dissociated cells by at least five orders of magnitude. In addition, mutant eyes demonstrate a rapid rate of degeneration in the presence of light. Our new allele is likely the strongest hypomorph described to date. Interestingly, the mutant protein is produced in the eyes but carries a single amino acid change of a conserved hydrophobic residue that has been assigned to the interface of interaction between Gαq and its downstream effector, PLC. Our study has thus uncovered possibly the first point mutation that specifically affects this interaction in vivo.

  18. 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

  19. A Single Active Site Mutation in the Pikromycin Thioesterase Generates a More Effective Macrocyclization Catalyst.

    Science.gov (United States)

    Koch, Aaron A; Hansen, Douglas A; Shende, Vikram V; Furan, Lawrence R; Houk, K N; Jiménez-Osés, Gonzalo; Sherman, David H

    2017-09-27

    Macrolactonization of natural product analogs presents a significant challenge to both biosynthetic assembly and synthetic chemistry. In the preceding paper , we identified a thioesterase (TE) domain catalytic bottleneck processing unnatural substrates in the pikromycin (Pik) system, preventing the formation of epimerized macrolactones. Here, we perform molecular dynamics simulations showing the epimerized hexaketide was accommodated within the Pik TE active site; however, intrinsic conformational preferences of the substrate resulted in predominately unproductive conformations, in agreement with the observed hydrolysis. Accordingly, we engineered the stereoselective Pik TE to yield a variant (TE S148C ) with improved reaction kinetics and gain-of-function processing of an unnatural, epimerized hexaketide. Quantum mechanical comparison of model TE S148C and TE WT reaction coordinate diagrams revealed a change in mechanism from a stepwise addition-elimination (TE WT ) to a lower energy concerted acyl substitution (TE S148C ), accounting for the gain-of-function and improved reaction kinetics. Finally, we introduced the S148C mutation into a polyketide synthase module (PikAIII-TE) to impart increased substrate flexibility, enabling the production of diastereomeric macrolactones.

  20. 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

  1. 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.

  2. Single-cell genetic expression of mutant GABAA receptors causing Human genetic epilepsy alters dendritic spine and GABAergic bouton formation in a mutation-specific manner

    Directory of Open Access Journals (Sweden)

    Pamela eLachance-Touchette

    2014-10-01

    Full Text Available Mutations in genes encoding for GABAA receptor subunits is a well-established cause of genetic generalized epilepsy. GABA neurotransmission is implicated in several developmental processes including neurite outgrowth and synapse formation. Alteration in excitatory/inhibitory synaptic activities plays a critical role in epilepsy, thus here we investigated whether mutations in α1 subunit of GABAA receptor may affect dendritic spine and GABAergic bouton formation. In particular, we examined the effects of three mutations of the GABRA1 gene (D219N, A322D and K353delins18X that were found in a cohort of families with genetic generalized epilepsy. We used a novel single-cell genetic approach, by preparing cortical organotypic cultures from GABRA1flox/flox mice and simultaneously inactivating endogenous GABRA1 and transfecting mutant α1 subunits in single glutamatergic pyramidal cells and basket GABAergic interneurons by biolistic transfection. We found that GABRA1-/- GABAergic cells showed reduced innervation field, which was rescued by co-expressing α1-A322D and α1-WT but not α1-D219N. We further found that the expression of the most severe GABRA1 missense mutation (α1-A322D induced a striking increase of spine density in pyramidal cells along with an increase in the number of mushroom-like spines. In addition, α1-A322D expression in GABAergic cells slightly increased perisomatic bouton density, whereas other mutations did not alter bouton formation. All together, these results suggest that the effects of different GABAAR mutations on GABAergic bouton and dendritic spine formation are specific to the mutation and cannot be always explained by a simple loss-of-function gene model. The use of single cell genetic manipulation in organotypic cultures may provide a better understanding of the specific and distinct neural circuit alterations caused by different GABAA receptor subunit mutations and will help define the pathophysiology of genetic

  3. Wavelet based automated postural event detection and activity classification with single imu - biomed 2013.

    Science.gov (United States)

    Lockhart, Thurmon E; Soangra, Rahul; Zhang, Jian; Wu, Xuefan

    2013-01-01

    and classification algorithm using denoised signals from single wireless IMU placed at sternum. The algorithm was further validated and verified with motion capture system in laboratory environment. Wavelet denoising highlighted postural events and transition durations that further provided clinical information on postural control and motor coordination. The presented method can be applied in real life ambulatory monitoring approaches for assessing condition of elderly.

  4. 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

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

    Indian Academy of Sciences (India)

    of target complementary DNA in the range 0.5 fM to 0.05 nM, with a detection limit of 0.36 ± 0.04 fM. ... reaction between single-stranded DNA (ssDNA) and its ... ing more selective and sensitive electrochemical DNA biosensors.12,13. Graphene, a new class of two-dimensional sheet material, which was discovered by Geim ...

  6. 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...

  7. 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

    screened FGFR3, PIK3CA, TP53, HRAS, NRAS and KRAS for mutations and quantitatively assessed the methylation status of APC, ARF, DBC1, INK4A, RARB, RASSF1A, SFRP1, SFRP2, SFRP4, SFRP5 and WIF1 in a prospective series of tumor biopsies (N = 105) and urine samples (N = 113) from 118 bladder tumor patients. We...

  8. 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.

  9. Mitigation of Temperature Induced Single Event Crosstalk Noise by Applying Adaptive Forward Body Bias

    Science.gov (United States)

    Bhowmik, Pankaj

    Soft Errors due to Single Event (SE) Transients is one of the important reliability issues, which is becoming very prominent in advanced technology and in space applications. Increasing coupling effects among interconnects, on the other hand, can cause SE Transients to contaminate electronically unrelated circuit paths, which in turn can increase circuit sensitivity to radiation. Coupling capacitance increases due to reducing distances between interconnect lines making crosstalk noise more important. On the other hand, chips now experience higher temperatures due to environmental factors and high performance of chips. High-performance VLSI circuits consume more power and hence experience higher temperature due to high utilization factor. The increased temperature affects both interconnect resistance and driving strength of interconnect buffers. This work shows that thermal effects increase the amount of crosstalk noise observed on the victim line at nominal supply voltages. With thermally induced crosstalk contribution, total crosstalk noise may exceed the noise margin of the subsequent gate causing a wrong value to be propagated. The crosstalk prevention measures taken such as victim driver sizing may not be sufficient if thermal effects are not properly considered. This work aims to provide a mitigation method for thermally induced crosstalk noise using adaptive forward body bias. At high temperature, drain current reduces, and adaptive body biasing makes the CMOS recover the lost the drain current. A temperature sensor is proposed here to generate a necessary voltage at the CMOS body. A good temperature sensitivity is achieved with the tiny sensors that keep constant driving strength. Interconnect is modeled in using 10-pi modeling and 45nm technology was use for this simulation. Our proposed method mitigates 90% of temperature induced crosstalk contribution.

  10. 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

  11. Single rat muscle Na+channel mutation confers batrachotoxin autoresistance found in poison-dart frogPhyllobates terribilis.

    Science.gov (United States)

    Wang, Sho-Ya; Wang, Ging Kuo

    2017-09-26

    Poison-dart Phyllobates terribilis frogs sequester lethal amounts of steroidal alkaloid batrachotoxin (BTX) in their skin as a defense mechanism against predators. BTX targets voltage-gated Na + channels and enables them to open persistently. How BTX autoresistance arises in such frogs remains a mystery. The BTX receptor has been delineated along the Na + channel inner cavity, which is formed jointly by four S6 transmembrane segments from domains D1 to D4. Within the P. terribilis muscle Na + channel, five amino acid (AA) substitutions have been identified at D1/S6 and D4/S6. We therefore investigated the role of these naturally occurring substitutions in BTX autoresistance by introducing them into rat Nav1.4 muscle Na + channel, both individually and in combination. Our results showed that combination mutants containing an N1584T substitution all conferred a complete BTX-resistant phenotype when expressed in mammalian HEK293t cells. The single N1584T mutant also retained its functional integrity and became exceptionally resistant to 5 µM BTX, aside from a small residual BTX effect. Single and combination mutants with the other four S6 residues (S429A, I433V, A445D, and V1583I) all remained highly BTX sensitive. These findings, along with diverse BTX phenotypes of N1584K/A/D/T mutant channels, led us to conclude that the conserved N1584 residue is indispensable for BTX actions, probably functioning as an integral part of the BTX receptor. Thus, complete BTX autoresistance found in P. terribilis muscle Na + channels could emerge primarily from a single AA substitution (asparagine→threonine) via a single nucleotide mutation (AAC→ACC).

  12. A single visit multidisciplinary model for managing patients with mutations in moderate and high-risk genes in a community practice setting.

    Science.gov (United States)

    O'Leary, Michael P; Goldner, Bryan S; Abboy, Sridevi; Mercado, Philip D; Plurad, Hong Yoon

    2018-01-01

    The introduction of screening for multiple high and moderate risk mutations in genes has resulted in a complex approach to patient care involving multiple disciplines. We sought to describe the feasibility of a single visit multidisciplinary approach to the management of patients with an identified high/moderate risk gene mutation. Patients who presented to our community hospital over a 1-year period who were found to have a high/moderate risk genetic mutation on a screening panel were referred to the High Risk Genetic Clinic. Thirty-five patients were included. The majority were female [34 (97.1%)], Hispanic [22 (62.9%)], with a family history of cancer [21 (60%)]. Mean age was 40.3 years. Most of the participants had a BRCA1 gene mutation [10 (28.6%)]. Patients were seen at the High Risk Genetic Clinic within a mean of 41.9 days from the day of genetic mutation diagnosis. Four patients did not show and were significantly younger (19.3 vs. 39.6 years, p = 0.014). In this community setting, we provided coordinated care within multiple disciplines related to a genetic mutation in a single clinic visit. Increased efforts at coordinating early care should be directed towards patients diagnosed at a younger age.

  13. 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.

  14. Single-Event Transient Testing of the Crane Aerospace and Electronics SMHF2812D Dual DC-DC Converter

    Science.gov (United States)

    Casey, Megan

    2015-01-01

    The purpose of this testing was to characterize the Crane Aerospace & Electronics (Crane) Interpoint SMHF2812D for single-event transient (SET) susceptibility. These data shall be used for flight lot evaluation, as well as qualification by similarity of the SMHF family of converters, all of which use the same active components.

  15. 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

  16. 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.

  17. Single-nucleotide mutation matrix: a new model for predicting the NF-κB DNA binding sites.

    Science.gov (United States)

    Du, Wenxin; Gao, Jing; Wang, Tingting; Wang, Jinke

    2014-01-01

    In this study, we established a single nucleotide mutation matrix (SNMM) model based on the relative binding affinities of NF-κB p50 homodimer to a wild-type binding site (GGGACTTTCC) and its all single-nucleotide mutants detected with the double-stranded DNA microarray. We evaluated this model by scoring different groups of 10-bp DNA sequences with this model and analyzing the correlations between the scores and the relative binding affinities detected with three wet experiments, including the electrophoresis mobility shift assay (EMSA), the protein-binding microarray (PBM) and the systematic evolution of ligands by exponential enrichment-sequencing (SELEX-Seq). The results revealed that the SNMM scores were strongly correlated with the detected binding affinities. We also scored the DNA sequences with other three models, including the principal coordinate (PC) model, the position weight matrix scoring algorithm (PWMSA) model and the Match model, and analyzed the correlations between the scores and the detected binding affinities. In comparison with these models, the SNMM model achieved reliable results. We finally determined 0.747 as the optimal threshold for predicting the NF-κB DNA-binding sites with the SNMM model. The SNMM model thus provides a new alternative model for scoring the relative binding affinities of NF-κB to the 10-bp DNA sequences and predicting the NF-κB DNA-binding sites.

  18. High speed single nucleotide polymorphism typing of a hereditary haemochromatosis mutation with capillary array electrophoresis microplates.

    Science.gov (United States)

    Medintz, I; Wong, W W; Sensabaugh, G; Mathies, R A

    2000-07-01

    A single nucleotide polymorphism (SNP) typing assay is developed and evaluated on a microfabricated capillary array electrophoresis system. Using fluorescently labeled allele-specific primers, the S65C (193A-->T) substitution associated with hereditary haemochromatosis in the HFE gene is genotyped. The covalently labeled polymerase chain reaction (PCR) products are separated on a microfabricated radial capillary array electrophoresis microplate using nondenaturing gel media in under two minutes. Detection is accomplished with a laser-excited rotary confocal scanner. The Rox-labeled A-allele specific amplicon (211 bp) is differentiated from the R110-labeled T-allele specific amplicon (201 bp) by both size and color. This study demonstrates the feasibility of using allele-specific PCR with covalently labeled primers for high speed fluorescent SNP typing on microfabricated radial capillary array electrophoresis microplates.

  19. 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 MySQL server >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.

  20. Searches for new physics in single-photon events and a search for charginos at the DELPHI experiment

    CERN Document Server

    Ask, S M

    2004-01-01

    A search for new physics using events with a single photon and missing energy has been made at the DELPHI experiment together with a search for charginos. The results were based on data collected up to and including the final year of 2000. An integrated luminosity of 650 pb−1 was used in the single photon analysis and 450 pb−1 in the chargino search. Center-of-mass energies up to 209 GeV were explored. Searches have been made for supersymmetry as well as for extra dimensions and non standard neutrino interactions. Since no signs of a signal have been observed in any of the searches the results have been used to set exclusion limits and to constrain the theoretical parameter spaces. The search results using single and acoplanar photon events from the four LEP experiments have also been combined within the searches for supersymmetry and extra dimensions.

  1. Criticality of Low-Energy Protons in Single-Event Effects Testing of Highly-Scaled Technologies

    Science.gov (United States)

    Pellish, Jonathan A.; Marshall, Paul W.; Rodbell, Kenneth P.; Gordon, Michael S.; LaBel, Kenneth A.; Schwank, James R.; Dodds, Nathaniel A.; Castaneda, Carlos M.; Berg, Melanie D.; Kim, Hak S.; hide

    2014-01-01

    We report low-energy proton and low-energy alpha particle single-event effects (SEE) data on a 32 nm silicon-on-insulator (SOI) complementary metal oxide semiconductor (CMOS) latches and static random access memory (SRAM) that demonstrates the criticality of using low-energy protons for SEE testing of highly-scaled technologies. Low-energy protons produced a significantly higher fraction of multi-bit upsets relative to single-bit upsets when compared to similar alpha particle data. This difference highlights the importance of performing hardness assurance testing with protons that include energy distribution components below 2 megaelectron-volt. The importance of low-energy protons to system-level single-event performance is based on the technology under investigation as well as the target radiation environment.

  2. 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

  3. 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

  4. 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

  5. A single hot event stimulates adult performance but reduces egg survival in the oriental fruit moth, Grapholitha molesta.

    Science.gov (United States)

    Liang, Li-Na; Zhang, Wei; Ma, Gang; Hoffmann, Ary A; Ma, Chun-Sen

    2014-01-01

    Climate warming is expected to increase the exposure of insects to hot events (involving a few hours at extreme high temperatures). These events are unlikely to cause widespread mortality but may modify population dynamics via impacting life history traits such as adult fecundity and egg hatching. These effects and their potential impact on population predictions are still largely unknown. In this study, we simulated a single hot event (maximum of 38°C lasting for 4 h) of a magnitude increasingly found under field conditions and examined its effect in the oriental fruit moth, Grapholitha molesta. This hot event had no impact on the survival of G. molesta adults, copulation periods or male longevity. However, the event increased female lifespan and the length of the oviposition period, leading to a potential increase in lifetime fecundity and suggesting hormesis. In contrast, exposure of males to this event markedly reduced the net reproductive value. Male heat treatment delayed the onset of oviposition in the females they mated with, as well as causing a decrease in the duration of oviposition period and lifetime fecundity. Both male and female stress also reduced egg hatch. Our findings of hormetic effects on female performance but concurrent detrimental effects on egg hatch suggest that hot events have unpredictable consequences on the population dynamics of this pest species with implications for likely effects associated with climate warming.

  6. A single hot event stimulates adult performance but reduces egg survival in the oriental fruit moth, Grapholitha molesta.

    Directory of Open Access Journals (Sweden)

    Li-Na Liang

    Full Text Available Climate warming is expected to increase the exposure of insects to hot events (involving a few hours at extreme high temperatures. These events are unlikely to cause widespread mortality but may modify population dynamics via impacting life history traits such as adult fecundity and egg hatching. These effects and their potential impact on population predictions are still largely unknown. In this study, we simulated a single hot event (maximum of 38°C lasting for 4 h of a magnitude increasingly found under field conditions and examined its effect in the oriental fruit moth, Grapholitha molesta. This hot event had no impact on the survival of G. molesta adults, copulation periods or male longevity. However, the event increased female lifespan and the length of the oviposition period, leading to a potential increase in lifetime fecundity and suggesting hormesis. In contrast, exposure of males to this event markedly reduced the net reproductive value. Male heat treatment delayed the onset of oviposition in the females they mated with, as well as causing a decrease in the duration of oviposition period and lifetime fecundity. Both male and female stress also reduced egg hatch. Our findings of hormetic effects on female performance but concurrent detrimental effects on egg hatch suggest that hot events have unpredictable consequences on the population dynamics of this pest species with implications for likely effects associated with climate warming.

  7. A Single Hot Event Stimulates Adult Performance but Reduces Egg Survival in the Oriental Fruit Moth, Grapholitha molesta

    Science.gov (United States)

    Ma, Gang; Hoffmann, Ary A.; Ma, Chun-Sen

    2014-01-01

    Climate warming is expected to increase the exposure of insects to hot events (involving a few hours at extreme high temperatures). These events are unlikely to cause widespread mortality but may modify population dynamics via impacting life history traits such as adult fecundity and egg hatching. These effects and their potential impact on population predictions are still largely unknown. In this study, we simulated a single hot event (maximum of 38°C lasting for 4 h) of a magnitude increasingly found under field conditions and examined its effect in the oriental fruit moth, Grapholitha molesta. This hot event had no impact on the survival of G. molesta adults, copulation periods or male longevity. However, the event increased female lifespan and the length of the oviposition period, leading to a potential increase in lifetime fecundity and suggesting hormesis. In contrast, exposure of males to this event markedly reduced the net reproductive value. Male heat treatment delayed the onset of oviposition in the females they mated with, as well as causing a decrease in the duration of oviposition period and lifetime fecundity. Both male and female stress also reduced egg hatch. Our findings of hormetic effects on female performance but concurrent detrimental effects on egg hatch suggest that hot events have unpredictable consequences on the population dynamics of this pest species with implications for likely effects associated with climate warming. PMID:25551751

  8. 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.

  9. 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...

  10. 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.

  11. 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)

  12. Bruton's tyrosine kinase gene mutations in Turkish patients with X-linked agammaglobulinemia from a single center: Novel mutations in βTK gene

    NARCIS (Netherlands)

    Ç. Aydoǧmuş (Çiǧdem); Y. Camcioǧlu (Yildiz); M. van der Burg (Mirjam); H. Çokuǧraş (H.); N. Akçakaya (Necla); J.J.M. van Dongen (Jacques)

    2013-01-01

    textabstractObjective: X-linked agammaglobulinemia (XLA) is caused by a mutation in the Bruton's tyrosine kinase gene and is characterized by a delay in the maturation and differentiation of B lymphocytes. Patients with XLA have either absent or very low levels of circulating mature B cells (<1%),

  13. An Analysis of the Sensitivity of Proteogenomic Mapping of Somatic Mutations and Novel Splicing Events in Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ruggles, Kelly V.; Tang, Zuojian; Wang, Xuya; Grover, Himanshu; Askenazi, Manor; Teubl, Jennifer; Cao, Song; McLellan, Michael D.; Clauser, Karl R.; Tabb, David L.; Mertins, Philipp; Slebos, Robbert; Erdmann-Gilmore, Petra; Li, Shunqiang; Gunawardena, Harsha P.; Xie, Ling; Liu, Tao; Zhou, Jian-Ying; Sun, Shisheng; Hoadley, Katherine A.; Perou, Charles M.; Chen, Xian; Davies, Sherri R.; Maher, Christopher A.; Kinsinger, Christopher R.; Rodland, Karen D.; Zhang, Hui; Zhang, Zhen; Ding, Li; Townsend, R. Reid; Rodriguez, Henry; Chan, Daniel; Smith, Richard D.; Liebler, Daniel C.; Carr, Steven A.; Payne, Samuel; Ellis, Matthew J.; Fenyő, David

    2015-12-02

    Improvements in mass spectrometry (MS)-based peptide sequencing provide a new opportunity to determine whether polymorphisms, mutations and splice variants identified in cancer cells are translated. Herein we therefore describe a proteogenomic data integration tool (QUILTS) and illustrate its application to whole genome, transcriptome and global MS peptide sequence datasets generated from a pair of luminal and basal-like breast cancer patient derived xenografts (PDX). The sensitivity of proteogenomic analysis for singe nucleotide variant (SNV) expression and novel splice junction (NSJ) detection was probed using multiple MS/MS process replicates. Despite over thirty sample replicates, only about 10% of all SNV (somatic and germline) were detected by both DNA and RNA sequencing were observed as peptides. An even smaller proportion of peptides corresponding to NSJ observed by RNA sequencing were detected (<0.1%). Peptides mapping to DNA-detected SNV without a detectable mRNA transcript were also observed demonstrating the transcriptome coverage was also incomplete (~80%). In contrast to germ-line variants, somatic variants were less likely to be detected at the peptide level in the basal-like tumor than the luminal tumor raising the possibility of differential translation or protein degradation effects. In conclusion, the QUILTS program integrates DNA, RNA and peptide sequencing to assess the degree to which somatic mutations are translated and therefore biologically active. By identifying gaps in sequence coverage QUILTS benchmarks current technology and assesses progress towards whole cancer proteome and transcriptome analysis.

  14. 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.

  15. 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.

  16. 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.

  17. Heuristic Value of a “Virtual Fruit” Model of Peach Fruit Quality and Sensitivity to Brown Rot : Impact of a Single Mutation and Design of Ideotypes

    OpenAIRE

    Génard, Michel; Quilot-Turion, Bénédicte; Ould Sidi, Mohamed Mahmoud; Kadrani, Abdeslam; Hilgert, Nadine; Lescourret, Francoise

    2015-01-01

    This work aimed at investigating the heuristic potential of a process-based model of peach fruit expressing seasonal changes in several quality attributes of fruit (e.g., size, percentages of flesh, water, sugar and acid contents) and fruit sensitivity to brown rot (skin density of cracks).[br/] Firstly, we showed that this “Virtual Fruit” could be used to analyze the impact of a single mutation which decreased the fruit’s requirement for carbon on peach fruit behavior. The mutation trigge...

  18. A Single Amino Acid Mutation (I1012F) of the RNA Polymerase of Marine Viral Hemorrhagic Septicemia Virus Changes In Vitro Virulence to Rainbow Trout Gill Epithelial Cells

    DEFF Research Database (Denmark)

    Kim, Sung-Hyun; Thu, Beate J.; Skall, Helle Frank

    2014-01-01

    was used in a gain-of-virulence approach based on the JF-09 backbone. Mutations were introduced into the G, NV, and L genes, and seven different virus clones were obtained. For the first time, we show that a single amino acid mutation in conserved region IV of the L protein, I1012F, rendered the virus able...... to in vivo virulence. In vitro virulence to gill epithelial cells (GECs) has been used as a proxy for in vivo virulence, and here we extend these studies further with the purpose of identifying residues associated with in vitro virulence. Genotype Ia (DK-3592B) and III (NO/650/07) isolates, which...

  19. 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.

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

    International Nuclear Information System (INIS)

    Gaillardin, M.; Raine, M.; Paillet, P.; Adell, P.C.; Girard, S.; Duhamel, O.; Andrieu, F.; Barraud, S.; Faynot, O.

    2015-01-01

    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.

  1. Highly sensitive detection of mutations in CHO cell recombinant DNA using multi-parallel single molecule real-time DNA sequencing.

    Science.gov (United States)

    Cartwright, Joseph F; Anderson, Karin; Longworth, Joseph; Lobb, Philip; James, David C

    2018-02-10

    High-fidelity replication of biologic-encoding recombinant DNA sequences by engineered mammalian cell cultures is an essential pre-requisite for the development of stable cell lines for the production of biotherapeutics. However, immortalized mammalian cells characteristically exhibit an increased point mutation frequency compared to mammalian cells in vivo, both across their genomes and at specific loci (hotspots). Thus unforeseen mutations in recombinant DNA sequences can arise and be maintained within producer cell populations. These may affect both the stability of recombinant gene expression and give rise to protein sequence variants with variable bioactivity and immunogenicity. Rigorous quantitative assessment of recombinant DNA integrity should therefore form part of the cell line development process and be an essential quality assurance metric for instances where synthetic/multi-component assemblies are utilized to engineer mammalian cells, such as the assessment of recombinant DNA fidelity or the mutability of single-site integration target loci. Based on Pacific Biosciences (Menlo Park, CA) single molecule real-time (SMRT™) circular consensus sequencing (CCS) technology we developed a rDNA sequence analysis tool to process the multi-parallel sequencing of ∼40,000 single recombinant DNA molecules. After statistical filtering of raw sequencing data, we show that this analytical method is capable of detecting single point mutations in rDNA to a minimum single mutation frequency of 0.0042% (sequence. There was no discernable difference between the mutation frequencies of coding and non-coding DNA. The putative ratio of non-synonymous and synonymous changes within the open reading frames (ORFs) in the plasmid sequence indicates that natural selection does not impact upon the prevalence of these mutations. Here we have demonstrated the abundance of mutations that fall outside of the reported range of detection of next generation sequencing (NGS) and second

  2. Topological events in single molecules of long genomic DNA confined in nanochannels

    Science.gov (United States)

    Reifenberger, Jeffrey; Dorfman, Kevin; Cao, Han

    2014-03-01

    ct- We present a rapid genome-wide analysis method based on new NanoChannel Array technology (IrysTM System) that confines and linearizes extremely long DNA molecules (100 to 1,000 kilobases) for direct image analysis at tens to hundred of gigabases per run. Genomic DNA is stained with YOYO and labeled specifically at the `GCTCTTC' sequence with fluorescent dyes allowing each molecule to be uniquely patterned and mapped to its corresponding reference. This high-throughput platform automates the imaging of such barcoded patterns on genomic DNA to identify wide spread structural variations in a genome. Here we describe a method to rule out possible topologically altered molecules in linear confinement by identifying possible topological events through a T-test looking for spikes in the fluorescence of the YOYO stained DNA backbone. These events are confirmed through aligning the marked individual molecules to a standard reference and measuring a distance differential between labels surrounding the suspected topological event compared to the reference. Such events could be flagged to distinguish from true structural variations.

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

    Indian Academy of Sciences (India)

    Unknown

    board pattern of 55h (01010101) and AAh (10101010) in alternate locations during irradiation. Data stored in the memory is continuously read and verified with the refer- ence data pattern. In the event of any upset, the failure is recorded and the data is re-written again. This reading and writing process continues during the ...

  4. 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.

  5. Deleting a Single Protein Restores Critical DNA Repair Process in Mice with Brca1 Gene Mutations | Center for Cancer Research

    Science.gov (United States)

    Women who carry a harmful mutation in the BRCA1 gene have up to an 85 percent greater lifetime risk of developing breast cancer than other women, and up to a 40 percent greater chance of developing ovarian cancer. Thus far, no effective therapies have been developed that overcome the susceptibility to cancer caused by mutations in BRCA1.

  6. 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 tb is performed.

  7. 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…

  8. 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.)

  9. 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

  10. Two single mutations in the fusion protein of Newcastle disease virus confer hemagglutinin-neuraminidase independent fusion promotion and attenuate the pathogenicity in chickens.

    Science.gov (United States)

    Ji, Yanhong; Liu, Tao; Jia, Yane; Liu, Bin; Yu, Qingzhong; Cui, Xiaole; Guo, Fengfeng; Chang, Huiyun; Zhu, Qiyun

    2017-09-01

    The fusion (F) protein of Newcastle disease virus (NDV) affects viral infection and pathogenicity through mediating membrane fusion. Previously, we found NDV with increased fusogenic activity in which contained T458D or G459D mutation in the F protein. Here, we investigated the effects of these two mutations on viral infection, fusogenicity and pathogenicity. Syncytium formation assays indicated that T458D or G459D increased the F protein cleavage activity and enhanced cell fusion with or without the presence of HN protein. The T458D- or G459D-mutated NDV resulted in a decrease in virus replication or release from cells. The animal study showed that the pathogenicity of the mutated NDVs was attenuated in chickens. These results indicate that these two single mutations in F altered or diminished the requirement of HN for promoting membrane fusion. The increased fusogenic activity may disrupt the cellular machinery and consequently decrease the virus replication and pathogenicity in chickens. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Autonomous Gait Event Detection with Portable Single-Camera Gait Kinematics Analysis System

    OpenAIRE

    Yang, Cheng.; Ugbolue, Ukadike C..; Kerr, Andrew.; Stankovic, Vladimir.; Stankovic, Lina.; Carse, Bruce.; Kaliarntas, Konstantinos T..; Rowe, Philip J..

    2016-01-01

    Laboratory-based nonwearable motion analysis systems have significantly advanced with robust objective measurement of the limb motion, resulting in quantified, standardized, and reliable outcome measures compared with traditional, semisubjective, observational gait analysis. However, the requirement for large laboratory space and operational expertise makes these systems impractical for gait analysis at local clinics and homes. In this paper, we focus on autonomous gait event detection with o...

  12. Mutations in HIV-1 Reverse Transcriptase Affect the Errors Made in a Single Cycle of Viral Replication

    Science.gov (United States)

    Abram, Michael E.; Ferris, Andrea L.; Das, Kalyan; Quinoñes, Octavio; Shao, Wei; Tuske, Steven; Alvord, W. Gregory; Arnold, Eddy

    2014-01-01

    ABSTRACT The genetic variation in HIV-1 in patients is due to the high rate of viral replication, the high viral load, and the errors made during viral replication. Some of the mutations in reverse transcriptase (RT) that alter the deoxynucleoside triphosphate (dNTP)-binding pocket, including those that confer resistance to nucleoside/nucleotide analogs, affect dNTP selection during replication. The effects of mutations in RT on the spectrum (nature, position, and frequency) of errors made in vivo are poorly understood. We previously determined the mutation rate and the frequency of different types of mutations and identified hot spots for mutations in a lacZα (the α complementing region of lacZ) reporter gene carried by an HIV-1 vector that replicates using wild-type RT. We show here that four mutations (Y115F, M184V, M184I, and Q151M) in the dNTP-binding pocket of RT that had relatively small effects on the overall HIV-1 mutation rate (less than 3-fold compared to the wild type) significantly increased mutations at some specific positions in the lacZα reporter gene. We also show that changes in a sequence that flanks the reporter gene can affect the mutations that arise in the reporter. These data show that changes either in HIV-1 RT or in the sequence of the nucleic acid template can affect the spectrum of mutations made during viral replication. This could, by implication, affect the generation of drug-resistant mutants and immunological-escape mutants in patients. IMPORTANCE RT is the viral enzyme that converts the RNA genome of HIV into DNA. Errors made during replication allow the virus to escape from the host's immune system and to develop resistance to the available anti-HIV drugs. We show that four different mutations in RT which are known to be associated with resistance to anti-RT drugs modestly increased the overall frequency of errors made during viral replication. However, the increased errors were not uniformly distributed; the additional errors

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. Real-time gait event detection for lower limb amputees using a single wearable sensor.

    Science.gov (United States)

    Maqbool, H F; Husman, M A B; Awad, M I; Abouhossein, A; Mehryar, P; Iqbal, N; Dehghani-Sanij, A A

    2016-08-01

    This paper presents a rule-based real-time gait event/phase detection system (R-GEDS) using a shank mounted inertial measurement unit (IMU) for lower limb amputees during the level ground walking. Development of the algorithm is based on the shank angular velocity in the sagittal plane and linear acceleration signal in the shank longitudinal direction. System performance was evaluated with four control subjects (CS) and one transfemoral amputee (TFA) and the results were validated with four FlexiForce footswitches (FSW). The results showed a data latency for initial contact (IC) and toe off (TO) within a range of ± 40 ms for both CS and TFA. A delay of about 3.7 ± 62 ms for a foot-flat start (FFS) and an early detection of -9.4 ± 66 ms for heel-off (HO) was found for CS. Prosthetic side showed an early detection of -105 ± 95 ms for FFS whereas intact side showed a delay of 141 ±73 ms for HO. The difference in the kinematics of the TFA and CS is one of the potential reasons for high variations in the time difference. Overall, detection accuracy was 99.78% for all the events in both groups. Based on the validated results, the proposed system can be used to accurately detect the temporal gait events in real-time that leads to the detection of gait phase system and therefore, can be utilized in gait analysis applications and the control of lower limb prostheses.

  18. Distinct pattern of p53 mutations in bladder cancer

    DEFF Research Database (Denmark)

    Spruck, C H; Rideout, W M; Olumi, A F

    1993-01-01

    A distinct mutational spectrum for the p53 tumor suppressor gene in bladder carcinomas was established in patients with known exposures to cigarette smoke. Single-strand conformational polymorphism analysis of exons 5 through 8 of the p53 gene showed inactivating mutations in 16 of 40 (40%) bladder...... double mutations, four of which were tandem mutations on the same allele. No double mutations were found in tumors from nonsmoking patients. None of the mutations in smokers were G:C-->T:A transversions, which would be anticipated for exposure to the suspected cigarette smoke carcinogen 4-aminobiphenyl....... The results suggest that, although cigarette smoke exposure may not significantly alter the kinds of mutations sustained in the p53 gene, it may act to increase the extent of DNA damage per mutagenic event....

  19. Single and multiple cardiovascular biomarkers in subjects without a previous cardiovascular event

    DEFF Research Database (Denmark)

    Pareek, Manan; Bhatt, Deepak L; Vaduganathan, Muthiah

    2017-01-01

    failure, stroke, or all-cause mortality. Predictive capabilities were evaluated using Cox proportional-hazards regression, Harrell's concordance index (C-index), and net reclassification improvement. Median age was 66 (interquartile range: 60-70) years, and 413 (31%) were female. During median 8.......6 (interquartile range: 8.1-9.2) follow-up years, 368 (28%) composite events occurred. NT-proBNP, hs-TnT, GDF-15, and IL-6 were significantly associated with outcome, independently of traditional risk factors, medications, and echocardiography ( p 

  20. 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.

  1. Single event upset tests of a RISC-based fault-tolerant computer

    Energy Technology Data Exchange (ETDEWEB)

    Kimbrough, J.R.; Butner, D.N.; Colella, N.J.; Kaschmitter, J.L.; Shaeffer, D.L.; McKnett, C.L.; Coakley, P.G.; Casteneda, C.

    1996-03-23

    The project successfully demonstrated that dual lock-step comparison of commercial RISC processors is a viable fault-tolerant approach to handling SEU in space environment. The fault tolerant approach on orbit error rate was 38 times less than the single processor error rate. The random nature of the upsets and appearance in critical code section show it is essential to incorporate both hardware and software in the design and operation of fault-tolerant computers.

  2. Do patients with recurrent episodes of campylobacteriosis differ from those with a single disease event?

    Directory of Open Access Journals (Sweden)

    Michel Pascal

    2011-01-01

    Full Text Available Abstract Background Although Campylobacter is the leading cause of reported bacterial gastro-enteritis in industrialized countries, little is known on its recurrence. The objective of this study is to describe the risk and the patient characteristics of recurrent episodes of human campylobacteriosis reported in Quebec. Methods Laboratory-confirmed cases of campylobacteriosis reported in the province of Quebec, Canada, through ongoing surveillance between 1996 and 2006 were analyzed. The risk of having a recurrent episode of campylobacteriosis was described using life table estimates. Logistic regression was used to assess if gender, age and patient residential location were associated with an increased risk of recurrence. Results Compared to the baseline risk, the risk for a recurrent disease event was higher for a period of four years and followed a decreasing trend. This increased risk of a recurrent event was similar across gender, but higher for people from rural areas and lower for children under four years of age. Conclusions These results may suggest the absence of durable immunity or clinical resilience following a first episode of campylobacteriosis and periodical re-exposure, at least among cases reported through the surveillance system.

  3. Do patients with recurrent episodes of campylobacteriosis differ from those with a single disease event?

    Science.gov (United States)

    2011-01-01

    Background Although Campylobacter is the leading cause of reported bacterial gastro-enteritis in industrialized countries, little is known on its recurrence. The objective of this study is to describe the risk and the patient characteristics of recurrent episodes of human campylobacteriosis reported in Quebec. Methods Laboratory-confirmed cases of campylobacteriosis reported in the province of Quebec, Canada, through ongoing surveillance between 1996 and 2006 were analyzed. The risk of having a recurrent episode of campylobacteriosis was described using life table estimates. Logistic regression was used to assess if gender, age and patient residential location were associated with an increased risk of recurrence. Results Compared to the baseline risk, the risk for a recurrent disease event was higher for a period of four years and followed a decreasing trend. This increased risk of a recurrent event was similar across gender, but higher for people from rural areas and lower for children under four years of age. Conclusions These results may suggest the absence of durable immunity or clinical resilience following a first episode of campylobacteriosis and periodical re-exposure, at least among cases reported through the surveillance system. PMID:21226938

  4. Measurement of s-channel single top-quark production with the ATLAS detector using total event likelihoods

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00333614

    2016-09-21

    A measurement of s-channel single top-quark production in proton-proton collisions at a centre-of-mass energy of $8\\,\\mathrm{TeV}$ is presented. The dataset has been recorded with the ATLAS detector at the LHC and corresponds to an integrated luminosity of 20.3$\\,\\mathrm{fb}^{−1}$. Collision events are selected so that a subset of the data is obtained where the signal fraction is relatively high. Selected events contain one isolated electron or muon, missing transverse momentum and 2 jets, both of which are induced by b-quarks. All of these objects have large transverse momenta. The resulting set of events is still dominated by background processes, most notably top-quark pair production and the production of W-bosons in association with jets. In order to further separate the signal from the backgrounds, several approximate event likelihoods are computed. They are based on different hypotheses regarding the scattering process at hand. Together they result in a function of the measured momenta which allows ...

  5. 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...

  6. Liquid Hole-Multipliers: A potential concept for large single-phase noble-liquid TPCs of rare events

    Science.gov (United States)

    Breskin, Amos

    2013-10-01

    A novel concept is proposed for large-volume single-phase noble-liquid TPC detectors for rare events. Both radiation-induced scintillation-light and ionization-charge are detected by Liquid Hole-Multipliers (LHM), immersed in the noble liquid. The latter may consist of cascaded Gas Electron Multipliers (GEM), Thick Gas Electron Multiplier (THGEM) electrodes or others, coated with CsI UV-photocathodes. Electrons, photo-induced on CsI by primary scintillation in the noble liquid, and event-correlated drifting ionization electrons are amplified in the cascaded elements primarily through electroluminescence, and possibly through additional moderate avalanche, occurring within the holes. The resulting charge-signals or light-pulses are recorded on anode pads or with photosensors - e.g. gaseous photomultipliers (GPM), respectively. Potential affordable solutions are proposed for multi-ton dark-matter detectors; open questions are formulated for validating this dream.

  7. Liquid Hole-Multipliers: A potential concept for large single-phase noble-liquid TPCs of rare events

    International Nuclear Information System (INIS)

    Breskin, Amos

    2013-01-01

    A novel concept is proposed for large-volume single-phase noble-liquid TPC detectors for rare events. Both radiation-induced scintillation-light and ionization-charge are detected by Liquid Hole-Multipliers (LHM), immersed in the noble liquid. The latter may consist of cascaded Gas Electron Multipliers (GEM), Thick Gas Electron Multiplier (THGEM) electrodes or others, coated with CsI UV-photocathodes. Electrons, photo-induced on CsI by primary scintillation in the noble liquid, and event-correlated drifting ionization electrons are amplified in the cascaded elements primarily through electroluminescence, and possibly through additional moderate avalanche, occurring within the holes. The resulting charge-signals or light-pulses are recorded on anode pads or with photosensors – e.g. gaseous photomultipliers (GPM), respectively. Potential affordable solutions are proposed for multi-ton dark-matter detectors; open questions are formulated for validating this dream

  8. 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.

  9. Multivariate Bayesian decoding of single-trial event-related fMRI responses for memory retrieval of voluntary actions.

    Directory of Open Access Journals (Sweden)

    Dongha Lee

    Full Text Available This study proposes a method for classifying event-related fMRI responses in a specialized setting of many known but few unknown stimuli presented in a rapid event-related design. Compared to block design fMRI signals, classification of the response to a single or a few stimulus trial(s is not a trivial problem due to contamination by preceding events as well as the low signal-to-noise ratio. To overcome such problems, we proposed a single trial-based classification method of rapid event-related fMRI signals utilizing sparse multivariate Bayesian decoding of spatio-temporal fMRI responses. We applied the proposed method to classification of memory retrieval processes for two different classes of episodic memories: a voluntarily conducted experience and a passive experience induced by watching a video of others' actions. A cross-validation showed higher classification performance of the proposed method compared to that of a support vector machine or of a classifier based on the general linear model. Evaluation of classification performances for one, two, and three stimuli from the same class and a correlation analysis between classification accuracy and target stimulus positions among trials suggest that presenting two target stimuli at longer inter-stimulus intervals is optimal in the design of classification experiments to identify the target stimuli. The proposed method for decoding subject-specific memory retrieval of voluntary behavior using fMRI would be useful in forensic applications in a natural environment, where many known trials can be extracted from a simulation of everyday tasks and few target stimuli from a crime scene.

  10. Saharan dust events at the Jungfraujoch: detection by wavelength dependence of the single scattering albedo and first climatology analysis

    Directory of Open Access Journals (Sweden)

    M. Collaud Coen

    2004-01-01

    Full Text Available Scattering and absorption coefficients have been measured continuously at several wavelengths since March 2001 at the high altitude site Jungfraujoch (3580ma.s.l.. From these data, the wavelength dependences of the Ångström exponent and particularly of the single scattering albedo are determined. While the exponent of the single scattering albedo usually increases with wavelength, it decreases with wavelength during Saharan dust events (SDE due to the greater size of the mineral aerosol particles and their different chemical composition. This change in the sign of the single scattering exponent turns out to be a sensitive means for detecting Saharan dust events. The occurrence of SDE detected by this new method was confirmed by visual inspection of filter colors and by studying long-range back-trajectories. An examination of SDE over a 22-month period shows that SDE are more frequent during the March-June period as well as during October and November. The trajectory analysis indicated a mean traveling time of 96.5h, with the most important source countries situated in the northern and north-western part of the Saharan desert. Most of the SDE do not lead to a detectable increase of the 48-h total suspended particulate matter (TSP concentration at the Jungfraujoch. During Saharan dust events, the average contribution of this dust to hourly TSP at the Jungfraujoch is 16µg/m3, which corresponds to an annual mean of 0.8µg/m3 or 24% of TSP.

  11. Analysis of single event transient pulse-width in 65 nm commercial radiation-hardened logic cell

    Science.gov (United States)

    Li, Haisong; Wu, Longsheng; Yang, Bo; Jiang, Yihu

    2017-08-01

    With the critical charge reduced to generate a single event effect (SEE) and high working frequency for a nanometer integrated circuit, the single event effect (SET) becomes increasingly serious for high performance SOC and DSP chips. To analyze the radiation-hardened method of SET for the nanometer integrated circuit, the n+ guard ring and p+ guard ring have been adopted in the layout for a 65 nm commercial radiation-hardened standard cell library. The weakest driving capacity inverter cell was used to evaluate the single event transient (SET) pulse-width distribution. We employed a dual-lane measurement circuit to get more accurate SET’s pulse-width. Six kinds of ions, which provide LETs of 12.5, 22.5, 32.5, 42, 63, and 79.5 {MeV}\\cdot {{cm}}2/{mg}, respectively, have been utilized to irradiate the SET test circuit in the Beijing Tandem Accelerator Nuclear Physics National Laboratory. The testing results reveal that the pulse-width of most SETs is shorter than 400 ps in the range of LETeff from 12.5 {MeV}\\cdot {{cm}}2/{mg} to 79.5 {MeV}\\cdot {{cm}}2/{mg} and the pulse-width presents saturation tendency when the effective linear energy transfer (LETeff) value is larger than 40 {MeV}\\cdot {{cm}}2/{mg}. The test results also show that the hardened commercial standard cell’s pulse-width concentrates on 33 to 264 ps, which decreases by 40% compared to the pulse-width of the 65 nm commercial unhardened standard cell.

  12. 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

  13. 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.

  14. 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

  15. 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)

  16. Search for supersymmetry in events with a single lepton, jets, and missing transverse momentum using a neural network

    CERN Document Server

    Chatterjee, Avishek

    A search for supersymmetry in proton-proton collisions at $\\sqrt{s} = 7$ TeV is presented, focusing on events with a single isolated lepton, energetic jets, and large missing transverse momentum. The analyzed data corresponds to a total integrated luminosity of 4.98 fb$^{−1}$ recorded by the CMS experiment. The search uses an artificial neural network to suppress Standard Model backgrounds, and estimates residual backgrounds using a fully data-driven method. The analysis is performed in both the muon and electron channels, and the combined result is interpreted in terms of limits on the CMSSM parameter space, as well as a simplified model.

  17. 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)

  18. Single event and TREE latchup mitigation for a star tracker sensor: An innovative approach to system level latchup mitigation

    Energy Technology Data Exchange (ETDEWEB)

    Kimbrough, J.R.; Colella, N.J.; Davis, R.W. [Lawrence Livermore National Lab., CA (United States); Bruener, D.B.; Coakley, P.G.; Lutjens, S.W.; Mallon, C.E. [JAYCOR, San Diego, CA (United States)

    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).

  19. 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)

  20. Mutations in exons 9 and 13 of KIT gene are rare events in gastrointestinal stromal tumors. A study of 200 cases.

    Science.gov (United States)

    Lasota, J; Wozniak, A; Sarlomo-Rikala, M; Rys, J; Kordek, R; Nassar, A; Sobin, L H; Miettinen, M

    2000-10-01

    Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, typically express the KIT protein. Activating mutations in the juxtamembrane domain (exon 11) of the c-kit gene have been shown in a subset of GISTs. These mutations lead into ligand-independent activation of the tyrosine kinase of c-kit, and have a transforming effect in vitro. Several groups have studied the clinical implication of the c-kit mutation status of exon 11 in GISTs and a possible relationship between c-kit mutations and malignant behavior has been established. Recently, a 1530ins6 mutation in exon 9 and missense mutations, 1945A>G in exon 13 of the c-kit gene were reported. The frequency and clinical importance of these findings are unknown. In this study we evaluated 200 GISTs for the presence of mutations in exons 9 and 13 of c-kit. Six cases revealed 1530ins6 mutation in exon 9 and two cases 1945A>G mutation in exon 13. All tumors with mutations in exon 9 and 13 lacked mutations in exon 11 of c-kit. None of the analyzed tumors had more than one type of c-kit mutation. All but one of the eight tumors with mutations in exon 9 or 13 of the c-kit gene were histologically and clinically malignant. All four of six cases with exon 9 mutation of which location of primary tumor was known, were small intestinal, suggesting that this type of mutation could preferentially occur in small intestinal tumors. Exon 9 and 13 mutations seem to be rare, and they cover only a small portion (8%) of the balance of GISTs that do not have mutations in exon 11 of c-kit. This finding indicates that other genetic alterations may activate c-kit in GISTs, or that KIT is not activated by mutations in all cases.

  1. 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

  2. Dynamics and Fate of Beneficial Mutations Under Lineage Contamination by Linked Deleterious Mutations

    Science.gov (United States)

    Pénisson, Sophie; Singh, Tanya; Sniegowski, Paul

    2017-01-01

    Beneficial mutations drive adaptive evolution, yet their selective advantage does not ensure their fixation. Haldane’s application of single-type branching process theory showed that genetic drift alone could cause the extinction of newly arising beneficial mutations with high probability. With linkage, deleterious mutations will affect the dynamics of beneficial mutations and might further increase their extinction probability. Here, we model the lineage dynamics of a newly arising beneficial mutation as a multitype branching process. Our approach accounts for the combined effects of drift and the stochastic accumulation of linked deleterious mutations, which we call lineage contamination. We first study the lineage-contamination phenomenon in isolation, deriving dynamics and survival probabilities (the complement of extinction probabilities) of beneficial lineages. We find that survival probability is zero when U≳sb, where U is deleterious mutation rate and sb is the selective advantage of the beneficial mutation in question, and is otherwise depressed below classical predictions by a factor bounded from below by ∼1−U/sb. We then put the lineage contamination phenomenon into the context of an evolving population by incorporating the effects of background selection. We find that, under the combined effects of lineage contamination and background selection, ensemble survival probability is never zero but is depressed below classical predictions by a factor bounded from below by e−εU/s¯b, where s¯b is mean selective advantage of beneficial mutations, and ε=1−e−1≈0.63. This factor, and other bounds derived from it, are independent of the fitness effects of deleterious mutations. At high enough mutation rates, lineage contamination can depress fixation probabilities to values that approach zero. This fact suggests that high mutation rates can, perhaps paradoxically, (1) alleviate competition among beneficial mutations, or (2) potentially even shut

  3. Single event transient modeling and mitigation techniques for mixed-signal delay locked loop (DLL) and clock circuits

    Science.gov (United States)

    Maillard, Pierre

    The purpose of this PhD work has been to investigate, model, test, develop and provide hardening techniques and guidelines for the mitigation of single event transients (SETs) in analog mixed-signal (AMS) delay locked loops (DLLs) for radiation-hardened applications. Delay-locked-loops (DLLs) are circuit substructures that are present in complex ASIC and system-on-a-chip designs. These circuits are widely used in on-chip clock distribution systems to reduce clock skew, to reduce jitter noise, and to recover clock signals at regional points within a global clock distribution system. DLLs are critical to the performance of many clock distribution systems, and in turn, the overall performance of the associated integrated system; as such, complex systems often employ multiple DLLs for clock deskew and distribution tasks. In radiation environments such as on-orbit, these critical circuits represent at-risk points of malfunction for large sections of integrated circuits due to vulnerabilities to radiation-generated transients (i.e. single event transients) that fan out across the system. The analysis of single event effects in analog DLLs has shown that each DLL sub-circuit primitive is vulnerable to single event transients. However, we have identified the voltage controlled delay line (VCDL) sub-circuit as the most sensitive to radiation-induced single event effects generating missing clock pulses that increase with the operating frequency of the circuit. This vulnerability increases with multiple instantiation of DLLs as clock distribution nodes throughout an integrated system on a chip. To our knowledge, no complete work in the rad-hard community regarding the hardening of mixed-signal DLLs against single event effects (missing pulses) has been developed. Most of the work present in the literature applies the "brute force" and well-established digital technique of triple modular redundancy (TMR) to the digital subcomponents. We have developed two novel design

  4. 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.

  5. Models of synchronized hippocampal bursts in the presence of inhibition. I. Single population events.

    Science.gov (United States)

    Traub, R D; Miles, R; Wong, R K

    1987-10-01

    1. We constructed model networks with 520 or 1,020 cells intended to represent the CA3 region of the hippocampus. Model neurons were simulated in enough detail to reproduce intrinsic bursting and the electrotonic flow of currents along dendritic cables. Neurons exerted either excitatory or inhibitory postsynaptic actions on other cells. The network models were simulated with different levels of excitatory and inhibitory synaptic strengths in order to study epileptic and other interesting collective behaviors in the system. 2. Excitatory synapses between neurons in the network were powerful enough so that burst firing in a presynaptic neuron would evoke bursting in its connected cells. Since orthodromic or antidromic stimulation evokes both a fast and a slow phase of inhibition, two types of inhibitory cells were simulated. The properties of these inhibitory cells were modeled to resemble those of two types of inhibitory cells characterized by dual intracellular recordings in the slice preparation. 3. With fast inhibition totally blocked, a stimulus to a single cell lead to a synchronized population burst. Thus the principles of our epileptic synchronization model, developed earlier, apply even when slow inhibitory postsynaptic potentials (IPSPs) are present, as apparently occurs in the epileptic hippocampal slice. The model performs in this way because bursting can propagate through several generations in the network before slow inhibition builds up enough to block burst propagation. This can occur, however, only if connectivity is sufficiently large. With very low connection densities, slow IPSPs will prevent the development of full synchronization. 4. We performed multiple simulations in which the fast inhibitory conductance strength was kept fixed at various levels while the strength of the excitatory synapses was varied. In each simulation, we stimulated either one or four cells. For each level of inhibition, the peak number of cells bursting depended

  6. 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.

  7. 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.

  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. Classification of single-trial auditory events using dry-wireless EEG during real and motion simulated flight.

    Science.gov (United States)

    Callan, Daniel E; Durantin, Gautier; Terzibas, Cengiz

    2015-01-01

    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 vs. silent periods. Evaluation of Independent component analysis (ICA) 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.

  10. 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.

  11. Clonal origin of multiple lung cancers: K-ras and p53 mutations determined by nonradioisotopic single-strand conformation polymorphism analysis.

    Science.gov (United States)

    Lau, D H; Yang, B; Hu, R; Benfield, J R

    1997-08-01

    Disease stage is the most important factor in determining prognosis and treatment of lung cancer. Staging of lung cancer is complicated by presentation of multiple pulmonary malignant lesions with a similar histology. It is a dilemma to decide if these lesions are synchronous primaries arising from different malignant clones or metastases from a single clone. Lung cancer is associated with multiple genetic abnormalities including mutations of K-ras and p53, which are believed to occur prior to onset of metastasis. To determine the clonal origin of multiple pulmonary malginant nodules, we analyzed point-mutations of K-ras and p53 by microdissection, polymerase chain reactions (PCR), nonradioisotopic single-strand conformation polymorphism (SSCP) analysis, and DNA sequencing. Each pulmonary lesion was microdissected from paraffin slides. Genomic DNA was amplified by two sequential PCRs followed by electrophoresis in a minigel and silver staining. Deoxyribonucleic acid sequencing was performed if necessary to confirm a mutation found upon SSCP analysis. Applying this molecular approach, we were able to differentiate the clonal origins of multiple malignant nodules of the lung as exemplified by the two cases presented.

  12. 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.

  13. Total ionizing dose (TID) effect and single event effect (SEE) in quasi-SOI nMOSFETs

    International Nuclear Information System (INIS)

    Tan, Fei; Huang, Ru; An, Xia; Wu, Weikang; Feng, Hui; Huang, Liangxi; Fan, Jiewen; Zhang, Xing; Wang, Yangyuan

    2014-01-01

    This paper studies the total ionizing dose (TID) and single event effect (SEE) in quasi-SOI nMOSFETs for the first time. After exposure to gamma rays, the off-state leakage current (I off ) of a quasi-SOI device increases with the accumulating TID, and the on-state bias configuration is shown to be the worst-case bias configuration during irradiation. Although an additional TID-sensitive region is introduced by the unique structure of the quasi-SOI device, the influence of positive charge trapped in L-type oxide layers on the degradation of device performance is neglectable. Since the TID-induced leakage path in the quasi-SOI device is greatly reduced due to the isolation of L-type oxide layers, the TID-induced I off  degradation in the quasi-SOI device is greatly suppressed. In addition, 3D simulation is performed to investigate the SEE of the quasi-SOI device. The full-width at half-maximum (FWHM) of worst-case drain current transient and collected charges of the quasi-SOI device after single-ion-striking is smaller than in a bulk Si device, indicating that the quasi-SOI device inherits the advantage of an SOI device in single event transient immunity. Therefore, the quasi-SOI device, which has improved electrical properties and radiation-hardened characteristics for both TID and SEE, can be considered as one of the promising candidates for space applications. (paper)

  14. 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...

  15. A pilot study of BRCA mutation carriers' knowledge about the clinical impact of prophylactic-oophorectomy and views on fertility consultation: a single-center pilot study.

    Science.gov (United States)

    Kim, J; Skrzynia, C; Mersereau, J E

    2015-02-01

    BRCA mutation carriers will experience early surgically induced menopause following prophylactic bilateral salpingo-oophorectomy (PBSO). This pilot study aimed to investigate their (1) knowledge about the clinical impact of PBSO; (2) views on fertility consultation (FC)/fertility preservation (FP) treatment; and (3) difficulties in conceiving compared to non-carriers. A cross-sectional, single institution web-survey was performed at a university-based IVF center. Women aged 18-50 years who were screened for BRCA gene mutations from 2005 to 2013 were recruited via mail. Forty-one BRCA-positive and 110 BRCA-negative women completed the survey (response rate: 50 %). The knowledge about the reproductive impact of PBSO was limited, with the majority of women in this highly educated sample only identifying the correct response 64 % of the time. Among BRCA mutation carriers, 24 (59 %) had positive views about FC/FP treatments. A larger proportion of women with no children at the time of BRCA testing, and those who were non-white tended to have positive views toward FP. Women with, versus without, BRCA mutations were more likely to have difficulty in conceiving (p = 0.08). This well-educated group had limited knowledge about the reproductive clinical impact of PBSO, or the benefit of a FP before PBSO. Most women with BRCA mutations were interested in FC/FP treatment if they had not completed childbearing at the time of screening. Targeted referrals for FC at the time of BRCA screening may help women improve knowledge and allow improved decision-making about reproductive options.

  16. 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.

  17. 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.

  18. 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.

  19. Microscopic mechanisms for long QT syndrome type 1 revealed by single-channel analysis of I(Ks) with S3 domain mutations in KCNQ1.

    Science.gov (United States)

    Eldstrom, Jodene; Wang, Zhuren; Werry, Daniel; Wong, Nathan; Fedida, David

    2015-02-01

    The slowly activating delayed rectifier current IKs participates in cardiac repolarization, particularly at high heart rates, and mutations in this K(+) channel complex underlie long QT syndrome (LQTS) types 1 and 5. The purpose of this study was to determine biophysical mechanisms of LQT1 through single-channel kinetic analysis of IKs carrying LQT1 mutations in the S3 transmembrane region of the pore-forming subunit KCNQ1. We analyzed cell-attached recordings from mammalian cells in which a single active KCNQ1 (wild type or mutant) and KCNE1 complex could be detected. The S3 mutants of KCNQ1 studied (D202H, I204F, V205M, and S209F), with the exception of S209F, all led to a reduction in channel activity through distinct kinetic mechanisms. D202H, I204F, and V205M showed decreased open probability (Po) compared with wild type (0.07, 0.04, and 0.12 vs 0.2); increased first latency from 1.66 to >2 seconds at +60 mV (I204F, V205M); variable-to-severe reductions in open dwell times (≥50% in V205M); stabilization of closed states (D202H); and an inability of channels to reach full conductance levels (V205M, I204F). S209F is a kinetic gain-of-function mutation with a high Po (0.40) and long open-state dwell times. S3 mutations in KCNQ1 cause diverse kinetic defects in I(Ks), affecting opening and closing properties, and can account for LQT1 phenotypes. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  20. 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.

  1. Mapping Mutations on Phylogenies

    DEFF Research Database (Denmark)

    Nielsen, Rasmus

    2005-01-01

    This chapter provides a short review of recent methodologies developed for mapping mutations on phylogenies. Mapping of mutations, or character changes in general, using the maximum parsimony principle has been one of the most powerful tools in phylogenetics, and it has been used in a variety...... uncertainty in the mapping. Recently developed probabilistic methods can incorporate statistical uncertainty in the character mappings. In these methods, focus is on a probability distribution of mutational mappings instead of a single estimate of the mutational mapping....

  2. 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)

  3. [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.

  4. Analysis of using protons in secondary beam on BEPC as a particle source in single event effects experiment study

    International Nuclear Information System (INIS)

    He Chaohui; Li Guozheng; Liu Enke

    1999-01-01

    The energy range and yield of the protons in the secondary beam on BEPC are first analyzed, at the point of using the protons as a particle source in the single event effects (SEE) experiment of semiconductor devices. The energy ranges of the proton produced by high energy electrons bombarding on targets in three methods are calculated and the corresponding cross sections are estimated. The cross section of producing protons can be increased by using heavy nucleus target and the differential yield of protons can reach 1.66 x 10 -3 s -1 ·sr -1 ·eV -1 . The protons can be used in SEE experiment of the semiconductor devices with the high SEE cross sections

  5. Proton-induced single event upset characterisation of a 1 giga-sample per second analog to digital converter

    International Nuclear Information System (INIS)

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

    1999-01-01

    The SPT7760 is an analog to digital converter that is used in satellite for digital processing. In this paper we describe the characterization and analysis of proton-induced single event upsets (SEU) for the SPT7760 operating at sample rates from 125 Msps (Mega-samples per second) to 1 Gsps. The SEU cross-section has been measured as a function of sample rate for various input levels. The data collected is clearly non-linear for all cases. The data shows that this device has a relative low cross-section for proton-induced SEUs and remains functional at a proton dose of 580 krad (Si). (A.C.)

  6. 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)

  7. Experimental and 2D simulation study of the single-event burnout in n-channel power MOSFETs

    International Nuclear Information System (INIS)

    Roubaud, F.; Dachs, C.; Palau, J.M.; Gasiot, J.

    1993-01-01

    The use of the 2D simulator MEDICI as a tool for Single Event Burnout (SEB) comprehension is investigated. Simulation results are compared to experimental currents induced in an N channel power MOSFET by the ions from a 252 Cf source. Current measurements have been carried out with a specially designed circuit. Simulations allow to analyze separately the effects of the ion impact and of the electrical environment parameters on the SEB phenomenon. Burnout sensitivity is found to be increased by increasing supply voltage, ion's LET and by decreasing load charge. These electrical tendencies are validated by experiments. Burnout sensitivity is also found to be sensitive to the ion impact position. The current shapes variations for given electrical parameters can be related to LET or ion impact position changes. However, some experimental current shapes are not reproduced by simulations

  8. Solid state detector for high spatial resolution coupled to a single event acquisition system for slow neutron detection

    Science.gov (United States)

    Casinini, F.; Petrillo, C.; Sacchetti, F.

    2012-05-01

    In the next years the slow neutron scattering community is waiting for a continuous improvement of the neutron detectors because of the development of the new and more intense neutron sources and to obtain a better performance of the neutron instrumentation to face the higher demands and new capabilities necessary for the novel experiments. In particular detectors having a faster response and a better shape of the time response must be produced, while new and more flexible acquisition systems must be introduced in order to collect in the proper way the information carried by the scattered neutrons. At present inside the neutron detector community the lack for detectors having a spatial resolution below 1 mm is evident. In the past it has been already demonstrated that a silicon microstrip detector coupled to a Gadolinium foil, used as neutron converter, provides a good performance neutron detector. In the present paper we present a 128 channel detector which has been designed for operation in the thermal neutron region with 0.55 mm spatial resolution, 100 ns time resolution and 25 ns time stamp accuracy. We present a new approach for the acquisition of the neutron arrival time, based on a single event storage by manipulating the detector digital output using a programmable acquisition system which takes advantage from high performance industrial standard hardware employing a FPGA and a real-time on board processor. We suggest the use of the single neutron event storing to make the time to energy transformation more efficient in the case of time of flight inelastic scattering, where the conversion from angle and time to momentum and energy is necessary.

  9. Absolute Quantification of Rifampicin by MALDI Imaging Mass Spectrometry Using Multiple TOF/TOF Events in a Single Laser Shot.

    Science.gov (United States)

    Prentice, Boone M; Chumbley, Chad W; Caprioli, Richard M

    2017-01-01

    Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) allows for the visualization of molecular distributions within tissue sections. While providing excellent molecular specificity and spatial information, absolute quantification by MALDI IMS remains challenging. Especially in the low molecular weight region of the spectrum, analysis is complicated by matrix interferences and ionization suppression. Though tandem mass spectrometry (MS/MS) can be used to ensure chemical specificity and improve sensitivity by eliminating chemical noise, typical MALDI MS/MS modalities only scan for a single MS/MS event per laser shot. Herein, we describe TOF/TOF instrumentation that enables multiple fragmentation events to be performed in a single laser shot, allowing the intensity of the analyte to be referenced to the intensity of the internal standard in each laser shot while maintaining the benefits of MS/MS. This approach is illustrated by the quantitative analyses of rifampicin (RIF), an antibiotic used to treat tuberculosis, in pooled human plasma using rifapentine (RPT) as an internal standard. The results show greater than 4-fold improvements in relative standard deviation as well as improved coefficients of determination (R 2 ) and accuracy (>93% quality controls, errors). This technology is used as an imaging modality to measure absolute RIF concentrations in liver tissue from an animal dosed in vivo. Each microspot in the quantitative image measures the local RIF concentration in the tissue section, providing absolute pixel-to-pixel quantification from different tissue microenvironments. The average concentration determined by IMS is in agreement with the concentration determined by HPLC-MS/MS, showing a percent difference of 10.6%. Graphical Abstract ᅟ.

  10. Single-Nucleotide Mutations in Reveal Novel Functions and Regulatory Mechanisms of the Fragile X Syndrome Protein FMRP

    Directory of Open Access Journals (Sweden)

    Joshua A. Suhl

    2015-01-01

    Full Text Available Fragile X syndrome is a monogenic disorder and a common cause of intellectual disability. Despite nearly 25 years of research on FMR1, the gene underlying the syndrome, very few pathological mutations other than the typical CGG-repeat expansion have been reported. This is in contrast to other X-linked, monogenic, intellectual disability disorders, such as Rett syndrome, where many point mutations have been validated as causative of the disorder. As technology has improved and significantly driven down the cost of sequencing, allowing for whole genes to be sequenced with relative ease, in-depth sequencing studies on FMR1 have recently been performed. These studies have led to the identification of novel variants in FMR1 , where some of which have been functionally evaluated and are likely pathogenic. In this review, we discuss recently identified FMR1 variants, the ways these novel variants cause dysfunction, and how they reveal new regulatory mechanisms and functionalities of the gene.

  11. Study of Single Event Effects induced by highly energetic charged particles of the space environment in CMOS image Sensors

    International Nuclear Information System (INIS)

    Lalucaa, Valerian

    2013-01-01

    This thesis studies the single event effects of space environment in CMOS image sensors (CIS). This work focuses on the effects of heavy ions on 3T standard photodiode pixels, and 4T and 5T pinned photodiode pixels. The first part describes the space radioactive environment and the sensor architecture. The most harmful events (SEL and SETs) are identified thanks to the scientific literature. The experimentally tested sensors agree with the theoretical work. SETs are compared to STARDUST simulations with a good agreement for all ions and sensors. The work explains why the SETs on 3T pixels are insensitive to the various photodiode designs, and they are decreased when an epitaxial substrate is used. A method using anti-blooming was successfully used in 4T and 5T pixels to prevent the spread of the SETs. The mechanism of latch-up in 4T pixel sensors is described. All the identified mechanisms are very useful to provide hardening methods for the CISs. (author) [fr

  12. Homozygosity Mapping and Whole Exome Sequencing to Detect SLC45A2 and G6PC3 Mutations in a Single Patient with Oculocutaneous Albinism and Neutropenia

    Science.gov (United States)

    Cullinane, Andrew R.; Vilboux, Thierry; O’Brien, Kevin; Curry, James A.; Maynard, Dawn M.; Carlson-Donohoe, Hannah; Ciccone, Carla; Markello, Thomas C.; Gunay-Aygun, Meral; Huizing, Marjan; Gahl, William A.

    2011-01-01

    We evaluated a 32 year-old woman whose oculocutaneous albinism, bleeding diathesis, neutropenia, and history of recurrent infections prompted consideration of the diagnosis of Hermansky-Pudlak syndrome type 2 (HPS-2). This was ruled out due to the presence of platelet delta granules and absence of AP3B1 mutations. Since parental consanguinity suggested an autosomal recessive mode of inheritance, we employed homozygosity mapping, followed by whole exome sequencing, to identify two candidate disease-causing genes, SLC45A2 and G6PC3. Conventional di-deoxy sequencing confirmed pathogenic mutations in SLC45A2, associated with oculocutaneous albinism type 4 (OCA-4), and G6PC3, associated with neutropenia. The substantial reduction of SLC45A2 protein in the patient’s melanocytes caused the mis-localization of tyrosinase from melanosomes to the plasma membrane and also led to the incorporation of tyrosinase into exosomes and secretion into the culture medium, explaining the hypopigmentation in OCA-4. Our patient’s G6PC3 mRNA expression level was also reduced, leading to increased apoptosis of her fibroblasts under ER stress. This report describes the first North American patient with OCA-4, the first culture of human OCA-4 melanocytes, and the use of homozygosity mapping followed by whole exome sequencing to identify disease-causing mutations in multiple genes in a single affected individual. PMID:21677667

  13. 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

  14. Sequencing of Single Pollen Nuclei Reveals Meiotic Recombination Events at Megabase Resolution and Circumvents Segregation Distortion Caused by Postmeiotic Processes

    Directory of Open Access Journals (Sweden)

    Steven Dreissig

    2017-09-01

    Full Text Available Meiotic recombination is a fundamental mechanism to generate novel allelic combinations which can be harnessed by breeders to achieve crop improvement. The recombination landscape of many crop species, including the major crop barley, is characterized by a dearth of recombination in 65% of the genome. In addition, segregation distortion caused by selection on genetically linked loci is a frequent and undesirable phenomenon in double haploid populations which hampers genetic mapping and breeding. Here, we present an approach to directly investigate recombination at the DNA sequence level by combining flow-sorting of haploid pollen nuclei of barley with single-cell genome sequencing. We confirm the skewed distribution of recombination events toward distal chromosomal regions at megabase resolution and show that segregation distortion is almost absent if directly measured in pollen. Furthermore, we show a bimodal distribution of inter-crossover distances, which supports the existence of two classes of crossovers which are sensitive or less sensitive to physical interference. We conclude that single pollen nuclei sequencing is an approach capable of revealing recombination patterns in the absence of segregation distortion.

  15. 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)

  16. A novel single point mutation of the LYST gene in two siblings with different phenotypic features of Chediak Higashi syndrome.

    Science.gov (United States)

    Kaya, Zuhre; Ehl, Stephan; Albayrak, Meryem; Maul-Pavicic, Andrea; Schwarz, Klaus; Kocak, Ulker; Ergun, Mehmet Ali; Gursel, Turkiz

    2011-07-01

    Chediak Higashi syndrome (CHS) is an autosomal-recessive disorder characterized by oculocutaneous albinism, recurrent infections and a progressive primary neurological disease. Here, we describe two siblings with CHS due to a novel homozygous R1836X mutation in the LYST gene associated with loss of NK cell degranulation and cytotoxicity. While one sibling was born with fair skin and hair and died of hemophagocytic lymphohistiocytosis (HLH) at 5 months of age, the other sibling had dark black hair and skin and developed HLH at the age of 4 years. Copyright © 2011 Wiley-Liss, Inc.

  17. Glutamate Excitotoxicity Is Involved in the Induction of Paralysis in Mice after Infection by a Human Coronavirus with a Single Point Mutation in Its Spike Protein▿

    Science.gov (United States)

    Brison, Elodie; Jacomy, Hélène; Desforges, Marc; Talbot, Pierre J.

    2011-01-01

    Human coronaviruses (HCoV) are recognized respiratory pathogens, and some strains, including HCoV-OC43, can infect human neuronal and glial cells of the central nervous system (CNS) and activate neuroinflammatory mechanisms. Moreover, HCoV-OC43 is neuroinvasive, neurotropic, and neurovirulent in susceptible mice, where it induces chronic encephalitis. Herein, we show that a single point mutation in the viral spike (S) glycoprotein (Y241H), acquired during viral persistence in human neural cells, led to a hind-limb paralytic disease in infected mice. Inhibition of glutamate excitotoxicity using a 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propranoic acid (AMPA) receptor antagonist (GYKI-52466) improved clinical scores related to the paralysis and motor disabilities in S mutant virus-infected mice, as well as protected the CNS from neuronal dysfunctions, as illustrated by restoration of the phosphorylation state of neurofilaments. Expression of the glial glutamate transporter GLT-1, responsible for glutamate homeostasis, was downregulated following infection, and GYKI-52466 also significantly restored its steady-state expression level. Finally, GYKI-52466 treatment of S mutant virus-infected mice led to reduced microglial activation, which may lead to improvement in the regulation of CNS glutamate homeostasis. Taken together, our results strongly suggest an involvement of excitotoxicity in the paralysis-associated neuropathology induced by an HCoV-OC43 mutant which harbors a single point mutation in its spike protein that is acquired upon persistent virus infection. PMID:21957311

  18. High rates of human immunodeficiency virus type 1 mutational profiles by single-genome amplification after 48-hour propagation in peripheral blood mononuclear cells at different levels of cell activation.

    Science.gov (United States)

    Russo, Cristiano Teodoro; Alkmim, Wagner; Munerato, Patricia; Zukurov, Jean; Maricato, Juliana T; Sucupira, M Cecília; Diaz, Ricardo S; Janini, Luiz Mário

    2014-01-01

    Human immunodeficiency virus type 1 (HIV-1) genetic diversity is one of the most important features of HIV-1 infections and the result of error accumulation during reverse transcription and of high viral turnover. HIV-1 reverse transcription is influenced by factors such as the level of nucleotides and/or the cellular activation state. HIV-1 diversity was investigated after 48 h of viral propagation in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors in three different cell culture conditions: (1) resting PBMCs, (2) simultaneous infection and PBMC activation, and (3) PBMC activation 72 h before infection. Cellular DNA was extracted and proviruses of each culture condition were amplified. Single-genome PCR clones were obtained and the protease and reverse transcriptase of the pol gene were sequenced. An elevated number of nucleotide substitutions in all three culture conditions were observed. In condition 1, the mutational rate observed ranged from 1.0 × 10(-3) to 2.1 × 10(-2), the genetic diversity was 0.6%, and hypermutation was observed in 7.1% of sequenced clones. In condition 2, the mutational rate ranged from 1.0 × 10(-3) to 1.0 × 10(-2), the genetic diversity was 0.8%, and hypermutation affected 6.7% of clones. In condition 3, the mutational rate ranged from 2.8 × 10(-3) to 1.1 × 10(-2), the genetic diversity was 1%, and 5.9% of clones were hypermutated. Substitutions occurred more frequently in some specific nucleotide stretches, and a common pattern for substitutions in all the different conditions was identified. There was a significant accumulation of mutations during the initial periods of in vitro HIV-1 propagation irrespective of culture conditions. The rapid accumulation of virus diversity might represent a viral strategy when colonizing new hosts. Complementary studies are necessary to allow for a better understanding of the initial periods of infection, which represent a crucial event related to disease progression.

  19. Single Tyrosine Mutation in AAV8 Vector Capsid Enhances Gene Lung Delivery and Does Not Alter Lung Morphofunction in Mice

    Directory of Open Access Journals (Sweden)

    Sabrina V. Martini

    2014-08-01

    Full Text Available Background/Aims: Vectors derived from adeno-associated viruses (AAVs are important gene delivery tools for treating pulmonary diseases. Phosphorylation of surface-exposed tyrosine residues from AAV2 capsid targets the viral particles for ubiquitination and proteasome-mediated degradation, and mutations of these tyrosine residues lead to highly efficient vector transduction in vitro and in vivo in different organs. We evaluated the pulmonary transduction efficiency of AAV8 vectors containing point mutations in surface-exposed capsid tyrosine residues. Methods: Male C57BL/6 mice (20-25 g, n=24 were randomly assigned into three groups: control group animals received intratracheal (i.t. instillation of saline (50 μl, wild-type AAV8 group, and capsid mutant Y733F AAV8 group, which received (i.t. AAV8 vectors containing the DNA sequence of enhanced green fluorescence protein (eGFP. Four weeks after instillation, lung mechanics and morphometry, vector transduction (immunohistochemistry and mRNA expression of eGFP, and inflammatory cytokines and growth factor expression were analyzed. Results: Tyrosine-mutant AAV8 vectors displayed significantly increased transduction efficiency in the lung compared with their wild-type counterparts. No significant differences were observed in lung mechanics and morphometry between experimental groups. There was no evidence of inflammatory response in any group. Conclusion: AAV8 vectors may be useful for new therapeutic strategies for the treatment of pulmonary diseases.

  20. 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.

  1. 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

  2. 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)

  3. 1D layered velocity models and microseismic event locations: synthetic examples for a case with a single linear receiver array

    Science.gov (United States)

    Akram, Jubran; Eaton, David W.

    2017-10-01

    We discuss various aspects of 1D velocity-model building for application to microseismic data analysis. We generate simple synthetic example data using a widely used single linear array geometry. The synthetic data contain 30 sources with known locations for a reference model based on previous studies of the Barnett shale. We investigate several key factors that should be considered, including selection of the calibration technique, inclusion of a priori information such as lateral heterogeneity and parameter ranges, and choice of algorithm for travel time computations. For the source-receiver geometry considered here, hypocenter location errors (±6 m in X and ±12 m in Z) can result from differently calibrated models only and without including the errors in picked arrival times and polarization estimates. We find that the errors in hypocenter locations are reduced (±3 m in X and ±6 m in Z) when a model calibrated with multiple shots simultaneously is used. Using four different models (vertical fault, dipping layers, channels, and these effects combined), we demonstrate that systematic errors in hypocenter locations can result when a 1D layered model is used in lieu of a laterally heterogeneous subsurface. Finally, we show that event locations from a velocity model calibrated using direct-arrival times are more stable than from a model calibrated with first-arrival times.

  4. 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)

  5. Contextual constraints on lexico-semantic processing in aging: Evidence from single-word event-related brain potentials.

    Science.gov (United States)

    Payne, Brennan R; Federmeier, Kara D

    2018-05-15

    The current study reports the effects of accumulating contextual constraints on neural indices of lexico-semantic processing (i.e., effects of word frequency and orthographic neighborhood) as a function of normal aging. Event-related brain potentials were measured from a sample of older adults as they read sentences that were semantically congruent, provided only syntactic constraints (syntactic prose), or were random word strings. A linear mixed-effects modeling approach was used to probe the effects of accumulating contextual constraints on N400 responses to individual words. Like young adults in prior work, older adults exhibited a classic word position context effect on the N400 in congruent sentences, although the magnitude of the effect was reduced in older relative to younger adults. Moreover, by modeling single-word variability in N400 responses, we observed robust effects of orthographic neighborhood density that were larger in older adults than the young, and preserved effects word frequency. Importantly, in older adults, frequency effects were not modulated by accumulating contextual constraints, unlike in the young. Collectively, these findings indicate that older adults are less likely (or able) to use accumulating top-down contextual constraints, and therefore rely more strongly on bottom-up lexical features to guide semantic access of individual words during sentence comprehension. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. An optical fiber coupled streak camera system for multichannel recording of simultaneous emission from a single plasma producing event

    International Nuclear Information System (INIS)

    Tan, T.H.; Williams, A.H.

    1983-01-01

    A streak camera system capable of multichannel sub-nanosecond recording of simultaneous emissions (photons and particles) from a single plasma interaction event (laser or particle beam) has been developed. In this system ultra-fast quenched (benzophenone) plastic scintillator detectors are coupled via optical fibers to a visible streak camera. The use of optical fibers presents two tractive features: miniaturization of detectors permits improved flexibility in placing detectors at the most desirable location and in greater number than can normally be accommodated; and the detectors are insensitive to electromagnetic noise generated both from the interacting plasmas and from the high voltage components associated with the laser or particle beam system. The fibers can be directly routed through vacuum tight couplers at the target chamber wall and brought into direct contact with the photocathode of the camera in most applications. In fusion experiments, however, the fiber florescence and Cerenkov radiation due to the copious emissions of energetic electrons and x-rays can present serious problems in the use of long fibers. Here, short fibers can be used and the visible streak camera is then focused through a glass port of the target chamber onto the open ends of these optical fibers

  7. Mutations in Exons 9 and 13 of KIT Gene Are Rare Events in Gastrointestinal Stromal Tumors : A Study of 200 Cases

    OpenAIRE

    Lasota, Jerzy; Wozniak, Agnieszka; Sarlomo-Rikala, Maarit; Rys, Janusz; Kordek, Radzislaw; Nassar, Aziza; Sobin, Leslie H.; Miettinen, Markku

    2000-01-01

    Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, typically express the KIT protein. Activating mutations in the juxtamembrane domain (exon 11) of the c-kit gene have been shown in a subset of GISTs. These mutations lead into ligand-independent activation of the tyrosine kinase of c-kit, and have a transforming effect in vitro. Several groups have studied the clinical implication of the c-kit mutation status of exon 11 in GISTs and a po...

  8. A systematic review of the association between a single strenuous event and the development of an inguinal hernia: A medicolegal grey area.

    Science.gov (United States)

    Patterson, Timothy; Currie, Peter; Spence, Robert; McNally, Sinead; Spence, Gary

    2018-03-10

    Inguinal hernia is a common surgical presentation. Evidence for its causation regarding occupational and recreational physical exposures is limited. The aim of this study is to conduct a systematic review objectively evaluating the evidence for a causal link between a single strenuous event and the development of an inguinal hernia. A systematic review was carried out in accordance with PRISMA guidelines. PubMed, Ovid Embase, SCOPUS, and Cochrane Library were searched. In addition, the ISRCTN register, ClinicalTrials.gov, ICTR Platform, and EU Clinical Trials Register were searched. Identified publications were collated and both reviewers independently reviewed their contents. 5508 records were identified, resulting in 5 studies being selected. These 5 studies were all case series. Of 957 patients identified, 1003 hernias were described, of which 983 were inguinal hernias which 255 (26%) were attributed by patients to a single strenuous event. Only two of these studies applied Smith's Criteria (causation of a hernia from a single strenuous event): officially reported, severe pain at the time of the event, no prior history of inguinal hernia, and the diagnosis was made by a doctor within 30 days (preferably 3 days). Only 2 of 54 patients (4%) met all four criteria and so could be considered as having an inguinal hernia relating to a single strenuous event. Many patients associate hernias to a single episode, however upon application of more stringent criteria such as Smith's, a much smaller proportion are deemed to be actually attributable to a single strenuous event. Copyright © 2018 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  9. Eradication of large solid tumors by gene therapy with a T cell receptor targeting a single cancer-specific point mutation

    Science.gov (United States)

    Leisegang, Matthias; Engels, Boris; Schreiber, Karin; Yew, Poh Yin; Kiyotani, Kazuma; Idel, Christian; Arina, Ainhoa; Duraiswamy, Jaikumar; Weichselbaum, Ralph R.; Uckert, Wolfgang; Nakamura, Yusuke; Schreiber, Hans

    2015-01-01

    Purpose Cancers usually contain multiple unique tumor-specific antigens produced by single amino acid substitutions (AAS) and encoded by somatic non-synonymous single nucleotide substitutions. We determined whether adoptively transferred T cells can reject large, well-established solid tumors when engineered to express a single type of T cell receptor (TCR) that is specific for a single AAS. Experimental Design By exome and RNA sequencing of an UV-induced tumor, we identified an AAS in p68 (mp68), a co-activator of p53. This AAS seemed to be an ideal tumor-specific neoepitope because it is encoded by a trunk mutation in the primary autochthonous cancer and binds with highest affinity to the MHC. A high-avidity mp68-specific TCR was used to genetically engineer T cells as well as to generate TCR-transgenic mice for adoptive therapy. Results When the neoepitope was expressed at high levels and by all cancer cells, their direct recognition sufficed to destroy intra-tumor vessels and eradicate large, long-established solid tumors. When the neoepitope was targeted as autochthonous antigen, T cells caused cancer regression followed by escape of antigen-negative variants. Escape could be thwarted by expressing the antigen at increased levels in all cancer cells or by combining T cell therapy with local irradiation. Therapeutic efficacies of TCR-transduced and TCR-transgenic T cells were similar. Conclusions Gene therapy with a single TCR targeting a single AAS can eradicate large established cancer but a uniform expression and/or sufficient levels of the targeted neoepitope or additional therapy are required to overcome tumor escape. PMID:26667491

  10. The Impact of Electronic Medical Records on Hospital-Acquired Adverse Safety Events: Differential Effects Between Single-Source and Multiple-Source Systems.

    Science.gov (United States)

    Bae, Jaeyong; Rask, Kimberly J; Becker, Edmund R

    The objective was to examine differential impacts between single-source and multiple-source electronic medical record (EMR) systems, as measured by number of vendor products, on hospital-acquired patient safety events. The data source was the 2009-2010 State Inpatient Databases of the Healthcare Cost and Utilization Project for California, New York, and Florida, and the Information Technology Supplement to the American Hospital Association's Annual Survey. Multivariable regression analyses were conducted to estimate the differential impacts of EMRs between single-source and multiple-source EMR systems on hospital-acquired patient safety events. In all, 1.98% of adult surgery hospitalizations had at least 1 hospital-acquired patient safety event. Basic EMRs with a single vendor or self-developed EMR systems were associated with a significant decrease in patient safety events by 0.38 percentage point, or 19.2%, whereas basic EMRs with multiple vendors had an insignificant association. A single-source EMR system enhances the impact of EMRs on reducing patient safety events.

  11. 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.

  12. 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/.

  13. Genetic analysis of allelic variants, single-step mutations, three allelic variants of the 15 STR loci in the population of Northeast Bosnia

    Directory of Open Access Journals (Sweden)

    Hadžiavdić Vesna

    2013-01-01

    Full Text Available Diversity of nuclear DNA microsatellite markers were analyzed in a reference sample of the population of northeast Bosnia. 437 samples taken from unrelated individuals were processed and three samples of paternity proof were shown. Detection effectiveness profile of the research, points to a valid choice of method of extraction, amplification and genotyping STR loci with PowerPlextm16. Genetic analysis of allelic variants of the 15 STR loci detected 17 samples determined as microvariants. Samples were divided into 15 different allelic variants at 7 different loci, and are: in locus D7S820, D16S539, D3S1358, D18S51, PENTA D, PENTA E and in locus vWA. Genetic analysis of mutations in cases of paternity determined three examples of single-step mutations in the loci FGA, Penta D and D3S1358. Genetic analysis of observed STR loci detected three allelic variant of genotype combination 7/10/11.3 in locus D7S820 Type II.

  14. 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

    An intramolecular electron-transfer process has previously been shown to take place between the Cys3--Cys26 radical-ion (RSSR-) produced pulse radiolytically and the Cu(II) ion in the blue single-copper protein, azurin [Farver, O. & Pecht, I. (1989) Proc. Natl Acad. Sci. USA 86, 6868-6972]. To fu...

  15. Recurrent LDL-receptor mutation causes familial ...

    African Journals Online (AJOL)

    1995-05-05

    May 5, 1995 ... mutation detection. Haplotype analysis with polymorphisms on both sides of the FH2 mutation indicated that the identical LDLR gene mutations found in two different South ... amplification refractory mutation system (ARMS)" and single- .... point mutations that cause familial defective apolipoprotein. 8-100 ...

  16. 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.

  17. 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.

  18. Simultaneous isolation of emm89-type Streptococcus pyogenes strains with a wild-type or mutated covS gene from a single streptococcal toxic shock syndrome patient.

    Science.gov (United States)

    Masuno, Katsuaki; Okada, Ryo; Zhang, Yan; Isaka, Masanori; Tatsuno, Ichiro; Shibata, Shinichiro; Hasegawa, Tadao

    2014-04-01

    Streptococcal toxic shock syndrome (STSS) is a re-emerging infectious disease in many developed countries. Recent studies have suggested that mutations in CovRS, a two-component regulatory system in Streptococcus pyogenes, play important roles in the pathogenesis of STSS. However, in vivo evidence of the significance of CovRS in human infections has not been fully demonstrated. We investigated five S. pyogenes strains isolated simultaneously from the pharynx, sputum, knee joint, cerebrospinal fluid and blood of a single STSS patient. All were emm89-type strains, and multilocus sequence typing (MLST) analysis revealed that the strains of pharynx and blood were isogenic. The growth rates of the strains from pharynx and sputum were faster than those of the other strains. Protein profiles of the culture supernatants of strains from the pharynx and sputum were also different from those of the other strains. Sequence analyses revealed that strains from the knee joint, cerebrospinal fluid and blood contained a single nucleotide difference in the covS coding region, resulting in one amino acid change, compared with the other strains. Introduction of a plasmid containing the covS gene from the pharynx strain to the blood strain increased the production of SpeB protein. This suggests that the one amino acid alteration in CovS was relevant to pathogenesis. This report supports the idea that mutated CovS plays important roles in vivo in the dissemination of S. pyogenes from the upper respiratory tract of human to aseptic tissues such as blood and cerebrospinal fluid.

  19. 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)

  20. The validity of assessing temporal events, sub-phases and trunk kinematics of the sit-to-walk movement in older adults using a single inertial sensor

    NARCIS (Netherlands)

    Walgaard, S.; Faber, G.S.; van Lummel, R.; van Dieen, J.H.; Kingma, I.

    2016-01-01

    The aim of this study was to develop a method to identify temporal events, sub-phases and trunk kinematics of the sit-to-walk (STW) using a single inertial sensor (IS) worn at the lower back and to determine the validity of this method. Twenty-seven healthy older adults performed a STW movement,

  1. A single point mutation within the coding sequence of cholera toxin B subunit will increase its expression yield.

    Science.gov (United States)

    Bakhshi, Bita; Boustanshenas, Mina; Ghorbani, Masoud

    2014-07-01

    Cholera toxin B subunit (CTB) has been extensively considered as an immunogenic and adjuvant protein, but its yield of expression is not satisfactory in many studies. The aim of this study was to compare the expression of native and mutant recombinant CTB (rCTB) in pQE vector. ctxB fragment from Vibrio cholerae O1 ATCC14035 containing the substitution of mutant ctxB for amino acid S128T was amplified by PCR and cloned in pGETM-T easy vector. It was then transformed to E. coli Top 10F' and cultured on LB agar plate containing ampicillin. Sequence analysis confirmed the mature ctxB gene sequence and the mutant one in both constructs which were further subcloned to pQE-30 vector. Both constructs were subsequently transformed to E. coli M15 (pREP4) for expression of mature and mutant rCTB. SDS-PAGE analysis showed the maximum expression of rCTB in both systems at 5 hours after induction and Western-blot analysis confirmed the presence of rCTB in blotting membranes. The expression of mutant rCTB was much higher than mature rCTB, which may be the result of serine-to-threonine substitution at position 128 of mature rCTB amino acid sequence created by PCR mutagenesis. The mutant rCTB retained pentameric stability and its ability to bind to anti- cholera toxin IgG antibodies. Point mutation in ctxB sequence resulted in over-expression of rCTB, probably due to the increase of solubility of produced rCTB. Consequently, this expression system can be used to produce rCTB in high yield.

  2. 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...

  3. Mutational Events in Cefotaximase Extended-Spectrum β-Lactamases of the CTX-M-1 Cluster Involved in Ceftazidime Resistance ▿

    Science.gov (United States)

    Novais, Ângela; Cantón, Rafael; Coque, Teresa M.; Moya, Andrés; Baquero, Fernando; Galán, Juan Carlos

    2008-01-01

    CTX-M β-lactamases, which show a high cefotaxime hydrolytic activity, constitute the most prevalent extended-spectrum β-lactamase (ESBL) type found among clinical isolates. The recent explosive diversification of CTX-M enzymes seems to have taken place due to the appearance of more efficient enzymes which are capable of hydrolyzing both cefotaxime and ceftazidime, especially among the CTX-M-1 cluster. A combined strategy of in vitro stepwise evolution experiments using blaCTX-M-1, blaCTX-M-3, and blaCTX-M-10 genes and site-directed mutagenesis has been used to evaluate the role of ceftazidime and other β-lactam antibiotics in triggering the diversity found among enzymes belonging to this cluster. Two types of mutants, P167S and D240G, displaying high ceftazidime MICs but reduced resistance to cefotaxime and/or cefepime, respectively, were identified. Such an antagonistic pleiotropic effect was particularly evident with P167S/T mutations. The incompatibility between P167S and D240G changes was demonstrated, since double mutants reduced susceptibility to both ceftazidime and cefotaxime-cefepime; this may explain the absence of strains containing both mutations in the clinical environment. The role of A77V and N106S mutations, which are frequently associated with P167S/T and/or D240G, respectively, in natural strains, was investigated. The presence of A77V and N106S contributes to restore a high-level cefotaxime resistance phenotype, but only when associated with mutations P167S and D240G, respectively. However, A77V mutation increases resistance to both cefotaxime and ceftazidime when associated with CTX-M-10. This suggests that in this context this mutation might be considered a primary site involved in resistance to broad-spectrum cephalosporins. PMID:18443114

  4. 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

    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 199...

  5. [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.

  6. Mutation Rates, Spectra, and Genome-Wide Distribution of Spontaneous Mutations in Mismatch Repair Deficient Yeast

    Science.gov (United States)

    Lang, Gregory I.; Parsons, Lance; Gammie, Alison E.

    2013-01-01

    DNA mismatch repair is a highly conserved DNA repair pathway. In humans, germline mutations in hMSH2 or hMLH1, key components of mismatch repair, have been associated with Lynch syndrome, a leading cause of inherited cancer mortality. Current estimates of the mutation rate and the mutational spectra in mismatch repair defective cells are primarily limited to a small number of individual reporter loci. Here we use the yeast Saccharomyces cerevisiae to generate a genome-wide view of the rates, spectra, and distribution of mutation in the absence of mismatch repair. We performed mutation accumulation assays and next generation sequencing on 19 strains, including 16 msh2 missense variants implicated in Lynch cancer syndrome. The mutation rate for DNA mismatch repair null strains was approximately 1 mutation per genome per generation, 225-fold greater than the wild-type rate. The mutations were distributed randomly throughout the genome, independent of replication timing. The mutation spectra included insertions/deletions at homopolymeric runs (87.7%) and at larger microsatellites (5.9%), as well as transitions (4.5%) and transversions (1.9%). Additionally, repeat regions with proximal repeats are more likely to be mutated. A bias toward deletions at homopolymers and insertions at (AT)n microsatellites suggests a different mechanism for mismatch generation at these sites. Interestingly, 5% of the single base pair substitutions might represent double-slippage events that occurred at the junction of immediately adjacent repeats, resulting in a shift in the repeat boundary. These data suggest a closer scrutiny of tumor suppressors with homopolymeric runs with proximal repeats as the potential drivers of oncogenesis in mismatch repair defective cells. PMID:23821616

  7. 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

  8. Founder mutations characterise the mutation panorama in 200 Swedish index cases referred for Long QT syndrome genetic testing

    Directory of Open Access Journals (Sweden)

    Stattin Eva-Lena

    2012-10-01

    Full Text Available Abstract Background Long QT syndrome (LQTS is an inherited arrhythmic disorder characterised by prolongation of the QT interval on ECG, presence of syncope and sudden death. The symptoms in LQTS patients are highly variable, and genotype influences the clinical course. This study aims to report the spectrum of LQTS mutations in a Swedish cohort. Methods Between March 2006 and October 2009, two hundred, unrelated index cases were referred to the Department of Clinical Genetics, Umeå University Hospital, Sweden, for LQTS genetic testing. We scanned five of the LQTS-susceptibility genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 for mutations by DHPLC and/or sequencing. We applied MLPA to detect large deletions or duplications in the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes. Furthermore, the gene RYR2 was screened in 36 selected LQTS genotype-negative patients to detect cases with the clinically overlapping disease catecholaminergic polymorphic ventricular tachycardia (CPVT. Results In total, a disease-causing mutation was identified in 103 of the 200 (52% index cases. Of these, altered exon copy numbers in the KCNH2 gene accounted for 2% of the mutations, whereas a RYR2 mutation accounted for 3% of the mutations. The genotype-positive cases stemmed from 64 distinct mutations, of which 28% were novel to this cohort. The majority of the distinct mutations were found in a single case (80%, whereas 20% of the mutations were observed more than once. Two founder mutations, KCNQ1 p.Y111C and KCNQ1 p.R518*, accounted for 25% of the genotype-positive index cases. Genetic cascade screening of 481 relatives to the 103 index cases with an identified mutation revealed 41% mutation carriers who were at risk of cardiac events such as syncope or sudden unexpected death. Conclusion In this cohort of Swedish index cases with suspected LQTS, a disease-causing mutation was identified in 52% of the referred patients. Copy number variations explained 2% of the

  9. Founder mutations characterise the mutation panorama in 200 Swedish index cases referred for Long QT syndrome genetic testing.

    Science.gov (United States)

    Stattin, Eva-Lena; Boström, Ida Maria; Winbo, Annika; Cederquist, Kristina; Jonasson, Jenni; Jonsson, Björn-Anders; Diamant, Ulla-Britt; Jensen, Steen M; Rydberg, Annika; Norberg, Anna

    2012-10-25

    Long QT syndrome (LQTS) is an inherited arrhythmic disorder characterised by prolongation of the QT interval on ECG, presence of syncope and sudden death. The symptoms in LQTS patients are highly variable, and genotype influences the clinical course. This study aims to report the spectrum of LQTS mutations in a Swedish cohort. Between March 2006 and October 2009, two hundred, unrelated index cases were referred to the Department of Clinical Genetics, Umeå University Hospital, Sweden, for LQTS genetic testing. We scanned five of the LQTS-susceptibility genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2) for mutations by DHPLC and/or sequencing. We applied MLPA to detect large deletions or duplications in the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes. Furthermore, the gene RYR2 was screened in 36 selected LQTS genotype-negative patients to detect cases with the clinically overlapping disease catecholaminergic polymorphic ventricular tachycardia (CPVT). In total, a disease-causing mutation was identified in 103 of the 200 (52%) index cases. Of these, altered exon copy numbers in the KCNH2 gene accounted for 2% of the mutations, whereas a RYR2 mutation accounted for 3% of the mutations. The genotype-positive cases stemmed from 64 distinct mutations, of which 28% were novel to this cohort. The majority of the distinct mutations were found in a single case (80%), whereas 20% of the mutations were observed more than once. Two founder mutations, KCNQ1 p.Y111C and KCNQ1 p.R518*, accounted for 25% of the genotype-positive index cases. Genetic cascade screening of 481 relatives to the 103 index cases with an identified mutation revealed 41% mutation carriers who were at risk of cardiac events such as syncope or sudden unexpected death. In this cohort of Swedish index cases with suspected LQTS, a disease-causing mutation was identified in 52% of the referred patients. Copy number variations explained 2% of the mutations and 3 of 36 selected cases (8%) harboured a mutation in the

  10. Mos1-mediated transgenesis to probe consequences of single gene mutations in variation-rich isolates of Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Maja Tarailo-Graovac

    Full Text Available Caenorhabditis elegans, especially the N2 isolate, is an invaluable biological model system. Numerous additional natural C. elegans isolates have been shown to have unexpected genotypic and phenotypic variations which has encouraged researchers to use next generation sequencing methodology to develop a more complete picture of genotypic variations among the isolates. To understand the phenotypic effects of a genomic variation (GV on a single gene, in a variation-rich genetic background, one should analyze that particular GV in a well understood genetic background. In C. elegans, the analysis is usually done in N2, which requires extensive crossing to bring in the GV. This can be a very time consuming procedure thus it is important to establish a fast and efficient approach to test the effect of GVs from different isolates in N2. Here we use a Mos1-mediated single-copy insertion (MosSCI method for phenotypic assessments of GVs from the variation-rich Hawaiian strain CB4856 in N2. Specifically, we investigate effects of variations identified in the CB4856 strain on tac-1 which is an essential gene that is necessary for mitotic spindle elongation and pronuclear migration. We show the usefulness of the MosSCI method by using EU1004 tac-1(or402 as a control. or402 is a temperature sensitive lethal allele within a well-conserved TACC domain (transforming acidic coiled-coil that results in a leucine to phenylalanine change at amino acid 229. CB4856 contains a variation that affects the second exon of tac-1 causing a cysteine to tryptophan change at amino acid 94 also within the TACC domain. Using the MosSCI method, we analyze tac-1 from CB4856 in the N2 background and demonstrate that the C94W change, albeit significant, does not cause any obvious decrease in viability. This MosSCI method has proven to be a rapid and efficient way to analyze GVs.

  11. Mos1-mediated transgenesis to probe consequences of single gene mutations in variation-rich isolates of Caenorhabditis elegans.

    Science.gov (United States)

    Tarailo-Graovac, Maja; Chen, Nansheng

    2012-01-01

    Caenorhabditis elegans, especially the N2 isolate, is an invaluable biological model system. Numerous additional natural C. elegans isolates have been shown to have unexpected genotypic and phenotypic variations which has encouraged researchers to use next generation sequencing methodology to develop a more complete picture of genotypic variations among the isolates. To understand the phenotypic effects of a genomic variation (GV) on a single gene, in a variation-rich genetic background, one should analyze that particular GV in a well understood genetic background. In C. elegans, the analysis is usually done in N2, which requires extensive crossing to bring in the GV. This can be a very time consuming procedure thus it is important to establish a fast and efficient approach to test the effect of GVs from different isolates in N2. Here we use a Mos1-mediated single-copy insertion (MosSCI) method for phenotypic assessments of GVs from the variation-rich Hawaiian strain CB4856 in N2. Specifically, we investigate effects of variations identified in the CB4856 strain on tac-1 which is an essential gene that is necessary for mitotic spindle elongation and pronuclear migration. We show the usefulness of the MosSCI method by using EU1004 tac-1(or402) as a control. or402 is a temperature sensitive lethal allele within a well-conserved TACC domain (transforming acidic coiled-coil) that results in a leucine to phenylalanine change at amino acid 229. CB4856 contains a variation that affects the second exon of tac-1 causing a cysteine to tryptophan change at amino acid 94 also within the TACC domain. Using the MosSCI method, we analyze tac-1 from CB4856 in the N2 background and demonstrate that the C94W change, albeit significant, does not cause any obvious decrease in viability. This MosSCI method has proven to be a rapid and efficient way to analyze GVs.

  12. Single point mutations in the helicase domain of the NS3 protein enhance dengue virus replicative capacity in human monocyte-derived dendritic cells and circumvent the type I interferon response.

    Science.gov (United States)

    Silveira, G F; Strottmann, D M; de Borba, L; Mansur, D S; Zanchin, N I T; Bordignon, J; dos Santos, C N Duarte

    2016-01-01

    Dengue is the most prevalent arboviral disease worldwide. The outcome of the infection is determined by the interplay of viral and host factors. In the present study, we evaluated the cellular response of human monocyte-derived DCs (mdDCs) infected with recombinant dengue virus type 1 (DV1) strains carrying a single point mutation in the NS3hel protein (L435S or L480S). Both mutated viruses infect and replicate more efficiently and produce more viral progeny in infected mdDCs compared with the parental, non-mutated virus (vBACDV1). Additionally, global gene expression analysis using cDNA microarrays revealed that the mutated DVs induce the up-regulation of the interferon (IFN) signalling and pattern recognition receptor (PRR) canonical pathways in mdDCs. Pronounced production of type I IFN were detected specifically in mdDCs infected with DV1-NS3hel-mutated virus compared with mdDCs infected with the parental virus. In addition, we showed that the type I IFN produced by mdDCs is able to reduce DV1 infection rates, suggesting that cytokine function is effective but not sufficient to mediate viral clearance of DV1-NS3hel-mutated strains. Our results demonstrate that single point mutations in subdomain 2 have important implications for adenosine triphosphatase (ATPase) activity of DV1-NS3hel. Although a direct functional connection between the increased ATPase activity and viral replication still requires further studies, these mutations speed up viral RNA replication and are sufficient to enhance viral replicative capacity in human primary cell infection and circumvent type I IFN activity. This information may have particular relevance for attenuated vaccine protocols designed for DV. © 2015 British Society for Immunology.

  13. A single mutation results in diploid gamete formation and parthenogenesis in a Drosophila yemanuclein-alpha meiosis I defective mutant.

    Science.gov (United States)

    Meyer, Régis E; Delaage, Michèle; Rosset, Roland; Capri, Michèle; Aït-Ahmed, Ounissa

    2010-11-16

    Sexual reproduction relies on two key events: formation of cells with a haploid genome (the gametes) and restoration of diploidy after fertilization. Therefore the underlying mechanisms must have been evolutionary linked and there is a need for evidence that could support such a model. We describe the identification and the characterization of yem1, the first yem-alpha mutant allele (V478E), which to some extent affects diploidy reduction and its restoration. Yem-alpha is a member of the Ubinuclein/HPC2 family of proteins that have recently been implicated in playing roles in chromatin remodeling in concert with HIRA histone chaperone. The yem1 mutant females exhibited disrupted chromosome behavior in the first meiotic division and produced very low numbers of viable progeny. Unexpectedly these progeny did not display paternal chromosome markers, suggesting that they developed from diploid gametes that underwent gynogenesis, a form of parthenogenesis that requires fertilization. We focus here on the analysis of the meiotic defects exhibited by yem1 oocytes that could account for the formation of diploid gametes. Our results suggest that yem1 affects chromosome segregation presumably by affecting kinetochores function in the first meiotic division. This work paves the way to further investigations on the evolution of the mechanisms that support sexual reproduction.

  14. A single mutation results in diploid gamete formation and parthenogenesis in a Drosophila yemanuclein-alpha meiosis I defective mutant

    Science.gov (United States)

    2010-01-01

    Background Sexual reproduction relies on two key events: formation of cells with a haploid genome (the gametes) and restoration of diploidy after fertilization. Therefore the underlying mechanisms must have been evolutionary linked and there is a need for evidence that could support such a model. Results We describe the identification and the characterization of yem1, the first yem-alpha mutant allele (V478E), which to some extent affects diploidy reduction and its restoration. Yem-alpha is a member of the Ubinuclein/HPC2 family of proteins that have recently been implicated in playing roles in chromatin remodeling in concert with HIRA histone chaperone. The yem1 mutant females exhibited disrupted chromosome behavior in the first meiotic division and produced very low numbers of viable progeny. Unexpectedly these progeny did not display paternal chromosome markers, suggesting that they developed from diploid gametes that underwent gynogenesis, a form of parthenogenesis that requires fertilization. Conclusions We focus here on the analysis of the meiotic defects exhibited by yem1 oocytes that could account for the formation of diploid gametes. Our results suggest that yem1 affects chromosome segregation presumably by affecting kinetochores function in the first meiotic division. This work paves the way to further investigations on the evolution of the mechanisms that support sexual reproduction. PMID:21080953

  15. A single mutation results in diploid gamete formation and parthenogenesis in a Drosophila yemanuclein-alpha meiosis I defective mutant

    Directory of Open Access Journals (Sweden)

    Capri Michèle

    2010-11-01

    Full Text Available Abstract Background Sexual reproduction relies on two key events: formation of cells with a haploid genome (the gametes and restoration of diploidy after fertilization. Therefore the underlying mechanisms must have been evolutionary linked and there is a need for evidence that could support such a model. Results We describe the identification and the characterization of yem1, the first yem-alpha mutant allele (V478E, which to some extent affects diploidy reduction and its restoration. Yem-alpha is a member of the Ubinuclein/HPC2 family of proteins that have recently been implicated in playing roles in chromatin remodeling in concert with HIRA histone chaperone. The yem1 mutant females exhibited disrupted chromosome behavior in the first meiotic division and produced very low numbers of viable progeny. Unexpectedly these progeny did not display paternal chromosome markers, suggesting that they developed from diploid gametes that underwent gynogenesis, a form of parthenogenesis that requires fertilization. Conclusions We focus here on the analysis of the meiotic defects exhibited by yem1 oocytes that could account for the formation of diploid gametes. Our results suggest that yem1 affects chromosome segregation presumably by affecting kinetochores function in the first meiotic division. This work paves the way to further investigations on the evolution of the mechanisms that support sexual reproduction.

  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. Genome-wide mRNA sequencing of a single canine cerebellar cortical degeneration case leads to the identification of a disease associated SPTBN2 mutation

    Directory of Open Access Journals (Sweden)

    Forman Oliver P

    2012-07-01

    Full Text Available Abstract Background Neonatal cerebellar cortical degeneration is a neurodegenerative disease described in several canine breeds including the Beagle. Affected Beagles are unable to ambulate normally from the onset of walking and the main pathological findings include Purkinje cell loss with swollen dendritic processes. Previous reports suggest an autosomal recessive mode of inheritance. The development of massively parallel sequencing techniques has presented the opportunity to investigate individual clinical cases using genome-wide sequencing approaches. We used genome-wide mRNA sequencing (mRNA-seq of cerebellum tissue from a single Beagle with neonatal cerebellar cortical degeneration as a method of candidate gene sequencing, with the aim of identifying the causal mutation. Results A four-week old Beagle dog presented with progressive signs of cerebellar ataxia and the owner elected euthanasia. Histopathology revealed findings consistent with cerebellar cortical degeneration. Genome-wide mRNA sequencing (mRNA-seq of RNA from cerebellum tissue was used as a method of candidate gene sequencing. After analysis of the canine orthologues of human spinocerebellar ataxia associated genes, we identified a homozygous 8 bp deletion in the β-III spectrin gene, SPTBN2, associated with spinocerebellar type 5 in humans. Genotype analysis of the sire, dam, ten clinically unaffected siblings, and an affected sibling from a previous litter, showed the mutation to fully segregate with the disorder. Previous studies have shown that β-III spectrin is critical for Purkinje cell development, and the absence of this protein can lead to cell damage through excitotoxicity, consistent with the observed Purkinje cell loss, degeneration of dendritic processes and associated neurological dysfunction in this Beagle. Conclusions An 8 bp deletion in the SPTBN2 gene encoding β-III spectrin is associated with neonatal cerebellar cortical degeneration in Beagle dogs

  18. Single amino acid mutation alters thermostability of the alkaline protease from Bacillus pumilus: thermodynamics and temperature dependence.

    Science.gov (United States)

    Huang, Rong; Yang, Qingjun; Feng, Hong

    2015-02-01

    Dehairing alkaline protease (DHAP) from Bacillus pumilus BA06 has been demonstrated to have high catalytic efficiency and good thermostability, with potential application in leather processing. In order to get insights into its catalytic mechanism, two mutants with single amino acid substitution according to the homology modeling and multiple sequence alignment were characterized in thermodynamics of thermal denaturation and temperature dependence of substrate hydrolysis. The results showed that both mutants of V149I and R249E have a systematic increase in catalytic efficiency (kcat/Km) in a wide range of temperatures, mainly due to an increase of k1 (substrate diffusion) and k2 (acylation) for V149I and of k2 and k3 (deacylation) for R249E. In comparison with the wild-type DHAP, the thermostability is increased for V149I and decreased for R249E. Thermodynamic analysis indicated that the free energy (ΔGa°) of activation for thermal denaturation may govern the thermostability. The value of ΔGa° is increased for V149I and decreased for R249E. Based on these data and the structural modeling, it is suggested that substitution of Val149 with Ile may disturb the local flexibility in the substrate-binding pocket, leading to enhancement of binding affinity for the substrate. In contrast, substitution of Arg249 with Glu leads to interruption of interaction with the C-terminal of enzyme, thus resulting in less thermostability. This study indicates that amino acid residues in the active center or in the substrate-binding pocket may disturb the catalytic process and can be selected as the target for protein engineering in the bacterial alkaline proteases. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

  19. Comparison of single-word and adjective-noun phrase production using event-related brain potentials

    DEFF Research Database (Denmark)

    Lange, Violaine Michel

    2015-01-01

    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...... 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...... 53 msec longer than single noun (1W) production. Waveform amplitude and topographic analyses carried out on stimulus- and response-aligned ERPs indicated that the two conditions differed in a late time-window, with a topographic pattern for 2W lasting from 300 to 480 msec after picture presentation...

  20. Distress after a single violent crime: how shame-proneness and event-related shame work together as risk factors for post-victimization symptoms.

    Science.gov (United States)

    Semb, Olof; Strömsten, Lotta M J; Sundbom, Elisabet; Fransson, Per; Henningsson, Mikael

    2011-08-01

    To increase understanding of post-victimization symptom development, the present study investigated the role of shame- and guilt-proneness and event-related shame and guilt as potential risk factors. 35 individuals (M age = 31.7 yr.; 48.5% women), recently victimized by a single event of severe violent crime, were assessed regarding shame- and guilt-proneness, event-related shame and guilt, and post-victimization symptoms. The mediating role of event-related shame was investigated with structural equation modeling (SEM), using bootstrapping. The guilt measures were unrelated to each other and to post-victimization symptoms. The shame measures were highly intercorrelated and were both positively correlated to more severe post-victimization symptom levels. Event-related shame as mediator between shame-proneness and post-victimization symptoms was demonstrated by prevalent significant indirect effects. Both shame measures are potent risk factors for distress after victimization, whereby part of the effect of shame-proneness on post-victimization symptoms is explained by event-related shame.

  1. Simultaneous Profiling of DNA Mutation and Methylation by Melting Analysis Using Magnetoresistive Biosensor Array.

    Science.gov (United States)

    Rizzi, Giovanni; Lee, Jung-Rok; Dahl, Christina; Guldberg, Per; Dufva, Martin; Wang, Shan X; Hansen, Mikkel F

    2017-09-26

    Epigenetic modifications, in particular DNA methylation, are gaining increasing interest as complementary information to DNA mutations for cancer diagnostics and prognostics. We introduce a method to simultaneously profile DNA mutation and methylation events for an array of sites with single site specificity. Genomic (mutation) or bisulphite-treated (methylation) DNA is amplified using nondiscriminatory primers, and the amplicons are then hybridized to a giant magnetoresistive (GMR) biosensor array followed by melting curve measurements. The GMR biosensor platform offers scalable multiplexed detection of DNA hybridization, which is insensitive to temperature variation. The melting curve approach further enhances the assay specificity and tolerance to variations in probe length. We demonstrate the utility of this method by simultaneously profiling five mutation and four methylation sites in human melanoma cell lines. The method correctly identified all mutation and methylation events and further provided quantitative assessment of methylation density validated by bisulphite pyrosequencing.

  2. 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.

  3. Detection and identification of sources of very distant seismic events in Western United States using single array seismograms

    International Nuclear Information System (INIS)

    Roy, Falguni; Basu, T.K.; Arora, S.K.

    1993-01-01

    In search of a new source discriminant based on the characteristics of PP signal, a study has been made by special further processing of Gauribidanur array (GBA) seismograms of underground explosions at Nevada Test Site (NTS) in Southern Nevada and of tectonic earthquakes in five provinces in the Western United States (US), both class of events being situated in the far teleseismic distance range (120deg<Δ<131deg) where GBA lies in the core shadow zone with respect to the source region. This study aims to evolve aids of detection and identification of such distant and small seismic events using GBA data alone. Preliminary analysis of the processed short period signals from seventeen Western US earthquakes and twelve NTS explosions shows that, for a given body wave magnitude (Mb), the relative high frequency spectral content of core-refracted P waves as well as the ratio of PP to P energy for the earthquakes are in general more than those of the explosions. The PP discriminant and the third moment of frequency (TMF) along with the Mb:Ms criterion, wherever possible, seem to be promising as an effective means of identifying Western US events. It is demonstrated that by applying in tandem the above three identifiers to the set of twenty-nine known events in the magnitude range 4.8≤Mb≤5.9, all the events of Mb 4.9 and above could be identified unambiguously. (author). 30 refs., 16 figs., 1 tab

  4. 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

  5. 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.

  6. Search for supersymmetry in pp collisions at $\\sqrt{s}$=7 TeV in events with a single lepton, jets, and missing transverse momentum

    CERN Document Server

    Chatrchyan, Serguei; Sirunyan, Albert M; Tumasyan, Armen; Adam, Wolfgang; Bergauer, Thomas; Dragicevic, Marko; Erö, Janos; Fabjan, Christian; Friedl, Markus; Fruehwirth, Rudolf; Ghete, Vasile Mihai; Hammer, Josef; Haensel, Stephan; Hoch, Michael; Hörmann, Natascha; Hrubec, Josef; Jeitler, Manfred; Kiesenhofer, Wolfgang; Krammer, Manfred; Liko, Dietrich; Mikulec, Ivan; Pernicka, Manfred; Rahbaran, Babak; Rohringer, Herbert; Schöfbeck, Robert; Strauss, Josef; Taurok, Anton; Teischinger, Florian; Wagner, Philipp; Waltenberger, Wolfgang; Walzel, Gerhard; Widl, Edmund; Wulz, Claudia-Elisabeth; Mossolov, Vladimir; Shumeiko, Nikolai; Suarez Gonzalez, Juan; Bansal, Sunil; Benucci, Leonardo; De Wolf, Eddi A; Janssen, Xavier; Maes, Joris; Maes, Thomas; Mucibello, Luca; Ochesanu, Silvia; Roland, Benoit; Rougny, Romain; Selvaggi, Michele; Van Haevermaet, Hans; Van Mechelen, Pierre; Van Remortel, Nick; Blekman, Freya; Blyweert, Stijn; D'Hondt, Jorgen; Devroede, Olivier; Gonzalez Suarez, Rebeca; Kalogeropoulos, Alexis; Maes, Michael; Van Doninck, Walter; Van Mulders, Petra; Van Onsem, Gerrit Patrick; Villella, Ilaria; Charaf, Otman; Clerbaux, Barbara; De Lentdecker, Gilles; Dero, Vincent; Gay, Arnaud; Hammad, Gregory Habib; Hreus, Tomas; Marage, Pierre Edouard; Thomas, Laurent; Vander Velde, Catherine; Vanlaer, Pascal; Adler, Volker; Cimmino, Anna; Costantini, Silvia; Grunewald, Martin; Klein, Benjamin; Lellouch, Jérémie; Marinov, Andrey; Mccartin, Joseph; Ryckbosch, Dirk; Thyssen, Filip; Tytgat, Michael; Vanelderen, Lukas; Verwilligen, Piet; Walsh, Sinead; Zaganidis, Nicolas; Basegmez, Suzan; Bruno, Giacomo; Caudron, Julien; Ceard, Ludivine; Cortina Gil, Eduardo; De Favereau De Jeneret, Jerome; Delaere, Christophe; Favart, Denis; Giammanco, Andrea; Grégoire, Ghislain; Hollar, Jonathan; Lemaitre, Vincent; Liao, Junhui; Militaru, Otilia; Nuttens, Claude; Ovyn, Severine; Pagano, Davide; Pin, Arnaud; Piotrzkowski, Krzysztof; Schul, Nicolas; Beliy, Nikita; Caebergs, Thierry; Daubie, Evelyne; Alves, Gilvan; Brito, Lucas; De Jesus Damiao, Dilson; Pol, Maria Elena; Henrique Gomes E Souza, Moacyr; Aldá Júnior, Walter Luiz; Carvalho, Wagner; Melo Da Costa, Eliza; De Oliveira Martins, Carley; Fonseca De Souza, Sandro; Mundim, Luiz; Nogima, Helio; Oguri, Vitor; Prado Da Silva, Wanda Lucia; Santoro, Alberto; Silva Do Amaral, Sheila Mara; Sznajder, Andre; Bernardes, Cesar Augusto; De Almeida Dias, Flavia; Tomei, Thiago; De Moraes Gregores, Eduardo; Lagana, Caio; Da Cunha Marinho, Franciole; Mercadante, Pedro G; Novaes, Sergio F; Padula, Sandra; Darmenov, Nikolay; Genchev, Vladimir; Iaydjiev, Plamen; Piperov, Stefan; Rodozov, Mircho; Stoykova, Stefka; Sultanov, Georgi; Tcholakov, Vanio; Trayanov, Rumen; Dimitrov, Anton; Hadjiiska, Roumyana; Karadzhinova, Aneliya; Kozhuharov, Venelin; Litov, Leander; Mateev, Matey; Pavlov, Borislav; Petkov, Peicho; Bian, Jian-Guo; Chen, Guo-Ming; Chen, He-Sheng; Jiang, Chun-Hua; Liang, Dong; Liang, Song; Meng, Xiangwei; Tao, Junquan; Wang, Jian; Wang, Jian; Wang, Xianyou; Wang, Zheng; Xiao, Hong; Xu, Ming; Zang, Jingjing; Zhang, Zhen; Ban, Yong; Guo, Shuang; Guo, Yifei; Li, Wenbo; Mao, Yajun; Qian, Si-Jin; Teng, Haiyun; Zhu, Bo; Zou, Wei; Cabrera, Andrés; Gomez Moreno, Bernardo; Ocampo Rios, Alberto Andres; Osorio Oliveros, Andres Felipe; Sanabria, Juan Carlos; Godinovic, Nikola; Lelas, Damir; Lelas, Karlo; Plestina, Roko; Polic, Dunja; Puljak, Ivica; Antunovic, Zeljko; Dzelalija, Mile; Brigljevic, Vuko; Duric, Senka; Kadija, Kreso; Morovic, Srecko; Attikis, Alexandros; Galanti, Mario; Mousa, Jehad; Nicolaou, Charalambos; Ptochos, Fotios; Razis, Panos A; Finger, Miroslav; Finger Jr, Michael; Assran, Yasser; Ellithi Kamel, Ali; Khalil, Shaaban; Mahmoud, Mohammed; Hektor, Andi; Kadastik, Mario; Müntel, Mait; Raidal, Martti; Rebane, Liis; Tiko, Andres; Azzolini, Virginia; Eerola, Paula; Fedi, Giacomo; Czellar, Sandor; Härkönen, Jaakko; Heikkinen, Mika Aatos; Karimäki, Veikko; Kinnunen, Ritva; Kortelainen, Matti J; Lampén, Tapio; Lassila-Perini, Kati; Lehti, Sami; Lindén, Tomas; Luukka, Panja-Riina; Mäenpää, Teppo; Tuominen, Eija; Tuominiemi, Jorma; Tuovinen, Esa; Ungaro, Donatella; Wendland, Lauri; Banzuzi, Kukka; Karjalainen, Ahti; Korpela, Arja; Tuuva, Tuure; Sillou, Daniel; Besancon, Marc; Choudhury, Somnath; Dejardin, Marc; Denegri, Daniel; Fabbro, Bernard; Faure, Jean-Louis; Ferri, Federico; Ganjour, Serguei; Gentit, François-Xavier; Givernaud, Alain; Gras, Philippe; Hamel de Monchenault, Gautier; Jarry, Patrick; Locci, Elizabeth; Malcles, Julie; Marionneau, Matthieu; Millischer, Laurent; Rander, John; Rosowsky, André; Shreyber, Irina; Titov, Maksym; Verrecchia, Patrice; Baffioni, Stephanie; Beaudette, Florian; Benhabib, Lamia; Bianchini, Lorenzo; Bluj, Michal; Broutin, Clementine; Busson, Philippe; Charlot, Claude; Dahms, Torsten; Dobrzynski, Ludwik; Elgammal, Sherif; Granier de Cassagnac, Raphael; Haguenauer, Maurice; Miné, Philippe; Mironov, Camelia; Ochando, Christophe; Paganini, Pascal; Sabes, David; Salerno, Roberto; Sirois, Yves; Thiebaux, Christophe; Wyslouch, Bolek; Zabi, Alexandre; Agram, Jean-Laurent; Andrea, Jeremy; Bloch, Daniel; Bodin, David; Brom, Jean-Marie; Cardaci, Marco; Chabert, Eric Christian; Collard, Caroline; Conte, Eric; Drouhin, Frédéric; Ferro, Cristina; Fontaine, Jean-Charles; Gelé, Denis; Goerlach, Ulrich; Greder, Sebastien; Juillot, Pierre; Karim, Mehdi; Le Bihan, Anne-Catherine; Mikami, Yoshinari; Van Hove, Pierre; Fassi, Farida; Mercier, Damien; Baty, Clement; Beauceron, Stephanie; Beaupere, Nicolas; Bedjidian, Marc; Bondu, Olivier; Boudoul, Gaelle; Boumediene, Djamel; Brun, Hugues; Chasserat, Julien; Chierici, Roberto; Contardo, Didier; Depasse, Pierre; El Mamouni, Houmani; Fay, Jean; Gascon, Susan; Ille, Bernard; Kurca, Tibor; Le Grand, Thomas; Lethuillier, Morgan; Mirabito, Laurent; Perries, Stephane; Sordini, Viola; Tosi, Silvano; Tschudi, Yohann; Verdier, Patrice; Lomidze, David; Anagnostou, Georgios; Beranek, Sarah; Edelhoff, Matthias; Feld, Lutz; Heracleous, Natalie; Hindrichs, Otto; Jussen, Ruediger; Klein, Katja; Merz, Jennifer; Mohr, Niklas; Ostapchuk, Andrey; Perieanu, Adrian; Raupach, Frank; Sammet, Jan; Schael, Stefan; Sprenger, Daniel; Weber, Hendrik; Weber, Martin; Wittmer, Bruno; Ata, Metin; Dietz-Laursonn, Erik; Erdmann, Martin; Hebbeker, Thomas; Heidemann, Carsten; Hinzmann, Andreas; Hoepfner, Kerstin; Klimkovich, Tatsiana; Klingebiel, Dennis; Kreuzer, Peter; Lanske, Dankfried; Lingemann, Joschka; Magass, Carsten; Merschmeyer, Markus; Meyer, Arnd; Papacz, Paul; Pieta, Holger; Reithler, Hans; Schmitz, Stefan Antonius; Sonnenschein, Lars; Steggemann, Jan; Teyssier, Daniel; Bontenackels, Michael; Davids, Martina; Duda, Markus; Flügge, Günter; Geenen, Heiko; Giffels, Manuel; Haj Ahmad, Wael; Heydhausen, Dirk; Hoehle, Felix; Kargoll, Bastian; Kress, Thomas; Kuessel, Yvonne; Linn, Alexander; Nowack, Andreas; Perchalla, Lars; Pooth, Oliver; Rennefeld, Jörg; Sauerland, Philip; Stahl, Achim; Thomas, Maarten; Tornier, Daiske; Zoeller, Marc Henning; Aldaya Martin, Maria; Behrenhoff, Wolf; Behrens, Ulf; Bergholz, Matthias; Bethani, Agni; Borras, Kerstin; Cakir, Altan; Campbell, Alan; Castro, Elena; Dammann, Dirk; Eckerlin, Guenter; Eckstein, Doris; Flossdorf, Alexander; Flucke, Gero; Geiser, Achim; Hauk, Johannes; Jung, Hannes; Kasemann, Matthias; Katkov, Igor; Katsas, Panagiotis; Kleinwort, Claus; Kluge, Hannelies; Knutsson, Albert; Krämer, Mira; Krücker, Dirk; Kuznetsova, Ekaterina; Lange, Wolfgang; Lohmann, Wolfgang; Mankel, Rainer; Marienfeld, Markus; Melzer-Pellmann, Isabell-Alissandra; Meyer, Andreas Bernhard; Mnich, Joachim; Mussgiller, Andreas; Olzem, Jan; Petrukhin, Alexey; Pitzl, Daniel; Raspereza, Alexei; Raval, Amita; Rosin, Michele; Schmidt, Ringo; Schoerner-Sadenius, Thomas; Sen, Niladri; Spiridonov, Alexander; Stein, Matthias; Tomaszewska, Justyna; Walsh, Roberval; Wissing, Christoph; Autermann, Christian; Blobel, Volker; Bobrovskyi, Sergei; Draeger, Jula; Enderle, Holger; Gebbert, Ulla; Görner, Martin; Hermanns, Thomas; Kaschube, Kolja; Kaussen, Gordon; Kirschenmann, Henning; Klanner, Robert; Lange, Jörn; Mura, Benedikt; Naumann-Emme, Sebastian; Nowak, Friederike; Pietsch, Niklas; Sander, Christian; Schettler, Hannes; Schleper, Peter; Schlieckau, Eike; Schröder, Matthias; Schum, Torben; Stadie, Hartmut; Steinbrück, Georg; Thomsen, Jan; Barth, Christian; Bauer, Julia; Berger, Joram; Buege, Volker; Chwalek, Thorsten; De Boer, Wim; Dierlamm, Alexander; Dirkes, Guido; Feindt, Michael; Gruschke, Jasmin; Hackstein, Christoph; Hartmann, Frank; Heinrich, Michael; Held, Hauke; Hoffmann, Karl-Heinz; Honc, Simon; Komaragiri, Jyothsna Rani; Kuhr, Thomas; Martschei, Daniel; Mueller, Steffen; Müller, Thomas; Niegel, Martin; Oberst, Oliver; Oehler, Andreas; Ott, Jochen; Peiffer, Thomas; Quast, Gunter; Rabbertz, Klaus; Ratnikov, Fedor; Ratnikova, Natalia; Renz, Manuel; Saout, Christophe; Scheurer, Armin; Schieferdecker, Philipp; Schilling, Frank-Peter; Schott, Gregory; Simonis, Hans-Jürgen; Stober, Fred-Markus Helmut; Troendle, Daniel; Wagner-Kuhr, Jeannine; Weiler, Thomas; Zeise, Manuel; Zhukov, Valery; Ziebarth, Eva Barbara; Daskalakis, Georgios; Geralis, Theodoros; Kesisoglou, Stilianos; Kyriakis, Aristotelis; Loukas, Demetrios; Manolakos, Ioannis; Markou, Athanasios; Markou, Christos; Mavrommatis, Charalampos; Ntomari, Eleni; Petrakou, Eleni; Gouskos, Loukas; Mertzimekis, Theodoros; Panagiotou, Apostolos; Stiliaris, Efstathios; Evangelou, Ioannis; Foudas, Costas; Kokkas, Panagiotis; Manthos, Nikolaos; Papadopoulos, Ioannis; Patras, Vaios; Triantis, Frixos A; Aranyi, Attila; Bencze, Gyorgy; Boldizsar, Laszlo; Hajdu, Csaba; Hidas, Pàl; Horvath, Dezso; Kapusi, Anita; Krajczar, Krisztian; Sikler, Ferenc; Veres, Gabor Istvan; Vesztergombi, Gyorgy; Beni, Noemi; Molnar, Jozsef; Palinkas, Jozsef; Szillasi, Zoltan; Veszpremi, Viktor; Raics, Peter; Trocsanyi, Zoltan Laszlo; Ujvari, Balazs; Beri, Suman Bala; Bhatnagar, Vipin; Dhingra, Nitish; Gupta, Ruchi; Jindal, Monika; Kaur, Manjit; Kohli, Jatinder Mohan; Mehta, Manuk Zubin; Nishu, Nishu; Saini, Lovedeep Kaur; Sharma, Archana; Singh, Anil; Singh, Jasbir; Singh, Supreet Pal; Ahuja, Sudha; Choudhary, Brajesh C; Gupta, Pooja; Jain, Sandhya; Kumar, Ashok; Kumar, Arun; Naimuddin, Md; Ranjan, Kirti; Shivpuri, Ram Krishen; Banerjee, Sunanda; Bhattacharya, Satyaki; Dutta, Suchandra; Gomber, Bhawna; Jain, Shilpi; Khurana, Raman; Sarkar, Subir; Choudhury, Rajani Kant; Dutta, Dipanwita; Kailas, Swaminathan; Kumar, Vineet; Mehta, Pourus; Mohanty, Ajit Kumar; Pant, Lalit Mohan; Shukla, Prashant; Aziz, Tariq; Guchait, Monoranjan; Gurtu, Atul; Maity, Manas; Majumder, Devdatta; Majumder, Gobinda; Mazumdar, Kajari; Mohanty, Gagan Bihari; Saha, Anirban; Sudhakar, Katta; Wickramage, Nadeesha; Banerjee, Sudeshna; Dugad, Shashikant; Mondal, Naba Kumar; Arfaei, Hessamaddin; Bakhshiansohi, Hamed; Etesami, Seyed Mohsen; Fahim, Ali; Hashemi, Majid; Hesari, Hoda; Jafari, Abideh; Khakzad, Mohsen; Mohammadi, Abdollah; Mohammadi Najafabadi, Mojtaba; Paktinat Mehdiabadi, Saeid; Safarzadeh, Batool; Zeinali, Maryam; Abbrescia, Marcello; Barbone, Lucia; Calabria, Cesare; Colaleo, Anna; Creanza, Donato; De Filippis, Nicola; De Palma, Mauro; Fiore, Luigi; Iaselli, Giuseppe; Lusito, Letizia; Maggi, Giorgio; Maggi, Marcello; Manna, Norman; Marangelli, Bartolomeo; My, Salvatore; Nuzzo, Salvatore; Pacifico, Nicola; Pierro, Giuseppe Antonio; Pompili, Alexis; Pugliese, Gabriella; Romano, Francesco; Roselli, Giuseppe; Selvaggi, Giovanna; Silvestris, Lucia; Trentadue, Raffaello; Tupputi, Salvatore; Zito, Giuseppe; Abbiendi, Giovanni; Benvenuti, Alberto; Bonacorsi, Daniele; Braibant-Giacomelli, Sylvie; Brigliadori, Luca; Capiluppi, Paolo; Castro, Andrea; Cavallo, Francesca Romana; Cuffiani, Marco; Dallavalle, Gaetano-Marco; Fabbri, Fabrizio; Fanfani, Alessandra; Fasanella, Daniele; Giacomelli, Paolo; Giunta, Marina; Grandi, Claudio; Marcellini, Stefano; Masetti, Gianni; Meneghelli, Marco; Montanari, Alessandro; Navarria, Francesco; Odorici, Fabrizio; Perrotta, Andrea; Primavera, Federica; Rossi, Antonio; Rovelli, Tiziano; Siroli, Gianni; Travaglini, Riccardo; Albergo, Sebastiano; Cappello, Gigi; Chiorboli, Massimiliano; Costa, Salvatore; Tricomi, Alessia; Tuve, Cristina; Barbagli, Giuseppe; Ciulli, Vitaliano; Civinini, Carlo; D'Alessandro, Raffaello; Focardi, Ettore; Frosali, Simone; Gallo, Elisabetta; Gonzi, Sandro; Lenzi, Piergiulio; Meschini, Marco; Paoletti, Simone; Sguazzoni, Giacomo; Tropiano, Antonio; Benussi, Luigi; Bianco, Stefano; Colafranceschi, Stefano; Fabbri, Franco; Piccolo, Davide; Fabbricatore, Pasquale; Musenich, Riccardo; Benaglia, Andrea; De Guio, Federico; Di Matteo, Leonardo; Gennai, Simone; Ghezzi, Alessio; Malvezzi, Sandra; Martelli, Arabella; Massironi, Andrea; Menasce, Dario; Moroni, Luigi; Paganoni, Marco; Pedrini, Daniele; Ragazzi, Stefano; Redaelli, Nicola; Sala, Silvano; Tabarelli de Fatis, Tommaso; Buontempo, Salvatore; Carrillo Montoya, Camilo Andres; Cavallo, Nicola; De Cosa, Annapaola; Fabozzi, Francesco; Iorio, Alberto Orso Maria; Lista, Luca; Merola, Mario; Paolucci, Pierluigi; Azzi, Patrizia; Bacchetta, Nicola; Bellan, Paolo; Bisello, Dario; Branca, Antonio; Carlin, Roberto; Checchia, Paolo; Dorigo, Tommaso; Dosselli, Umberto; Gasparini, Fabrizio; Gasparini, Ugo; Gozzelino, Andrea; Lacaprara, Stefano; Lazzizzera, Ignazio; Margoni, Martino; Mazzucato, Mirco; Meneguzzo, Anna Teresa; Nespolo, Massimo; Passaseo, Marina; Perrozzi, Luca; Pozzobon, Nicola; Ronchese, Paolo; Simonetto, Franco; Torassa, Ezio; Tosi, Mia; Vanini, Sara; Zotto, Pierluigi; Zumerle, Gianni; Baesso, Paolo; Berzano, Umberto; Ratti, Sergio P; Riccardi, Cristina; Torre, Paola; Vitulo, Paolo; Viviani, Claudio; Biasini, Maurizio; Bilei, Gian Mario; Caponeri, Benedetta; Fanò, Livio; Lariccia, Paolo; Lucaroni, Andrea; Mantovani, Giancarlo; Menichelli, Mauro; Nappi, Aniello; Romeo, Francesco; Santocchia, Attilio; Taroni, Silvia; Valdata, Marisa; Azzurri, Paolo; Bagliesi, Giuseppe; Bernardini, Jacopo; Boccali, Tommaso; Broccolo, Giuseppe; Castaldi, Rino; D'Agnolo, Raffaele Tito; Dell'Orso, Roberto; Fiori, Francesco; Foà, Lorenzo; Giassi, Alessandro; Kraan, Aafke; Ligabue, Franco; Lomtadze, Teimuraz; Martini, Luca; Messineo, Alberto; Palla, Fabrizio; Segneri, Gabriele; Serban, Alin Titus; Spagnolo, Paolo; Tenchini, Roberto; Tonelli, Guido; Venturi, Andrea; Verdini, Piero Giorgio; Barone, Luciano; Cavallari, Francesca; Del Re, Daniele; Di Marco, Emanuele; Diemoz, Marcella; Franci, Daniele; Grassi, Marco; Longo, Egidio; Meridiani, Paolo; Nourbakhsh, Shervin; Organtini, Giovanni; Pandolfi, Francesco; Paramatti, Riccardo; Rahatlou, Shahram; Rovelli, Chiara; Amapane, Nicola; Arcidiacono, Roberta; Argiro, Stefano; Arneodo, Michele; Biino, Cristina; Botta, Cristina; Cartiglia, Nicolo; Castello, Roberto; Costa, Marco; Demaria, Natale; Graziano, Alberto; Mariotti, Chiara; Marone, Matteo; Maselli, Silvia; Migliore, Ernesto; Mila, Giorgia; Monaco, Vincenzo; Musich, Marco; Obertino, Maria Margherita; Pastrone, Nadia; Pelliccioni, Mario; Potenza, Alberto; Romero, Alessandra; Ruspa, Marta; Sacchi, Roberto; Sola, Valentina; Solano, Ada; Staiano, Amedeo; Vilela Pereira, Antonio; Belforte, Stefano; Cossutti, Fabio; Della Ricca, Giuseppe; Gobbo, Benigno; Montanino, Damiana; Penzo, Aldo; Heo, Seong Gu; Nam, Soon-Kwon; Chang, Sunghyun; Chung, Jin Hyuk; Kim, Dong Hee; Kim, Gui Nyun; Kim, Ji Eun; Kong, Dae Jung; Park, Hyangkyu; Ro, Sang-Ryul; Son, Dohhee; Son, Dong-Chul; Son, Taejin; Kim, Jaeho; Kim, Jae Yool; Song, Sanghyeon; Choi, Suyong; Hong, Byung-Sik; Jo, Mihee; Kim, Hyunchul; Kim, Ji Hyun; Kim, Tae Jeong; Lee, Kyong Sei; Moon, Dong Ho; Park, Sung Keun; Sim, Kwang Souk; Choi, Minkyoo; Kang, Seokon; Kim, Hyunyong; Park, Chawon; Park, Inkyu; Park, Sangnam; Ryu, Geonmo; Choi, Young-Il; Choi, Young Kyu; Goh, Junghwan; Kim, Min Suk; Lee, Jongseok; Lee, Sungeun; Seo, Hyunkwan; Yu, Intae; Bilinskas, Mykolas Jurgis; Grigelionis, Ignas; Janulis, Mindaugas; Martisiute, Dalia; Petrov, Pavel; Sabonis, Tomas; Castilla-Valdez, Heriberto; De La Cruz-Burelo, Eduard; Heredia-de La Cruz, Ivan; Lopez-Fernandez, Ricardo; Magaña Villalba, Ricardo; Sánchez-Hernández, Alberto; Villasenor-Cendejas, Luis Manuel; Carrillo Moreno, Salvador; Vazquez Valencia, Fabiola; Salazar Ibarguen, Humberto Antonio; Casimiro Linares, Edgar; Morelos Pineda, Antonio; Reyes-Santos, Marco A; Krofcheck, David; Tam, Jason; Butler, Philip H; Doesburg, Robert; Silverwood, Hamish; Ahmad, Muhammad; Ahmed, Ijaz; Asghar, Muhammad Irfan; Hoorani, Hafeez R; Khan, Wajid Ali; Khurshid, Taimoor; Qazi, Shamona; Brona, Grzegorz; Cwiok, Mikolaj; Dominik, Wojciech; Doroba, Krzysztof; Kalinowski, Artur; Konecki, Marcin; Krolikowski, Jan; Frueboes, Tomasz; Gokieli, Ryszard; Górski, Maciej; Kazana, Malgorzata; Nawrocki, Krzysztof; Romanowska-Rybinska, Katarzyna; Szleper, Michal; Wrochna, Grzegorz; Zalewski, Piotr; Almeida, Nuno; Bargassa, Pedrame; David Tinoco Mendes, Andre; Faccioli, Pietro; Ferreira Parracho, Pedro Guilherme; Gallinaro, Michele; Musella, Pasquale; Nayak, Aruna; Pela, Joao; Ribeiro, Pedro Quinaz; Seixas, Joao; Varela, Joao; Afanasiev, Serguei; Belotelov, Ivan; Bunin, Pavel; Golutvin, Igor; Karjavin, Vladimir; Kozlov, Guennady; Lanev, Alexander; Moisenz, Petr; Palichik, Vladimir; Perelygin, Victor; Savina, Maria; Shmatov, Sergey; Smirnov, Vitaly; Volodko, Anton; Zarubin, Anatoli; Golovtsov, Victor; Ivanov, Yury; Kim, Victor; Levchenko, Petr; Murzin, Victor; Oreshkin, Vadim; Smirnov, Igor; Sulimov, Valentin; Uvarov, Lev; Vavilov, Sergey; Vorobyev, Alexey; Vorobyev, Andrey; Andreev, Yuri; Dermenev, Alexander; Gninenko, Sergei; Golubev, Nikolai; Kirsanov, Mikhail; Krasnikov, Nikolai; Matveev, Viktor; Pashenkov, Anatoli; Toropin, Alexander; Troitsky, Sergey; Epshteyn, Vladimir; Gavrilov, Vladimir; Kaftanov, Vitali; Kossov, Mikhail; Krokhotin, Andrey; Lychkovskaya, Natalia; Popov, Vladimir; Safronov, Grigory; Semenov, Sergey; Stolin, Viatcheslav; Vlasov, Evgueni; Zhokin, Alexander; Boos, Edouard; Dubinin, Mikhail; Dudko, Lev; Ershov, Alexander; Gribushin, Andrey; Kodolova, Olga; Lokhtin, Igor; Markina, Anastasia; Obraztsov, Stepan; Perfilov, Maxim; Petrushanko, Sergey; Sarycheva, Ludmila; Savrin, Viktor; Snigirev, Alexander; Andreev, Vladimir; Azarkin, Maksim; Dremin, Igor; Kirakosyan, Martin; Leonidov, Andrey; Rusakov, Sergey V; Vinogradov, Alexey; Azhgirey, Igor; Bayshev, Igor; Bitioukov, Sergei; Grishin, Viatcheslav; Kachanov, Vassili; Konstantinov, Dmitri; Korablev, Andrey; Krychkine, Victor; Petrov, Vladimir; Ryutin, Roman; Sobol, Andrei; Tourtchanovitch, Leonid; Troshin, Sergey; Tyurin, Nikolay; Uzunian, Andrey; Volkov, Alexey; Adzic, Petar; Djordjevic, Milos; Krpic, Dragomir; Milosevic, Jovan; Aguilar-Benitez, Manuel; Alcaraz Maestre, Juan; Arce, Pedro; Battilana, Carlo; Calvo, Enrique; Cepeda, Maria; Cerrada, Marcos; Chamizo Llatas, Maria; Colino, Nicanor; De La Cruz, Begona; Delgado Peris, Antonio; Diez Pardos, Carmen; Domínguez Vázquez, Daniel; Fernandez Bedoya, Cristina; Fernández Ramos, Juan Pablo; Ferrando, Antonio; Flix, Jose; Fouz, Maria Cruz; Garcia-Abia, Pablo; Gonzalez Lopez, Oscar; Goy Lopez, Silvia; Hernandez, Jose M; Josa, Maria Isabel; Merino, Gonzalo; Puerta Pelayo, Jesus; Redondo, Ignacio; Romero, Luciano; Santaolalla, Javier; Senghi Soares, Mara; Willmott, Carlos; Albajar, Carmen; Codispoti, Giuseppe; de Trocóniz, Jorge F; Cuevas, Javier; Fernandez Menendez, Javier; Folgueras, Santiago; Gonzalez Caballero, Isidro; Lloret Iglesias, Lara; Vizan Garcia, Jesus Manuel; Brochero Cifuentes, Javier Andres; Cabrillo, Iban Jose; Calderon, Alicia; Chuang, Shan-Huei; Duarte Campderros, Jordi; Felcini, Marta; Fernandez, Marcos; Gomez, Gervasio; Gonzalez Sanchez, Javier; Jorda, Clara; Lobelle Pardo, Patricia; Lopez Virto, Amparo; Marco, Jesus; Marco, Rafael; Martinez Rivero, Celso; Matorras, Francisco; Munoz Sanchez, Francisca Javiela; Piedra Gomez, Jonatan; Rodrigo, Teresa; Rodríguez-Marrero, Ana Yaiza; Ruiz-Jimeno, Alberto; Scodellaro, Luca; Sobron Sanudo, Mar; Vila, Ivan; Vilar Cortabitarte, Rocio; Abbaneo, Duccio; Auffray, Etiennette; Auzinger, Georg; Baillon, Paul; Ball, Austin; Barney, David; Bell, Alan James; Benedetti, Daniele; Bernet, Colin; Bialas, Wojciech; Bloch, Philippe; Bocci, Andrea; Bolognesi, Sara; Bona, Marcella; Breuker, Horst; Bunkowski, Karol; Camporesi, Tiziano; Cerminara, Gianluca; Christiansen, Tim; Coarasa Perez, Jose Antonio; Curé, Benoît; D'Enterria, David; De Roeck, Albert; Di Guida, Salvatore; Dupont-Sagorin, Niels; Elliott-Peisert, Anna; Frisch, Benjamin; Funk, Wolfgang; Gaddi, Andrea; Georgiou, Georgios; Gerwig, Hubert; Gigi, Dominique; Gill, Karl; Giordano, Domenico; Glege, Frank; Gomez-Reino Garrido, Robert; Gouzevitch, Maxime; Govoni, Pietro; Gowdy, Stephen; Guiducci, Luigi; Hansen, Magnus; Hartl, Christian; Harvey, John; Hegeman, Jeroen; Hegner, Benedikt; Hoffmann, Hans Falk; Honma, Alan; Innocente, Vincenzo; Janot, Patrick; Kaadze, Ketino; Karavakis, Edward; Lecoq, Paul; Lourenco, Carlos; Maki, Tuula; Malberti, Martina; Malgeri, Luca; Mannelli, Marcello; Masetti, Lorenzo; Maurisset, Aurelie; Meijers, Frans; Mersi, Stefano; Meschi, Emilio; Moser, Roland; Mozer, Matthias Ulrich; Mulders, Martijn; Nesvold, Erik; Nguyen, Matthew; Orimoto, Toyoko; Orsini, Luciano; Palencia Cortezon, Enrique; Perez, Emmanuelle; Petrilli, Achille; Pfeiffer, Andreas; Pierini, Maurizio; Pimiä, Martti; Piparo, Danilo; Polese, Giovanni; Racz, Attila; Reece, William; Rodrigues Antunes, Joao; Rolandi, Gigi; Rommerskirchen, Tanja; Rovere, Marco; Sakulin, Hannes; Schäfer, Christoph; Schwick, Christoph; Segoni, Ilaria; Sharma, Archana; Siegrist, Patrice; Silva, Pedro; Simon, Michal; Sphicas, Paraskevas; Spiropulu, Maria; Stoye, Markus; Tropea, Paola; Tsirou, Andromachi; Vichoudis, Paschalis; Voutilainen, Mikko; Zeuner, Wolfram Dietrich; Bertl, Willi; Deiters, Konrad; Erdmann, Wolfram; Gabathuler, Kurt; Horisberger, Roland; Ingram, Quentin; Kaestli, Hans-Christian; König, Stefan; Kotlinski, Danek; Langenegger, Urs; Meier, Frank; Renker, Dieter; Rohe, Tilman; Sibille, Jennifer; Starodumov, Andrei; Bäni, Lukas; Bortignon, Pierluigi; Caminada, Lea; Casal, Bruno; Chanon, Nicolas; Chen, Zhiling; Cittolin, Sergio; Dissertori, Günther; Dittmar, Michael; Eugster, Jürg; Freudenreich, Klaus; Grab, Christoph; Hintz, Wieland; Lecomte, Pierre; Lustermann, Werner; Marchica, Carmelo; Martinez Ruiz del Arbol, Pablo; Milenovic, Predrag; Moortgat, Filip; Nägeli, Christoph; Nef, Pascal; Nessi-Tedaldi, Francesca; Pape, Luc; Pauss, Felicitas; Punz, Thomas; Rizzi, Andrea; Ronga, Frederic Jean; Rossini, Marco; Sala, Leonardo; Sanchez, Ann - Karin; Sawley, Marie-Christine; Stieger, Benjamin; Tauscher, Ludwig; Thea, Alessandro; Theofilatos, Konstantinos; Treille, Daniel; Urscheler, Christina; Wallny, Rainer; Weber, Matthias; Wehrli, Lukas; Weng, Joanna; Aguilo, Ernest; Amsler, Claude; Chiochia, Vincenzo; De Visscher, Simon; Favaro, Carlotta; Ivova Rikova, Mirena; Millan Mejias, Barbara; Otiougova, Polina; Regenfus, Christian; Robmann, Peter; Schmidt, Alexander; Snoek, Hella; Chang, Yuan-Hann; Chen, Kuan-Hsin; Kuo, Chia-Ming; Li, Syue-Wei; Lin, Willis; Liu, Zong-Kai; Lu, Yun-Ju; Mekterovic, Darko; Volpe, Roberta; Wu, Jing-Han; Yu, Shin-Shan; Bartalini, Paolo; Chang, Paoti; Chang, You-Hao; Chang, Yu-Wei; Chao, Yuan; Chen, Kai-Feng; Hou, George Wei-Shu; Hsiung, Yee; Kao, Kai-Yi; Lei, Yeong-Jyi; Lu, Rong-Shyang; Shiu, Jing-Ge; Tzeng, Yeng-Ming; Wang, Minzu; Adiguzel, Aytul; Bakirci, Mustafa Numan; Cerci, Salim; Dozen, Candan; Dumanoglu, Isa; Eskut, Eda; Girgis, Semiray; Gokbulut, Gul; Hos, Ilknur; Kangal, Evrim Ersin; Kayis Topaksu, Aysel; Onengut, Gulsen; Ozdemir, Kadri; Ozturk, Sertac; Polatoz, Ayse; Sogut, Kenan; Sunar Cerci, Deniz; Tali, Bayram; Topakli, Huseyin; Uzun, Dilber; Vergili, Latife Nukhet; Vergili, Mehmet; Akin, Ilina Vasileva; Aliev, Takhmasib; Bilin, Bugra; Bilmis, Selcuk; Deniz, Muhammed; Gamsizkan, Halil; Guler, Ali Murat; Ocalan, Kadir; Ozpineci, Altug; Serin, Meltem; Sever, Ramazan; Surat, Ugur Emrah; Yildirim, Eda; Zeyrek, Mehmet; Deliomeroglu, Mehmet; Demir, Durmus; Gülmez, Erhan; Isildak, Bora; Kaya, Mithat; Kaya, Ozlem; Özbek, Melih; Ozkorucuklu, Suat; Sonmez, Nasuf; Levchuk, Leonid; Bostock, Francis; Brooke, James John; Cheng, Teh Lee; Clement, Emyr; Cussans, David; Frazier, Robert; Goldstein, Joel; Grimes, Mark; Hartley, Dominic; Heath, Greg P; Heath, Helen F; Kreczko, Lukasz; Metson, Simon; Newbold, Dave M; Nirunpong, Kachanon; Poll, Anthony; Senkin, Sergey; Smith, Vincent J; Basso, Lorenzo; Bell, Ken W; Belyaev, Alexander; Brew, Christopher; Brown, Robert M; Camanzi, Barbara; Cockerill, David JA; Coughlan, John A; Harder, Kristian; Harper, Sam; Jackson, James; Kennedy, Bruce W; Olaiya, Emmanuel; Petyt, David; Radburn-Smith, Benjamin Charles; Shepherd-Themistocleous, Claire; Tomalin, Ian R; Womersley, William John; Worm, Steven; Bainbridge, Robert; Ball, Gordon; Ballin, Jamie; Beuselinck, Raymond; Buchmuller, Oliver; Colling, David; Cripps, Nicholas; Cutajar, Michael; Davies, Gavin; Della Negra, Michel; Ferguson, William; Fulcher, Jonathan; Futyan, David; Gilbert, Andrew; Guneratne Bryer, Arlo; Hall, Geoffrey; Hatherell, Zoe; Hays, Jonathan; Iles, Gregory; Jarvis, Martyn; Karapostoli, Georgia; Lyons, Louis; MacEvoy, Barry C; Magnan, Anne-Marie; Marrouche, Jad; Mathias, Bryn; Nandi, Robin; Nash, Jordan; Nikitenko, Alexander; Papageorgiou, Anastasios; Pesaresi, Mark; Petridis, Konstantinos; Pioppi, Michele; Raymond, David Mark; Rogerson, Samuel; Rompotis, Nikolaos; Rose, Andrew; Ryan, Matthew John; Seez, Christopher; Sharp, Peter; Sparrow, Alex; Tapper, Alexander; Tourneur, Stephane; Vazquez Acosta, Monica; Virdee, Tejinder; Wakefield, Stuart; Wardle, Nicholas; Wardrope, David; Whyntie, Tom; Barrett, Matthew; Chadwick, Matthew; Cole, Joanne; Hobson, Peter R; Khan, Akram; Kyberd, Paul; Leslie, Dawn; Martin, William; Reid, Ivan; Teodorescu, Liliana; Hatakeyama, Kenichi; Liu, Hongxuan; Henderson, Conor; Bose, Tulika; Carrera Jarrin, Edgar; Fantasia, Cory; Heister, Arno; St John, Jason; Lawson, Philip; Lazic, Dragoslav; Rohlf, James; Sperka, David; Sulak, Lawrence; Avetisyan, Aram; Bhattacharya, Saptaparna; 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Clare, Robert; Ellison, John Anthony; Gary, J William; Giordano, Ferdinando; Hanson, Gail; Jeng, Geng-Yuan; Kao, Shih-Chuan; Liu, Feng; Liu, Hongliang; Long, Owen Rosser; Luthra, Arun; Nguyen, Harold; Shen, Benjamin C; Stringer, Robert; Sturdy, Jared; Sumowidagdo, Suharyo; Wilken, Rachel; Wimpenny, Stephen; Andrews, Warren; Branson, James G; Cerati, Giuseppe Benedetto; Evans, David; Golf, Frank; Holzner, André; Kelley, Ryan; Lebourgeois, Matthew; Letts, James; Mangano, Boris; Padhi, Sanjay; Palmer, Christopher; Petrucciani, Giovanni; Pi, Haifeng; Pieri, Marco; Ranieri, Riccardo; Sani, Matteo; Sharma, Vivek; Simon, Sean; Sudano, Elizabeth; Tadel, Matevz; Tu, Yanjun; Vartak, Adish; Wasserbaech, Steven; Würthwein, Frank; Yagil, Avraham; Yoo, Jaehyeok; Barge, Derek; Bellan, Riccardo; Campagnari, Claudio; D'Alfonso, Mariarosaria; Danielson, Thomas; Flowers, Kristen; Geffert, Paul; Incandela, Joe; Justus, Christopher; Kalavase, Puneeth; Koay, Sue Ann; Kovalskyi, Dmytro; Krutelyov, Vyacheslav; Lowette, Steven; Mccoll, Nickolas; Pavlunin, Viktor; Rebassoo, Finn; Ribnik, Jacob; Richman, Jeffrey; Rossin, Roberto; Stuart, David; To, Wing; Vlimant, Jean-Roch; Apresyan, Artur; Bornheim, Adolf; Bunn, Julian; Chen, Yi; Gataullin, Marat; Ma, Yousi; Mott, Alexander; Newman, Harvey B; Rogan, Christopher; Shin, Kyoungha; Timciuc, Vladlen; Traczyk, Piotr; Veverka, Jan; Wilkinson, Richard; Yang, Yong; Zhu, Ren-Yuan; Akgun, Bora; Carroll, Ryan; Ferguson, Thomas; Iiyama, Yutaro; Jang, Dong Wook; Jun, Soon Yung; Liu, Yueh-Feng; Paulini, Manfred; Russ, James; Vogel, Helmut; Vorobiev, Igor; Cumalat, John Perry; Dinardo, Mauro Emanuele; Drell, Brian Robert; Edelmaier, Christopher; Ford, William T; Gaz, Alessandro; Heyburn, Bernadette; Luiggi Lopez, Eduardo; Nauenberg, Uriel; Smith, James; Stenson, Kevin; Ulmer, Keith; Wagner, Stephen Robert; Zang, Shi-Lei; Agostino, Lorenzo; Alexander, James; Cassel, David; Chatterjee, Avishek; Eggert, Nicholas; Gibbons, Lawrence Kent; Heltsley, Brian; Hopkins, Walter; 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Kunori, Shuichi; Kwan, Simon; Leonidopoulos, Christos; Limon, Peter; Lincoln, Don; Lipton, Ron; Lykken, Joseph; Maeshima, Kaori; Marraffino, John Michael; Mason, David; McBride, Patricia; Miao, Ting; Mishra, Kalanand; Mrenna, Stephen; Musienko, Yuri; Newman-Holmes, Catherine; O'Dell, Vivian; Pordes, Ruth; Prokofyev, Oleg; Saoulidou, Niki; Sexton-Kennedy, Elizabeth; Sharma, Seema; Spalding, William J; Spiegel, Leonard; Tan, Ping; Taylor, Lucas; Tkaczyk, Slawek; Uplegger, Lorenzo; Vaandering, Eric Wayne; Vidal, Richard; Whitmore, Juliana; Wu, Weimin; Yang, Fan; Yumiceva, Francisco; Yun, Jae Chul; Acosta, Darin; Avery, Paul; Bourilkov, Dimitri; Chen, Mingshui; Das, Souvik; De Gruttola, Michele; Di Giovanni, Gian Piero; Dobur, Didar; Drozdetskiy, Alexey; Field, Richard D; Fisher, Matthew; Fu, Yu; Furic, Ivan-Kresimir; Gartner, Joseph; Hugon, Justin; Kim, Bockjoo; Konigsberg, Jacobo; Korytov, Andrey; Kropivnitskaya, Anna; Kypreos, Theodore; Matchev, Konstantin; Mitselmakher, Guenakh; Muniz, Lana; Prescott, Craig; Remington, Ronald; Rinkevicius, Aurelijus; Schmitt, Michael Houston; Scurlock, Bobby; Sellers, Paul; Skhirtladze, Nikoloz; Snowball, Matthew; Wang, Dayong; Yelton, John; Zakaria, Mohammed; Gaultney, Vanessa; Kramer, Laird; Lebolo, Luis Miguel; Linn, Stephan; Markowitz, Pete; Martinez, German; Rodriguez, Jorge Luis; Adams, Todd; Askew, Andrew; Bochenek, Joseph; Chen, Jie; Diamond, Brendan; Gleyzer, Sergei V; Haas, Jeff; Hagopian, Sharon; Hagopian, Vasken; Jenkins, Merrill; Johnson, Kurtis F; Prosper, Harrison; Quertenmont, Loic; Sekmen, Sezen; Veeraraghavan, Venkatesh; Baarmand, Marc M; Dorney, Brian; Guragain, Samir; Hohlmann, Marcus; Kalakhety, Himali; Ralich, Robert; Vodopiyanov, Igor; Adams, Mark Raymond; Anghel, Ioana Maria; Apanasevich, Leonard; Bai, Yuting; Bazterra, Victor Eduardo; Betts, Russell Richard; Callner, Jeremy; Cavanaugh, Richard; Dragoiu, Cosmin; Gauthier, Lucie; Gerber, Cecilia Elena; Hofman, David Jonathan; Khalatyan, Samvel; Kunde, Gerd J; Lacroix, Florent; Malek, Magdalena; O'Brien, Christine; Silkworth, Christopher; Silvestre, Catherine; Smoron, Agata; Strom, Derek; Varelas, Nikos; Akgun, Ugur; Albayrak, Elif Asli; Bilki, Burak; Clarida, Warren; Duru, Firdevs; Lae, Chung Khim; McCliment, Edward; Merlo, Jean-Pierre; Mermerkaya, Hamit; Mestvirishvili, Alexi; Moeller, Anthony; Nachtman, Jane; Newsom, Charles Ray; Norbeck, Edwin; Olson, Jonathan; Onel, Yasar; Ozok, Ferhat; Sen, Sercan; Wetzel, James; Yetkin, Taylan; Yi, Kai; Barnett, Bruce Arnold; Blumenfeld, Barry; Bonato, Alessio; Eskew, Christopher; Fehling, David; Giurgiu, Gavril; Gritsan, Andrei; Guo, Zijin; Hu, Guofan; Maksimovic, Petar; Rappoccio, Salvatore; Swartz, Morris; Tran, Nhan Viet; Whitbeck, Andrew; Baringer, Philip; Bean, Alice; Benelli, Gabriele; Grachov, Oleg; Kenny Iii, Raymond Patrick; Murray, Michael; Noonan, Daniel; Sanders, Stephen; Wood, Jeffrey Scott; Zhukova, Victoria; Barfuss, Anne-fleur; Bolton, Tim; Chakaberia, Irakli; Ivanov, Andrew; Khalil, Sadia; Makouski, Mikhail; Maravin, Yurii; Shrestha, Shruti; Svintradze, Irakli; Wan, Zongru; Gronberg, Jeffrey; Lange, David; Wright, Douglas; Baden, Drew; Boutemeur, Madjid; Eno, Sarah Catherine; Ferencek, Dinko; Gomez, Jaime; Hadley, Nicholas John; Kellogg, Richard G; Kirn, Malina; Lu, Ying; Mignerey, Alice; Rossato, Kenneth; Rumerio, Paolo; Santanastasio, Francesco; Skuja, Andris; Temple, Jeffrey; Tonjes, Marguerite; Tonwar, Suresh C; Twedt, Elizabeth; Alver, Burak; Bauer, Gerry; Bendavid, Joshua; Busza, Wit; Butz, Erik; Cali, Ivan Amos; Chan, Matthew; Dutta, Valentina; Everaerts, Pieter; Gomez Ceballos, Guillelmo; Goncharov, Maxim; Hahn, Kristan Allan; Harris, Philip; Kim, Yongsun; Klute, Markus; Lee, Yen-Jie; Li, Wei; Loizides, Constantinos; Luckey, Paul David; Ma, Teng; Nahn, Steve; Paus, Christoph; Ralph, Duncan; Roland, Christof; Roland, Gunther; Rudolph, Matthew; Stephans, George; Stöckli, Fabian; Sumorok, Konstanty; Sung, Kevin; Velicanu, Dragos; Wenger, Edward Allen; Wolf, Roger; Xie, Si; Yang, Mingming; Yilmaz, Yetkin; Yoon, Sungho; Zanetti, Marco; Cooper, Seth; Cushman, Priscilla; Dahmes, Bryan; De Benedetti, Abraham; Dudero, Phillip Russell; Franzoni, Giovanni; Haupt, Jason; Klapoetke, Kevin; Kubota, Yuichi; Mans, Jeremy; Pastika, Nathaniel; Rekovic, Vladimir; Rusack, Roger; Sasseville, Michael; Singovsky, Alexander; Tambe, Norbert; Cremaldi, Lucien Marcus; Godang, Romulus; Kroeger, Rob; Perera, Lalith; Rahmat, Rahmat; Sanders, David A; Summers, Don; Bloom, Kenneth; Bose, Suvadeep; Butt, Jamila; Claes, Daniel R; Dominguez, Aaron; Eads, Michael; Keller, Jason; Kelly, Tony; Kravchenko, Ilya; Lazo-Flores, Jose; Malbouisson, Helena; Malik, Sudhir; Snow, Gregory R; Baur, Ulrich; Godshalk, Andrew; Iashvili, Ia; Jain, Supriya; Kharchilava, Avto; Kumar, Ashish; Shipkowski, Simon Peter; Smith, Kenneth; Zennamo, Joseph; Alverson, George; Barberis, Emanuela; Baumgartel, Darin; Boeriu, Oana; Chasco, Matthew; Reucroft, Steve; Swain, John; Trocino, Daniele; Wood, Darien; Zhang, Jinzhong; Anastassov, Anton; Kubik, Andrew; Odell, Nathaniel; Ofierzynski, Radoslaw Adrian; Pollack, Brian; Pozdnyakov, Andrey; Schmitt, Michael Henry; Stoynev, Stoyan; Velasco, Mayda; Won, Steven; Antonelli, Louis; Berry, Douglas; Brinkerhoff, Andrew; Hildreth, Michael; Jessop, Colin; Karmgard, Daniel John; Kolb, Jeff; Kolberg, Ted; Lannon, Kevin; Luo, Wuming; Lynch, Sean; Marinelli, Nancy; Morse, David Michael; Pearson, Tessa; Ruchti, Randy; Slaunwhite, Jason; Valls, Nil; Wayne, Mitchell; Ziegler, Jill; Bylsma, Ben; Durkin, Lloyd Stanley; Gu, Jianhui; Hill, Christopher; Killewald, Phillip; Kotov, Khristian; Ling, Ta-Yung; Rodenburg, Marissa; Williams, Grayson; Adam, Nadia; Berry, Edmund; Elmer, Peter; Gerbaudo, Davide; Halyo, Valerie; Hebda, Philip; Hunt, Adam; Jones, John; Laird, Edward; Lopes Pegna, David; Marlow, Daniel; Medvedeva, Tatiana; Mooney, Michael; Olsen, James; Piroué, Pierre; Quan, Xiaohang; Safdi, Ben; Saka, Halil; Stickland, David; Tully, Christopher; Werner, Jeremy Scott; Zuranski, Andrzej; Acosta, Jhon Gabriel; Huang, Xing Tao; Lopez, Angel; Mendez, Hector; Oliveros, Sandra; Ramirez Vargas, Juan Eduardo; Zatserklyaniy, Andriy; Alagoz, Enver; Barnes, Virgil E; Bolla, Gino; Borrello, Laura; Bortoletto, Daniela; De Mattia, Marco; Everett, Adam; Garfinkel, Arthur F; Gutay, Laszlo; Hu, Zhen; Jones, Matthew; Koybasi, Ozhan; Kress, Matthew; Laasanen, Alvin T; Leonardo, Nuno; Liu, Chang; Maroussov, Vassili; Merkel, Petra; Miller, David Harry; Neumeister, Norbert; Shipsey, Ian; Silvers, David; Svyatkovskiy, Alexey; Yoo, Hwi Dong; Zablocki, Jakub; Zheng, Yu; Jindal, Pratima; Parashar, Neeti; Boulahouache, Chaouki; Ecklund, Karl Matthew; Geurts, Frank JM; Padley, Brian Paul; Redjimi, Radia; Roberts, Jay; Zabel, James; Betchart, Burton; Bodek, Arie; Chung, Yeon Sei; Covarelli, Roberto; de Barbaro, Pawel; Demina, Regina; Eshaq, Yossof; Flacher, Henning; Garcia-Bellido, Aran; Goldenzweig, Pablo; Gotra, Yury; Han, Jiyeon; Harel, Amnon; Miner, Daniel Carl; Orbaker, Douglas; Petrillo, Gianluca; Sakumoto, Willis; Vishnevskiy, Dmitry; Zielinski, Marek; Bhatti, Anwar; Ciesielski, Robert; Demortier, Luc; Goulianos, Konstantin; Lungu, Gheorghe; Malik, Sarah; Mesropian, Christina; Atramentov, Oleksiy; Barker, Anthony; Duggan, Daniel; Gershtein, Yuri; Gray, Richard; Halkiadakis, Eva; Hidas, Dean; Hits, Dmitry; Lath, Amitabh; Panwalkar, Shruti; Patel, Rishi; Rose, Keith; Schnetzer, Steve; Somalwar, Sunil; Stone, Robert; Thomas, Scott; Cerizza, Giordano; Hollingsworth, Matthew; Spanier, Stefan; Yang, Zong-Chang; York, Andrew; Eusebi, Ricardo; Flanagan, Will; Gilmore, Jason; Gurrola, Alfredo; Kamon, Teruki; Khotilovich, Vadim; Montalvo, Roy; Osipenkov, Ilya; Pakhotin, Yuriy; Pivarski, James; Safonov, Alexei; Sengupta, Sinjini; Tatarinov, Aysen; Toback, David; Weinberger, Michael; Akchurin, Nural; Bardak, Cemile; Damgov, Jordan; Jeong, Chiyoung; Kovitanggoon, Kittikul; Lee, Sung Won; Libeiro, Terence; Mane, Poonam; Roh, Youn; Sill, Alan; Volobouev, Igor; Wigmans, Richard; Yazgan, Efe; Appelt, Eric; Brownson, Eric; Engh, Daniel; Florez, Carlos; Gabella, William; Issah, Michael; Johns, Willard; Kurt, Pelin; Maguire, Charles; Melo, Andrew; Sheldon, Paul; Snook, Benjamin; Tuo, Shengquan; Velkovska, Julia; Arenton, Michael Wayne; Balazs, Michael; Boutle, Sarah; Cox, Bradley; Francis, Brian; Hirosky, Robert; Ledovskoy, Alexander; Lin, Chuanzhe; Neu, Christopher; Yohay, Rachel; Gollapinni, Sowjanya; Harr, Robert; Karchin, Paul Edmund; Lamichhane, Pramod; Mattson, Mark; Milstène, Caroline; Sakharov, Alexandre; Anderson, Michael; Bachtis, Michail; Bellinger, James Nugent; Carlsmith, Duncan; Dasu, Sridhara; Efron, Jonathan; Gray, Lindsey; Grogg, Kira Suzanne; Grothe, Monika; Hall-Wilton, Richard; Herndon, Matthew; Hervé, Alain; Klabbers, Pamela; Klukas, Jeffrey; Lanaro, Armando; Lazaridis, Christos; Leonard, Jessica; Loveless, Richard; Mohapatra, Ajit; Palmonari, Francesco; Reeder, Don; Ross, Ian; Savin, Alexander; Smith, Wesley H; Swanson, Joshua; Weinberg, Marc

    2011-01-01

    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.

  7. 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.

  8. The physiological consequences of varied heat exposure events in adult Myzus persicae: a single prolonged exposure compared to repeated shorter exposures

    Directory of Open Access Journals (Sweden)

    Behnaz Ghaedi

    2016-08-01

    Full Text Available The study of environmental stress tolerance in aphids has primarily been at low temperatures. In these cases, and in the rare cases of high temperature tolerance assessments, all exposures had been during a single stress event. In the present study, we examined the physiological consequences of repeated high temperature exposure with recovery periods between these stress events in Myzus persicae. We subjected individuals to either a single prolonged three hour heating event, or three one hour heating events with a recovery time of 24 h between bouts. Aphids exposed to repeated bouts of high temperatures had more glucose and higher expression of proteins and osmolyte compounds, such as glycerol, compared to the prolonged exposure group. However, aphids exposed to the repeated high temperature treatment had reduced sources of energy such as trehalose and triglyceride compounds than the prolonged exposure group. Recovery time had more physiological costs (based on production of more protein and consumption of more trehalose and triglyceride and benefits (based on production of more osmolytes in repeated high temperature treatments. As aphids are known to respond differently to constant versus ‘natural’ fluctuating temperature regimes, conclusions drawn from constant temperature data sets may be problematic. We suggest future experiments assessing insect responses to thermal stress incorporate a repeated stress and recovery pattern into their methodologies.

  9. The physiological consequences of varied heat exposure events in adult Myzus persicae: a single prolonged exposure compared to repeated shorter exposures

    Science.gov (United States)

    Andrew, Nigel R.

    2016-01-01

    The study of environmental stress tolerance in aphids has primarily been at low temperatures. In these cases, and in the rare cases of high temperature tolerance assessments, all exposures had been during a single stress event. In the present study, we examined the physiological consequences of repeated high temperature exposure with recovery periods between these stress events in Myzus persicae. We subjected individuals to either a single prolonged three hour heating event, or three one hour heating events with a recovery time of 24 h between bouts. Aphids exposed to repeated bouts of high temperatures had more glucose and higher expression of proteins and osmolyte compounds, such as glycerol, compared to the prolonged exposure group. However, aphids exposed to the repeated high temperature treatment had reduced sources of energy such as trehalose and triglyceride compounds than the prolonged exposure group. Recovery time had more physiological costs (based on production of more protein and consumption of more trehalose and triglyceride) and benefits (based on production of more osmolytes) in repeated high temperature treatments. As aphids are known to respond differently to constant versus ‘natural’ fluctuating temperature regimes, conclusions drawn from constant temperature data sets may be problematic. We suggest future experiments assessing insect responses to thermal stress incorporate a repeated stress and recovery pattern into their methodologies. PMID:27547583

  10. Multi-nucleotide de novo Mutations in Humans.

    Directory of Open Access Journals (Sweden)

    Søren Besenbacher

    2016-11-01

    Full Text Available Mutation of the DNA molecule is one of the most fundamental processes in biology. In this study, we use 283 parent-offspring trios to estimate the rate of mutation for both single nucleotide variants (SNVs and short length variants (indels in humans and examine the mutation process. We found 17812 SNVs, corresponding to a mutation rate of 1.29 × 10-8 per position per generation (PPPG and 1282 indels corresponding to a rate of 9.29 × 10-10 PPPG. We estimate that around 3% of human de novo SNVs are part of a multi-nucleotide mutation (MNM, with 558 (3.1% of mutations positioned less than 20kb from another mutation in the same individual (median distance of 525bp. The rate of de novo mutations is greater in late replicating regions (p = 8.29 × 10-19 and nearer recombination events (p = 0.0038 than elsewhere in the genome.

  11. 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.

  12. Identification of the timing-of-events model with multiple competing exit risks from single-spell data

    NARCIS (Netherlands)

    Drepper, Bettina; Effraimidis, Georgios

    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 the

  13. 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...

  14. Single-point ACT2 gene mutation in the Arabidopsis root hair mutant der1-3 affects overall actin organization, root growth and plant development.

    Science.gov (United States)

    Vaškebová, L; Šamaj, J; Ovecka, M

    2017-12-27

    The actin cytoskeleton forms a dynamic network in plant cells. A single-point mutation in the DER1 (deformed root hairs1) locus located in the sequence of ACTIN2, a gene for major actin in vegetative tissues of Arabidopsis thaliana, leads to impaired root hair development (Ringli C, Baumberger N, Diet A, Frey B, Keller B. 2002. ACTIN2 is essential for bulge site selection and tip growth during root hair development of Arabidopsis. Plant Physiology129: 1464-1472). Only root hair phenotypes have been described so far in der1 mutants, but here we demonstrate obvious aberrations in the organization of the actin cytoskeleton and overall plant development. Organization of the actin cytoskeleton in epidermal cells of cotyledons, hypocotyls and roots was studied qualitatively and quantitatively by live-cell imaging of transgenic lines carrying the GFP-FABD2 fusion protein and in fixed cells after phalloidin labelling. Patterns of root growth were characterized by FM4-64 vital staining, light-sheet microscopy imaging and microtubule immunolabelling. Plant phenotyping included analyses of germination, root growth and plant biomass. Speed of germination, plant fresh weight and total leaf area were significantly reduced in the der1-3 mutant in comparison with the C24 wild-type. Actin filaments in root, hypocotyl and cotyledon epidermal cells of the der1-3 mutant were shorter, thinner and arranged in more random orientations, while actin bundles were shorter and had altered orientations. The wavy pattern of root growth in der1-3 mutant was connected with higher frequencies of shifted cell division planes (CDPs) in root cells, which was consistent with the shifted positioning of microtubule-based preprophase bands and phragmoplasts. The organization of cortical microtubules in the root cells of the der1-3 mutant, however, was not altered. Root growth rate of the der1-3 mutant is not reduced, but changes in the actin cytoskeleton organization can induce a wavy root growth pattern

  15. Single Top quark production via W-gluon fusion at LHC.Simulation with PYTHIA 5.7 Event Generator

    CERN Document Server

    Ahmedov, A; Kukhtin, V V; Mehdiyev, R; Metreveli, Z V; Salihagic, D

    1999-01-01

    The electroweak production of single top quarks via so-called W-gluon fusion in proton-proton interactions at sqrt(s)=14 TeV has been studied. Single Top quark production cross sections have been calculated. Simulations of the top quark production in W-gluon fusion process with further decay to Wb -> l nu b final state and of the corresponding backgrounds have been performed. The use of several kinematical distributions allowed to suppress backgrounds and to perform the reconstruction of the mass of the e - nu - jet system.

  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, 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

  17. The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founder

    NARCIS (Netherlands)

    Smith, Bradley N.; Newhouse, Stephen; Shatunov, Aleksey; Vance, Caroline; Topp, Simon; Johnson, Lauren; Miller, Jack; Lee, Younbok; Troakes, Claire; Scott, Kirsten M.; Jones, Ashley; Gray, Ian; Wright, Jamie; Hortobágyi, Tibor; Al-Sarraj, Safa; Rogelj, Boris; Powell, John; Lupton, Michelle; Lovestone, Simon; Sapp, Peter C.; Weber, Markus; Nestor, Peter J.; Schelhaas, Helenius J.; ten Asbroek, A. A.; Silani, Vincenzo; Gellera, Cinzia; Taroni, Franco; Ticozzi, Nicola; van den Berg, Leonard; Veldink, Jan; van Damme, Phillip; Robberecht, Wim; Shaw, Pamela J.; Kirby, Janine; Pall, Hardev; Morrison, Karen E.; Morris, Alex; de Belleroche, Jacqueline; de Jong, J. M. B. Vianney; Baas, Frank; Andersen, Peter M.; Landers, John; Brown, Robert H.; Weale, Michael E.; Al-Chalabi, Ammar; Shaw, Christopher E.

    2013-01-01

    A massive hexanucleotide repeat expansion mutation (HREM) in C9ORF72 has recently been linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we describe the frequency, origin and stability of this mutation in ALS+/-FTD from five European cohorts (total n=1347).

  18. Measurement of the top quark mass using single top quark events in proton-proton collisions at [Formula: see text] TeV.

    Science.gov (United States)

    Sirunyan, A M; Tumasyan, A; Adam, W; Asilar, E; Bergauer, T; Brandstetter, J; Brondolin, E; Dragicevic, M; Erö, J; Flechl, M; Friedl, M; Frühwirth, R; Ghete, V M; Hartl, C; Hörmann, N; Hrubec, J; Jeitler, M; König, A; Krätschmer, I; Liko, D; Matsushita, T; Mikulec, I; Rabady, D; Rad, N; Rahbaran, B; Rohringer, H; Schieck, J; Strauss, J; Waltenberger, W; Wulz, C-E; Dvornikov, O; Makarenko, V; Mossolov, V; Gonzalez, J Suarez; Zykunov, V; Shumeiko, N; Alderweireldt, S; De Wolf, E A; Janssen, X; Lauwers, J; Van De Klundert, M; Van Haevermaet, H; Van Mechelen, P; Van Remortel, N; Van Spilbeeck, A; Abu Zeid, S; Blekman, F; D'Hondt, J; Daci, N; De Bruyn, I; Deroover, K; Lowette, S; Moortgat, S; Moreels, L; Olbrechts, A; Python, Q; Skovpen, K; Tavernier, S; Van Doninck, W; Van Mulders, P; Van Parijs, I; Brun, H; Clerbaux, B; De Lentdecker, G; Delannoy, H; Fasanella, G; Favart, L; Goldouzian, R; Grebenyuk, A; Karapostoli, G; Lenzi, T; Léonard, A; Luetic, J; Maerschalk, T; Marinov, A; Randle-Conde, A; Seva, T; Vander Velde, C; Vanlaer, P; Vannerom, D; Yonamine, R; Zenoni, F; Zhang, F; Cimmino, A; Cornelis, T; Dobur, D; Fagot, A; Gul, M; Khvastunov, I; Poyraz, D; Salva, S; Schöfbeck, R; Tytgat, M; Van Driessche, W; Yazgan, E; Zaganidis, N; Bakhshiansohi, H; Beluffi, C; Bondu, O; Brochet, S; Bruno, G; Caudron, A; De Visscher, S; Delaere, C; Delcourt, M; Francois, B; Giammanco, A; Jafari, A; Komm, M; Krintiras, G; Lemaitre, V; Magitteri, A; Mertens, A; Musich, M; Piotrzkowski, K; Quertenmont, L; Selvaggi, M; Marono, M Vidal; Wertz, S; Beliy, N; Aldá Júnior, W L; Alves, F L; Alves, G A; Brito, L; Hensel, C; Moraes, A; Pol, M E; Rebello Teles, P; Belchior Batista Das Chagas, E; Carvalho, W; Chinellato, J; Custódio, A; Da Costa, E M; Da Silveira, G G; De Jesus Damiao, D; De Oliveira Martins, C; Fonseca De Souza, S; Huertas Guativa, L M; Malbouisson, H; Matos Figueiredo, D; Mora Herrera, C; Mundim, L; Nogima, H; Prado Da Silva, W L; Santoro, A; Sznajder, A; Tonelli Manganote, E J; Torres Da Silva De Araujo, F; Vilela Pereira, A; Ahuja, S; Bernardes, C A; Dogra, S; Fernandez Perez Tomei, T R; Gregores, E M; Mercadante, P G; Moon, C S; Novaes, S F; Padula, Sandra S; Romero Abad, D; Ruiz Vargas, J C; Aleksandrov, A; Hadjiiska, R; Iaydjiev, P; Rodozov, M; Stoykova, S; Sultanov, G; Vutova, M; Dimitrov, A; Glushkov, I; Litov, L; Pavlov, B; Petkov, P; Fang, W; Ahmad, M; Bian, J G; Chen, G M; Chen, H S; Chen, M; Chen, Y; Cheng, T; Jiang, C H; Leggat, D; Liu, Z; Romeo, F; Ruan, M; Shaheen, S M; Spiezia, A; Tao, J; Wang, C; Wang, Z; Zhang, H; Zhao, J; Ban, Y; Chen, G; Li, Q; Liu, S; Mao, Y; Qian, S J; Wang, D; Xu, Z; Avila, C; Cabrera, A; Chaparro Sierra, L F; Florez, C; Gomez, J P; González Hernández, C F; Ruiz Alvarez, J D; Sanabria, J C; Godinovic, N; Lelas, D; Puljak, I; Ribeiro Cipriano, P M; Sculac, T; Antunovic, Z; Kovac, M; Brigljevic, V; Ferencek, D; Kadija, K; Mesic, B; Susa, T; Attikis, A; Mavromanolakis, G; Mousa, J; Nicolaou, C; Ptochos, F; Razis, P A; Rykaczewski, H; Tsiakkouri, D; Finger, M; Finger, M; Carrera Jarrin, E; El-Khateeb, E; Elgammal, S; Mohamed, A; Kadastik, M; Perrini, L; Raidal, M; Tiko, A; Veelken, C; Eerola, P; Pekkanen, J; Voutilainen, M; Härkönen, J; Järvinen, T; Karimäki, V; Kinnunen, R; Lampén, T; Lassila-Perini, K; Lehti, S; Lindén, T; Luukka, P; Tuominiemi, J; Tuovinen, E; Wendland, L; Talvitie, J; Tuuva, T; Besancon, M; Couderc, F; Dejardin, M; Denegri, D; Fabbro, B; Faure, J L; Favaro, C; Ferri, F; Ganjour, S; Ghosh, S; Givernaud, A; Gras, P; Hamel de Monchenault, G; Jarry, P; Kucher, I; Locci, E; Machet, M; Malcles, J; Rander, J; Rosowsky, A; Titov, M; Abdulsalam, A; Antropov, I; Baffioni, S; Beaudette, F; Busson, P; Cadamuro, L; Chapon, E; Charlot, C; Davignon, O; Granier de Cassagnac, R; Jo, M; Lisniak, S; Miné, P; Nguyen, M; Ochando, C; Ortona, G; Paganini, P; Pigard, P; Regnard, S; Salerno, R; Sirois, Y; Stahl Leiton, A G; Strebler, T; Yilmaz, Y; Zabi, A; Zghiche, A; Agram, J-L; Andrea, J; Aubin, A; Bloch, D; Brom, J-M; Buttignol, M; Chabert, E C; Chanon, N; Collard, C; Conte, E; Coubez, X; Fontaine, J-C; Gelé, D; Goerlach, U; Le Bihan, A-C; Van Hove, P; Gadrat, S; Beauceron, S; Bernet, C; Boudoul, G; Carrillo Montoya, C A; Chierici, R; Contardo, D; Courbon, B; Depasse, P; Mamouni, H El; Fay, J; Gascon, S; Gouzevitch, M; Grenier, G; Ille, B; Lagarde, F; Laktineh, I B; Lethuillier, M; Mirabito, L; Pequegnot, A L; Perries, S; Popov, A; Sabes, D; Sordini, V; Vander Donckt, M; Verdier, P; Viret, S; Khvedelidze, A; Tsamalaidze, Z; Autermann, C; Beranek, S; Feld, L; Kiesel, M K; Klein, K; Lipinski, M; Preuten, M; Schomakers, C; Schulz, J; Verlage, T; Albert, A; Brodski, M; Dietz-Laursonn, E; Duchardt, D; Endres, M; Erdmann, M; Erdweg, S; Esch, T; Fischer, R; Güth, A; Hamer, M; Hebbeker, T; Heidemann, C; Hoepfner, K

    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.

  19. 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 ...

  20. 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; 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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; 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    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...

  1. 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.

  2. A single amino acid mutation affects elicitor and expansins-like activities of cerato-platanin, a non-catalytic fungal protein.

    Directory of Open Access Journals (Sweden)

    Simone Luti

    Full Text Available Cerato-platanin (CP is a non-catalytic, cysteine-rich protein, the first member of the cerato-platanin family. It is a single-domain protein with a double Ψ/β barrel domain resembling the D1 domain of plant and bacterial expansins. Similarly to expansins, CP shows a cell wall-loosening activity on cellulose and can be defined as an expanisin-like protein, in spite of the missing D2 domain, normally present in plant expansins. The weakening activity shown on cellulose may facilitate the CP-host interaction, corroborating the role of CP in eliciting plant defence response. Indeed, CP is an elicitor of primary defences acting as a Pathogen-Associated Molecular Patterns (PAMP. So far, structure-function relationship study has been mainly performed on the bacterial BsEXLX1 expansin, probably due to difficulties in expressing plant expansins in heterologous systems. Here, we report a subcloning and purification method of CP in the engineered E. coli SHuffle cells, which proved to be suitable to obtain the properly folded and biologically active protein. The method also enabled the production of the mutant D77A, rationally designed to be inactive. The wild-type and the mutated CP were characterized for cellulose weakening activity and for PAMP activity (i.e. induction of Reactive Oxygen Species synthesis and phytoalexins production. Our analysis reveals that the carboxyl group of D77 is crucial for expansin-like and PAMP activities, thus permitting to establish a correlation between the ability to weaken cellulose and the capacity to induce defence responses in plants. Our results enable the structural and functional characterization of a mono-domain eukaryotic expansin and identify the essential role of a specific aspartic residue in cellulose weakening.

  3. A Bacillus flagellar motor that can use both Na+ and K+ as a coupling ion is converted by a single mutation to use only Na+.

    Directory of Open Access Journals (Sweden)

    Naoya Terahara

    Full Text Available In bacteria, the sodium ion (Na(+ cycle plays a critical role in negotiating the challenges of an extremely alkaline and sodium-rich environment. Alkaliphilic bacteria that grow optimally at high pH values use Na(+ for solute uptake and flagellar rotation because the proton (H(+ motive force is insufficient for use at extremely alkaline pH. Only three types of electrically driven rotary motors exist in nature: the F-type ATPase, the V-type ATPase, and the bacterial flagellar motor. Until now, only H(+ and Na(+ have been reported as coupling ions for these motors. Here, we report that the alkaliphilic bacterium Bacillus alcalophilus Vedder 1934 can grow not only under a Na(+-rich and potassium ion (K(+-poor condition but also under the opposite condition in an extremely alkaline environment. In this organism, swimming performance depends on concentrations of Na(+, K(+ or Rb(+. In the absence of Na(+, swimming behavior is clearly K(+- dependent. This pattern was confirmed in swimming assays of stator-less Bacillus subtilis and Escherichia coli mutants expressing MotPS from B. alcalophilus (BA-MotPS. Furthermore, a single mutation in BA-MotS was identified that converted the naturally bi-functional BA-MotPS to stators that cannot use K(+ or Rb(+. This is the first report that describes a flagellar motor that can use K(+ and Rb(+ as coupling ions. The finding will affect the understanding of the operating principles of flagellar motors and the molecular mechanisms of ion selectivity, the field of the evolution of environmental changes and stresses, and areas of nanotechnology.

  4. A Bacillus flagellar motor that can use both Na+ and K+ as a coupling ion is converted by a single mutation to use only Na+.

    Science.gov (United States)

    Terahara, Naoya; Sano, Motohiko; Ito, Masahiro

    2012-01-01

    In bacteria, the sodium ion (Na(+)) cycle plays a critical role in negotiating the challenges of an extremely alkaline and sodium-rich environment. Alkaliphilic bacteria that grow optimally at high pH values use Na(+) for solute uptake and flagellar rotation because the proton (H(+)) motive force is insufficient for use at extremely alkaline pH. Only three types of electrically driven rotary motors exist in nature: the F-type ATPase, the V-type ATPase, and the bacterial flagellar motor. Until now, only H(+) and Na(+) have been reported as coupling ions for these motors. Here, we report that the alkaliphilic bacterium Bacillus alcalophilus Vedder 1934 can grow not only under a Na(+)-rich and potassium ion (K(+))-poor condition but also under the opposite condition in an extremely alkaline environment. In this organism, swimming performance depends on concentrations of Na(+), K(+) or Rb(+). In the absence of Na(+), swimming behavior is clearly K(+)- dependent. This pattern was confirmed in swimming assays of stator-less Bacillus subtilis and Escherichia coli mutants expressing MotPS from B. alcalophilus (BA-MotPS). Furthermore, a single mutation in BA-MotS was identified that converted the naturally bi-functional BA-MotPS to stators that cannot use K(+) or Rb(+). This is the first report that describes a flagellar motor that can use K(+) and Rb(+) as coupling ions. The finding will affect the understanding of the operating principles of flagellar motors and the molecular mechanisms of ion selectivity, the field of the evolution of environmental changes and stresses, and areas of nanotechnology.

  5. 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

    2012-09-01

    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. 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. 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. 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.

  6. Dipyridamole thallium-201 single-photon emission computed tomography for prediction of perioperative cardiac events in patients with arteriosclerosis obliterans undergoing vascular surgery

    Energy Technology Data Exchange (ETDEWEB)

    Ziyang, Huang; Komori, Sadayoshi; Sawanobori, Takao [Yamanashi Medical Univ., Tamaho (Japan)] [and others

    1998-04-01

    The aim of the study was to determine whether or not dipyridamole thallium-201 single-photon emission computed tomography ({sup 201}Tl-SPECT) has significant additive value for predicting perioperative cardiac events in patients with arteriosclerosis obliterans (ASO) undergoing vascular surgery. Routine preoperative {sup 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<0.01). Perioperative cardiac events occurred in 9 patients, including 4 cardiac deaths, 1 non-fatal myocardial infarction, and 4 cases of unstable angina. Although clinical risk stratification was useful in predicting cardiac events (19% in the high-risk group vs 2% in the low-risk group, p<0.01), the positive predictive value was low. When considering a combination of 2 or more than 2 risk factors and a large reversible defect as a predictor, the positive predictive value and specificity increased from 19% to 47% and from 64% to 91%, respectively, whereas the sensitivity remained unchanged (89%). These results suggest that the addition of {sup 201}Tl-SPECT data to clinical risk-stratified patients with ASO allows better prediction of perioperative cardiac events. (author)

  7. Protective effect of KCNH2 single nucleotide polymorphism K897T in LQTS families and identification of novel KCNQ1 and KCNH2 mutations

    Directory of Open Access Journals (Sweden)

    Oberti Carlos

    2008-09-01

    Full Text Available Abstract Background KCNQ1 and KCNH2 are the two most common potassium channel genes causing long QT syndrome (LQTS, an inherited cardiac arrhythmia featured by QT prolongation and increased risks of developing torsade de pointes and sudden death. To investigate the disease expressivity, this study aimed to identify mutations and common variants that can modify LQTS phenotype. Methods In this study, a cohort of 112 LQTS families were investigated. Among them two large LQTS families linkage analysis with markers spanning known LQTS genes was carried out to identify the specific gene for mutational analysis. All exons and exon-intron boundaries of KCNH2 and KCNQ1 were sequenced for mutational analysis. Results LQTS-associated mutations were identified in eight of 112 families. Two novel mutations, L187P in KCNQ1 and 2020insAG in KCNH2, were identified. Furthermore, in another LQTS family we found that KCNH2 mutation A490T co-segregated with a common SNP K897T in KCNH2. KCNH2 SNP K897T was reported to exert a modifying effect on QTc, but it remains controversial whether it confers a risk or protective effect. Notably, we have found that SNP K897T interacts with mutation A490T in cis orientation. Seven carriers for A490T and the minor allele T of SNP K897T showed shorter QTc and fewer symptoms than carriers with A490T or A490P (P Conclusion Our family-based approach provides support that KCNH2 SNP K897T confers a protective effect on LQTS patients. Our study is the first to investigate the effect of SNP K897T on another KCNH2 mutation located in cis orientation. Together, our results expand the mutational and clinical spectrum of LQTS and provide insights into the factors that determine QT prolongation associated with increased risk of ventricular tachycardia and sudden death.

  8. 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.

  9. 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.

  10. Error-prone polymerase activity causes multinucleotide mutations in humans.

    Science.gov (United States)

    Harris, Kelley; Nielsen, Rasmus

    2014-09-01

    About 2% of human genetic polymorphisms have been hypothesized to arise via multinucleotide mutations (MNMs), complex events that generate SNPs at multiple sites in a single generation. MNMs have the potential to accelerate the pace at which single genes evolve and to confound studies of demography and selection that assume all SNPs arise independently. In this paper, we examine clustered mutations that are segregating in a set of 1092 human genomes, demonstrating that the signature of MNM becomes enriched as large numbers of individuals are sampled. We estimate the percentage of linked SNP pairs that were generated by simultaneous mutation as a function of the distance between affected sites and show that MNMs exhibit a high percentage of transversions relative to transitions, findings that are reproducible in data from multiple sequencing platforms and cannot be attributed to sequencing error. Among tandem mutations that occur simultaneously at adjacent sites, we find an especially skewed distribution of ancestral and derived alleles, with GC → AA, GA → TT, and their reverse complements making up 27% of the total. These mutations have been previously shown to dominate the spectrum of the error-prone polymerase Pol ζ, suggesting that low-fidelity DNA replication by Pol ζ is at least partly responsible for the MNMs that are segregating in the human population. We develop statistical estimates of MNM prevalence that can be used to correct phylogenetic and population genetic inferences for the presence of complex mutations. © 2014 Harris and Nielsen; Published by Cold Spring Harbor Laboratory Press.

  11. 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.

  12. 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)

  13. The supply voltage scaled dependency of the recovery of single event upset in advanced complementary metal—oxide—semiconductor static random-access memory cells

    Science.gov (United States)

    Li, Da-Wei; Qin, Jun-Rui; Chen, Shu-Ming

    2013-02-01

    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.

  14. Amplification-refractory mutation system (ARMS) analysis of point mutations.

    Science.gov (United States)

    Little, S

    2001-05-01

    The amplification-refractory mutation system (ARMS) is a simple method for detecting any mutation involving single base changes or small deletions. ARMS is based on the use of sequence-specific PCR primers that allow amplification of test DNA only when the target allele is contained within the sample. Following an ARMS reaction the presence or absence of a PCR product is diagnostic for the presence or absence of the target allele. The protocols detailed here outline methods that can be used to analyze human genomic DNA for one or more mutations. The Basic Protocol describes the development and application of an ARMS test for a single mutation; the Alternate Protocol extends this to multiplex ARMS for the analysis of two or more mutations. The Support Protocol describes a rapid DNA extraction method from blood or mouthwash samples that yields DNA compatible with the type of tests described. The amplification-refractory mutation system (ARMS) is a simple method for detecting any mutation involving single base change The amplification-refractory mutation system (ARMS) is a simple method for detecting any mutation involving single base change.

  15. The usefulness of dipyridamole thallium-201 single photon emission computed tomography for predicting perioperative cardiac events in patients undergoing non-cardiac vascular surgery

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Tao; Kuwabara, Yasuo; Tsutsui, Hiroyuki; Sasaki, Masayuki; Nakagawa, Makoto; Koga, Hirofumi; Kaneko, Kouichirou; Komori, Kimihiro; Masuda, Kouji [Kyushu Univ., Fukuoka (Japan). Graduate School of Medical Sciences)

    2002-02-01

    The aim of this study was to evaluate the usefulness of dipyridamole Tl-201 myocardium single photon emission computed tomography ({sup 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 {sup 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<0.001). In 180 patients who underwent vascular surgery, 9 patients (5.0%) had perioperative cardiac events, including heart failure (n=1), 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 {sup 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 {sup 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)

  16. Correlation of JAK2V617F mutational status in primary myelofibrosis with clinico-hematologic characteristics and international prognostic scoring system scoring: A single center experience

    Directory of Open Access Journals (Sweden)

    Neha Singh

    2015-01-01

    Full Text Available Introduction: Somatic mutation in the exon 14 of Janus Kinase 2 gene is an established diagnostic marker in bcr-abl negative myeloproliferative neoplasms, especially primary idiopathic myelofibrosis (PIMF. Aim: Our primary aim was to find out the correlation between the JAK2V617F mutational status and the clinico-hematologic characteristics, as well as the international prognostic scoring system (IPSS scoring of patients with PIMF. Materials and Methods: Clinical and hematologic features were reviewed for 68 patients with primary idiopathic myelofibrosis (PIMF. JAK2V617F mutation status was analyzed by amplification refractory mutation screening-polymerase chain reaction. The patients were further stratified into low, intermediate-1, intermediate-2 and high-risk groups on the basis of IPSS scoring. Results: The JAK2V617F mutation was detected in 58.8% patients. Univariate analysis of variables at presentation identified that JAK2V617F negative patients were significantly associated with more severe anemia (P = 0.045, younger age (P = 0.008, higher transfusion requirement (P = 0.017, and thrombocytopenia (P = 0.015. Patients who were homozygous for JAK2V617F mutation were associated with thrombocytosis (P = 0.014 and also had higher median total leucocyte count (P = 0.20 than the other groups. No significant correlation was detected between JAK2V617F mutational status and the presence of constitutional symptoms, spleen size, grade of bone marrow fibrosis or prognostic risk stratification of the PIMF patients. Conclusion: The variations in the prognostic implication of PIMF patients with mutation status as stated by various publications worldwide, reinstates the need for larger prospective studies using standardized JAK2V617F quantification methods as well as estimation of other newer molecular markers to develop deeper insight into various molecular alterations involving PIMF patients in India as well as worldwide.

  17. 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.

  18. A framework for the detection of de novo mutations in family-based sequencing data

    NARCIS (Netherlands)

    L.C. Francioli (Laurent); M. Cretu-Stancu (Mircea); K.V. Garimella (Kiran); M. Fromer (Menachem); W.P. Kloosterman (Wigard); Genome of the Netherlands Consortium; K. Samocha (Kaitlin); B. Neale (Benjamin); M.J. Daly (Mark); E. Banks (Eric); M.A. DePristo (Mark); P.I.W. de Bakker (Paul)

    2017-01-01

    textabstractGermline mutation detection from human DNA sequence data is challenging due to the rarity of such events relative to the intrinsic error rates of sequencing technologies and the uneven coverage across the genome. We developed PhaseByTransmission (PBT) to identify de novo single

  19. A framework for the detection of de novo mutations in family-based sequencing data

    NARCIS (Netherlands)

    Francioli, Laurent C.; Cretu-Stancu, Mircea; Garimella, Kiran V.; Fromer, Menachem; Kloosterman, Wigard P.; Samocha, Kaitlin E.; Neale, Benjamin M.; Daly, Mark J.; Banks, Eric; DePristo, Mark A.; de Bakker, Paul IW

    2016-01-01

    Germline mutation detection from human DNA sequence data is challenging due to the rarity of such events relative to the intrinsic error rates of sequencing technologies and the uneven coverage across the genome. We developed PhaseByTransmission (PBT) to identify de novo single nucleotide variants

  20. Single base mutation in the pro. alpha. 2(I) collagen gene that causes efficient splicing of RNA from exon 27 to exon 29 and synthesis of a shortened but in-frame pro. alpha. 2(I) chain

    Energy Technology Data Exchange (ETDEWEB)

    Tromp, G.; Prockop, D.J. (Thomas Jefferson Univ., Philadelphia, PA (USA))

    1988-07-01

    Previous observations demonstrated that a lethal variant of osteogenesis imperfecta had two altered alleles for pro{alpha}2(I) chains of type I procollagen. One mutation produced a nonfunctioning allele in that there was synthesis of mRNA but no detectable synthesis of pro{alpha}2(I) chains from the allele. The mutation in the other allele caused synthesis of shortened pro{alpha}2(I) chains that lacked most or all of the 18 amino acids encoded by exon 28. Subclones of the pro{alpha}2(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 pro{alpha}2(I) gene except that four subclones had a single base mutation at the 3{prime} end of intervening sequence 27. The mutation was a substitution of guanine for adenine that changed the universal consensus sequence for the 3{prime} splicing site of RNA from -AG- to -GG-. S1 nuclease experiments demonstrated that about half the pro{alpha}2(I) mRNA in the proband's fibroblasts was abnormally spliced and that the major species of abnormal pro{alpha}2(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.

  1. 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

    Directory of Open Access Journals (Sweden)

    Krishna R Kalari

    2012-02-01

    Full Text Available 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 NFkB, ERK1/2 and AKT pathways. A 27 gene mutant KRAS-specific sub network was extracted based on gene-gene connections within the integrated network, and interrogated for druggable targets. Our results confirm previous evidence that mutant KRAS tumors exhibit activated NFkB, 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.

  2. 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 integr