147 research outputs found

    Constrained optimization in seismic reflection tomography: a Gauss-Newton augmented Lagrangian approach

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    International audienceS U M M A R Y Seismic reflection tomography is a method for determining a subsurface velocity model from the traveltimes of seismic waves reflecting on geological interfaces. From an optimization viewpoint , the problem consists in minimizing a non-linear least-squares function measuring the mismatch between observed traveltimes and those calculated by ray tracing in this model. The introduction of a priori information on the model is crucial to reduce the under-determination. The contribution of this paper is to introduce a technique able to take into account geological a priori information in the reflection tomography problem expressed as inequality constraints in the optimization problem. This technique is based on a Gauss-Newton (GN) sequential quadratic programming approach. At each GN step, a solution to a convex quadratic optimization problem subject to linear constraints is computed thanks to an augmented Lagrangian algorithm. Our choice for this optimization method is motivated and its original aspects are described. First applications on real data sets are presented to illustrate the potential of the approach in practical use of reflection tomography

    Water-Window X-Ray Pulses from a Laser-Plasma Driven Undulator

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    Femtosecond (fs) x-ray pulses are a key tool to study the structure and dynamics of matter on its natural length and time scale. To complement radio-frequency accelerator-based large-scale facilities, novel laser-based mechanisms hold promise for compact laboratory-scale x-ray sources. Laser-plasma driven undulator radiation in particular offers high peak-brightness, optically synchronized few-fs pulses reaching into the few-nanometer (nm) regime. To date, however, few experiments have successfully demonstrated plasma-driven undulator radiation. Those that have, typically operated at single and comparably long wavelengths. Here we demonstrate plasma-driven undulator radiation with octave-spanning tuneability at discrete wavelengths reaching from 13nm to 4nm. Studying spontaneous undulator radiation is an important step towards a plasma-driven free-electron laser. Our specific setup creates a photon pulse, which closely resembles the plasma electron bunch length and charge profile and thus might enable novel methods to characterize the longitudinal electron phase space

    The FLASHForward Facility at DESY

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    The FLASHForward project at DESY is a pioneering plasma-wakefield acceleration experiment that aims to produce, in a few centimetres of ionised hydrogen, beams with energy of order GeV that are of quality sufficient to be used in a free-electron laser. The plasma wave will be driven by high-current density electron beams from the FLASH linear accelerator and will explore both external and internal witness-beam injection techniques. The plasma is created by ionising a gas in a gas cell with a multi-TW laser system, which can also be used to provide optical diagnostics of the plasma and electron beams due to the <30 fs synchronisation between the laser and the driving electron beam. The operation parameters of the experiment are discussed, as well as the scientific program.Comment: 19 pages, 9 figure

    Comparative effect of intraoperative propacetamol versus placebo on morphine consumption after elective reduction mammoplasty under remifentanil-based anesthesia: a randomized control trial [ISRCTN71723173]

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    BACKGROUND: Postoperative administration of paracetamol or its prodrug propacetamol has been shown to decrease pain with a morphine sparing effect. However, the effect of propacetamol administered intra-operatively on post-operative pain and early postoperative morphine consumption has not been clearly evaluated. In order to evaluate the effectiveness of analgesic protocols in the management of post-operative pain, a standardized anesthesia protocol without long-acting opioids is crucial. Thus, for ethical reasons, the surgical procedure under general anesthesia with remifentanil as the only intraoperative analgesic must be associated with a moderate predictable postoperative pain. METHODS: We were interested in determining the postoperative effect of propacetamol administered intraoperatively after intraoperative remifentanil. Thirty-six adult women undergoing mammoplasty with remifentanil-based anesthesia were randomly assigned to receive propacetamol 2 g or placebo one hour before the end of surgery. After remifentanil interruption and tracheal extubation in recovery room, pain was assessed and intravenous titrated morphine was given. The primary end-point was the cumulative dose of morphine administered in the recovery room. The secondary end-points were the pain score after tracheal extubation and one hour after, the delay for obtaining a Simplified Numerical Pain Scale (SNPS) less than 4, and the incidence of morphine side effects in the recovery room. For intergroup comparisons, categorical variables were compared using the chi-squared test and continuous variables were compared using the Student t test or Mann-Whitney U test, as appropriate. A p value less than 0.05 was considered as significant. RESULTS: In recovery room, morphine consumption was lower in the propacetamol group than in the placebo group (p = 0.01). Pain scores were similar in both groups after tracheal extubation and lower in the propacetamol group (p = 0.003) one hour after tracheal extubation. The time to reach a SNPS < 4 was significantly shorter in the propacetamol group (p = 0.02). The incidence of morphine related side effects did not differ between the two groups. CONCLUSIONS: Intraoperative propacetamol administration with remifentanil based-anesthesia improved significantly early postoperative pain by sparing morphine and shortening the delay to achieve pain relief

    The Fanconi Anemia Core Complex Is Dispensable during Somatic Hypermutation and Class Switch Recombination

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    To generate high affinity antibodies during an immune response, B cells undergo somatic hypermutation (SHM) of their immunoglobulin genes. Error-prone translesion synthesis (TLS) DNA polymerases have been reported to be responsible for all mutations at template A/T and at least a fraction of G/C transversions. In contrast to A/T mutations which depend on PCNA ubiquitination, it remains unclear how G/C transversions are regulated during SHM. Several lines of evidence indicate a mechanistic link between the Fanconi Anemia (FA) pathway and TLS. To investigate the contribution of the FA pathway in SHM we analyzed FancG-deficient B cells. B cells deficient for FancG, an essential member of the FA core complex, were hypersensitive to treatment with cross-linking agents. However, the frequencies and nucleotide exchange spectra of SHM remained comparable between wild-type and FancG-deficient B cells. These data indicate that the FA pathway is not involved in regulating the outcome of SHM in mammals. In addition, the FA pathway appears dispensable for class switch recombination

    Lysine Residue 185 of Rad1 Is a Topological but Not a Functional Counterpart of Lysine Residue 164 of PCNA

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    Monoubiquitylation of the homotrimeric DNA sliding clamp PCNA at lysine residue 164 (PCNAK164) is a highly conserved, DNA damage-inducible process that is mediated by the E2/E3 complex Rad6/Rad18. This ubiquitylation event recruits translesion synthesis (TLS) polymerases capable of replicating across damaged DNA templates. Besides PCNA, the Rad6/Rad18 complex was recently shown in yeast to ubiquitylate also 9-1-1, a heterotrimeric DNA sliding clamp composed of Rad9, Rad1, and Hus1 in a DNA damage-inducible manner. Based on the highly similar crystal structures of PCNA and 9-1-1, K185 of Rad1 (Rad1K185) was identified as the only topological equivalent of PCNAK164. To investigate a potential role of posttranslational modifications of Rad1K185 in DNA damage management, we here generated a mouse model with a conditional deletable Rad1K185R allele. The Rad1K185 residue was found to be dispensable for Chk1 activation, DNA damage survival, and class switch recombination of immunoglobulin genes as well as recruitment of TLS polymerases during somatic hypermutation of immunoglobulin genes. Our data indicate that Rad1K185 is not a functional counterpart of PCNAK164

    Serogroup-Specific Meningococcal Carriage by Age Group::A Systematic Review and Meta-Analysis

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    Objective Neisseria meningitidis carriage prevalence has known variation across the lifespan, but it is unclear whether carriage varies among meningococcal capsular groups. Therefore, we aimed to characterise group-specific meningococcal carriage by age group and world region from 2007 to 2016.Design Systematic review and meta-analysis.Data sources MEDLINE, Embase, Global Health Database, WHO Global Health Library, Web of Science, Current Contents Connects, China National Knowledge Infrastructure and Wanfang were systematically searched. Database searches were conducted through July 2018 and Google Scholar forward searches of included studies were conducted through August 2018. References of included studies and relevant conference abstracts were also searched to identify additional articles for inclusion.Eligibility criteria Studies were eligible for inclusion if they reported capsular group-specific meningococcal carriage in a healthy population of a specified age group and geographical region. For this review, only studies conducted between 2007 and 2016 were included.Data extraction and synthesis Data were independently extracted by two authors into Microsoft Access. Studies were assessed for risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Studies eligible for inclusion in quantitative analyses by pre-specified age groups were pooled using random effects meta-analyses. Results are reported by capsular group, age group and WHO region. Where meta-analyses were not appropriate, study results were discussed narratively.Results 7511 articles were identified and 65 were eligible for inclusion. Adolescents and young adults were the focus of many studies (n=24), especially in the Americas and Europe. Studies from China and Africa, typically, included data from a wider age range. The overall carriage prevalence varied markedly by age group and region. Based on the available data, 21 studies were included in meta-analyses reporting serogroup carriage for: all ages in Africa, 18–24-year olds in the Americas, and 11–17 and 18–24-year olds in Europe. Capsular groups W, X, Y and ‘other’ (non-ABCWXY, including non-groupable) were the most prevalent in Africa, and 5–17-year olds had higher carriage prevalence than other age groups. ‘Other’ serogroups (11.5%, 95% CI 1.6% to 16.1%) were the most common among 18–24-year olds from the Americas. In Europe, 18–24-year old were carriers more frequently than 11–17-year olds, and groups B (5.0%, 95% CI 3.0% to 7.5%), Y (3.9%, 95% CI 1.3% to 7.8%) and ‘other’ (6.4%, 95% CI 3.1% to 10.8%) were the most commonly carried in the older age group.Conclusions Of the age groups included in the analysis, carriage patterns by age were similar across capsular groups within a region but differed between regions. Data gaps remain for age- and capsular group-specific carriage in many regions, especially in the Eastern Mediterranean and South-East Asia. As such, clear and robust conclusions about the variation of capsular group-specific carriage by age group and WHO region were unable to be determined
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