168 research outputs found

    Approximation of the critical buckling factor for composite panels

    Get PDF
    This article is concerned with the approximation of the critical buckling factor for thin composite plates. A new method to improve the approximation of this critical factor is applied based on its behavior with respect to lamination parameters and loading conditions. This method allows accurate approximation of the critical buckling factor for non-orthotropic laminates under complex combined loadings (including shear loading). The influence of the stacking sequence and loading conditions is extensively studied as well as properties of the critical buckling factor behavior (e.g concavity over tensor D or out-of-plane lamination parameters). Moreover, the critical buckling factor is numerically shown to be piecewise linear for orthotropic laminates under combined loading whenever shear remains low and it is also shown to be piecewise continuous in the general case. Based on the numerically observed behavior, a new scheme for the approximation is applied that separates each buckling mode and builds linear, polynomial or rational regressions for each mode. Results of this approach and applications to structural optimization are presented

    Chitayat-Hall and Schaaf-Yang syndromes: a common aetiology: expanding the phenotype of MAGEL2-related disorders

    Get PDF
    Chitayat-Hall syndrome, initially described in 1990, is a rare condition characterised by distal arthrogryposis, intellectual disability, dysmorphic features and hypopituitarism, in particular growth hormone deficiency. The genetic aetiology has not been identified.Background Chitayat-Hall syndrome, initially described in 1990, is a rare condition characterised by distal arthrogryposis, intellectual disability, dysmorphic features and hypopituitarism, in particular growth hormone deficiency. The genetic aetiology has not been identified. Methods and results We identified three unrelated families with a total of six affected patients with the clinical manifestations of Chitayat-Hall syndrome. Through whole exome or whole genome sequencing, pathogenic variants in the MAGEL2 gene were identified in all affected patients. All disease-causing sequence variants detected are predicted to result in a truncated protein, including one complex variant that comprised a deletion and inversion. Conclusions Chitayat-Hall syndrome is caused by pathogenic variants in MAGEL2 and shares a common aetiology with the recently described Schaaf-Yang syndrome. The phenotype of MAGEL2-related disorders is expanded to include growth hormone deficiency as an important and treatable complicationhe McLaughlin Centre, University of Toronto, Toronto, Canada, and Fondation Jeanne et Jean- Louis Lévesque (JLM). The Centre for Genetic Medicine, The Hospital for Sick Children, Toronto, Canada. FDL has a fellowship funded by FCT - Fundação para a Ciência e a Tecnologia (SFRH/BD/84650/2010)info:eu-repo/semantics/publishedVersio

    Validation of MIPAS HNO3 operational data

    Get PDF
    Nitric acid (HNO3) is one of the key products that are operationally retrieved by the European Space Agency (ESA) from the emission spectra measured by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) onboard ENVISAT. The product version 4.61/4.62 for the observation period between July 2002 and March 2004 is validated by comparisons with a number of independent observations from ground-based stations, aircraft/balloon campaigns, and satellites. Individual HNO3 profiles of the ESA MIPAS level-2 product show good agreement with those of MIPAS-B and MIPAS-STR (the balloon and aircraft version of MIPAS, respectively), and the balloon-borne infrared spectrometers MkIV and SPIRALE, mostly matching the reference data within the combined instrument error bars. In most cases differences between the correlative measurement pairs are less than 1 ppbv (5-10%) throughout the entire altitude range up to about 38 km (similar to 6 hPa), and below 0.5 ppbv (15-20% or more) above 30 km (similar to 17 hPa). However, differences up to 4 ppbv compared to MkIV have been found at high latitudes in December 2002 in the presence of polar stratospheric clouds. The degree of consistency is further largely affected by the temporal and spatial coincidence, and differences of 2 ppbv may be observed between 22 and 26 km (similar to 50 and 30 hPa) at high latitudes near the vortex boundary, due to large horizontal inhomogeneity of HNO3. Similar features are also observed in the mean differences of the MIPAS ESA HNO3 VMRs with respect to the ground-based FTIR measurements at five stations, aircraft-based SAFIRE-A and ASUR, and the balloon campaign IBEX. The mean relative differences between the MIPAS and FTIR HNO3 partial columns are within +/- 2%, comparable to the MIPAS systematic error of similar to 2%. For the vertical profiles, the biases between the MIPAS and FTIR data are generally below 10% in the altitudes of 10 to 30 km. The MIPAS and SAFIRE HNO3 data generally match within their total error bars for the mid and high latitude flights, despite the larger atmospheric inhomogeneities that characterize the measurement scenario at higher latitudes. The MIPAS and ASUR comparison reveals generally good agreements better than 10-13% at 20-34 km. The MIPAS and IBEX measurements agree reasonably well (mean relative differences within +/- 15%) between 17 and 32 km. Statistical comparisons of the MIPAS profiles correlated with those of Odin/SMR, ILAS-II, and ACE-FTS generally show good consistency. The mean differences averaged over individual latitude bands or all bands are within the combined instrument errors, and generally within 1, 0.5, and 0.3 ppbv between 10 and 40 km (similar to 260 and 4.5 hPa) for Odin/SMR, ILAS-II, and ACE-FTS, respectively. The standard deviations of the differences are between 1 to 2 ppbv. The standard deviations for the satellite comparisons and for almost all other comparisons are generally larger than the estimated measurement uncertainty. This is associated with the temporal and spatial coincidence error and the horizontal smoothing error which are not taken into account in our error budget. Both errors become large when the spatial variability of the target molecule is high.Peer reviewe

    Comparing HLA Shared Epitopes in French Caucasian Patients with Scleroderma

    Get PDF
    Although many studies have analyzed HLA allele frequencies in several ethnic groups in patients with scleroderma (SSc), none has been done in French Caucasian patients and none has evaluated which one of the common amino acid sequences, 67FLEDR71, shared by HLA-DRB susceptibility alleles, or 71TRAELDT77, shared by HLA-DQB1 susceptibility alleles in SSc, was the most important to develop the disease. HLA-DRB and DQB typing was performed for a total of 468 healthy controls and 282 patients with SSc allowing FLEDR and TRAELDT analyses. Results were stratified according to patient’s clinical subtypes and autoantibody status. Moreover, standardized HLA-DRß1 and DRß5 reverse transcriptase Taqman PCR assays were developed to quantify ß1 and ß5 mRNA in 20 subjects with HLA-DRB1*15 and/or DRB1*11 haplotypes. FLEDR motif is highly associated with diffuse SSc (χ2 = 28.4, p<10−6) and with anti-topoisomerase antibody (ATA) production (χ2 = 43.9, p<10−9) whereas TRAELDT association is weaker in both subgroups (χ2 = 7.2, p = 0.027 and χ2 = 14.6, p = 0.0007 respectively). Moreover, FLEDR motif- association among patients with diffuse SSc remains significant only in ATA subgroup. The risk to develop ATA positive SSc is higher with double dose FLEDR than single dose with respectively, adjusted standardised residuals of 5.1 and 2.6. The increase in FLEDR motif is mostly due to the higher frequency of HLA-DRB1*11 and DRB1*15 haplotypes. Furthermore, FLEDR is always carried by the most abundantly expressed ß chain: ß1 in HLA DRB1*11 haplotypes and ß5 in HLA-DRB1*15 haplotypes

    Imaging biomarker roadmap for cancer studies.

    Get PDF
    Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution

    Mitochondrial phylogeography and population structure of the cattle tick Rhipicephalus appendiculatus in the African Great Lakes region

    Get PDF
    Abstract Background The ixodid tick Rhipicephalus appendiculatus is the main vector of Theileria parva, wich causes the highly fatal cattle disease East Coast fever (ECF) in sub-Saharan Africa. Rhipicephalus appendiculatus populations differ in their ecology, diapause behaviour and vector competence. Thus, their expansion in new areas may change the genetic structure and consequently affect the vector-pathogen system and disease outcomes. In this study we investigated the genetic distribution of R. appendiculatus across agro-ecological zones (AEZs) in the African Great Lakes region to better understand the epidemiology of ECF and elucidate R. appendiculatus evolutionary history and biogeographical colonization in Africa. Methods Sequencing was performed on two mitochondrial genes (cox1 and 12S rRNA) of 218 ticks collected from cattle across six AEZs along an altitudinal gradient in the Democratic Republic of Congo, Rwanda, Burundi and Tanzania. Phylogenetic relationships between tick populations were determined and evolutionary population dynamics models were assessed by mismach distribution. Results Population genetic analysis yielded 22 cox1 and 9 12S haplotypes in a total of 209 and 126 nucleotide sequences, respectively. Phylogenetic algorithms grouped these haplotypes for both genes into two major clades (lineages A and B). We observed significant genetic variation segregating the two lineages and low structure among populations with high degree of migration. The observed high gene flow indicates population admixture between AEZs. However, reduced number of migrants was observed between lowlands and highlands. Mismatch analysis detected a signature of rapid demographic and range expansion of lineage A. The star-like pattern of isolated and published haplotypes indicates that the two lineages evolve independently and have been subjected to expansion across Africa. Conclusions Two sympatric R. appendiculatus lineages occur in the Great Lakes region. Lineage A, the most diverse and ubiquitous, has experienced rapid population growth and range expansion in all AEZs probably through cattle movement, whereas lineage B, the less abundant, has probably established a founder population from recent colonization events and its occurrence decreases with altitude. These two lineages are sympatric in central and eastern Africa and allopatric in southern Africa. The observed colonization pattern may strongly affect the transmission system and may explain ECF endemic instability in the tick distribution fringes

    NS2 Protein of Hepatitis C Virus Interacts with Structural and Non-Structural Proteins towards Virus Assembly

    Get PDF
    Growing experimental evidence indicates that, in addition to the physical virion components, the non-structural proteins of hepatitis C virus (HCV) are intimately involved in orchestrating morphogenesis. Since it is dispensable for HCV RNA replication, the non-structural viral protein NS2 is suggested to play a central role in HCV particle assembly. However, despite genetic evidences, we have almost no understanding about NS2 protein-protein interactions and their role in the production of infectious particles. Here, we used co-immunoprecipitation and/or fluorescence resonance energy transfer with fluorescence lifetime imaging microscopy analyses to study the interactions between NS2 and the viroporin p7 and the HCV glycoprotein E2. In addition, we used alanine scanning insertion mutagenesis as well as other mutations in the context of an infectious virus to investigate the functional role of NS2 in HCV assembly. Finally, the subcellular localization of NS2 and several mutants was analyzed by confocal microscopy. Our data demonstrate molecular interactions between NS2 and p7 and E2. Furthermore, we show that, in the context of an infectious virus, NS2 accumulates over time in endoplasmic reticulum-derived dotted structures and colocalizes with both the envelope glycoproteins and components of the replication complex in close proximity to the HCV core protein and lipid droplets, a location that has been shown to be essential for virus assembly. We show that NS2 transmembrane region is crucial for both E2 interaction and subcellular localization. Moreover, specific mutations in core, envelope proteins, p7 and NS5A reported to abolish viral assembly changed the subcellular localization of NS2 protein. Together, these observations indicate that NS2 protein attracts the envelope proteins at the assembly site and it crosstalks with non-structural proteins for virus assembly

    Imaging biomarker roadmap for cancer studies.

    Get PDF
    Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution
    corecore