Structure and stability of non-symmetric Burgers vortices

We investigate, numerically and analytically, the structure and stability of steady and quasi-steady solutions of the Navier–Stokes equations corresponding to stretched vortices embedded in a uniform non-symmetric straining field, ([alpha]x, [beta]y, [gamma]z), [alpha]+[beta]+[gamma]=0, one principal axis of extensional strain of which is aligned with the vorticity. These are known as non-symmetric Burgers vortices (Robinson & Saffman 1984). We consider vortex Reynolds numbers R=[Gamma]/(2[pi]v) where [Gamma] is the vortex circulation and v the kinematic viscosity, in the range R=1[minus sign]104, and a broad range of strain ratios [lambda]=([beta][minus sign][alpha])/([beta]+[alpha]) including [lambda]>1, and in some cases [lambda][dbl greater-than sign]1. A pseudo-spectral method is used to obtain numerical solutions corresponding to steady and quasi-steady vortex states over our whole (R, [lambda]) parameter space including [lambda] where arguments proposed by Moffatt, Kida & Ohkitani (1994) demonstrate the non-existence of strictly steady solutions. When [lambda][dbl greater-than sign]1, R[dbl greater-than sign]1 and [epsilon][identical with][lambda]/R[double less-than sign]1, we find an accurate asymptotic form for the vorticity in a region 11. An iterative technique based on the power method is used to estimate the largest eigenvalues for the non-symmetric case [lambda]>0. Stability is found for 0[less-than-or-eq, slant][lambda][less-than-or-eq, slant]1, and a neutrally convective mode of instability is found and analysed for [lambda]>1. Our general conclusion is that the generalized non-symmetric Burgers vortex is unconditionally stable to two-dimensional disturbances for all R, 0[less-than-or-eq, slant][lambda][less-than-or-eq, slant]1, and that when [lambda]>1, the vortex will decay only through exponentially slow leakage of vorticity, indicating extreme robustness in this case

Balancing scientific interests and the rights of participants in designing a recall by genotype study

Recall by genotype (RbG) studies aim to better understand the phenotypes that correspond to genetic variants of interest, by recruiting carriers of such variants for further phenotyping. RbG approaches pose major ethical and legal challenges related to the disclosure of possibly unwanted genetic information. The Cooperative Health Research in South Tyrol (CHRIS) study is a longitudinal cohort study based in South Tyrol, Italy. Demand has grown for CHRIS study participants to be enrolled in RbG studies, thus making the design of a suitable ethical framework a pressing need. We here report upon the design of a pilot RbG study conducted with CHRIS study participants. By reviewing the literature and by consulting relevant stakeholders (CHRIS participants, clinical geneticists, ethics board, GPs), we identified key ethical issues in RbG approaches (e.g. complexity of the context, communication of genetic results, measures to further protect participants). The design of the pilot was based on a feasibility assessment, the selection of a suitable test case within the ProtectMove Research Unit on reduced penetrance of hereditary movement disorders, and the development of appropriate recruitment and communication strategies. An empirical study was embedded in the pilot study with the aim of understanding participants’ views on RbG. Our experience with the pilot study in CHRIS allowed us to contribute to the development of best practices and policies for RbG studies by drawing recommendations: addressing the possibility of RbG in the original consent, implementing tailored communication strategies, engaging stakeholders, designing embedded empirical studies, and sharing research experiences and methodology

A Rare Disease Patient Manager

ABSTRACT publicado: 6th International Conference on Practical Applications of Computational Biology & Bioinformatics (PACBB. Salamanca, 28-30 Março 2012The personal health implications behind rare diseases are seldom considered in widespread medical care. The low incidence rate and complex treatment process makes rare disease research an underrated field in the life sciences. However, it is in these particular conditions that the strongest relations between genotypes and phenotypes are identified. The rare disease patient manager, detailed in this manuscript, presents an innovative perspective for a patient-centric portal integrating genetic and medical data. With this strategy, patient’s digital records are transparently integrated and connected to wet-lab genetics research in a seamless working environment. The resulting knowledge base offers multiple data views, geared towards medical staff, with patient treatment and monitoring data; genetics researchers, through a custom locus-specific database; and patients, who for once play an active role in their treatment and rare diseases research

The Slavic NBN founder mutation: a role for reproductive fitness?

The vast majority of patients with Nijmegen Breakage Syndrome (NBS) are of Slavic origin and carry a deleterious deletion (c.657del5; rs587776650) in the NBN gene on chromosome 8q21. This mutation is essentially confined to Slavic populations and may thus be considered a Slavic founder mutation. Notably, not a single parenthood of a homozygous c.657del5 carrier has been reported to date, while heterozygous carriers do reproduce but have an increased cancer risk. These observations seem to conflict with the considerable carrier frequency of c.657del5 of 0.5% to 1% as observed in different Slavic populations because deleterious mutations would be eliminated quite rapidly by purifying selection. Therefore, we propose that heterozygous c.657del5 carriers have increased reproductive success, i.e., that the mutation confers heterozygote advantage. In fact, in our cohort study of the reproductive history of 24 NBS pedigrees from the Czech Republic, we observed that female carriers gave birth to more children on average than female non-carriers, while no such reproductive differences were observed for males. We also estimate that c.657del5 likely occurred less than 300 generations ago, thus supporting the view that the original mutation predated the historic split and subsequent spread of the 'Slavic people'. We surmise that the higher fertility of female c.657del5 carriers reflects a lower miscarriage rate in these women, thereby reflecting the role of the NBN gene product, nibrin, in the repair of DNA double strand breaks and their processing in immune gene rearrangements, telomere maintenance, and meiotic recombination, akin to the previously described role of the DNA repair genes BRCA1 and BRCA2

Genome-wide association analysis and fine mapping of NT-proBNP level provide novel insight into the role of the MTHFR-CLCN6-NPPA-NPPB gene cluster

High blood concentration of the N-terminal cleavage product of the B-type natriuretic peptide (NT-proBNP) is strongly associated with cardiac dysfunction and is increasingly used for heart failure diagnosis. To identify genetic variants associated with NT-proBNP level, we performed a genome-wide association analysis in 1325 individuals from South Tyrol, Italy, and followed up the most significant results in 1746 individuals from two German population-based studies. A genome-wide significant signal in the MTHFR-CLCN6-NPPA-NPPB gene cluster was replicated, after correction for multiple testing (replication one-sided P-value = 8.4 × 10−10). A conditional regression analysis of 128 single-nucleotide polymorphisms in the region of interest identified novel variants in the CLCN6 gene as independently associated with NT-proBNP. In this locus, four haplotypes were associated with increased NT-proBNP levels (haplotype-specific combined P-values from 8.3 × 10−03 to 9.3 × 10−11). The observed increase in the NT-proBNP level was proportional to the number of haplotype copies present (i.e. dosage effect), with an increase associated with two copies that varied between 20 and 100 pg/ml across populations. The identification of novel variants in the MTHFR-CLCN6-NPPA-NPPB cluster provides new insights into the biological mechanisms of cardiac dysfunction

Maturity-Onset Diabetes of the Young in Children With Incidental Hyperglycemia:: A multicenter Italian study of 172 families

OBJECTIVE - To investigate the prevalence of maturity-onset diabetes of the young (MODY) in Italian children With incidental hyperglycemia. RESEARCH DESIGN AND METHODS - Among 748 subjects age 1-18 years with incidental hyperglycemia, minimal diagnostic criteria for MODY were met by 172 families. Mutational analyses of the glucokinase (GCK) and hepatocyte nuclear factor lot (HNF1A) genes were performed. RESULTS - We identified 85 GCK gene mutations in 109 probands and 10 HNF1A mutations in 12 probands. In GCK patients, the median neonatal weight and age at the first evaluation were lower than those found in patients with HNF1A mutations. Median fasting plasma glucose and impaired fasting glucose/impaired glucose tolerance frequency after oral glucose tolerance testing were higher in GCK patients, who also showed a lower frequency of diabetes than HNF1A patients. CONCLUSIONS - GCK mutations are the prevailing cause of MODY (63.4%) when the index case is recruited in Italian children with incidental hyperglycemia

Rickettsial infection in Amblyomma cajennense ticks and capybaras (Hydrochoerus hydrochaeris) in a Brazilian spotted fever-endemic area

Brazilian spotted fever (BSF), caused by the bacterium Rickettsia rickettsii, is the deadliest spotted fever of the world. In most of the BSF-endemic areas, capybaras (Hydrochoerus hydrochaeris) are the principal host for the tick Amblyomma cajennense, which is the main vector of BSF. In 2012, a BSF case was confirmed in a child that was bitten by ticks in a residential park area inhabited by A. cajennense-infested capybaras in Itú municipality, southeastern Brazil. Host questing A. cajennense adult ticks were collected in the residential park and brought alive to the laboratory, where they were macerated and intraperitoneally inoculated into guinea pigs. A tick-inoculated guinea pig that presented high fever was euthanized and its internal organs were macerated and inoculated into additional guinea pigs (guinea pig passage). Tissue samples from guinea pig passages were also used to inoculate Vero cells through the shell vial technique. Infected cells were used for molecular characterization of the rickettsial isolate through PCR and DNA sequencing of fragments of three rickettsial genes (gltA, ompA, and ompB). Blood serum samples were collected from 172 capybaras that inhabited the residential park. Sera were tested through the immunofluorescence assay using R. rickettsii antigen. A tick-inoculated guinea pig presented high fever accompanied by scrotal reactions (edema and marked redness). These signs were reproduced by consecutive guinea pig passages. Rickettsia was successfully isolated in Vero cells that were inoculated with brain homogenate derived from a 3rd passage-febrile guinea pig. Molecular characterization of this rickettsial isolate (designated as strain ITU) yielded DNA sequences that were all 100% identical to corresponding sequences of R. rickettsii in Genbank. A total of 83 (48.3%) out of 172 capybaras were seroreactive to R. rickettsii, with endpoint titers ranging from 64 to 8192. A viable isolate of R. rickettsii was obtained from the tick A. cajennense, comprising the first viable R. rickettsi isolate from this tick species during the last 60 years. Nearly half of the capybara population of the residential park was seroreactive to R. rickettsii, corroborating the findings that the local A. cajennense population was infected by R. rickettsii.We are grateful to the administrative staff of the residential park that provided logistic support for the present study, and to the “Superintendência de Controle de Endemias” of the state of São Paulo (SUCEN) for their valuable help in collecting ticks. This work was supported by the Brazilian funding agencies FAPESP, CNPq, and CAPES

Fabrication par imprégnation directe et assemblage par soudage de composites thermoplastiques structuraux à renfort textile en fibres végétales

National audience* Développement d’une technique originale d'imprégnation directe de renforts continus de lin par des thermoplastiques totalement ou partiellement bio-sourcés, par injection dans un moule fermé* Étude multi-échelles des mécanismes d'imprégnation / gonflement sous contraintes thermo-hydromécaniques des fibres végétales. Déduction des évolutions de propriétés physiques et mécaniques* Étude des mécanismes d’imprégnation de composites moulés à haute cadence avec des thermoplastiques mono- ou bi-composants de haute fluidité* Assemblage de pièces composites renforcées de fibres végétales par soudage laser* Qualification de la résistance des joints de soudure des composites thermoplastiques bio-sourcé