Direct carrier detection by in situ suppression hybridization with cosmid clones of the Duchenne/Becker muscular dystrophy locus

A basic problem in genetic counseling of families with Duchenne/Becker muscular dystrophy (DMD/BMD) concerns the carrier status of female relatives of an affected male. In about 60% of these patients, deletions of one or more exons of the dystrophin gene can be identified. These deletions preferentially include exon 45, which can be detected by multiplex polymerase chain reaction (PCR) and Southern blot analysis of genomic cosmid clones that map to this critical region. As a new approach for definitive carrier detection, we have performed chromosomal in situ suppression (CISS) hybridization with these cosmid clones in female relatives of four unrelated patients. In normal females, most metaphases showed signals on both×chromosomes, whereas only one×chromosome was labeled in carriers. Our results demonstrate that CISS hybridization can define the carrier status in female relatives of DMD patients exhibiting a deletion in the dystrophin gene

Instrução contendo a estrutura rítmica da habilidade melhora a eficiência na aprendizagem da pernada do nado peito

A aprendizagem de habilidades motoras pode ser promovida mediante instrução visual ou auditiva que transmite informações sobre diversas características da habilidade, tais como espaciais ou rítmicas. Para habilidades aquáticas como a pernada do nado peito, os manuais técnicos enfatizam características espaciais, negligenciando aspectos rítmicos da habilidade, apesar de a teoria da aprendizagem motora considerar o timing relativo uma característica crucial na distinção entre uma habilidade e outra. Objetivou-se analisar o impacto da instrução com e sem a informação sobre a estrutura rítmica correta, transmitida visual ou auditivamente, sobre a aprendizagem da pernada do nado peito. Cinquenta estudantes de Educação Física foram distribuídos em quatro grupos experimentais (instrução auditiva, visual, com e sem informação rítmica correta) e realizaram 400 tentativas de aquisição da pernada do nado peito, mais 50 de retenção e 50 de transferência, durante as quais foram mapeados os índices de pernada, de configuração rítmica e espacial. Os resultados mostraram índices marginalmente melhores (p=0,075), no teste de retenção, dos participantes que receberam a instrução com a informação rítmica correta, e uma forte correlação entre os índices de pernada com os de configuração rítmica ao longo de todo o processo, mas não com os de configuração espacial. Não houve diferença entre os grupos de instrução visual e auditiva. Esses resultados corroboram resultados anteriores sobre os efeitos da informação rítmica na aprendizagem de uma habilidade motora complexa, e reforçam o papel do ritmo na eficiência na execução de uma habilidade e consequentemente na sua aprendizagem.Motor learning can be fostered by visual or auditory instruction conveying information on different features of the skill, like spatial and rhythmic characteristics. For swimming skills like the breaststroke kick, manuals predominantly emphasise spatial features, neglecting rhythmic aspects – even though motor learning considers movement rhythm crucial for distinguishing one skill from another. We aimed to analyse the impact of instruction containing or not the adequate rhythmic pattern information, conveyed by visual or auditory stimulus, on learning the breaststroke kick. Fifty university students, assigned to four experimental groups (auditory, visual, with and without rhythmic information), performed 400 acquisition plus 50 retention and 50 transfer trials during which stroke index, rhythmic and spatial pattern indices and instruction request frequency were mapped. Results showed a marginal difference (p= .075) between higher indices in the retention test of participants receiving information about adequate rhythm, as well as a strong correlation between stroke index and rhythm pattern index, but not with spatial pattern index. No difference between auditory and visual groups was found. This result supports earlier research on the impact of rhythmic information on the learning of complex motor skills, and emphasises the role rhythm plays in skill efficiency and consequently in motor learning

Space Shuttle orbiter entry heating and TPS response: STS-1 predictions and flight data

Aerothermodynamic development flight test data from the first orbital flight test of the Space Transportation System (STS) transmitted after entry blackout is given. Engineering predictions of boundary layer transition and numerical simulations of the orbiter flow field were confirmed. The data tended to substantiate preflight predictions of surface catalysis phenomena. The thermal response of the thermal protection system was as expected. The only exception is that internal free convection was found to be significant in limiting the peak temperature of the structure in areas which do not have internal insulation

Identification of potential off-grid municipalities with 100% renewable energy supply

An increasing number of municipalities are striving for energy autonomy. This study determines in which municipalities and at what additional cost energy autonomy is feasible for a case study of Germany. An existing municipal energy system optimization model is extended to include the personal transport, industrial and commercial sectors. A machine learning approach identifies a regression model among 19 methods, which is best suited for the transfer of individual optimization results to all municipalities. The resulting levelized cost of energy (LCOE) from the optimization of 15 case studies are transferred using a stepwise linear regression model. The regression model shows a mean absolute percentage error of 12.5%. The study demonstrates that energy autonomy is technically feasible in 6,314 (56%) municipalities. Thereby, the LCOEs increase in the autonomous case on average by 0.41 €/kWh compared to the minimum cost scenario. Apart from energy demand, base-load-capable bioenergy and deep geothermal energy appear to have the greatest influence on the LCOEs. This study represents a starting point for defining possible scenarios in studies of future national energy system or transmission grid expansion planning, which for the first time consider completely energy autonomous municipalities

Translocation of southern mountain caribou using a soft-release technique

Southern mountain caribou (Rangifer tarandus caribou, SMC) in British Columbia, Canada, are experiencing a precipitous population decline and range recession. In 2019, the two southernmost herds, the South Selkirks and the Purcells-South herds, were functionally extirpated and facing imminent extinction. To rescue the remaining animals, a translocation into the Columbia North herd range was performed using a soft-release method. The translocated animals were released alongside a captive-reared yearling and a resident adult female from the Columbia North SMC herd. A comparison of habitat selection behaviours at the 2nd order of selection demonstrated that the released animals responded to habitat and elevational conditions similarly to resident caribou. The translocation and soft release of Purcells-South and South Selkirks individuals demonstrates that soft release of wild translocated and captive-reared SMC can be successful and should be considered where and when feasible

Weakly Nonlinear Analysis of Electroconvection in a Suspended Fluid Film

It has been experimentally observed that weakly conducting suspended films of smectic liquid crystals undergo electroconvection when subjected to a large enough potential difference. The resulting counter-rotating vortices form a very simple convection pattern and exhibit a variety of interesting nonlinear effects. The linear stability problem for this system has recently been solved. The convection mechanism, which involves charge separation at the free surfaces of the film, is applicable to any sufficiently two-dimensional fluid. In this paper, we derive an amplitude equation which describes the weakly nonlinear regime, by starting from the basic electrohydrodynamic equations. This regime has been the subject of several recent experimental studies. The lowest order amplitude equation we derive is of the Ginzburg-Landau form, and describes a forward bifurcation as is observed experimentally. The coefficients of the amplitude equation are calculated and compared with the values independently deduced from the linear stability calculation.Comment: 26 pages, 2 included eps figures, submitted to Phys Rev E. For more information, see http://mobydick.physics.utoronto.c

Transferrin-modified chitosan nanoparticles for targeted nose-to-brain delivery of proteins

Nose-to-brain delivery presents a promising alternative route compared to classical blood-brain barrier passage, especially for the delivery of high molecular weight drugs. In general, macromolecules are rapidly degraded in physiological environment. Therefore, nanoparticulate systems can be used to protect biomolecules from premature degradation. Furthermore, targeting ligands on the surface of nanoparticles are able to improve bioavailability by enhancing cellular uptake due to specific binding and longer residence time. In this work, transferrin-decorated chitosan nanoparticles are used to evaluate the passage of a model protein through the nasal epithelial barrier in vitro. It was demonstrated that strain-promoted azide-alkyne cycloaddition reaction can be utilized to attach a functional group to both transferrin and chitosan enabling a rapid covalent surface-conjugation under mild reaction conditions after chitosan nanoparticle preparation. The intactness of transferrin and its binding efficiency were confirmed via SDS-PAGE and SPR measurements. Resulting transferrin-decorated nanoparticles exhibited a size of about 110-150 nm with a positive surface potential. Nanoparticles with the highest amount of surface bound targeting ligand also displayed the highest cellular uptake into a human nasal epithelial cell line (RPMI 2650). In an air-liquid interface co-culture model with glioblastoma cells (U87), transferrin-decorated nanoparticles showed a faster passage through the epithelial cell layer as well as increased cellular uptake into glioblastoma cells. These findings demonstrate the beneficial characteristics of a specific targeting ligand. With this chemical and technological formulation concept, a variety of targeting ligands can be attached to the surface after nanoparticle formation while maintaining cargo integrity