Research on metal solidification in zero-g state

The containerless solidification of several pure metals and metallic alloys was studied in a low gravity environment. The tests were performed in the MSFC 4.2 s drop tower using a rapid wire melting apparatus designed and built for this purpose. Pure iron and nickel, and alloys of iron-nickel, iron-carbon, nickel-aluminum and tungsten-rhenium were all melted and solidified at a gravity level of approximately 100.000/-4 g. Interpretation of the results has led to an appreciation of the factors controlling the successful execution of this drop test experiment and to a delineation of the limits of applicability of the apparatus. Preliminary metallurgical evaluations are presented of the overall shapes, lattice parameters, surface microstructure,, cross-sectional microstructures, solidification and transformation sequences, evaporative segregation, and localized solute redistribution observed in the low-gravity specimens. The effects of low gravity on metallic solidification are discussed with particular emphasis on observations of spontaneous undercooling and evaporative segregation in uncontained melts

Évaluation du secteur communautaire du Service social de la Ville de Genève

Le Conseil administratif de la Ville de Genève a mandaté l'IDHEAP en tant qu'expert indépendant pour évaluer le secteur communautaire, une unité administrative rattachée au Service social. En prenant en considération les enjeux socio-sanitaires auxquels la Ville de Genève est confrontée, le concept d'étude proposé par l'Unité de politiques locales et d'évaluation de l'IDHEAP vise à établir un bilan de l'action du secteur communautaire, à déterminer la pertinence de cette action, son efficacité et son efficience, à tracer des perspectives en tenant compte notamment des prestations fournies par d'autres acteurs présents dans les domaines de la cohésion sociale et de la prévention socio-sanitaire, ainsi qu'à proposer des recommandations

Spinocerebellar ataxia type 19/22 mutations alter heterocomplex Kv4.3 channel function and gating in a dominant manner

The dominantly inherited cerebellar ataxias are a heterogeneous group of neurodegenerative disorders caused by Purkinje cell loss in the cerebellum. Recently, we identified loss-of-function mutations in the KCND3 gene as the cause of spinocerebellar ataxia type 19/22 (SCA19/22), revealing a previously unknown role for the voltage-gated potassium channel, Kv4.3, in Purkinje cell survival. However, how mutant Kv4.3 affects wild-type Kv4.3 channel functioning remains unknown. We provide evidence that SCA19/22-mutant Kv4.3 exerts a dominant negative effect on the trafficking and surface expression of wild-type Kv4.3 in the absence of its regulatory subunit, KChIP2. Notably, this dominant negative effect can be rescued by the presence of KChIP2. We also found that all SCA19/22-mutant subunits either suppress wild-type Kv4.3 current amplitude or alter channel gating in a dominant manner. Our findings suggest that altered Kv4.3 channel localization and/or functioning resulting from SCA19/22 mutations may lead to Purkinje cell loss, neurodegeneration and ataxia

Frequency of KCNC3 DNA Variants as Causes of Spinocerebellar Ataxia 13 (SCA13)

Gain-of function or dominant-negative mutations in the voltage-gated potassium channel KCNC3 (Kv3.3) were recently identified as a cause of autosomal dominant spinocerebellar ataxia. Our objective was to describe the frequency of mutations associated with KCNC3 in a large cohort of index patients with sporadic or familial ataxia presenting to three US ataxia clinics at academic medical centers.DNA sequence analysis of the coding region of the KCNC3 gene was performed in 327 index cases with ataxia. Analysis of channel function was performed by expression of DNA variants in Xenopus oocytes.Sequence analysis revealed two non-synonymous substitutions in exon 2 and five intronic changes, which were not predicted to alter splicing. We identified another pedigree with the p.Arg423His mutation in the highly conserved S4 domain of this channel. This family had an early-onset of disease and associated seizures in one individual. The second coding change, p.Gly263Asp, subtly altered biophysical properties of the channel, but was unlikely to be disease-associated as it occurred in an individual with an expansion of the CAG repeat in the CACNA1A calcium channel.Mutations in KCNC3 are a rare cause of spinocerebellar ataxia with a frequency of less than 1%. The p.Arg423His mutation is recurrent in different populations and associated with early onset. In contrast to previous p.Arg423His mutation carriers, we now observed seizures and mild mental retardation in one individual. This study confirms the wide phenotypic spectrum in SCA13

Myasthenia gravis and pregnancy: clinical implications and neonatal outcome

BACKGROUND: The myasthenia gravis is twice as common in women as in men and frequently affects young women in the second and third decades of life, overlapping with the childbearing years. Generally, during pregnancy in one third of patients the disease exacerbates, whereas in two thirds it remains clinically unchanged. Complete remission can occur in some patients. METHODS: To describe the clinical course, delivery and neonatal outcome of 18 pregnant women with the diagnosis of myasthenia gravis. Retrospective chart review of pregnant patients with myasthenia gravis, followed at the National Institute of Perinatology in Mexico City over an 8-year period. Data was abstracted from the medical records on the clinical course during pregnancy, delivery and neonatal outcome. RESULTS: From January 1, 1996 to December 31, 2003 18 patients with myasthenia gravis were identified and included in the study. The mean ± SD maternal age was 27.4 ± 4.0 years. During pregnancy 2 women (11%) had an improvement in the clinical symptoms of myasthenia gravis, 7 women (39%) had clinical worsening of the condition of 9 other patients (50%) remained clinically unchanged. Nine patients delivered vaginally, 8 delivered by cesarean section and 1 pregnancy ended in fetal loss. Seventeen infants were born at mean ± SD gestational age of 37.5 ± 3.0 weeks and a mean birth weight of 2710 ± 73 g. Only one infant presented with transient neonatal myasthenia gravis. No congenital anomalies were identified in any of the newborns. CONCLUSIONS: The clinical course of myasthenia gravis during pregnancy is variable, with a significant proportion of patients experiencing worsening of the clinical symptoms. However, neonatal transient myasthenia was uncommon in our patient population