An improved continuous compositional-spread technique based on pulsed-laser deposition and applicable to large substrate areas

A new method for continuous compositional-spread (CCS) thin-film fabrication based on pulsed-laser deposition (PLD) is introduced. This approach is based on a translation of the substrate heater and the synchronized firing of the excimer laser, with the deposition occurring through a slit-shaped aperture. Alloying is achieved during film growth (possible at elevated temperature) by the repeated sequential deposition of sub-monolayer amounts. Our approach overcomes serious shortcomings in previous in-situ implementations of CCS based on sputtering or PLD, in particular the variations of thickness across the compositional spread and the differing deposition energetics as function of position. While moving-shutter techniques are appropriate for PLD-approaches yielding complete spreads on small substrates (i.e. small as compared to distances over which the deposition parameters in PLD vary, typically about 1 cm), our method can be used to fabricate samples that are large enough for individual compositions to be analyzed by conventional techniques, including temperature-dependent measurements of resistivity and dielectric and magnetic and properties (i.e. SQUID magnetometry). Initial results are shown for spreads of (Sr,Ca)RuO$_3$.Comment: 6 pages, 8 figures, accepted for publication in Rev. Sci. Instru

The extinction law in high redshift galaxies

We estimate the dust extinction laws in two intermediate redshift galaxies. The dust in the lens galaxy of LBQS1009-0252, which has an estimated lens redshift of zl~0.88, appears to be similar to that of the SMC with no significant feature at 2175 A. Only if the lens galaxy is at a redshift of zl~0.3, completely inconsistent with the galaxy colors, luminosity or location on the fundamental plane, can the data be fit with a normal Galactic extinction curve. The dust in the zl=0.68 lens galaxy for B0218+357, whose reddened image lies behind a molecular cloud, requires a very flat ultraviolet extinction curve with (formally) R(V)=12 +- 2. Both lens systems seem to have unusual extinction curves by Galactic standards.Comment: 15 pages, 3 figures. ApJ in pres

A novel PLP1 mutation further expands the clinical heterogeneity at the locus

Objectives: To characterize at clinical and molecular levels a family presenting with X-linked recessive Hereditary Spastic Paraplegia (HSP). Background: HSPs are a large group of genetically heterogeneous neurodegenerative disorders characterized by progressive upper motor neuron signs. Mutations in the proteolipid protein (PLP1) gene have been identified in families linked to the SPG2 locus on chromosome Xq22. However, Pelizaeus-Merzbacher disease (PMD) is also an X-linked recessive neurological disorder caused by PLP1 mutations. Methods: The SPG2 locus was investigated by linkage analysis in the family. The PLP1 gene was screened by sequencing. We present findings in a large French-Canadian family with an X-linked recessive HSP. The proband presented early with developmental delay and developed progressive spastic paraplegia. He has been wheelchair-bound since the age of three years. At the latest follow-up, he was 20 years-old and had severe spasticity predominantly affecting the lower extremities, moderate cerebellar dysfunction, and optic atrophy. Results: Linkage to SPG2 was established and a G to A mutation (MIR) in the initiation codon of the PLP1 gene was identified, likely resulting in the complete absence of proteolipid protein. Conclusions: We report a new PLP1 gene mutation in a patient with a clinical phenotype consistent with a PLP1 null syndrome

Comparative analysis of anti-polyglutamine Fab crystals grown on Earth and in microgravity

Huntington's disease is one of nine neurodegenerative diseases caused by a polyglutamine (polyQ)-repeat expansion. An anti-polyQ antigen-binding fragment, MW1 Fab, was crystallized both on Earth and on the International Space Station, a microgravity environment where convection is limited. Once the crystals returned to Earth, the number, size and morphology of all crystals were recorded, and X-ray data were collected from representative crystals. The results generally agreed with previous microgravity crystallization studies. On average, microgravity-grown crystals were 20% larger than control crystals grown on Earth, and microgravity-grown crystals had a slightly improved mosaicity (decreased by 0.03°) and diffraction resolution (decreased by 0.2 Å) compared with control crystals grown on Earth. However, the highest resolution and lowest mosaicity crystals were formed on Earth, and the highest-quality crystal overall was formed on Earth after return from microgravity

Detection of antihydrogen annihilations with a Si-micro-strip and pure CsI detector

In 2002, the ATHENA collaboration reported the creation and detection of cold (~15 K) antihydrogen atoms [1]. The observation was based on the complete reconstruction of antihydrogen annihilations, simultaneous and spatially correlated annihilations of an antiproton and a positron. Annihilation byproducts are measured with a cylindrically symmetric detector system consisting of two layers of double sided Si-micro-strip modules that are surrounded by 16 rows of 12 pure CsI crystals (13 x 17.5 x 17 mm^3). This paper gives a brief overview of the experiment, the detector system, and event reconstruction. Reference 1. M. Amoretti et al., Nature 419, 456 (2002).Comment: 7 pages, 5 figures; Proceedings for the 8th ICATPP Conference on Astroparticle, Particle, Space Physics, Detectors and Medical Physics Applications (Como, Italy October 2003) to be published by World Scientific (style file included

Training physicians in behavioural change counseling: A systematic review

Background: Poor health behaviours (e.g., smoking, physical inactivity) represent major underlying causes of non-communicable chronic diseases (NCDs). Prescriptive behaviour change interventions employed by physicians show limited effectiveness. Physician training in evidence-based behaviour change counselling (BCC) may improve behavioural risk factor management, but the efficacy and feasibility of current programs remains unclear. Objective: (1) To systematically review the efficacy of BCC training programs for physicians, and (2) to describe program content, dose and structure, informing better design and dissemination. Methods: Using PRISMA guidelines, a database search up to January 2018, yielded 1889 unique articles, screened by 2 authors; 9 studies met inclusion criteria and were retained for analysis. Results: 100% of studies reported significant improvements in BCC skills among physicians, most programs targeting provider-patient collaboration, supporting patient autonomy, and use of open questions to elicit “change-talk”. Limitation included: poor reporting quality, high program heterogeneity, small sample sizes, 78% of studies having no comparison group, and less than 30% of skills taught being formally assessed. Conclusion: Training programs were efficacious, but methodological weaknesses limit the ability to determine content and delivery. Caution is necessary when interpreting the results

Luminosities and mass-loss rates of SMC and LMC AGB stars and Red Supergiants

(Abridged) Dust radiative transfer models are presented for 101 carbon stars and 86 oxygen-rich evolved stars in the Magellanic Clouds for which 5-35 \mum\ {\it Spitzer} IRS spectra are available. The spectra are complemented with available optical and infrared photometry to construct the spectral energy distribution. A minimisation procedure is used to fit luminosity, mass-loss rate and dust temperature at the inner radius. Different effective temperatures and dust content are also considered. Periods from the literature and from new OGLE-III data are compiled and derived. The O-rich stars are classified in foreground objects, AGB stars and Red Super Giants. For the O-rich stars silicates based on laboratory optical constants are compared to "astronomical silicates". Overall, the grain type by Volk & Kwok (1988) fit the data best. However, the fit based on laboratory optical constants for the grains can be improved by abandoning the small-particle limit. The influence of grain size, core-mantle grains and porosity are explored. Relations between mass-loss rates and luminosity and pulsation period are presented and compared to the predictions of evolutionary models, those by Vassiliadis & Wood (1993) and their adopted mass-loss recipe, and those based on a Reimers mass-loss law with a scaling of a factor of five. The Vassiliadis & Wood models describe the data better, although there are also some deficiencies, in particular to the maximum adopted mass-loss rate. The OGLE-III data reveal an O-rich star in the SMC with a period of 1749 days. Its absolute magnitude of $M_{\rm bol}= -8.0$ makes it a good candidate for a super-AGB star.Comment: A&A accepte

A pentanucleotide ATTTC repeat insertion in the non-coding region of DAB1, mapping to SCA37, causes spinocerebellar ataxia.

Advances in human genetics in recent years have largely been driven by next-generation sequencing (NGS); however, the discovery of disease-related gene mutations has been biased toward the exome because the large and very repetitive regions that characterize the non-coding genome remain difficult to reach by that technology. For autosomal-dominant spinocerebellar ataxias (SCAs), 28 genes have been identified, but only five SCAs originate from non-coding mutations. Over half of SCA-affected families, however, remain without a genetic diagnosis. We used genome-wide linkage analysis, NGS, and repeat analysis to identify an (ATTTC)n insertion in a polymorphic ATTTT repeat in DAB1 in chromosomal region 1p32.2 as the cause of autosomal-dominant SCA; this region has been previously linked to SCA37. The non-pathogenic and pathogenic alleles have the configurations [(ATTTT)7-400] and [(ATTTT)60-79(ATTTC)31-75(ATTTT)58-90], respectively. (ATTTC)n insertions are present on a distinct haplotype and show an inverse correlation between size and age of onset. In the DAB1-oriented strand, (ATTTC)n is located in 5' UTR introns of cerebellar-specific transcripts arising mostly during human fetal brain development from the usage of alternative promoters, but it is maintained in the adult cerebellum. Overexpression of the transfected (ATTTC)58 insertion, but not (ATTTT)n, leads to abnormal nuclear RNA accumulation. Zebrafish embryos injected with RNA of the (AUUUC)58 insertion, but not (AUUUU)n, showed lethal developmental malformations. Together, these results establish an unstable repeat insertion in DAB1 as a cause of cerebellar degeneration; on the basis of the genetic and phenotypic evidence, we propose this mutation as the molecular basis for SCA37.We thank the families who participated in this study. We are grateful to Goncalo Abecasis, Miguel Costa, Tito Vieira, and Andre Torres for help with MERLIN analysis; Beatriz Sobrino, Jorge Amigo, and Pilar Cacheiro for next-generation sequencing analysis, performed at the Santiago de Compostela node of the Spanish National Genotyping Center; Nuno Santarem and Anabela Cordeiro-da-Silva for assistance with cloning; Antonio Amorim, Laura Vilarinho, and Paula Jorge for samples from the Portuguese population; and Paula Magalhaes from the Institute for Molecular and Cell Biology Cell Culture and Genotyping Core for DNA extraction. This work was financed by Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020 Operational Program for Competitiveness and Internationalization (POCI) of Portugal 2020 and by Portuguese funds through the Fundacao para a Ciencia e a Tecnologia (FCT) and Ministerio da Ciencia, Tecnologia, e Inovacao in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274); and by FCT grant PTDC/SAU-GMG/098305/2008 to I.S. A. I.S. was the recipient of an FCT scholarship (SFRH/BD/30702/2006). J.R.L. was supported by scholarships from PEst-C/SAU/LA0002/2013 and the European Molecular Biology Organization (ASTF494-2015). C.L.O. was supported by a scholarship from PEst-C/SAU/LA0002/2013. This work was also financed by the Porto Neurosciences and Neurologic Disease Research Initiative at the Instituto de Investigacao e Inovacao em Saude (Norte-01-0145-FEDER-000008), supported by Norte Portugal Regional Operational Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement through FEDER, and by the Fondo de Investigacion Sanitaria of the Instituto de Salud Carlos III (grant PI12/00742)