Sequential Adaptive Detection for In-Situ Transmission Electron Microscopy (TEM)

We develop new efficient online algorithms for detecting transient sparse signals in TEM video sequences, by adopting the recently developed framework for sequential detection jointly with online convex optimization [1]. We cast the problem as detecting an unknown sparse mean shift of Gaussian observations, and develop adaptive CUSUM and adaptive SSRS procedures, which are based on likelihood ratio statistics with post-change mean vector being online maximum likelihood estimators with $\ell_1$. We demonstrate the meritorious performance of our algorithms for TEM imaging using real data

Superconducting magnesium diboride films with Tc \approx 24K grown by pulsed laser deposition with in-situ anneal

Thin superconducting films of magnesium diboride (MgB2) with Tc \approx 24K were prepared on various oxide substrates by pulsed laser deposition (PLD) followed by an in-situ anneal. A systematic study of the influence of various in-situ annealing parameters shows an optimum temperature of about 600C in a background of 0.7 atm. of Ar/4%H2 for layers consisting of a mixture of magnesium and boron. Contrary to ex-situ approaches (e.g. reacting boron films with magnesium vapor at 900C), these films are processed below the decomposition temperature of MgB2. This may prove enabling in the formation of multilayers, junctions, and epitaxial films in future work. Issues related to the improvement of these films and to the possible in-situ growth of MgB2 at elevated temperature are discussed.Comment: 5 pages, 4 figure

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

Improvement in the molecular diagnosis of Machado-Joseph disease

Abstract BACKGROUND: Direct detection of the gene mutation allows for the confirmation of the clinical diagnosis of Machado-Joseph disease (MJD), the most frequent cause of autosomal dominant spinocerebellar ataxia worldwide. OBJECTIVE: To address the main difficulties in our national MJD predictive testing program. The first was the emergence of intermediate alleles, for which it is not yet possible to determine whether they will cause disease. The second was the issue of homoallelism, ie, homozygosity for 2 normal alleles with exactly the same (CAG)(n) length, which occurs in about 10% of all test results. METHODS: A large pedigree with 1 affected patient carrying a 71 and a 51 CAG repeat and 2 asymptomatic relatives carrying the 51 CAG repeat and normal-size alleles underwent clinical and molecular studies. Intragenic haplotypes for these alleles were determined. A representative sample of the healthy population in the region was obtained to assess the distribution of the normal (CAG)(n) length. We established the genotype for 4 intragenic polymorphisms in the gene for MJD (MJD1) in 21 homoallelic individuals, to distinguish their 2 normal chromosomes. In addition, we developed a new Southern blot method to completely exclude cases of nonamplification of expanded alleles in the homoallelic individuals. RESULTS: The study of the family in which the 51 CAG repeat was found suggests that the allele is apparently not associated with disease. These intermediate alleles were not present in a large sample of the healthy population from the same region. Intragenic polymorphisms allowed distinction of the 2 different normal alleles in all cases of homoallelism. The absence of an expanded allele was also confirmed by Southern blot. CONCLUSIONS: We propose an improved protocol for molecular testing for MJD. These strategies, developed to overcome the practical difficulties mostly in the presymptomatic and prenatal diagnosis of MJD, should prove useful for other polyglutamine-related disorders

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

Biomarker testing in oncology - Requirements for organizing external quality assessment programs to improve the performance of laboratory testing:revision of an expert opinion paper on behalf of IQNPath ABSL

In personalized medicine, predictive biomarker testing is the basis for an appropriate choice of therapy for patients with cancer. An important tool for laboratories to ensure accurate results is participation in external quality assurance (EQA) programs. Several providers offer predictive EQA programs for different cancer types, test methods, and sample types. In 2013, a guideline was published on the requirements for organizing high-quality EQA programs in molecular pathology. Now, after six years, steps were taken to further harmonize these EQA programs as an initiative by IQNPath ABSL, an umbrella organization founded by various EQA providers. This revision is based on current knowledge, adds recommendations for programs developed for predictive biomarkers by in situ methodologies (immunohistochemistry and in situ hybridization), and emphasized transparency and an evidence-based approach. In addition, this updated version also has the aim to give an overview of current practices from various EQA providers

Variation in nomenclature of somatic variants for selection of oncological therapies:Can we reach a consensus soon?

A standardized nomenclature for reporting oncology biomarker variants is key to avoid misinterpretation of results and unambiguous registration in clinical databases. External quality assessment (EQA) schemes have revealed a need for more consistent nomenclature use in clinical genetics. We evaluated the propensity of EQA for improvement of compliance with Human Genome Variation Society (HGVS) recommendations for reporting of predictive somatic variants in lung and colorectal cancer. Variant entries between 2012 and 2018 were collected from written reports and electronic results sheets. In total, 4,053 variants were assessed, of which 12.1% complied with HGVS recommendations. Compliance improved over time from 2.1% (2012) to 22.3% (2018), especially when laboratories participated in multiple EQA schemes. Compliance was better for next-generation sequencing (20.9%) compared with targeted techniques (9.8%). In the 1792 reports, HGVS recommendations for reference sequences were met for 31.9% of reports, for 36.0% of noncommercial, and 26.5% of commercial test methods. Compliance improved from 16.7% (2012) to 33.1% (2018), and after repeated EQA participation. EQA participation improves compliance with HGVS recommendations. The residual percentage of errors in the most recent schemes suggests that laboratories, companies, and EQA providers need to collaborate for additional improvement of harmonization in clinical test reporting

Inherited cavernous malformations of the central nervous system: clinical and genetic features in 19 Swiss families

Cavernous malformations (CCMs) are benign, well-circumscribed, and mulberry-like vascular malformations that may be found in the central nervous system in up to 0.5% of the population. Cavernous malformations can be sporadic or inherited. The common symptoms are epilepsy, hemorrhages, focal neurological deficits, and headaches. However, CCMs are often asymptomatic. The familiar form is associated with three gene loci, namely 7q21-q22 (CCM1), 7p13-p15 (CCM2), and 3q25.2-q27 (CCM3) and is inherited as an autosomal dominant trait with incomplete penetrance. The CCM genes are identified as Krit 1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3). Here, we present the clinical and genetic features of CCMs in 19 Swiss families. Furthermore, surgical aspects in such families are also discusse