2D seismic tomography of Somma-Vesuvius: Description of the experiment and preliminary results

A multidisciplinary project for the investigation of Mt. Vesuvius structure was started in 1993. The core of the project is represented by a high resolution seismic tomography study by using controlled and natural sources. The main research objective is to investigate the feeding system of the volcano and to retrieve details of the upper crustal structure in the area. A first 2D active seismic experiment was performed in May 1994, with the aim of studing the feasibility of using tomographic techniques for exploring the volcano interiors. Particularly, this experiment was designed to obtain information on the optimal sources-receivers configuration and on the depth extension of the volume sampled by shot-generated seismic waves. 66 three-component seismic stations and 16 single-component analogue instruments were installed by several Italian and French groups to record signals generated by three on-land, underground explosions. Sources and geophones were deployed along a 30-km NW-SE profile passing through the volcano crater. Receivers were placed at an average spacing of 250 m in the middle of the recording line and at 500 m outside. The arrival time data base was complemented by first P and S readings of microearthquakes which occurred in the recent past within the volcano. The first arrival data set was preliminarily used to determine the shallow structure of the volcano by applying Thurber's (1983) tomographic inversion technique. This analysis shows evidence for a high-velocity body which extends vertically from about 400 m below the crater down to at least 3000 m and for a shallow 300-500 m thick low-velocity cover which borders the edifice. Data from the distant shot show evidence for arrivals of deep reflected/converted phases and provide information on the deeper structure under the volcano. The results from the interpretation of 2D data are used for planning a 3D tomographic survey which will be carried out in 1996

Chromosome 19p13.3 deletion in a child with Peutz-Jeghers syndrome, congenital heart defect, high myopia, learning difficulties and dysmorphic features: Clinical and molecular characterization of a new contiguous gene syndrome

The Peutz-Jeghers syndrome (PJS) is an autosomal-dominant hamartomatous polyposis syndrome characterized by mucocutaneous pigmentation, gastrointestinal polyps and the increased risk of multiple cancers. The causative point mutation in the STK11 gene of most patients accounts for about 30% of the cases of partial and complete gene deletion. This is a report on a girl with PJS features, learning difficulties, dysmorphic features and cardiac malformation, bearing a de novo 1.1 Mb deletion at 19p13.3. This deletion encompasses at least 47 genes, including STK11. This is the first report on 19p13.3 deletion associated with a PJS phenotype, as well as other atypical manifestations, thereby implying a new contiguous gene syndrome

Permanent Neonatal Diabetes Caused by Creation of an Ectopic Splice Site within the INS Gene

PublishedCase ReportsJournal ArticleResearch Support, Non-U.S. Gov'tBACKGROUND: The aim of this study was to characterize the genetic etiology in a patient who presented with permanent neonatal diabetes at 2 months of age. METHODOLOGY/PRINCIPAL FINDINGS: Regulatory elements and coding exons 2 and 3 of the INS gene were amplified and sequenced from genomic and complementary DNA samples. A novel heterozygous INS mutation within the terminal intron of the gene was identified in the proband and her affected father. This mutation introduces an ectopic splice site leading to the insertion of 29 nucleotides from the intronic sequence into the mature mRNA, which results in a longer and abnormal transcript. CONCLUSIONS/SIGNIFICANCE: This study highlights the importance of routinely sequencing the exon-intron boundaries and the need to carry out additional studies to confirm the pathogenicity of any identified intronic genetic variants.Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas (CIBERDEM)Instituto de Salud Carlos III of the Spanish Ministry of HealthFIS-programsWellcome Trus

Recommendations for the use of tolvaptan in autosomal dominant polycystic kidney disease:a position statement on behalf of the ERA-EDTA Working Groups on Inherited Kidney Disorders and European Renal Best Practice

Recently, the European Medicines Agency approved the use of the vasopressin V2 receptor antagonist tolvaptan to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adult patients with chronic kidney disease stages 1-3 at initiation of treatment with evidence of rapidly progressing disease. In this paper, on behalf of the ERA-EDTA Working Groups of Inherited Kidney Disorders and European Renal Best Practice, we aim to provide guidance for making the decision as to which ADPKD patients to treat with tolvaptan. The present position statement includes a series of recommendations resulting in a hierarchical decision algorithm that encompasses a sequence of risk-factor assessments in a descending order of reliability. By examining the best-validated markers first, we aim to identify ADPKD patients who have documented rapid disease progression or are likely to have rapid disease progression. We believe that this procedure offers the best opportunity to select patients who are most likely to benefit from tolvaptan, thus improving the benefit-to-risk ratio and cost-effectiveness of this treatment. It is important to emphasize that the decision to initiate treatment requires the consideration of many factors besides eligibility, such as contraindications, potential adverse events, as well as patient motivation and lifestyle factors, and requires shared decision-making with the patient.</p

Real-time estimation of horizontal gaze angle by saccade integration using in-ear electrooculography

The manuscript proposes and evaluates a real-time algorithm for estimating eye gaze angle based solely on single-channel electrooculography (EOG), which can be obtained directly from the ear canal using conductive ear moulds. In contrast to conventional high-pass filtering, we used an algorithm that calculates absolute eye gaze angle via statistical analysis of detected saccades. The estimated eye positions of the new algorithm were still noisy. However, the performance in terms of Pearson product-moment correlation coefficients was significantly better than the conventional approach in some instances. The results suggest that in-ear EOG signals captured with conductive ear moulds could serve as a basis for lightweight and portable horizontal eye gaze angle estimation suitable for a broad range of applications. For instance, for hearing aids to steer the directivity of microphones in the direction of the user’s eye gaze

Posterior Association Networks and Functional Modules Inferred from Rich Phenotypes of Gene Perturbations

Combinatorial gene perturbations provide rich information for a systematic exploration of genetic interactions. Despite successful applications to bacteria and yeast, the scalability of this approach remains a major challenge for higher organisms such as humans. Here, we report a novel experimental and computational framework to efficiently address this challenge by limiting the ‘search space’ for important genetic interactions. We propose to integrate rich phenotypes of multiple single gene perturbations to robustly predict functional modules, which can subsequently be subjected to further experimental investigations such as combinatorial gene silencing. We present posterior association networks (PANs) to predict functional interactions between genes estimated using a Bayesian mixture modelling approach. The major advantage of this approach over conventional hypothesis tests is that prior knowledge can be incorporated to enhance predictive power. We demonstrate in a simulation study and on biological data, that integrating complementary information greatly improves prediction accuracy. To search for significant modules, we perform hierarchical clustering with multiscale bootstrap resampling. We demonstrate the power of the proposed methodologies in applications to Ewing's sarcoma and human adult stem cells using publicly available and custom generated data, respectively. In the former application, we identify a gene module including many confirmed and highly promising therapeutic targets. Genes in the module are also significantly overrepresented in signalling pathways that are known to be critical for proliferation of Ewing's sarcoma cells. In the latter application, we predict a functional network of chromatin factors controlling epidermal stem cell fate. Further examinations using ChIP-seq, ChIP-qPCR and RT-qPCR reveal that the basis of their genetic interactions may arise from transcriptional cross regulation. A Bioconductor package implementing PAN is freely available online at http://bioconductor.org/packages/release/bioc/html/PANR.html