Arbeitsbericht Nr. 2010-03, November 2010

Ilmenauer Beiträge zur Wirtschaftsinformatik Nr. 2010-03 / Technische Universität Ilmenau, Fakultät für Wirtschaftswissenschaften, Institut für Wirtschaftsinformatik ISSN 1861-9223 ISBN 978-3-938940-31-

A RISC-V MCU with adaptive reverse body bias and ultra-low-power retention mode in 22 nm FD-SOI

We present a low-power, energy efficient 32-bit RISC-V microprocessor unit (MCU) in 22 nm FD-SOI. It achieves ultra-low leakage,even at high temperatures, by using an adaptive reverse body biasing aware sign-off approach, a low-power optimized physical implementation, and custom SRAM macros with retention mode. We demonstrate the robustness of the chip with measurements over the full industrial temperature range, from -40 {\deg}C to 125 {\deg}C. Our results match the state of the art (SOTA) with 4.8 uW / MHz at 50 MHz in active mode and surpass the SOTA in ultra-low-power retention mode.Comment: accepted at ISOCC 202

Cancer Predisposition Cascade Screening for Hereditary Breast/Ovarian Cancer and Lynch Syndromes in Switzerland: Study Protocol

Background : Breast, colorectal, ovarian, and endometrial cancers constitute approximately 30% of newly diagnosed cancer cases in Switzerland, affecting more than 12,000 individuals annually. Hundreds of these patients are likely to carry germline pathogenic variants associated with hereditary breast ovarian cancer (HBOC) or Lynch syndrome (LS). Genetic services (counseling and testing) for hereditary susceptibility to cancer can prevent many cancer diagnoses and deaths through early identification and risk management. Objective : Cascade screening is the systematic identification and testing of relatives of a known mutation carrier. It determines whether asymptomatic relatives also carry the known variant, needing management options to reduce future harmful outcomes. Specific aims of the CASCADE study are to (1) survey index cases with HBOC or LS from clinic-based genetic testing records and determine their current cancer status and surveillance practices, needs for coordination of medical care, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to serve as advocates for cancer genetic services to blood relatives, (2) survey first- and second-degree relatives and first-cousins identified from pedigrees or family history records of HBOC and LS index cases and determine their current cancer and mutation status, cancer surveillance practices, needs for coordination of medical care, barriers and facilitators to using cancer genetic services, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to participate in a study designed to increase use of cancer genetic services, and (3) explore the influence of patient-provider communication about genetic cancer risk on patient-family communication and the acceptability of a family-based communication, coping, and decision support intervention with focus group(s) of mutation carriers and relatives. Methods: CASCADE is a longitudinal study using surveys (online or paper/pencil) and focus groups, designed to elicit factors that enhance cascade genetic testing for HBOC and LS in Switzerland. Repeated observations are the optimal way for assessing these outcomes. Focus groups will examine barriers in patient-provider and patient-family communication, and the acceptability of a family-based communication, coping, and decision-support intervention. The survey will be developed in English, translated into three languages (German, French, and Italian), and back-translated into English, except for scales with validated versions in these languages. Results: Descriptive analyses will include calculating means, standard deviations, frequencies, and percentages of variables and participant descriptors. Bivariate analyses (Pearson correlations, chi-square test for differences in proportions, and t test for differences in means) will assess associations between demographics and clinical characteristics. Regression analyses will incorporate generalized estimating equations for pairing index cases with their relatives and explore whether predictors are in direct, mediating, or moderating relationship to an outcome. Focus group data will be transcribed verbatim and analyzed for common themes. Conclusions: Robust evidence from basic science and descriptive population-based studies in Switzerland support the necessity of cascade screening for genetic predisposition to HBOC and LS. CASCADE is designed to address translation of this knowledge into public health interventions. Trial Registration: ClinicalTrials.gov NCT03124212; https://clinicaltrials.gov/ct2/show/NCT03124212 (Archived by WebCite at http://www.webcitation.org/6tKZnNDBt

Integrative Analysis of the Mitochondrial Proteome in Yeast

In this study yeast mitochondria were used as a model system to apply, evaluate, and integrate different genomic approaches to define the proteins of an organelle. Liquid chromatography mass spectrometry applied to purified mitochondria identified 546 proteins. By expression analysis and comparison to other proteome studies, we demonstrate that the proteomic approach identifies primarily highly abundant proteins. By expanding our evaluation to other types of genomic approaches, including systematic deletion phenotype screening, expression profiling, subcellular localization studies, protein interaction analyses, and computational predictions, we show that an integration of approaches moves beyond the limitations of any single approach. We report the success of each approach by benchmarking it against a reference set of known mitochondrial proteins, and predict approximately 700 proteins associated with the mitochondrial organelle from the integration of 22 datasets. We show that a combination of complementary approaches like deletion phenotype screening and mass spectrometry can identify over 75% of the known mitochondrial proteome. These findings have implications for choosing optimal genome-wide approaches for the study of other cellular systems, including organelles and pathways in various species. Furthermore, our systematic identification of genes involved in mitochondrial function and biogenesis in yeast expands the candidate genes available for mapping Mendelian and complex mitochondrial disorders in humans

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Complete Sequence of Probiotic Symbioflor 2 Escherichia coli Strain G3/10 and Draft Sequences of Symbioflor 2 E. coli Strains G1/2, G4/9, G5, G6/7, and G8.

The complete genome of probiotic Escherichia coli strain G3/10 is presented here. In addition, the probiotic E. coli strains G1/2, G4/9, G5, G6/7, and G8 are presented in draft form. These six strains together comprise the probiotic product Symbioflor 2 (DSM 17252)

Sex differences in outcomes of primary prevention implantable cardioverter-defibrillator therapy:combined registry data from eleven European countries

Abstract Aims: Therapy with an implantable cardioverter defibrillator (ICD) is established for the prevention of sudden cardiac death (SCD) in high risk patients. We aimed to determine the effectiveness of primary prevention ICD therapy by analysing registry data from 14 centres in 11 European countries compiled between 2002 and 2014, with emphasis on outcomes in women who have been underrepresented in all trials. Methods and results: Retrospective data of 14 local registries of primary prevention ICD implantations between 2002 and 2014 were compiled in a central database. Predefined primary outcome measures were overall mortality and first appropriate and first inappropriate shocks. A multivariable model enforcing a common hazard ratio for sex category across the centres, but allowing for centre-specific baseline hazards and centre specific effects of other covariates, was adjusted for age, the presence of ischaemic cardiomyopathy or a CRT-D, and left ventricular ejection fraction ≤25%. Of the 5033 patients, 957 (19%) were women. During a median follow-up of 33 months (IQR 16–55 months) 129 women (13%) and 807 men (20%) died (HR 0.65; 95% CI: [0.53, 0.79], P-value < 0.0001). An appropriate ICD shock occurred in 66 women (8%) and 514 men (14%; HR 0.61; 95% CI: 0.47–0.79; P = 0.0002). Conclusion: Our retrospective analysis of 14 local registries in 11 European countries demonstrates that fewer women than men undergo ICD implantation for primary prevention. After multivariate adjustment, women have a significantly lower mortality and receive fewer appropriate ICD shocks

Verification of Proteomic Candidates by Mitochondrial Import

<p>Samples were incubated in the presence or absence of a membrane potential (MP) and of proteinase K (PK). Cases where import was accompanied by removal of the signal peptide (SP) are marked as “SP-processing” (+). Su9(1–69)DHFR and AAC serve as positive controls for a processed matrix protein and a nonprocessed inner membrane protein, respectively. The bar graphs indicate if a protein was more likely to be found in either the membrane or the matrix fractions of our proteomic data. The height of the bar corresponds to the number of samples in which a protein was identified with higher tag number—in the mitochondrial membrane or mitochondrial matrix fractions, respectively.</p

Evaluation of Proteomic Data for Protein Abundance and Mitochondrial Localization

<div><p>(A) Coverage of known mitochondrial proteins (Mref) by two MS proteome studies (this study and <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020160#pbio-0020160-Sickmann1" target="_blank">Sickmann et al. [2003]</a>). We evaluated the 340 proteins of the mitochondrial reference set for which protein abundance data existed (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020160#pbio-0020160-Ghaemmaghami1" target="_blank">Ghaemmaghami et al. 2003</a>). The x-axis represents the median protein abundance of ten consecutive, equally sized bins of proteins.</p> <p>(B) Distribution and overlap of proteins identified by the two MS studies and known mitochondrial proteins. The total number of entries for each dataset is indicated in parentheses outside each circle. The number inside each circle indicates the number of proteins in each of the categories. In addition, the percentage of proteins that were localized to mitochondria by GFP tagging (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020160#pbio-0020160-Huh1" target="_blank">Huh et al. 2003</a>) is given in parentheses for each category.</p></div