UNMANNED UNDERWATER VEHICLE MISSION SYSTEMS ENGINEERING PRODUCT REUSE RETURN ON INVESTMENT

Unmanned Underwater Vehicles (UUVs) accomplish a wide spectrum of missions ranging from generic to extremely specific. Although not all UUVs can accomplish all missions, there is significant replication of the requirements and the systems across the family of UUVs. The design process for UUVs balances operational requirements, design feasibility, expected performance, schedule, budget, and ultimate system and life-cycle costs. The U.S. Department of Defense does not have an established process for developing UUV Systems Engineering (SE) requirements. This results in duplicative development efforts adding unnecessary costs to UUV programs. This paper investigates the SE requirements and interfaces across various UUV mission spaces to establish complexity and reuse weights. A Constructive SE Cost Model (COSYSMO) is applied to determine the cost advantage to reuse SE requirements for UUV assets across different mission spaces to determine an overall SE effort. Requirements from the baseline mission are then compared with requirements from eight other missions, and the efforts compared to determine a return on investment (ROI) for using previous missions as a baseline. Utilizing the resulting UUV requirement cost versus ROI can serve as a starting point for future UUV program concept design.Civilian, Department of the NavyCivilian, Department of the NavyCivilian, Department of the NavyCivilian, Department of the NavyCivilian, Department of the NavyApproved for public release. Distribution is unlimited

A Microfluidic Device for Whole-Animal Drug Screening Using Electrophysiological Measures in the Nematode C. Elegans

This paper describes the fabrication and use of a microfluidic device for performing whole-animal chemical screens using non-invasive electrophysiological readouts of neuromuscular function in the nematode worm, C. elegans. The device consists of an array of microchannels to which electrodes are attached to form recording modules capable of detecting the electrical activity of the pharynx, a heart-like neuromuscular organ involved in feeding. The array is coupled to a tree-like arrangement of distribution channels that automatically delivers one nematode to each recording module. The same channels are then used to perfuse the recording modules with test solutions while recording the electropharyngeogram (EPG) from each worm with sufficient sensitivity to detect each pharyngeal contraction. The device accurately reported the acute effects of known anthelmintics (anti-nematode drugs) and also correctly distinguished a specific drug-resistant mutant strain of C. elegans from wild type. The approach described here is readily adaptable to parasitic species for the identification of novel anthelmintics. It is also applicable in toxicology and drug discovery programs for human metabolic and degenerative diseases for which C. elegans is used as a model.Chemistry and Chemical Biolog

A Framework For Detecting Noncoding Rare-Variant associations of Large-Scale Whole-Genome Sequencing Studies

Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV association. However, existing methods have limited ability in analyzing the noncoding genome. We propose a computationally efficient and robust noncoding RV association detection framework, STAARpipeline, to automatically annotate a whole-genome sequencing study and perform flexible noncoding RV association analysis, including gene-centric analysis and fixed window-based and dynamic window-based non-gene-centric analysis by incorporating variant functional annotations. In gene-centric analysis, STAARpipeline uses STAAR to group noncoding variants based on functional categories of genes and incorporate multiple functional annotations. In non-gene-centric analysis, STAARpipeline uses SCANG-STAAR to incorporate dynamic window sizes and multiple functional annotations. We apply STAARpipeline to identify noncoding RV sets associated with four lipid traits in 21,015 discovery samples from the Trans-Omics for Precision Medicine (TOPMed) program and replicate several of them in an additional 9,123 toPMed samples. We also analyze five non-lipid toPMed traits

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Olga Litvak, Conscription and the Search for Modern Russian Jewry, Bloomington: Indiana University Press, 2006, 273 pages.

Many American Jew are convinced that their ancestors fled the Russian Empire in the 1880s to flee pogroms and forced conscription, even of young Jewish boys.  But as historians have long pointed out, forced conscriptions of young Jewish boys had ended decades before mass emigration.  And yet in Jewish memory, the khapers (“grabbers”: Jews who captured and handed over Jewish lads to the tsarist recruiters) and conscription continue to loom large among tsarist Russia’s most cruel antisemitic po..

[Tarp gimtinės ir Tėvynės : Lietuvos SSR gyventojų repatriacija į Lenkiją (1944-1947, 1955-1959 m.)] : recenzija

Recenzuojama Vitalijos Stravinskienės monografija: Tarp gimtinės ir tėvynės: Lietuvos SSR gyventojų repatriacija į Lenkiją (1944–1947, 1955–1959 m.), Vilnius: Lietuvos istorijos instituto leidykla, 2011, 510 p. Po antrojo pasaulinio karo daugybė Vidurio Europos gyventojų kėlėsi į kaimynines valstybes. Vokietijos ir Lenkijos istoriografijoje šis reiškinys sulaukė nemažai tyrimų. Tuo tarpu Lietuvos istoriografijoje pokario Lietuvos gyventojų migracija į kitas Europos šalis labai mažai tyrinėta. Todėl sovietinės Lietuvos gyventojų migracijai į Lenkiją skirta Stravinskienės monografija, anot recenzento, yra vertingas tyrimas. Taip pat atkreipiamas dėmesys į išskirtinę Stravinskienės laikyseną pokario Europos gyventojų migracijos vertinime. Priešingai nei kitų šalių istorikai, recenzuojamos knygos autorė vengia vertinti moralinę šio reiškinio pusę. Recenzentas akcentuoja, jog Stravinskienės monografija pasižymi daugybe privalumų, tarp kurių išskiriamas Lenkijos istorikų darbų panaudojimas, kruopštus darbas su archyviniais šaltiniais. Taip pat pabrėžiama, jog recenzuojama monografija dar ilgai bus pagrindiniu darbu, skirtu gyventojų migracijai iš sovietinės Lietuvos į Lenkiją. Išreiškiamas lūkestis, jog lietuvių kalba pasirodžiusi monografija bus išversta į lenkų kalbą. Recenzentas pažymi, kad ne su visomis Stravinskienės tyrimo išvadomis galima sutikti. Tačiau apibendrindamas savo įžvalgas jis akcentuoja, kad recenzuojama knyga yra puiki, įdomi ir profesionaliai parengta. Reikšminiai žodžiai: Antrasis pasaulinis karas, 1939-1945 (World War II); Priverstinė repatriacija; Repatriacija; Gyventojų mažumos; Priverstinė migracija; Nacionaliniai santykiai; Rezistencijos ir stalinizmo laikotarpis, 1944-1953; Second World War, 1939-1945; Forced repatriation; Repatriation; Minorities of the population; Forced migration; National relationships; Period of resistance and Stalinism, 1944-195