The Enabler: A reevaluation of design concepts and construction of a scaled model

The basic objective of the student's work this quarter was to make an in depth examination of the design concepts used on the lunar vehicle 'The Enabler'. Several changes were made to the vehicle including a redesigned wheel, a more compact boom and a reduced articulation angle. The vehicle's final dimensions were determined through an optimization process by defining mathematical equations for several of the vehicle's defined objectives. These included the ability to scale a one meter object, traverse a one meter crevice, and maintain a wheel-to-wheel clearance of three inches while at maximum articulation. The final dimensions of the vehicle were used to construct an approximate 1/4 scale model of the chassis and wheels. The boom, however, was constructed on a 1/5 scale (from the original design). This was due to the redesign of the boom and the limitations of the constructing material and PVC fittings

SUPERball: Exploring Tensegrities for Planetary Probes

The Dynamic Tensegrity Robotics Lab (DTRL) at NASA Ames Research Center is developing a compliant and distributed tensegrity robotic platform for planetary exploration. Working in collaboration with Ghent University, the DTRL built an untethered prototype robot, the SUPERball. In this work, multiple issues with the current SUPERball design are addressed, when considering an example mission to Titan. Specifically, engineering requirements for the mission are empirically validated, and the current design is extended under these requirements to meet expanded goals.Survival of impact forces under entry, descent, and landing are verified with a physical experiment performed in collaboration with the University of Idaho. Then, concepts for a fully-actuated redesign of SUPERball are generated, compared, and validated against current engineering requirements. This exploratory work moves the SUPERball project toward an eventual flight-ready design.

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

Usage Scenarios for an Automated Model Compiler

Abstract. This paper is meant to motivate tools and methods research in the field of model-based embedded software development. In particular, we include usage scenarios to describe how an automated model assembler called a model compiler could support automotive embedded control systems development. We describe some desired characteristics and features of the envisioned model compiler and place particular emphasis on support for model compatibility checking. Finally, we describe characteristics of model components that are commonly used in practice.

The Carnitine Shuttle Pathway is Altered in Patients With Neovascular Age-Related Macular Degeneration

To identify metabolites and metabolic pathways altered in neovascular age-related macular degeneration (NVAMD). We performed metabolomics analysis using high-resolution C18 liquid chromatography-mass spectrometry on plasma samples from 100 NVAMD patients and 192 controls. Data for mass/charge ratio ranging from 85 to 850 were captured, and metabolic features were extracted using xMSanalyzer. Nested feature selection was used to identify metabolites that discriminated between NVAMD patients and controls. Pathway analysis was performed with Mummichog 2.0. Hierarchical clustering was used to examine the relationship between the discriminating metabolites and NVAMD patients and controls. Of the 10,917 metabolic features analyzed, a set of 159 was identified that distinguished NVAMD patients from controls (area under the curve of 0.83). Of these features, 39 were annotated with confidence and included multiple carnitine metabolites. Pathway analysis revealed that the carnitine shuttle pathway was significantly altered in NVAMD patients (P = 0.0001). Tandem mass spectrometry confirmed the molecular identity of five carnitine shuttle pathway acylcarnitine intermediates that were increased in NVAMD patients. Hierarchical cluster analysis revealed that 51% of the NVAMD patients had similar metabolic profiles, whereas the remaining 49% displayed greater variability in their metabolic profiles. Multiple long-chain acylcarnitines that are part of the carnitine shuttle pathway were significantly increased in NVAMD patients compared to controls, suggesting that fatty acid metabolism may be involved in NVAMD pathophysiology. Cluster analysis suggested that clinically indistinguishable NVAMD patients can be separated into distinct subgroups based on metabolic profiles

A cell cycle-dependent co-repressor mediates photoreceptor cell-specific nuclear receptor function

Photoreceptor cell-specific nuclear receptor (PNR) (NR2E3) acts as a sequence-specific repressor that controls neuronal differentiation in the developing retina. We identified a novel PNR co-repressor, Ret-CoR, that is expressed in the developing retina and brain. Biochemical purification of Ret-CoR identified a multiprotein complex that included E2F/Myb-associated proteins, histone deacetylases (HDACs) and NCoR/HDAC complex-related components. Ret-CoR appeared to function as a platform protein for the complex, and interacted with PNR via two CoRNR motifs. Purified Ret-CoR complex exhibited HDAC activity, co-repressed PNR transrepression function in vitro, and co-repressed PNR function in PNR target gene promoters, presumably in the retinal progenitor cells. Notably, the appearance of Ret-CoR protein was cell-cycle-stage-dependent (from G1 to S). Therefore, Ret-CoR appears to act as a component of an HDAC co-repressor complex that supports PNR repression function in the developing retina, and may represent a co-regulator class that supports transcriptional regulator function via cell-cycle-dependent expression

Pathway Analysis Integrating Genome-Wide and Functional Data Identifies PLCG2 as a Candidate Gene for Age-Related Macular Degeneration

PURPOSE. Age-related macular degeneration (AMD) is the worldwide leading cause of blindness among the elderly. Although genome-wide association studies (GWAS) have identified AMD risk variants, their roles in disease etiology are not well-characterized, and they only explain a portion of AMD heritability. METHODS. We performed pathway analyses using summary statistics from the International AMD Genomics Consortium's 2016 GWAS and multiple pathway databases to identify biological pathways wherein genetic association signals for AMD may be aggregating. We determined which genes contributed most to significant pathway signals across the databases. We characterized these genes by constructing protein-protein interaction networks and performing motif analysis. RESULTS. We determined that eight genes (C2, C3, LIPC, MICA, NOTCH4, PLCG2, PPARA, and RAD51B) drive'' the statistical signals observed across pathways curated in the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Gene Ontology (GO) databases. We further refined our definition of statistical driver gene to identify PLCG2 as a candidate gene for AMD due to its significant gene-level signals (P < 0.0001) across KEGG, Reactome, GO, and NetPath pathways. CONCLUSIONS. We performed pathway analyses on the largest available collection of advanced AMD cases and controls in the world. Eight genes strongly contributed to significant pathways from the three larger databases, and one gene (PLCG2) was central to significant pathways from all four databases. This is, to our knowledge, the first study to identify PLCG2 as a candidate gene for AMD based solely on genetic burden. Our findings reinforce the utility of integrating in silico genetic and biological pathway data to investigate the genetic architecture of AMD