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1	Dynamiques épigénétiques du macrosatellite D4Z4 par la protéine SMCHD1 dans deux pathologies rares : exploitation du modèle IPSCs / Macrosatellite D4Z4 epigenetic dynamics by the SMCHD1 protein in two unrelated diseases : lesson from IPSCs Dion, Camille 18 May 2018 (has links) La dystrophie Facio-Scapulo-Humérale (FSHD) est caractérisée par un affaiblissement asymétrique des muscles de la face, de la ceinture scapulaire et des bras. Dans 95% des cas (FSHD1), elle est liée à la contraction d’un élément macrosatellite en 4q35, D4Z4. Dans les 5% des cas qui ne présentent pas de contraction de D4Z4 (FSHD2), des mutations dans le gène SMCHD1 sont retrouvées. Des mutations dans ce gène sont aussi associées à un syndrome développemental très rare, le syndrome de Bosma (BAMS). Les individus présentent des anomalies cranio-faciales mais aucun signe musculaire.Nous avons développé une méthode pour l’analyse de la méthylation de D4Z4 associant modification de l’ADN au bisulfite de sodium et séquençage à haut débit. Nous observons une hypométhylation marquée chez les patients FSHD2 et BAMS au niveau de la partie proximale de cet élément. L’étude de la méthylation au cours de la reprogrammation de fibroblastes primaires en cellules souches pluripotentes induites montre que D4Z4 est reméthylé de façon spécifique dans les cellules contrôles et FSHD1 mais est peu modulée dans les cellules FSHD2 et BAMS. Cette méthylation élevée est une caractéristique de la pluripotence et implique SMCHD1. La reméthylation ne dépend pas non plus de la mémoire épigénétique héritée des fibroblastes ni du nombre de répétitions D4Z4. Ces résultats suggèrent un mécanisme de régulation dynamique. L’hypométhylation de D4Z4 n’est pas observée lors de l’invalidation somatique du gène indiquant que SMCHD1 est impliqué dans la mise en place de la méthylation et non sa maintenance.SMCHD1 est donc impliqué dans la mise en place de la méthylation de D4Z4 dans les cellules pluripotentes. / Facio-Scapulo-Humeral Dystrophy is characterized by the involvement of specific facial, scapulo-humeral and anterior foreleg muscles. In 95% of cases (FSHD1) the disease is associated with a reduction of a macrosatellite element, D4Z4, at the 4q35 locus. In the 5% remaining cases (FSHD2), there is no D4Z4 contraction and patients carry mutations in the SMCHD1 gene. Mutations in SMCHD1 are also involved in a very rare developmental syndrome called Bosma Arhinia Microphtalmia syndrome (BAMS) characterized by cranio-facial abnormalities but no muscular dystrophy.To analyze D4Z4 methylation we developed an approach based on the Sodium Bisulfite treatment method followed by high-throughput sequencing. We showed a significant hypomethylation in the proximal region of D4Z4 in FSHD and BAMS patients compared to controls. Our methylation analysis in primary fibroblasts and corresponding human induced pluripotent stem cells showed that D4Z4 is specifically remethylated upon reprogramming in FSHD1 cells but not in SMCHD1-mutated cells. The high methylation level is a feature of pluripotency likely dependent on SMCHD1. Strikingly, hypomethylation is not observed in somatic cells invalidated for SMCHD1 suggesting a key role for this factor in de novo the methylation. D4Z4 methylation pattern does not depend on the epigenetic memory inherited form donor cells and on the number of the D4Z4 copies and it is a tightly regulated process.In conclusion, SMCHD1 plays a role in the D4Z4 methyl mark deposition at the pluripotency state. Epigénétique Fshd Bams Smchd1 Méthylation IPSCs Epigenetic Fshd Bams Smchd1 Methylation IPSCs
2	The effective use of multiple unmanned aerial vehicles in surface search and control Berner, Robert Andrew 12 1900 (has links) Approved for public release; distribution in unlimited. / This study analyzes the effective use of multiple unmanned aerial vehicles (UAVs) for the Navy's Surface Search and Control mission. In the future, the Navy hopes to leverage the capabilities of a family of UAVs to provide increased situational awareness in the maritime environment. This family of UAVs includes a Broad Area Maritime Surveillance (BAMS) UAV and Vertical Take-Off UAVs (VTUAVs). The concepts of operations for how these UAVs work together have yet to be determined. Questions exist about the best number of UAVs, types of UAVs, and tactics that will provide increased capabilities. Through modeling and agent-based simulation, this study explores the validity of future UAV requirements and provides insights into the effectiveness of different UAV combinations. For the scenarios modeled, the best UAV combination is BAMS plus two or three VTUAVs. However, analysis shows that small numbers of VTUAVs can perform as well without BAMS as they do with BAMS. For combinations with multiple UAVs, BAMS proves to be a valuable asset that not only reduces the number of missed classifications, but greatly improves the amount of coverage on all contacts in the maritime environment. BAMS tactics have less effect than the mere presence of BAMS itself. / Lieutenant, United States Navy Drone aircraft Military surveillance Naval tactics Sea control Unmanned Aerial Vehicles UAVs Agent-based modeling MANA Surface Search and Control Surface Surveillance Coordination SSC Broad Area Maritime Surveillance BAMS VTUAV Common Operational Picture
3	A plm implementation for aerospace systems engineering-conceptual rotorcraft design Hart, Peter Bartholomew 08 April 2009 (has links) The thesis will discuss the Systems Engineering phase of an original Conceptual Design Engineering Methodology for Aerospace Engineering-Vehicle Synthesis. This iterative phase is shown to benefit from digitization of Integrated Product&Process Design (IPPD) activities, through the application of Product Lifecycle Management (PLM) technologies. Requirements analysis through the use of Quality Function Deployment (QFD) and 7 MaP tools is explored as an illustration. A "Requirements Data Manager" (RDM) is used to show the ability to reduce the time and cost to design for both new and legacy/derivative designs. Here the COTS tool Teamcenter Systems Engineering (TCSE) is used as the RDM. The utility of the new methodology is explored through consideration of a legacy RFP based vehicle design proposal and associated aerospace engineering. The 2001 American Helicopter Society (AHS) 18th Student Design Competition RFP is considered as a starting point for the Systems Engineering phase. A Conceptual Design Engineering activity was conducted in 2000/2001 by Graduate students (including the author) in Rotorcraft Engineering at the Daniel Guggenheim School of Aerospace Engineering at the Georgia Institute of Technology, Atlanta GA. This resulted in the "Kingfisher" vehicle design, an advanced search and rescue rotorcraft capable of performing the "Perfect Storm" mission, from the movie of the same name. The associated requirements, architectures, and work breakdown structure data sets for the Kingfisher are used to relate the capabilities of the proposed Integrated Digital Environment (IDE). The IDE is discussed as a repository for legacy knowledge capture, management, and design template creation. A primary thesis theme is to promote the automation of the up-front conceptual definition of complex systems, specifically aerospace vehicles, while anticipating downstream preliminary and full spectrum lifecycle design activities. The thesis forms a basis for additional discussions of PLM tool integration across the engineering, manufacturing, MRO and EOL lifecycle phases to support business management processes. Teamcenter systems engineering Teamcenter community Teamcenter unified Teamcenter engineering Teamcenter manufacturing CATIA V5 Rotorcraft design Boeing AHS Joint heavy lift VPLM MBOM EBOM Product change control Product definition Configuration management Product structure architecture Design engineering Aerospace engineering System engineering PLM CIE IDE SE Affordability Cost savings Executive helicopter Joint chiefs of staff Marine CAE CAD CAM CAA MDO RSM DOE Consulting Engineering management Perfect storm Engineering software Requirements data management CATIA V4 NX Engineering communications RFP Digitization Air Force Navy Army BAMS FIPER ACSYNT Sikorsky Bell Georgia Tech Engineering methodology Requirements engineering System engineering Search Rescue IDE Integrated digital environment Kingfisher Search and rescue Helicopter Helicopter engineering QFD Legacy design IPPD Quality engineering Defense systems acquisition Coast Guard Decision support systems Rotors (Helicopters) Design Concurrent engineering

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