Methodology of tolerance synthesis using bond graph

International audienceThis paper presents a methodology of parametric tolerance synthesis with respect to output aleatory uncertainty specifications. It relies on density function propagation through the inverse model. The resulting parameter density function is then used to synthesize a confidence interval suitable for sizing purpose. As an illustration, parametric tolerance synthesis on a DC motor rotating a load is processed

Tolerance synthesis using bond graph inversion and fuzzy logic

International audienceIn the context of mechatronic systems design, this paper addresses a parameter tolerance synthesis with respect to specifications including output epistemic uncertainties. The methodology proposed here concerns uncertainties modelled with fuzzy logic. The procedure relies on output uncertainties propagation through an inverse model. Design parameter tolerance is then synthesized. The results are validated injecting designed parameters in the direct model. The methodology is illustrated on a linear model with specifications including combined uncertainties

Bond Graph Representation of Standard Interconnection Model

International audienceThe study of the robustness of a system's parametric uncertainties is based on state representations which separate the nominal part of the system from the uncertain part. The most used form is the standard interconnection model. Recent works have been formulated so as to find this representation graphically by the bond graph approach. A new procedure is proposed in this paper to determine an uncertain model adapted to the study of robustness and for robust control. The advantage of this procedure is in simplifying the resulting graphical model

Structural analysis by bond graph approach: Duality between causal and bicausal procedure

Postprint version.International audienceThe infinite structure of linear time-invariant systems has been principally used to solve control problems. Nevertheless, this system characterization appears interesting in the design and sizing of mechatronic systems as well. Indeed, based on the bond graph language and inverse modelling, a methodology has already been developed for sizing mechatronic systems according to energy and dynamic criteria. One of the novelties of this methodology is its structural analysis step. This step enables structural properties to be deduced and helps in the formulation of the specifications. The aim of this paper is to add new graphical procedures to the structural analysis step to determine some structural properties (infinite pole orders and relative orders) from the inverse model (bicausal bond graph model). The structural analysis of the inverse model remains interesting since the essential orders are immediately obtained on the bicausal model. A discussion is carried out regarding the duality between the causal and bicausal procedures

Chemical genetics analysis of an aniline mustard anticancer agent reveals complex I of the electron transport chain as a target

Supplementary information is available at the Journal of Biological Chemistry website.The antitumor agent 11β (CAS 865070-37-7), consisting of a DNA-damaging aniline mustard linked to an androgen receptor (AR) ligand, is known to form covalent DNA adducts and to induce apoptosis potently in AR-positive prostate cancer cells in vitro; it also strongly prevents growth of LNCaP xenografts in mice. The present study describes the unexpectedly strong activity of 11β against the AR-negative HeLa cells, both in cell culture and tumor xenografts, and uncovers a new mechanism of action that likely explains this activity. Cellular fractionation experiments indicated that mitochondria are the major intracellular sink for 11β; flow cytometry studies showed that 11β exposure rapidly induced oxidative stress, mitochondria being an important source of reactive oxygen species (ROS). Additionally, 11β inhibited oxygen consumption both in intact HeLa cells and in isolated mitochondria. Specifically, 11β blocked uncoupled oxygen consumption when mitochondria were incubated with complex I substrates, but it had no effect on oxygen consumption driven by substrates acting downstream of complex I in the mitochondrial electron transport chain. Moreover, 11β enhanced ROS generation in isolated mitochondria, suggesting that complex I inhibition is responsible for ROS production. At the cellular level, the presence of antioxidants (N-acetylcysteine or vitamin E) significantly reduced the toxicity of 11β, implicating ROS production as an important contributor to cytotoxicity. Collectively, our findings establish complex I inhibition and ROS generation as a new mechanism of action for 11β, which supplements conventional DNA adduct formation to promote cancer cell death.National Institutes of Health (U.S.) (Grant R01 CA077743)United States. Dept. of Defense (Prostate Cancer Research Program Award DAMD17-98-1-8520

Mantle Flow and Deforming Continents: From India-Asia Convergence to Pacific Subduction

The formation of mountain belts or rift zones is commonly attributed to interactions between plates along their boundaries, but the widely distributed deformation of Asia from Himalaya to the Japan Sea and other back-arc basins is difficult to reconcile with this notion. Through comparison of the tectonic and kinematic records of the last 50 Ma with seismic tomography and anisotropy models, we show that the closure of the former Tethys Ocean and the extensional deformation of East Asia can be best explained if the asthenospheric mantle transporting India northward, forming the Himalaya and the Tibetan Plateau, reaches East Asia where it overrides the westward flowing Pacific mantle and contributes to subduction dynamics, distributing extensional deformation over a 3,000-km wide region. This deep asthenospheric flow partly controls the compressional stresses transmitted through the continent-continent collision, driving crustal thickening below the Himalayas and Tibet and the propagation of strike-slip faults across Asian lithosphere further north and east, as well as with the lithospheric and crustal flow powered by slab retreat east of the collision zone below East and SE Asia. The main shortening direction in the deforming continent between the collision zone and the Pacific subduction zones may in this case be a proxy for the direction of flow in the asthenosphere underneath, which may become a useful tool for studying mantle flow in the distant past. Our model of the India-Asia collision emphasizes the role of asthenospheric flow underneath continents and may offer alternative ways of understanding tectonic processes

Back arc extension and collision : an experimental approach of the tectonics of Asia

International audienceThe deformation of the eastern Asian lithosphere during the first part of the India-Asia collision was dominated by subduction-related extension interacting with far effects of the collision. In order to investigate the role of large-scale extension in collision tectonics, we performed analogue experiments of indentation with a model of lithosphere subjected to extension. We used a three-layer rheological model of continental lithosphere resting upon an asthenosphere of low viscosity and strained along its southern boundary by a rigid indenter progressing northward. The lithosphere model was scaled to be gravitationally unstable and to spread under its ownweight, so that extension occurred in thewhole model. The eastern boundarywas free or weakly confined and always allowed eastward spreading of the model. We studied the pattern of deformation for different boundary conditions. The experimental pattern of deformation includes a thickened zone in front of the indenter, a major northeast-trending left-lateral shear zone starting from the northwest corner of the indenter, antithetic north-south right-lateral shear zones more or less developed to the east of the indenter, and a purely extensional domain in the southeastern part of the model. In this domain, graben opening is driven by gravitational spreading, whereas it is driven by gravitational spreading and indentation in the northeastern part where grabens opened along strike-slip faults. The results are compared with the Oligo- Miocene deformation pattern of Asia consecutive to the collision of India. Our experiments bring a physical basis to models which favour distributed deformation within a slowly extruded wide region extending from the Baikal Rift to the Okhotsk Sea and to southeast Asia and Indonesia. In this large domain, the opening of backarc basins (Japan Sea, Okinawa Trough, South China Sea) and continental grabens (North China grabens) have been associated with approximately north-south-trending right-lateral strike-slip faults, which accommodated the northward penetration of India into Eurasia

Rare coding variants in ten genes confer substantial risk for schizophrenia

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, PPeer reviewe