34 research outputs found

    Contested Public Authority in Marginal Urban Areas: Challenges for Humanitarians

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    In urban contexts where multiple governance actors compete for authority, a clearer approach is needed on whether and how to engage these various actors in order to reach the most vulnerable host and refugee populations

    The rejuvenating power of the Buena Vista Social Club

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    26S proteasome, a major regulatory protease in eukaryotes, consists of a 20S proteolytic core particle (CP) capped by a 19S regulatory particle (RP). The 19S RP is divisible into base and lid sub-complexes. Even within the lid, subunits have been demarcated into two modules: module 1 (Rpn5, Rpn6, Rpn8, Rpn9 and Rpn11), which interacts with both CP and base sub-complexes and module 2 (Rpn3, Rpn7, Rpn12 and Rpn15) that is attached mainly to module 1. We now show that suppression of RPN11 expression halted lid assembly yet enabled the base and 20S CP to pre-assemble and form a base-CP. A key role for Regulatory particle non-ATPase 11 (Rpn11) in bridging lid module 1 and module 2 subunits together is inferred from observing defective proteasomes in rpn11–m1, a mutant expressing a truncated form of Rpn11 and displaying mitochondrial phenotypes. An incomplete lid made up of five module 1 subunits attached to base-CP was identified in proteasomes isolated from this mutant. Re-introducing the C-terminal portion of Rpn11 enabled recruitment of missing module 2 subunits. In vitro, module 1 was reconstituted stepwise, initiated by Rpn11–Rpn8 heterodimerization. Upon recruitment of Rpn6, the module 1 intermediate was competent to lock into base-CP and reconstitute an incomplete 26S proteasome. Thus, base-CP can serve as a platform for gradual incorporation of lid, along a proteasome assembly pathway. Identification of proteasome intermediates and reconstitution of minimal functional units should clarify aspects of the inner workings of this machine and how multiple catalytic processes are synchronized within the 26S proteasome holoenzymes

    Structural Basis for the Inhibitory Effects of Ubistatins in the Ubiquitin-Proteasome Pathway

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    The discovery of ubistatins, small molecules that impair proteasomal degradation of proteins by directly binding to polyubiquitin, makes ubiquitin itself a potential therapeutic target. Although ubistatins have the potential for drug development and clinical applications, the lack of structural details of ubiquitin-ubistatin interactions has impeded their development. Here, we characterized a panel of new ubistatin derivatives using functional and binding assays. The structures of ubiquitin complexes with ubistatin B and hemi-ubistatin revealed direct interactions with ubiquitin's hydrophobic surface patch and the basic/polar residues surrounding it. Ubistatin B binds ubiquitin and diubiquitin tighter than a high-affinity ubiquitin receptor and shows strong preference for K48 linkages over K11 and K63. Furthermore, ubistatin B shields ubiquitin conjugates from disassembly by a range of deubiquitinases and by the 26S proteasome. Finally, ubistatin B penetrates cancer cells and alters the cellular ubiquitin landscape. These findings highlight versatile properties of ubistatins and have implications for their future development and use in targeting ubiquitin-signaling pathways

    Methodology for Fuel Saving Optimization of a Serial Hybrid Electric Vehicle using Gas Turbine as Energy Converter

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    International audienceSignificant research efforts have been invested in the automotive industry on hybrid-electrified powertrains inorder to reduce the passenger cars’ dependence on oil. Powertrains electrification resulted in a wide rangeof hybrid vehicle architectures. Fuel consumption of these powertrains strongly relies on the energyconverter performance, as well as on the energy management strategy deployed on-board. This paperinvestigates the potential of fuel consumption savings of a serial hybrid electric vehicle (SHEV) using a gasturbine (GT) as energy converter instead of the conventional internal combustion engine (ICE). An exergotechnoexplicit analysis is conducted to identify the best GT-system configuration. An intercooledregenerative reheat cycle is prioritized, offering higher efficiency and power density compared to otherinvestigated GT-systems. A SHEV model is developed and powertrain components are sized consideringvehicle performance criteria. Energy consumption simulations are performed on WLTP cycle using dynamicprograming as global optimal energy management strategy. A sensitivity analysis is also carried out in orderto evaluate the effect of the battery size on the fuel consumption. Results show improved fuel consumptionwith GT as auxiliary power unit (APU) compared to ICE. Moreover, GT offers other intrinsic advantages suchas reduced mass, suitable vehicle integration as well as a multi-fuel use capability. Consequently, thestudied GT-APU presents a potential for implementation on SHEVs

    Exergo-technological explicit methodology for gas-turbine system optimization for series hybrid electric vehicles

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    International audienceSignificant research efforts have been invested in the automotive industry on hybrid-electrified powertrains in order to reduce the passenger cars’ dependence on oil. Powertrains electrification resulted in a wide range of hybrid vehicle architectures. Fuel consumption of these powertrains strongly relies on the energy converter performance, as well as on the energy management strategy deployed on-board. This paper investigates the potential of fuel consumption savings of a series hybrid electric vehicle (SHEV) using a gas turbine (GT) as energy converter instead of the conventional internal combustion engine (ICE). An exergo-technological explicit analysis is conducted to identify the best GT-system configuration. An intercooled regenerative reheat cycle is prioritized, offering higher efficiency and power density compared to other investigated GT-systems. A SHEV model is developed and powertrain components are sized considering vehicle performance criteria. Energy consumption simulations are performed on the worldwide-harmonized light vehicles test procedure (WLTP) driving cycle using dynamic programing as global optimal energy management strategy. A sensitivity analysis is also carried out in order to evaluate the impact of the battery size on the fuel consumption, for self-sustaining and plug-in hybrid SHEV configurations. Results show 22% to 25% improved fuel consumption with GT as auxiliary power unit (APU) compared to ICE. Consequently,the studied GT-APU presents a potential for implementation on SHEVs
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