The Experts below are selected from a list of 168 Experts worldwide ranked by ideXlab platform
Pierre Mangin - One of the best experts on this subject based on the ideXlab platform.
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Combined deficiency of RAB32 and RAB38 in the mouse mimics Hermansky-Pudlak syndrome and critically impairs thrombosis
Blood Advances, 2019Co-Authors: Alicia Aguilar, Josiane Weber, Julie Boscher, Monique Freund, Catherine Ziessel, Anita Eckly, Stéphanie Magnenat, Catherine Bourdon, Béatrice Hechler, Pierre ManginAbstract:Contrary to rat platelets, mouse platelets express both RAB32 and RAB38 that play Fully redundant roles for dense granule biogenesis. • Combined RAB32 and RAB38 deficiency mimics severe Hermansky-Pudlak syndrome with albinism and profound defects in hemostasis. The biogenesis of lysosome related organelles is defective in Hermansky-Pudlak syndrome (HPS), a disorder characterized by oculocutaneous albinism and platelet dense granule (DG) defects. The first animal model of HPS was the fawn-hooded rat, harboring a spontaneous mutation inactivating the small guanosine triphosphatase Rab38. This leads to coat color dilution associated with the absence of DGs and lung morphological defects. Another RAB38 mutant, the cht mouse, has normal DGs, which has raised controversy about the role of RAB38 in DG biogenesis. We show here that murine and human, but not rat, platelets also express the closely related RAB32. To elucidate the parts played by RAB32 and RAB38 in the biogenesis of DGs in vivo and their effects on platelet functions, we generated mice inactivated for Rab32, Rab38, and both genes. Single Rab38 inactivation mimicked cht mice, whereas single Rab32 inactivation had no effect in DGs, coat color, or lung morphology. By contrast, Rab32/38 double inactivation mimicked severe HPS, with strong coat and eye pigment dilution, some enlarged lung multilamellar bodies associated with a decrease in the number of DGs. These organelles were morphologically abnormal, decreased in number, and devoid of 5-hydroxytryptamine content. In line with the storage pool defect, platelet activation was affected, resulting in severely impaired thrombus growth and prolongation of the bleeding time. Overall, our study demonstrates the absence of impact of RAB38 or RAB32 single deficiency in platelet biogenesis and function resulting from Full Redundancy, and characterized a new mouse model mimicking HPS devoid of DG content.
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Combined deficiency of RAB32 and RAB38 in the mouse mimics Hermansky-Pudlak syndrome and critically impairs thrombosis.
Blood advances, 2019Co-Authors: Alicia Aguilar, Josiane Weber, Julie Boscher, Monique Freund, Catherine Ziessel, Anita Eckly, Stéphanie Magnenat, Catherine Bourdon, Béatrice Hechler, Pierre ManginAbstract:The biogenesis of lysosome related organelles is defective in Hermansky-Pudlak syndrome (HPS), a disorder characterized by oculocutaneous albinism and platelet dense granule (DG) defects. The first animal model of HPS was the fawn-hooded rat, harboring a spontaneous mutation inactivating the small guanosine triphosphatase Rab38 This leads to coat color dilution associated with the absence of DGs and lung morphological defects. Another RAB38 mutant, the cht mouse, has normal DGs, which has raised controversy about the role of RAB38 in DG biogenesis. We show here that murine and human, but not rat, platelets also express the closely related RAB32. To elucidate the parts played by RAB32 and RAB38 in the biogenesis of DGs in vivo and their effects on platelet functions, we generated mice inactivated for Rab32, Rab38, and both genes. Single Rab38 inactivation mimicked cht mice, whereas single Rab32 inactivation had no effect in DGs, coat color, or lung morphology. By contrast, Rab32/38 double inactivation mimicked severe HPS, with strong coat and eye pigment dilution, some enlarged lung multilamellar bodies associated with a decrease in the number of DGs. These organelles were morphologically abnormal, decreased in number, and devoid of 5-hydroxytryptamine content. In line with the storage pool defect, platelet activation was affected, resulting in severely impaired thrombus growth and prolongation of the bleeding time. Overall, our study demonstrates the absence of impact of RAB38 or RAB32 single deficiency in platelet biogenesis and function resulting from Full Redundancy, and characterized a new mouse model mimicking HPS devoid of DG content.
Cornelia Lex - One of the best experts on this subject based on the ideXlab platform.
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Suspension influences on a steer-by-wire torque vectoring vehicle
Proceedings, 2018Co-Authors: Gerald Reiter, K. Pohlmans, C. Miano, Andreas Hackl, Cornelia LexAbstract:Conventional steering systems with a mechanical connection between steering wheel and road wheels are limited in terms of adapting the steering ratio and the steering torque in dependence of the current operating condition. Steer-by-wire systems enable to decouple the mechanical connection of the steering wheel and the road wheels, thus enabling situation-dependent feedback to the driver’s steering inputs and also the possibility of autonomous steering interventions for automated driving. Because of the high safety requirements for steering systems, steer-by-wire systems require either a fail-safe system with a mechanical fallback solution e.g. actuated with a clutch, or a fail-tolerant system, [1]. These fail-tolerant systems can be achieved for example with Full Redundancy of all safety-critical components, but also by using torque vectoring (TV) as a redundant steering function, [2].
Alicia Aguilar - One of the best experts on this subject based on the ideXlab platform.
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Combined deficiency of RAB32 and RAB38 in the mouse mimics Hermansky-Pudlak syndrome and critically impairs thrombosis
Blood Advances, 2019Co-Authors: Alicia Aguilar, Josiane Weber, Julie Boscher, Monique Freund, Catherine Ziessel, Anita Eckly, Stéphanie Magnenat, Catherine Bourdon, Béatrice Hechler, Pierre ManginAbstract:Contrary to rat platelets, mouse platelets express both RAB32 and RAB38 that play Fully redundant roles for dense granule biogenesis. • Combined RAB32 and RAB38 deficiency mimics severe Hermansky-Pudlak syndrome with albinism and profound defects in hemostasis. The biogenesis of lysosome related organelles is defective in Hermansky-Pudlak syndrome (HPS), a disorder characterized by oculocutaneous albinism and platelet dense granule (DG) defects. The first animal model of HPS was the fawn-hooded rat, harboring a spontaneous mutation inactivating the small guanosine triphosphatase Rab38. This leads to coat color dilution associated with the absence of DGs and lung morphological defects. Another RAB38 mutant, the cht mouse, has normal DGs, which has raised controversy about the role of RAB38 in DG biogenesis. We show here that murine and human, but not rat, platelets also express the closely related RAB32. To elucidate the parts played by RAB32 and RAB38 in the biogenesis of DGs in vivo and their effects on platelet functions, we generated mice inactivated for Rab32, Rab38, and both genes. Single Rab38 inactivation mimicked cht mice, whereas single Rab32 inactivation had no effect in DGs, coat color, or lung morphology. By contrast, Rab32/38 double inactivation mimicked severe HPS, with strong coat and eye pigment dilution, some enlarged lung multilamellar bodies associated with a decrease in the number of DGs. These organelles were morphologically abnormal, decreased in number, and devoid of 5-hydroxytryptamine content. In line with the storage pool defect, platelet activation was affected, resulting in severely impaired thrombus growth and prolongation of the bleeding time. Overall, our study demonstrates the absence of impact of RAB38 or RAB32 single deficiency in platelet biogenesis and function resulting from Full Redundancy, and characterized a new mouse model mimicking HPS devoid of DG content.
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Combined deficiency of RAB32 and RAB38 in the mouse mimics Hermansky-Pudlak syndrome and critically impairs thrombosis.
Blood advances, 2019Co-Authors: Alicia Aguilar, Josiane Weber, Julie Boscher, Monique Freund, Catherine Ziessel, Anita Eckly, Stéphanie Magnenat, Catherine Bourdon, Béatrice Hechler, Pierre ManginAbstract:The biogenesis of lysosome related organelles is defective in Hermansky-Pudlak syndrome (HPS), a disorder characterized by oculocutaneous albinism and platelet dense granule (DG) defects. The first animal model of HPS was the fawn-hooded rat, harboring a spontaneous mutation inactivating the small guanosine triphosphatase Rab38 This leads to coat color dilution associated with the absence of DGs and lung morphological defects. Another RAB38 mutant, the cht mouse, has normal DGs, which has raised controversy about the role of RAB38 in DG biogenesis. We show here that murine and human, but not rat, platelets also express the closely related RAB32. To elucidate the parts played by RAB32 and RAB38 in the biogenesis of DGs in vivo and their effects on platelet functions, we generated mice inactivated for Rab32, Rab38, and both genes. Single Rab38 inactivation mimicked cht mice, whereas single Rab32 inactivation had no effect in DGs, coat color, or lung morphology. By contrast, Rab32/38 double inactivation mimicked severe HPS, with strong coat and eye pigment dilution, some enlarged lung multilamellar bodies associated with a decrease in the number of DGs. These organelles were morphologically abnormal, decreased in number, and devoid of 5-hydroxytryptamine content. In line with the storage pool defect, platelet activation was affected, resulting in severely impaired thrombus growth and prolongation of the bleeding time. Overall, our study demonstrates the absence of impact of RAB38 or RAB32 single deficiency in platelet biogenesis and function resulting from Full Redundancy, and characterized a new mouse model mimicking HPS devoid of DG content.
Kristof Polmans - One of the best experts on this subject based on the ideXlab platform.
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Torque vectoring as redundant steering for automated driving or steer-by-wire
Proceedings, 2014Co-Authors: Kristof PolmansAbstract:There are two visible trends that can be observed in the automotive industry that have a big impact on the steering system. The first is the development towards automated driving. Up to level 2 of the SAE Standard (see figure 1), the required steering functionality can be offered by a standard EPS system. However, from level 3 onwards where the driver can be taken out of the loop, the standard EPS system is not sufficient anymore. In that case, a Full Redundancy of the steering system is required to guarantee Full functionality at all times. The second trend, which is not independent of the first one, is the development towards Steer by Wire (SbW) systems. It has always been clear that SbW would be the next logical step in the development of new steering systems. However, the technical challenges and the costs of such a system are quite high when weighed against the direct customer benefits. The trend towards automated driving however is a new driver for SbW systems. A redundant SbW system is the only solution to be able to develop complete new interior concepts and HMI’s for automated driving vehicles.
T. N. Vijaykumar - One of the best experts on this subject based on the ideXlab platform.
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ISCA - Opportunistic Transient-Fault Detection
32nd International Symposium on Computer Architecture (ISCA'05), 1Co-Authors: Mohamed Gomaa, T. N. VijaykumarAbstract:CMOS scaling increases susceptibility of microprocessors to transient faults. Most current proposals for transient-fault detection use Full Redundancy to achieve perfect coverage while incurring significant performance degradation. However, most commodity systems do not need or provide perfect coverage. A recent paper explores this leniency to reduce the soft-error rate of the issue queue during L2 misses while incurring minimal performance degradation. Whereas the previous paper reduces soft-error rate without using any Redundancy, we target better coverage while incurring similarly-minimal performance degradation by opportunistically using Redundancy. We propose two semi-complementary techniques, called partial explicit Redundancy (PER) and implicit Redundancy through reuse (IRTR), to explore the trade-off between soft-error rate and performance. PER opportunistically exploits low-ILP phases and L2 misses to introduce explicit Redundancy with minimal performance degradation. Because PER covers the entire pipeline and exploits not only L2 misses but all low-ILP phases, PER achieves better coverage than the previous work. To achieve coverage in high-ILP phases as well, we propose implicit Redundancy through reuse (IRTR). Previous work exploits the phenomenon of instruction reuse to avoid redundant execution while falling back on redundant execution when there is no reuse. IRTR takes reuse to the extreme of performance-coverage trade-off and completely avoids explicit Redundancy by exploiting reuseýs implicit Redundancy within the main thread for fault detection with virtually no performance degradation. Using simulations with SPEC2000, we show that PER and IRTR achieve better trade-off between soft-error rate and performance degradation than the previous schemes.
