Nouveau concept de carter de boite de vitesses allégé en aluminium et plastique en utilisant l'optimisation topologique multimatériau

Lightweight materials and innovative designs have always been an important topic in industrial product development. Among others, constraints on energy consumption and CO2 emissions, efforts to improve resource efficiency as well the continuous search for increasing the range of EVs and their dynamic behavior have greatly stressed the importance of this topic over the last years in automotive. A dedicated Interreg project entitled LightVehicle 2025 (LV2025) has been launched in the Euregio Meuse Rhine (EMR) region since 2018 to develop four demonstrators exhibiting the best technologies mastered in the Region in this field. The project partners have selected four demonstrators revisiting typical vehicle components to highlight lightweight technologies. A consortium of industrial partners has been built around each demonstrator to support all steps of the component redesign from preliminary design, virtual prototyping and simulation, pre series prototyping and testing, virtual manufacturing and mass production. The present work focuses on the redesign of an electric vehicle gearbox rear cover. Traditionally produced by aluminum and die casting, the gearbox cover offers a good opportunity to showcase the lightweighting potential in powertrain components. A two materials design (aluminum and plastic) is explored to take advantage of the complementary properties of the several materials. A multi-material topology optimization (TO) is used to exhibit innovative designs. Several TO results, with different combinations of volume fractions of each material, with or without stiffeners, give a valuable insight on how the new part should be redesigned. Several alternative layouts are also proposed. The metallic material is used to act as stiffness skeleton while plastic material offers skin functions as oil containment. The plastic material used in this study belongs in the family of styrene maleic anhydride (SMA) copolymers and is glass fiber filled. In a second step, injection insert molding is chosen to produce the new concepts based on the TO results. Given the fabrication process, a concurrent work between designers and fabrication experts is carried out to adapt the topology optimized layout to cope with the limitations of plastic injection process. Appropriate mechanical interlocks are added to ensure the impeccable connection of the two materials. The injection insert molding is simulated while the filling and warpage behavior is investigated. Subsequently, a final structural analysis on the resulting part is performed as a final assessment stage, taking into consideration the simulation findings such as the real fiber orientations. Finally, the weight reduction achieved with this new concept is well within the -25% as requested by the target of the project. In addition, a LCA analysis is also performed showing that the new multi material design falls well over the expected 25% reduction of the CO2 emissions too.Lightvehicle 202

Inhibition of histone deacetylase 6 (HDAC6) protects against vincristine-induced peripheral neuropathies and inhibits tumor growth

As cancer is becoming more and more a chronic disease, a large proportion of patients is confronted with devastating side effects of certain anti-cancer drugs. The most common neurological complications are painful peripheral neuropathies. Chemotherapeutics that interfere with microtubules, including plant-derived vinca-alkaloids such as vincristine, can cause these chemotherapy-induced peripheral neuropathies (CIPN). Available treatments focus on symptom alleviation and pain reduction rather than prevention of the neuropathy. The aim of this study was to investigate the potential of specific histone deacetylase 6 (HDAC6) inhibitors as a preventive therapy for CIPN using multiple rodent models for vincristine-induced peripheral neuropathies (VIPN). HDAC6 inhibition increased the level of acetylated α-tubulin in tissues of rodents undergoing vincristine-based chemotherapy, which correlates to a reduced severity of the neurological symptoms, both at the electrophysiological and the behavioral level. Mechanistically, disturbances in axonal transport of mitochondria is considered as an important contributing factor in the pathophysiology of VIPN. As vincristine interferes with the polymerization of microtubules, we investigated whether disturbances in axonal transport could contribute to VIPN. We observed that increasing α-tubulin acetylation through HDAC6 inhibition restores vincristine-induced defects of axonal transport in cultured dorsal root ganglion neurons. Finally, we assured that HDAC6-inhibition offers neuroprotection without interfering with the anti-cancer efficacy of vincristine using a mouse model for acute lymphoblastic leukemia. Taken together, our results emphasize the therapeutic potential of HDAC6 inhibitors with beneficial effects both on vincristine-induced neurotoxicity, as well as on tumor proliferation. ispartof: Neurobiology of Disease vol:111 pages:59-69 ispartof: location:United States status: publishe

Conditional deletion of Id2 or Notch1 in oligodendrocyte progenitor cells does not ameliorate disease outcome in SOD1(G93A) mice

Oligodendrocytes are essential for structural and trophic support of motor axons. Their impairment has been implicated in amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder of motor neurons. Oligodendrocyte progenitor cells fail to differentiate into mature oligodendrocytes and thereby jeopardize the health of motor neurons. Here, we report that oligodendrocytic ablation of inhibitor of DNA binding 2 (Id2) or Notch receptor 1 (Notch1), 2 negative master modulators of oligodendrocyte differentiation, fails to alleviate oligodendrocyte dysfunction or alter disease outcome in a murine model of ALS. Our data suggest that these inhibitors are not suitable targets for intervention in ALS.status: publishe

Une approche générique pour capitaliser l'expérience en conception et en optimisation

peer reviewedAs design changes in the production phase can be hundreds of times more costly than in the design phase, it is crucial to make sure that the designed product is actually manufacturable before start of production. To this aim nowadays often many manual iterations are needed between the designers and manufacturing experts, which leads to an inefficient design process and delayed time-to-market that in turn are detrimental for company competitiveness. Here we present the outline of a research effort to realize a substantially more integrated design process tailored towards both performance aspects and manufacturability. Key to this is the formalisation of Design for Manufacturing (DfM) rules within the functional CAD design stage. The traditional design approach is exemplified further in this work for the design of a gearbox housing for electric vehicle transmission systems. To realize substantial weight reduction without compromising performance, a novel multi-material design is proposed, constituting of both aluminum, to ensure structural integrity, and high performance polymer for additional structural integrity and leak-tightness under operating condition. Results shown include Topology Optimization (TO) under realistic loading conditions, scrutinizing material volume fraction boundary conditions and mesh sensitivity. Finally, some DfM rules and considerations in order to come to a manufacturable CAD design, are highlighted.Lightvehicle 202

Concpetion allégée d'une portière de camion en utilisant l'optimisation topologique

To reduce the CO2 emissions and the energy consumption of vehicle, light weight design is the major target for automotive industry in the coming years. A dedicated European Interreg EMR project LightVehicle 2025 (LV2025) has been launched in the cross-border region gathering Belgium, The Netherland and Germany. The project aims at developing four demonstrators revisiting typical vehicle components to highlight lightweight technologies. Each demonstrator has to support all steps of the component redesign from preliminary design to virtual manufacturing and mass production. The present demonstrator investigates the design of a truck door. To reach out the ambitious target of 20% of mass saving and of 20% reduction of CO2 emissions, the project combines Topology Optimization to generate novel structural designs with material substitution, functionality integration and new production processes. The traditional steel sheet body is hereby replaced with short-fiber reinforced PE shell structure designed for the novel robot molding process and supported by a steel beam structure as an insert in the same production process. Various structural optimization strategies are applied from the conceptual design up to the detailed design and validation. In the current contribution, the focus is set on the topology optimization of the preliminary design of the door structure. We present here the results of the topology optimization assignment given as an educational design project to engineering students at University of Liege. At first simplified geometrical models are established to be used in topology optimization, resulting in a nice compromise between a good accuracy of the performance predictions and a modest computer effort in topology optimization loops. The commercial Topology Optimization tool NX-TOPOL is adopted. A quasi 2D model is first used to identify the placement of beam structure supporting the door skin. Three major static load cases are retained, while a specification on natural vibrations is also considered as a restriction. A 3D model is also investigated providing a new insight on the optimized reinforcement concepts. While 2D models lead to classical layouts, 3D models are able to exhibit break-through concepts taking advantage of the new manufacturing capabilities of robot molding and functional integration of the door parts.Lightvehicle 202

A New Series of Uranium Isotope Reference Materials for Investigating the Linearity of Secondary Electron Multipliers in Isotope Mass Spectrometry

A new series of gravimetrically prepared uranium isotope reference materials, the so-called IRMM-074 series, with the n(235U)/n(238U) isotope ratio held constant at unity and the n(233U)/n(238U) isotope ratios varying from 1.0 to 10-6 has been prepared and certified. The methods for the preparation, the mixing and the certification are described. Additionally, recent observations regarding the linearity response of secondary electron multipliers (SEM) and suitable reference materials for investigating detector linearity are reviewed. Two measurement procedures for applying the IRMM-072 and IRMM-073 (diluted from the remaining fraction of IRMM-072) series as well as the new IRMM-074 series for assessing SEM linearity are described. The procedures are tailor-made for the specific instrumental characteristics of Thermal Ionization Mass Spectrometers (TIMS) and Multiple-Collector Inductively Coupled Plasma Mass Spectrometers (MC-ICPMS) but can be adapted also for further types of isotope ratio mass spectrometers.JRC.D.4-Isotope measurement

Inhibition of histone deacetylase 6 (HDAC6) protects against vincristine-induced peripheral neuropathies and inhibits tumor growth

As cancer is becoming more and more a chronic disease, a large proportion of patients is confronted with devastating side effects of certain anti-cancer drugs. The most common neurological complications are painful peripheral neuropathies. Chemotherapeutics that interfere with microtubules, including plant-derived vinca-alkaloids such as vincristine, can cause these chemotherapy-induced peripheral neuropathies (CIPN). Available treatments focus on symptom alleviation and pain reduction rather than prevention of the neuropathy. The aim of this study was to investigate the potential of specific histone deacetylase 6 (HDAC6) inhibitors as a preventive therapy for CIPN using multiple rodent models for vincristine-induced peripheral neuropathies (VIPN). HDAC6 inhibition increased the level of acetylated α-tubulin in tissues of rodents undergoing vincristine-based chemotherapy, which correlates to a reduced severity of the neurological symptoms, both at the electrophysiological and the behavioral level. Mechanistically, disturbances in axonal transport of mitochondria is considered as an important contributing factor in the pathophysiology of VIPN. As vincristine interferes with the polymerization of microtubules, we investigated whether disturbances in axonal transport could contribute to VIPN. We observed that increasing α-tubulin acetylation through HDAC6 inhibition restores vincristine-induced defects of axonal transport in cultured dorsal root ganglion neurons. Finally, we assured that HDAC6-inhibition offers neuroprotection without interfering with the anti-cancer efficacy of vincristine using a mouse model for acute lymphoblastic leukemia. Taken together, our results emphasize the therapeutic potential of HDAC6 inhibitors with beneficial effects both on vincristine-induced neurotoxicity, as well as on tumor proliferation.status: publishe

AAV9-mediated gene delivery of MCT1 to oligodendrocytes does not provide a therapeutic benefit in a mouse model of ALS

Oligodendrocyte dysfunction has been implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by progressive motor neuron loss. The failure of trophic support provided by oligodendrocytes is associated with a concomitant reduction in oligodendroglial monocarboxylate transporter 1 (MCT1) expression and is detrimental for the long-term survival of motor neuron axons. Therefore, we established an adeno-associated virus 9 (AAV9)-based platform by which MCT1 was targeted mostly to white matter oligodendrocytes to investigate whether this approach could provide a therapeutic benefit in the SOD1G93A mouse model of ALS. Despite good oligodendrocyte transduction and AAV-mediated MCT1 transgene expression, the disease outcome of SOD1G93A mice was not altered. Our study further increases our current understanding about the complex nature of oligodendrocyte pathology in ALS and provides valuable insights into the future development of therapeutic strategies to efficiently modulate these cells

Elongator subunit 3 (ELP3) modifies ALS through tRNA modification

Amyotrophic Lateral Sclerosis (ALS) is a fatal degenerative motor neuron disorder of which the progression is influenced by several disease-modifying factors. Here, we investigated ELP3, a subunit of the elongator complex that modifies tRNA wobble uridines, as one of such ALS disease modifiers. ELP3 attenuated the axonopathy of a mutant SOD1, as well as of a mutant C9orf72 ALS zebrafish model. Furthermore, expression of ELP3 in the SOD1G93A mouse extended the survival and attenuated the denervation in this model. Depletion of ELP3 in vitro reduced the modified tRNA wobble uridine mcm5s2U and increased abundance of insoluble mutant SOD1, which was reverted by exogenous ELP3 expression. Interestingly, the expression of ELP3 in the motor cortex of ALS patients was reduced and correlated with mcm5s2U levels. Our results demonstrate that ELP3 is a modifier of ALS and suggest a link between tRNA modification and neurodegeneration.status: publishe