200 research outputs found
Simulation of the deflected cutting tool trajectory in complex surface milling
Since industry is rapidly developing, either locally
or globally, manufacturers witness harder challenges due to
the growing competitivity. This urges them to better consider the four factors linked to production and output: quality, quantity, cost and price, quality being of course the most important factor which constitutes their main concern. Efforts will be concentratedâin this researchâon improving the quality and securing more accuracy for a machined surface in ball-end milling. Quality and precision are two essential criteria in industrial milling. However, milling errors and imperfections, duemainly to the cutting tool deflection, hinder the full achieving of these targets. Our task, all along this paper, consists in studying and realizing the simulation of the deflected cutting tool trajectory, by using the methods which are available. In a future stage, and in the frame of a deeper
research, the simulation process will help to carry out the
correction and the compensation of the errors resulting from
the tool deflection. The corrected trajectory which is obtained by the method mirror will be sent to the machine. To achieve this goal, the next process consistsâas a first stepâin selecting a model of cutting forces for a ball-end mill. This allows to defineâlater onâthe behavior of this tool, and the emergence of three methods namely the analytical model, the finite elements method, and the experimental method. It is possible to tackle the cutting forces simulation, all along the tool trajectory, while this latter is carrying out the sweeping of the part to be machined in milling and taking into consideration the cutting conditions, as well as the geography of the workpiece. A simulation of the deflected cutting tool trajectory dependent on the cutting forces has been realized
Real time noise and wavelength correlations in octave-spanning supercontinuum generation
We use dispersive Fourier transformation to measure shot-to-shot spectral
instabilities in femtosecond supercontinuum generation. We study both the onset
phase of supercontinuum generation with distinct dispersive wave generation, as
well as a highly-unstable supercontinuum regime spanning an octave in
bandwidth. Wavelength correlation maps allow interactions between separated
spectral components to be identified, even when such interactions are not
apparent in shot-to-shot or average measurements. Experimental results are
interpreted using numerical simulations. Our results show the clear advantages
of dispersive Fourier transformation for studying spectral noise during
supercontinuum generation.Comment: 14 pages, 5 figure
Inverse EEG source problems and approximation
International audienceWe consider the inverse EEG (ElectroEncephaloGraphy) problem that consists in recovering, from measurements on electrodes of the electric potential on the scalp, a distribution of pointwise dipolar current sources located in the brain and modeling e.g. the presence of epileptic foci
Simulation de l'effet des surcharges sur le comportement mécanique des P.T.H à couples de matériaux différents
International audienceThe reliability of total hip arthroplasties (THA) is not any more to show. It is allowed by all. Indeed, the retreat of such interventions exceeds now fifteen years and the hopes which the first clinicians formulated are now realities. Nevertheless, the deformation and the wear of cup components remain an inevitable mechanism and loosening appear in long-term. Prevention of loosening passes by the reduction of this wear. This study deals with a simulation of the effect of overloads on THA with different materials. Three materials are analyzed in order to choose the couple which has better bio functionality.La fiabilité des arthroplasties totales de hanche n'est plus à démontrer. Elle est admise par tous. En effet, le recul de telles interventions dépasse maintenant quinze ans et les espérances que les premiers cliniciens ont formulées à leur égard sont maintenant des réalités. Néanmoins, la déformation et l'usure des composants acétabulaires restent un mécanisme inévitable et des descellements asceptiques apparaissent à long terme. La prévention du descellement passe donc par la réduction de cette usure. Cette étude porte sur une simulation de l'effet de certains paramÚtres mécaniques, entre autres « les surcharges » sur le comportement des PTH hybrides à couples de matériaux différents. Trois couples de matériaux sont analysés, en vue de choisir celui qui offre une meilleure biofonctionnalité
Biallelic variants in OGDH encoding oxoglutarate dehydrogenase lead to a neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities
PURPOSE: This study aimed to establish the genetic cause of a novel autosomal recessive neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities. METHODS: We performed a detailed clinical characterization of 4 unrelated individuals from consanguineous families with a neurodevelopmental disorder. We used exome sequencing or targeted-exome sequencing, cosegregation, in silico protein modeling, and functional analyses of variants in HEK293 cells and Drosophila melanogaster, as well as in proband-derived fibroblast cells. RESULTS: In the 4 individuals, we identified 3 novel homozygous variants in oxoglutarate dehydrogenase (OGDH) (NM_002541.3), which encodes a subunit of the tricarboxylic acid cycle enzyme α-ketoglutarate dehydrogenase. In silico homology modeling predicts that c.566C>T:p.(Pro189Leu) and c.890C>A:p.(Ser297Tyr) variants interfere with the structure and function of OGDH. Fibroblasts from individual 1 showed that the p.(Ser297Tyr) variant led to a higher degradation rate of the OGDH protein. OGDH protein with p.(Pro189Leu) or p.(Ser297Tyr) variants in HEK293 cells showed significantly lower levels than the wild-type protein. Furthermore, we showed that expression of Drosophila Ogdh (dOgdh) carrying variants homologous to p.(Pro189Leu) or p.(Ser297Tyr), failed to rescue developmental lethality caused by loss of dOgdh. SpliceAI, a variant splice predictor, predicted that the c.935G>A:p.(Arg312Lys)/p.(Phe264_Arg312del) variant impacts splicing, which was confirmed through a mini-gene assay in HEK293 cells. CONCLUSION: We established that biallelic variants in OGDH cause a neurodevelopmental disorder with metabolic and movement abnormalities
The global distribution and diversity of protein vaccine candidate antigens in the highly virulent Streptococcus pnuemoniae serotype 1
Serotype 1 is one of the most common causes of pneumococcal disease worldwide. Pneumococcal protein vaccines are currently being developed as an alternate intervention strategy to pneumococcal conjugate vaccines. Pre-requisites for an efficacious pneumococcal protein vaccine are universal presence and minimal variation of the target antigen in the pneumococcal population, and the capability to induce a robust human immune response. We used in silico analysis to assess the prevalence of seven protein vaccine candidates (CbpA, PcpA, PhtD, PspA, SP0148, SP1912, SP2108) among 445 serotype 1 pneumococci from 26 different countries, across four continents. CbpA (76%), PspA (68%), PhtD (28%), PcpA (11%) were not universally encoded in the study population, and would not provide full coverage against serotype 1. PcpA was widely present in the European (82%), but not in the African (2%) population. A multi-valent vaccine incorporating CbpA, PcpA, PhtD and PspA was predicted to provide coverage against 86% of the global population. SP0148, SP1912 and SP2108 were universally encoded and we further assessed their predicted amino acid, antigenic and structural variation. Multiple allelic variants of these proteins were identified, different allelic variants dominated in different continents; the observed variation was predicted to impact the antigenicity and structure of two SP0148 variants, one SP1912 variant and four SP2108 variants, however these variants were each only present in a small fraction of the global population (<2%). The vast majority of the observed variation was predicted to have no impact on the efficaciousness of a protein vaccine incorporating a single variant of SP0148, SP1912 and/or SP2108 from S. pneumoniae TIGR4. Our findings emphasise the importance of taking geographic differences into account when designing global vaccine interventions and support the continued development of SP0148, SP1912 and SP2108 as protein vaccine candidates against this important pneumococcal serotype
Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders.
Genetic variants in chromatin regulators are frequently found in neurodevelopmental disorders, but their effect in disease etiology is rarely determined. Here, we uncover and functionally define pathogenic variants in the chromatin modifier EZH1 as the cause of dominant and recessive neurodevelopmental disorders in 19 individuals. EZH1 encodes one of the two alternative histone H3 lysine 27 methyltransferases of the PRC2 complex. Unlike the other PRC2 subunits, which are involved in cancers and developmental syndromes, the implication of EZH1 in human development and disease is largely unknown. Using cellular and biochemical studies, we demonstrate that recessive variants impair EZH1 expression causing loss of function effects, while dominant variants are missense mutations that affect evolutionarily conserved aminoacids, likely impacting EZH1 structure or function. Accordingly, we found increased methyltransferase activity leading to gain of function of two EZH1 missense variants. Furthermore, we show that EZH1 is necessary and sufficient for differentiation of neural progenitor cells in the developing chick embryo neural tube. Finally, using human pluripotent stem cell-derived neural cultures and forebrain organoids, we demonstrate that EZH1 variants perturb cortical neuron differentiation. Overall, our work reveals a critical role of EZH1 in neurogenesis regulation and provides molecular diagnosis for previously undefined neurodevelopmental disorders
Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders
Genetic variants in chromatin regulators are frequently found in neurodevelopmental disorders, but their effect in disease etiology is rarely determined. Here, we uncover and functionally define pathogenic variants in the chromatin modifier EZH1 as the cause of dominant and recessive neurodevelopmental disorders in 19 individuals. EZH1 encodes one of the two alternative histone H3 lysine 27 methyltransferases of the PRC2 complex. Unlike the other PRC2 subunits, which are involved in cancers and developmental syndromes, the implication of EZH1 in human development and disease is largely unknown. Using cellular and biochemical studies, we demonstrate that recessive variants impair EZH1 expression causing loss of function effects, while dominant variants are missense mutations that affect evolutionarily conserved aminoacids, likely impacting EZH1 structure or function. Accordingly, we found increased methyltransferase activity leading to gain of function of two EZH1 missense variants. Furthermore, we show that EZH1 is necessary and sufficient for differentiation of neural progenitor cells in the developing chick embryo neural tube. Finally, using human pluripotent stem cell-derived neural cultures and forebrain organoids, we demonstrate that EZH1 variants perturb cortical neuron differentiation. Overall, our work reveals a critical role of EZH1 in neurogenesis regulation and provides molecular diagnosis for previously undefined neurodevelopmental disorders
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