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

Maximum-likelihood GPS parameter estimation

ABSTRACT: Recently we proposed an acquisition process for a maximum-likelihood GPS receiver that considers the joint processing of all GPS satellite waveforms. The resulting estimator was shown to provide an elegant solution to the near -far problem and to perform better than the suboptimal sliding-correlator estimator. However, the proposed acquisition model included only the code search, which estimates just the time of arrival (TOA) between a GPS satellite and a maximum-likelihood GPS receiver. In this paper we enhance the acquisition process by including the estimation of Doppler along with the estimation of the TOA, which results in a two-dimensional Doppler and code search. A maximum-likelihood GPS receiver would require only one front-end hardware section for processing all GPS signals in view, thus simplifying the entire architecture of a GPS receiver. An assessment based on theoretical performance and simulation results indicates that a maximum-likelihood GPS receiver can achieve an order-of-magnitude performance improvement relative to a sliding-correlator GPS receiver. Simulation data will be validated in the near future using GPS acquisition data from the Novatel ProPack AG-G2ϩDB9-RT2 , and the results of this work will be presented in a future publication

Modélisation de la topographie microgéométrique. Application à la prévision de l’écrasement de surfaces

Nous avons développé une modélisation de la microgéométrie qui consiste à décrire la dimension des aspérités (altitude du sommet et rayon moyen). La variabilité de ces deux paramètres conduit à une approche statistique utilisant des fonctions de distribution pour chacun d’eux. Ces fonctions sont dimensionnées au moyen de quatre paramètres de rugosité et deux paramètres d’ondulation issus de la procédure normalisée utilisant les « motifs ».La modélisation des microgéométries permet de quantifier la fonctionnalité des surfaces et nous proposons, dans ce document, l’analyse mécanique du contact entre surfaces rugueuses. La modélisation développée intègre les trois principaux types de comportement pour les aspérités en contact élastique, élasto-plastique ou totalement plastique

A Solution to the Recursive Generalized Eigenvalue Problem

Dr. Matthew Bromberg is an independent consultant. For the last 6 years Dr. Bromberg has been involved in the research and development of array processing algorithms for reuse enhancement for wireless communication systems and for interference mitigation for both commercial and military applications while he was at Radix Technologies. Dr. Bromberg was a key inventor of the technology that led to the formation and funding of Beam Reach Networks and the formation of Protean Radio Networks. He has authored several papers and patents in this area. Abstract Previously, we have discussed a recursive solution to the vector normal equation utilizing the recursive Cholesky and Modified Gram-Schmidt Orthogonalization (MGSO) algorithms. Previously, we have also discussed a blind adaptive approach for detection and extraction of signals of interest in the presence of noise and interference without relying on preamble or training sequences. The heart of the blind adaptive algorithm is based upon solving the recursive generalized eigenvalue problem, the solution of which is discussed in this paper based on the recursive Cholesky or QR factors and the Householder and QL algorithm with implicit shifts. Even though, the solution to the recursive generalized eigenvalue problem is slightly more efficient than the solution to the direct generalized eigenvalue when all the eigenvalues and eigenvectors are required, the improvement is more noticeable when only one eigenvalue and the corresponding eigenvector are required. Therefore, the solution that is proposed here serves well for recursive generalized eigenvalue problems that require only one eigenvalue and the corresponding eigenvector

Influence de la présence de pollutions abrasives sur le comportement tribologique de contacts lubrifiés

ans cette étude, on se propose d'analyser le comportement tribologique de contact lubrifié en présence de pollutions abrasives. Celles-ci sont des particules de sable dont les dimensions (taille inférieure ou égale à 50 $\mu$m) sont compatibles avec la traversée des filtres à air des moteurs installés sur les chantiers de forage Algériens, provoquant des avaries importantes. Pour cela, nous utilisons un tribomètre pion-disque permettant la réalisation d'essai en immersion dans l'huile (polluée ou non par les particules abrasives). La caractérisation du coefficient de frottement et de l'usure, pour 2 matériaux différents (bronze avec ou sans addition de plomb), a révélé des comportements très différents. Outre le cas classique d'une augmentation de l'usure en présence de pollution (par effet abrasif), nous avons observé, avec le bronze au plomb, certaines situations pour lesquelles l'usure est plus faible en présence d'abrasifs en raison d'incrustations de fines particules à la surface du frotteur en bronz

An experimental model for mixed friction during running-in

Mechanical engineering often uses fluid lubrication to limit friction. Even in the presence of a lubricant, metallic contact between the sliding surfaces may readily occur. In running-in, the oil film thickness can be so thin that contact arises at the summit of asperities, thus, increasing both the friction coefficient and wear. Such regimes are the so-called mixed or boundary lubrication. In these situations, the friction coefficient varies continuously and it is therefore, necessary to calculate the friction coefficient at any given moment.http://www.sciencedirect.com/science/article/B6V5B-45TTS3T-2/1/9cea27f4f6f36a68b715ad2f6c3e7d8