Sclerosing bone disorders: a lot of knowns but still some unknowns

Abstract: In the last decade, many advances have been made in understanding how osteoclasts and osteoblasts work and communicate by elucidation of the molecular genetic causes of many rare bone dysplasias. The relationship between the clinical findings and the molecular defects underlying these aberrant bone phenotypes has given new insights into the molecular machinery of the different bone cell types, and into how they act and interact to regulate bone mass. The study of sclerosing bone dysplasias caused by a disturbance of the balance between bone formation and bone resorption has had an especially high impact. Furthermore, it has also become clear that genetic variation within several of the identified genes contributes to the risk to develop osteoporosis and that in some cases the metabolic pathways involved provide interesting targets for the development of novel treatments for osteoporosis. In this review, some of the sclerosing bone diseases are discussed, focusing on the underlying mechanisms and the broader implications of the insights gained

Analysis of deep submicron VLSI technological risks: A new qualification process for professional electronics

International audienceA large range of commercial deep submicron VLSI devices are used for avionic designs. Due to the scaling down, an ever higher level of integration and the use of new materials in foundries, the main failure mechanisms are changing while new ones appear. Lifetimes related to these failure mechanisms are suspected of being shorter and shorter so failure rate prediction becomes a great challenge for deep submicron (DSM) semiconductor reliability. We propose in this paper, a new approach based on technologies analysis in order to determine potential reliability risks regarding the specific use of DSM components for avionic applications

3D current path in stacked devices : metrics and challenges

Although magnetic current imaging (MCI) is useful in fault isolation of devices with 2D current distributions, MCI alone cannot give the exact information of current paths in complex 3D stacked devices. Previous work has demonstrated the ability of a simulation approach to find a short circuit in 3D geometry. This approach has been challenged in the case of dense and complex 3D current paths. In this paper, the aim is to demonstrate how we can overcome this issue by using a new simulation approach instead of the previous segment by segment approach. The new approach has been validated on a complex chip with daisy chains vertically connected by vias. From the study of the simulation of three hypothesized current paths of various current lines of interest, excluding and including the interactions with neighbouring current lines (both locally and globally), it was found that interactions of a current line with its global neighbours have very important effects, compared to no interactions or only interactions with local neighbours. By simulating all the currents, it was possible to minimize the error given by the presence of several current lines in a small volume.Accepted versio

Magnetic field spatial fourier analysis : a new opportunity for high resolution current localization

Magnetic microscopy has proven its usefulness throughout the years. It allows current localization with a certain degree of precision by using an inversion algorithm to invert the Biot–Savart law. The goal is to obtain the current distribution once the magnetic field is given. However, in order to obtain a stable solution, the magnetic data is severely low-pass filtered in the spatial Fourier domain, and some important information is lost. In this paper, the contribution given by the different spatial frequencies was studied: it was demonstrated how this information can be used to obtain additional information regarding the position of the currents. A comparative study between the theoretical approach and the application to the measurements is also shown.Accepted versio

Two novel WTX mutations underscore the unpredictability of male survival in osteopathia striata with cranial sclerosis

Osteopathia striata with cranial sclerosis (OMIM ##300373) is an X-linked dominant sclerosing bone dysplasia that presents in females with macrocephaly, cleft palate, mild learning disabilities, sclerosis of the long bones and skull, and longitudinal striations visible on radiographs of the long bones, pelvis, and scapulae. In males this entity is usually associated with foetal or neonatal lethality, because of severe heart defects and/or gastrointestinal malformations, and is often accompanied by bilateral fibula aplasia. Recently, the disease-causing gene was identified as the WTX gene (FAM123B). Initially it was suggested that the mutations in the 5' region of the WTX gene are associated with male lethality. Mutation analysis in individuals of two families diagnosed with OSCS revealed two novel WTX mutations. In one family, the affected male is still alive in his teens. These mutations underline the unpredictability of male survival and suggest that WTX mutations should be considered in cases of male cranial sclerosis, even if striations are not present. An overview of all known mutations and their associated characteristics provide a valuable resource for the molecular analysis of OSC