Influence of LRP5 polymorphisms on normal variation in BMD

Genetic studies based on cohorts with rare and extreme bone phenotypes have shown that the LRP5 gene is an important genetic modulator of BMD. Using family-based and case-control approaches, this study examines the role of the LRP5 gene in determining normal population variation of BMD and describes significant association and suggestive linkage between LRP5 gene polymorphisms and BMD in >900 individuals with a broad range of BMD. Introduction: Osteoporosis is a common, highly heritable condition determined by complex interactions of genetic and environmental etiologies. Genetic factors alone can account for 50-80% of the interindividual variation in BMD. Mutations in the LRP5 gene on chromosome 11q12-13 have been associated with rare syndromes characterized by extremely low or high BMD, but little is known about the contribution of this gene to the development of osteoporosis and determination of BMD in a normal population. Materials and Methods: To examine the entire spectrum of low to high BMD, 152 osteoporotic probands, their families (597 individuals), and 160 women with elevated BMD (T score > 2.5) were recruited. BMD at the lumbar spine, femoral neck, and hip were measured in each subject using DXA. Results: PAGE sequencing of the LRP5 gene revealed 10 single nucleotide polymorphisms (SNPs), 8 of which had allele frequencies of >5%, in exons 8, 9, 10, 15, and 18 and in introns 6, 7, and 21. Within families, a strong association was observed between an SNP at nucleotide C171346A in intron 21 and total hip BMD (p < 1 × 10-5 in men only, p = 0.0019 in both men and women). This association was also observed in comparisons of osteoporotic probands and unrelated elevated BMD in women (p = 0.03), along with associations with markers in exons 8 (C135242T, p = 0.007) and 9 (C141759T, p = 0.02). Haplotypes composed of two to three of the SNPs G121513A, C135242T, G138351A, and C141759T were strongly associated with BMD when comparing osteoporotic probands and high BMD cases (p < 0.003). An SNP at nucleotide C165215T in exon 18 was linked to BMD at the lumbar spine, femoral neck, and total hip (parametric LOD scores = 2.8, 2.5, and 2.2 and nonparametric LOD scores = 0.3, 1.1, and 2.2, respectively) but was not genetically associated with BMD variation. Conclusion: These results show that common LRP5 polymorphisms contribute to the determination of BMD in the general population.

In situ reaction furnace for real-time XRD studies

The new furnace at the Materials Characterization by X-ray Diffraction beamline at Elettra has been designed for powder diffraction measurements at high temperature (up to 1373 K at the present state). Around the measurement region the geometry of the radiative heating element assures a negligible temperature gradient along the capillary and can accommodate either powder samples in capillary or small flat samples. A double capillary holder allows flow-through of gas in the inner sample capillary while the outer one serves as the reaction chamber. The furnace is coupled to a translating curved imaging-plate detector, allowing the collection of diffraction patterns up to 2[theta] [asymptotically equal to] 130°.

Cyclic plastic deformation characteristics of subgrade under moving train wheel load

Cyclic plastic deformation of subgrade and other engineered layers is generally not taken into account in the design of railway bridge transition zones, although the plastic deformation is the governing factor of frequent track deterioration. Actual stress behavior of fine grained subgrade/embankment layers under train traffic is, however, difficult to replicate using the conventional laboratory test apparatus and techniques. A new type of torsional simple shear apparatus, known as multi-ring shear apparatus, was therefore developed to evaluate the actual stress state and the corresponding cyclic plastic deformation characteristics of subgrade materials under moving wheel load conditions. Multi-ring shear test results has been validated using a theoretical model test results; the capability of the multi-ring shear apparatus for replicating the cyclic plastic deformation characteristics of subgrade under moving train wheel load conditions is thus established. This paper describes the effects of principal stress rotation (PSR) of the subgrade materials to the cyclic plastic deformation in a railroad and impacts of testing methods in evaluating the influence of principal stress rotation to the track deterioration of rail track.