Genome-wide association with bone mass and geometry in the Framingham Heart Study

BACKGROUND:Osteoporosis is characterized by low bone mass and compromised bone structure, heritable traits that contribute to fracture risk. There have been no genome-wide association and linkage studies for these traits using high-density genotyping platforms.METHODS:We used the Affymetrix 100K SNP GeneChip marker set in the Framingham Heart Study (FHS) to examine genetic associations with ten primary quantitative traits: bone mineral density (BMD), calcaneal ultrasound, and geometric indices of the hip. To test associations with multivariable-adjusted residual trait values, we used additive generalized estimating equation (GEE) and family-based association tests (FBAT) models within each sex as well as sexes combined. We evaluated 70,987 autosomal SNPs with genotypic call rates [greater than or equal to]80%, HWE p [greater than or equal to] 0.001, and MAF [greater than or equal to]10% in up to 1141 phenotyped individuals (495 men and 646 women, mean age 62.5 yrs). Variance component linkage analysis was performed using 11,200 markers.RESULTS:Heritability estimates for all bone phenotypes were 30-66%. LOD scores [greater than or equal to]3.0 were found on chromosomes 15 (1.5 LOD confidence interval: 51,336,679-58,934,236 bp) and 22 (35,890,398-48,603,847 bp) for femoral shaft section modulus. The ten primary phenotypes had 12 associations with 100K SNPs in GEE models at p < 0.000001 and 2 associations in FBAT models at p < 0.000001. The 25 most significant p-values for GEE and FBAT were all less than 3.5 x 10-6 and 2.5 x 10-5, respectively. Of the 40 top SNPs with the greatest numbers of significantly associated BMD traits (including femoral neck, trochanter, and lumbar spine), one half to two-thirds were in or near genes that have not previously been studied for osteoporosis. Notably, pleiotropic associations between BMD and bone geometric traits were uncommon. Evidence for association (FBAT or GEE p < 0.05) was observed for several SNPs in candidate genes for osteoporosis, such as rs1801133 in MTHFR; rs1884052 and rs3778099 in ESR1; rs4988300 in LRP5; rs2189480 in VDR; rs2075555 in COLIA1; rs10519297 and rs2008691 in CYP19, as well as SNPs in PPARG (rs10510418 and rs2938392) and ANKH (rs2454873 and rs379016). All GEE, FBAT and linkage results are provided as an open-access results resource at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.CONCLUSION:The FHS 100K SNP project offers an unbiased genome-wide strategy to identify new candidate loci and to replicate previously suggested candidate genes for osteoporosis.

Let´s teach geometry

In this work we present an activity for High School students in which various mathematical concepts of plane and spatial geometry are involved. The final objective of the proposed tasks is constructing a particular polyhedron, the cube, by using a modality of origami called modular origami.

Conceptualización de área del rectángulo con la mediación del programa Cabri Geometry

En esta charla se presentará el trabajo realizado durante el año 2010 por el grupo Nuevas Tecnologías de EDUMAT-UIS coordinado por el Dr. Martín Eduardo Acosta Gempeler. El grupo viene realizando un trabajo de capacitación a profesores de varios colegios del área metropolitana de Bucaramanga en cuanto a la implementación de software de geometría dinámica en la enseñanza de diferentes conceptos geométricos en secundaria.

Ethnomathematical research and drama in education techniques: developing a dialogue in a geometry class of 10th grade students

Ethnomathematical research, together with digital technologies (WebQuest) and Drama-in- Education (DiE) techniques, can create a fruitful learning environment in a mathematics classroom—a hybrid/third space—enabling increased student participation and higher levels of cognitive engagement. This article examines how ethnomathematical ideas processed within the experiential environment established by the Drama-in-Education techniques challenged students‘ conceptions of the nature of mathematics, the ways in which students engaged with mathematics learning using mind and body, and the ̳dialogue‘ that was developed between the Discourse situated in a particular practice and the classroom Discourse of mathematics teaching. The analysis focuses on an interdisciplinary project based on an ethnomathematical study of a designing tradition carried out by the researchers themselves, involving a search for informal mathematics and the connections with context and culture; 10th grade students in a public school in Athens were introduced to the mathematics content via an original WebQuest based on this previous ethnomathematical study; Geometry content was further introduced and mediated using the Drama-in-Education (DiE) techniques. Students contributed in an unfolding dialogue between formal and informal knowledge, renegotiating both mathematical concepts and their perception of mathematics as a discipline.

Material properties, geometry and their effect on the fatigue life of two flip-chip models

This paper describes how modeling technology has been used in providing fatigue life time data of two flip-chip models. Full-scale three-dimensional modeling of flip-chips under cyclic thermal loading has been combined with solder joint stand-off height prediction to analyze the stress and strain conditions in the two models. The Coffin-Manson empirical relationship is employed to predict the fatigue life times of the solder interconnects. In order to help designers in selecting the underfill material and the printed circuit board, the Young's modulus and the coefficient of thermal expansion of the underfill, as well as the thickness of the printed circuit boards are treated as variable parameters. Fatigue life times are therefore calculated over a range of these material and geometry parameters. In this paper we will also describe how the use of micro-via technology may affect fatigue life

Low temperature crystal structures of two rhodanine derivatives, 3-amino rhodanine and 3-methyl rhodanine: geometry of the rhodanine ring

Rhodanines (2-thio-4-oxothiazolidines) are synthetic small molecular weight organic molecules with diverse applications in biochemistry, medicinal chemistry, photochemistry, coordination chemistry and industry. The X-ray crystal structure determination of two rhodanine derivatives, namely (I), 3-aminorhodanine [3-amino-2-thio-4-oxothiazolidine], C3H4N2OS2, and (II) 3-methylrhodanine [3-methyl-2-thio-4-oxothiazolidine], C4H5NOS2, have been conducted at 100 K. I crystallizes in the monoclinic space group P2(1)/n with unit cell parameters a = 9.662(2), b = 9.234(2), c = 13.384(2) angstrom, beta = 105.425(3)degrees, V = 1151.1(3) angstrom(3), Z = 8 (2 independent molecules per asymmetric unit), density (calculated) = 1.710 mg/m(3), absorption coefficient = 0.815 mm(-1). II crystallizes in the orthorhombic space group Iba2 with unit cell a = 20.117(4), b = 23.449(5), c = 7.852(2) angstrom, V = 3703.9(12) angstrom(3), Z = 24 (three independent molecules per asymmetric unit), density (calculated) = 1.584 mg/m(3), absorption coefficient 0.755 mm(-1). For I in the final refinement cycle the data/restraints/parameter ratios were 2639/0/161, goodness-of-fit on F-2 = 0.934, final R indices [I > 2sigma(I)] were R1 = 0.0299, wR2 = 0.0545 and R indices (all data) R1 = 0.0399, wR2 = 0.0568. The largest difference peak and hole were 0.402 and -0.259 e angstrom(-3). For II in the final refinement cycle the data/restraints/parameter ratios were 3372/1/221, goodness-of-fit on F(2) = 0.950, final R indices [I > 2sigma(I)] were R1 = 0.0407, wR2 = 0.1048 and R indices (all data) R1 = 0.0450, wR2 = 0.1088. The absolute structure parameter = 0.19(9) and largest difference peak and hole 0.934 and -0.301 e angstrom(-3). Details of the geometry of the five molecules (two for I and three for II) and the crystal structures are fully discussed. Corresponding features of the molecular geometry are highly consistent and firmly establish the geometry of the rhodanine

An Investigation of the Flow Field through a Variable Geometry Turbine Stator with Vane Endwall Clearance

Variable geometry turbines provide an extra degree of flexibility in air management in turbocharged engines. The pivoting stator vanes used to achieve the variable turbine geometry necessitate the inclusion of stator vane endwall clearances. The consequent leakage flow through the endwall clearances impacts the flow in the stator vane passages and an understanding of the impact of the leakage flow on stator loss is required. A numerical model of a typical variable geometry turbine was developed using the commercial CFX-10 computational fluid dynamics software, and validated using laser doppler velocimetry and static pressure measurements from a variable geometry turbine with stator vane endwall clearance. Two different stator vane positions were investigated, each at three different operating conditions representing different vane loadings. The vane endwall leakage was found to have a significant impact on the stator loss and on the uniformity of flow entering the turbine rotor. The leakage flow changed considerably at different vane positions and flow incidence at vane inlet was found to have a significant impact.