High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene.

Chromosome 17q11-q21 is a region of the genome likely to harbor susceptibility to autism (MIM(209850)) based on earlier evidence of linkage to the disorder. This linkage is specific to multiplex pedigrees containing only male probands (MO) within the Autism Genetic Resource Exchange (AGRE). Earlier, Stone et al.(1) completed a high-density single nucleotide polymorphism association study of 13.7 Mb within this interval, but common variant association was not sufficient to account for the linkage signal. Here, we extend this single nucleotide polymorphism-based association study to complete the coverage of the two-LOD support interval around the chromosome 17q linkage peak by testing the majority of common alleles in 284 MO trios. Markers within an interval containing the gene, CACNA1G, were found to be associated with Autism Spectrum Disorder at a locally significant level (P=1.9 × 10(-5)). While establishing CACNA1G as a novel candidate gene for autism, these alleles do not contribute a sufficient genetic effect to explain the observed linkage, indicating that there is substantial genetic heterogeneity despite the clear linkage signal. The region thus likely harbors a combination of multiple common and rare alleles contributing to the genetic risk. These data, along with earlier studies of chromosomes 5 and 7q3, suggest few if any major common risk alleles account for Autism Spectrum Disorder risk under major linkage peaks in the AGRE sample. This provides important evidence for strategies to identify Autism Spectrum Disorder genes, suggesting that they should focus on identifying rare variants and common variants of small effect

Midwinter suppression of baroclinic storm activity on Mars: observations and models

Baroclinic instability and intense traveling wave activity on Mars is well known to occur in “storm zones” (Hollingsworth et al. 1996) close to the edge of the advancing or retreating polar ice cap. Such activity usually sets in during Martian fall and continues until the onset of the summer season when large-scale instability mostly ceases as the atmosphere is no longer baroclinically unstable. The stormy season is typically characterized by large-scale, zonally-propagating waves with zonal wavenumbers m = 1-3, the lower wavenumber modes typically penetrating to considerable altitude though may also be surface-intensified. As we show below, however, some observations suggest that this eddy activity does not persist uniformly throughout the autumn, winter and spring seasons, but appears to die down quite consistently within 10 sols or so either side of the winter solstice. This midwinter ‘solsticial pause’ appears to be a sufficiently consistent feature of each winter season in both hemispheres to be regarded as a significant feature of Martian climatology, and could affect a variety of aspects of Martian meteorology including global heat and momentum transport, occurrence of dust storms etc. A somewhat similar phenomenon has also been documented for the Earth (e.g. Nakamura 1992; Penny et al. 2010), especially in relation to seasonal variations in the north Pacific storm tracks. The cause of this phenomenon is still not well established, though suggested mechanisms include the effects of enhanced barotropic shear (the so-called ‘barotropic governor’ (James & Gray 1986) and interactions with topography over central Asia. In this presentation we examine evidence for this phenomenon in the assimilated record of Martian climate from the Thermal Emission Spectrometer on board the Mars Global Surveyor mission (MGSTES), in conjunction with the UK version of the LMD-Oxford-OU-IAA Mars GCM (Forget et al. 1999; Montabone et al. 2006; Lewis et al. 2007). This is further corroborated in other evidence from seasonal variations in the incidence of local and regional dust storms that owe their origin to circumpolar baroclinic storms. We also discuss the extent to which this ‘solsticial pause’ phenomenon is reproduced in stand-alone atmospheric models and present results of some simulations to test a number of hypotheses for its dynamical origin on Mars

High power coupled CO2 waveguide laser array

A hollow-bore ridge waveguide technique for phase locking arrays of coupled CO2 rf excited waveguide lasers was demonstrated. Stable phase-locked operation of two- and three-channel arrays has been demonstrated at the 50 W output level. Preliminary experiments with a five-element array generated an output power of 95 W but phase-locked operation was not conclusively demonstrated

Stretching an heteropolymer

We study the influence of some quenched disorder in the sequence of monomers on the entropic elasticity of long polymeric chains. Starting from the Kratky-Porod model, we show numerically that some randomness in the favoured angles between successive segments induces a change in the elongation versus force characteristics, and this change can be well described by a simple renormalisation of the elastic constant. The effective coupling constant is computed by an analytic study of the low force regime.Comment: Latex, 7 pages, 3 postscript figur

A variational principle for stationary, axisymmetric solutions of Einstein's equations

Stationary, axisymmetric, vacuum, solutions of Einstein's equations are obtained as critical points of the total mass among all axisymmetric and $(t,\phi)$ symmetric initial data with fixed angular momentum. In this variational principle the mass is written as a positive definite integral over a spacelike hypersurface. It is also proved that if absolute minimum exists then it is equal to the absolute minimum of the mass among all maximal, axisymmetric, vacuum, initial data with fixed angular momentum. Arguments are given to support the conjecture that this minimum exists and is the extreme Kerr initial data.Comment: 21 page

Traumatic brain injury: future assessment tools and treatment prospects

Traumatic brain injury (TBI) is widespread and leads to death and disability in millions of individuals around the world each year. Overall incidence and prevalence of TBI are likely to increase in absolute terms in the future. Tackling the problem of treating TBI successfully will require improvements in the understanding of normal cerebral anatomy, physiology, and function throughout the lifespan, as well as the pathological and recuperative responses that result from trauma. New treatment approaches and combinations will need to be targeted to the heterogeneous needs of TBI populations. This article explores and evaluates the research evidence in areas that will likely lead to a reduction in TBI-related morbidity and improved outcomes. These include emerging assessment instruments and techniques in areas of structural/chemical and functional neuroimaging and neuropsychology, advances in the realms of cell-based therapies and genetics, promising cognitive rehabilitation techniques including cognitive remediation and the use of electronic technologies including assistive devices and virtual reality, and the emerging field of complementary and alternative medicine

Sports and Real Estate Development As Tools for Changing Patterns of Regional Economic Activity: Managing the Effects of Teams and Venues on Local Communities.

While the ways in which fans interact and consume sports has evolved in response to new and broadcast media, the most profound change for cities from sports is its linkage to real estate development. This emerging dimension to the ability of sports to redistribute regional economic activity creates critical public policy, business, and urban planning outcomes and potential. This dissertation identifies the ways in which the sports business has changed and illustrates the ways in which these effects can be channeled to benefit cities. For desired outcomes to occur, however, management and administrative systems have to be created that permit cities to realize the possible advantages. It is also possible that the ways in which sports projects are explained and presented to voters also needs to be changed. These understandings are vital because the positive outcomes for cities from sports and real estate development cannot occur without new decision-making presentations and management systems. This dissertation contributes to a greater understanding of these new requirements and the relationship between sports and real estate development (and its effects on cities) through three separate studies centered on the issues of decision-making, urban planning, and economic and neighborhood development. The research is fashioned to examine processes, designs, and approaches that increase the probability of gains for both teams and the public sector in their development partnerships. The research efforts are interconnected in that they contribute to and expand upon an innovative, developing thread of scholarship in the spatial effects of sports for local economies. Each study covers an important segment of the sports and urban development process that frames this new approach to sport management. The studies focus on (a) voter preferences and reactions to public subsidies for sports facility construction, (b) planned and unforeseen outcomes of a master planned neighborhood anchored by a new ballpark, and (c) the formation of the needed organizational structures to ensure outcomes from a linkage of sports to real estate development can be facilitated to produce desired local effects.PhDKinesiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/108767/1/michcant_1.pd

Study of heterogeneous nucleation of eutectic Si in high-purity Al-Si alloys with Sr addition

The official published version can be accessed from the link below - Copyright @ 2010 The Minerals, Metals & Materials Society and ASM InternationalAl-5 wt pct Si master-alloys with controlled Sr and/or P addition/s were produced using super purity Al 99.99 wt pct and Si 99.999 wt pct materials in an arc melter. The master-alloy was melt-spun resulting in the production of thin ribbons. The Al matrix of the ribbons contained entrained Al-Si eutectic droplets that were subsequently investigated. Differential scanning calorimetry, thermodynamic calculations, and transmission electron microscopy techniques were employed to examine the effect of the Sr and P additions on eutectic undercoolings and nucleation phenomenon. Results indicate that, unlike P, Sr does not promote nucleation. Increasing Sr additions depressed the eutectic nucleation temperature. This may be a result of the formation of a Sr phase that could consume or detrimentally affect potent AlP nucleation sites.This work is financially supported by the Higher Education Commission of Pakistan and managerially supported from the OAD

Evaluation of positive G sub Z tolerance following simulated weightlessness (bedrest)

The magnitude of physiologic changes which are known to occur in human subjects exposed to varying levels of + G sub Z acceleration following bed rest simulation of weightlessness was studied. Bed rest effects were documented by fluid and electrolyte balance studies, maximal exercise capability, 70 deg passive tilt and lower body negative pressure tests and the ability to endure randomly prescribed acceleration profiles of +2G sub Z, +3G sub Z, and +4G sub Z. Six healthy male volunteers were studied during two weeks of bed rest after adequate control observations, followed by two weeks of recovery, followed by a second two-week period of bed rest at which time an Air Force cutaway anti-G suit was used to determine its effectiveness as a countermeasure for observed cardiovascular changes during acceleration. Results showed uniform and significant changes in all measured parameters as a consequence of bed rest including a reduced ability to tolerate +G sub Z acceleration. The use of anti-G suits significantly improved subject tolerance to all G exposures and returned measured parameters such as heart rate and blood pressure towards or to pre-bed-rest (control) values in four of the six cases

Osmotic pressure induced coupling between cooperativity and stability of a helix-coil transition

Most helix-coil transition theories can be characterized by a set of three parameters: energetic, describing the (free) energy cost of forming a helical state in one repeating unit; entropic, accounting for the decrease of entropy due to the helical state formation; and geometric, indicating how many repeating units are affected by the formation of one helical state. Depending on their effect on the helix-coil transition, solvents or co-solutes can be classified with respect to their action on these parameters. Solvent interactions that alter the entropic cost of helix formation by their osmotic action can affect both the stability (transition temperature) and the cooperativity (transition interval) of the helix-coil transition. A consistent inclusion of osmotic pressure effects in a description of helix-coil transition for poly(L-glutamic acid) in solution with polyethylene glycol can offer an explanation of the experimentally observed linear dependence of transition temperature on osmotic pressure as well as the concurrent changes in the cooperativity of the transition.Comment: 5 pages, 3 figures. To be submitted to Phys.Rev.Let