Whole-genome association study of bipolar disorder.

We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the University College London sample collections with successful genotyping for 372,193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P=1.66 x 10(-7)) and tetraspanin-8 (TSPAN8; P=6.11 x 10(-7)). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P=2.04 x 10(-8), TSPAN8; P=7.57 x 10(-7) and EGFR; P=8.36 x 10(-8)). For replication, we genotyped 304 SNPs in family-based NIMH samples (n=409 trios) and University of Edinburgh case-control samples (n=365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case-Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.

Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor.

Identification of the genetic bases for bipolar disorder remains a challenge for the understanding of this disease. Association between 76 candidate genes and bipolar disorder was tested by genotyping 90 single-nucleotide polymorphisms (SNPs) in these genes in 136 parent-proband trios. In this preliminary analysis, SNPs in two genes, brain-derived neurotrophic factor (BDNF) and the alpha subunit of the voltage-dependent calcium channel were associated with bipolar disorder at the P<0.05 level. In view of the large number of hypotheses tested, the two nominally positive associations were then tested in independent populations of bipolar patients and only BDNF remains a potential risk gene. In the replication samples, excess transmission of the valine allele of amino acid 66 of BDNF was observed in the direction of the original result in an additional sample of 334 parent-proband trios (T/U=108/87, P=0.066). Resequencing of 29 kb surrounding the BDNF gene identified 44 additional SNPs. Genotyping eight common SNPs identified three additional markers transmitted to bipolar probands at the P < 0.05 level. Strong LD was observed across this region and all adjacent pairwise haplotypes showed excess transmission to the bipolar proband. Analysis of these haplotypes using TRANSMIT revealed a global P value of 0.03. A single haplotype was identified that is shared by both the original dataset and the replication sample that is uniquely marked by both the rare A allele of the original SNP and a novel allele 11.5 kb 3'. Therefore, this study of 76 candidate genes has identified BDNF as a potential risk allele that will require additional study to confirm.

An efficient model of an equipment loaded panel for active control design studies.

An effective investigation of alternative control strategies for the reduction of vibration levels in satellite structures requires realistic, yet efficient, structural models to simulate the dynamics of the system. These models should include the effects of the sources, receivers, supporting structure, sensors, and actuators. In this paper, a modeling technique which meets these requirements is developed and some active control strategies are briefly investigated. The particular subject of investigation is an equipment-loaded panel and the equations of motion are derived using the Lagrange-Rayleigh-Ritz (LRR) approach. The various pieces of equipment on the panel are mounted on active or passive suspensions, and resonators are used to represent the internal dynamics of the mounted equipment. Control of the panel, which transmits vibrations from sources to receivers, is by means of piezoelectric patches and the excitation consists of dynamic loads acting on the equipment enclosures and/or directly on the panel. The control objective is to minimize the displacement at an arbitrary output location. The LRR model developed is verified against one produced by using the finite-element method. Finally, some initial controller design studies are undertaken to investigate and compare the effectiveness of different control strategies (e.g., minimization at the source, along the vibration path, or at the receiver).

A modeling technique for active control design studies with application to spacecraft microvibrations.

Microvibrations, at frequencies between 1 and 1000 Hz, generated by on board equipment, can propagate throughout a spacecraft structure and affect the performance of sensitive payloads. To investigate strategies to reduce these dynamic disturbances by means of active control systems, realistic yet simple structural models are necessary to represent the dynamics of the electromechanical system. In this paper a modeling technique which meets this requirement is presented, and the resulting mathematical model is used to develop some initial results on active control strategies. Attention is focused on a mass loaded panel subjected to point excitation sources, the objective being to minimize the displacement at an arbitrary output location. Piezoelectric patches acting as sensors and actuators are employed. The equations of motion are derived by using Lagrange's equation with vibration mode shapes as the Ritz functions. The number of sensors/actuators and their location is variable. The set of equations obtained is then transformed into state variables and some initial controller design studies are undertaken. These are based on standard linear systems optimal control theory where the resulting controller is implemented by a state observer. It is demonstrated that the proposed modeling technique is a feasible realistic basis for in-depth controller design/evaluation studies.

Luminal surface fabrication for cardiovascular prostheses.

Methods to produce highly ordered, specific surface morphologies on poly-tetrafluoroethylene (PTFE Teflon) surfaces were developed. These methods included the use of photolithographic techniques for pattern definition and directed argon ion beam sputter etching to produce the desired surface morphology. Use of these techniques resulted in the formation of regular arrays of sharply defined hexagonal pillars with smooth, vertical walls with heights of up to 80 microns. Pillar height-to-width ratios ranged up to 5.2-1. Surface hole depths of up to approximately 80 microns were also obtained. These surface morphologies could have an important application in medicine for improving the patency of cardiovascular prostheses. This would be accomplished by creating a luminal surface in the implant which promotes the development of a healthy neointima lining.