Joint analysis of SNP and gene expression data in genetic association studies of complex diseases

Genetic association studies have been a popular approach for assessing the association between common Single Nucleotide Polymorphisms (SNPs) and complex diseases. However, other genomic data involved in the mechanism from SNPs to disease, for example, gene expressions, are usually neglected in these association studies. In this paper, we propose to exploit gene expression information to more powerfully test the association between SNPs and diseases by jointly modeling the relations among SNPs, gene expressions and diseases. We propose a variance component test for the total effect of SNPs and a gene expression on disease risk. We cast the test within the causal mediation analysis framework with the gene expression as a potential mediator. For eQTL SNPs, the use of gene expression information can enhance power to test for the total effect of a SNP-set, which is the combined direct and indirect effects of the SNPs mediated through the gene expression, on disease risk. We show that the test statistic under the null hypothesis follows a mixture of $\chi^2$ distributions, which can be evaluated analytically or empirically using the resampling-based perturbation method. We construct tests for each of three disease models that are determined by SNPs only, SNPs and gene expression, or include also their interactions. As the true disease model is unknown in practice, we further propose an omnibus test to accommodate different underlying disease models. We evaluate the finite sample performance of the proposed methods using simulation studies, and show that our proposed test performs well and the omnibus test can almost reach the optimal power where the disease model is known and correctly specified. We apply our method to reanalyze the overall effect of the SNP-set and expression of the ORMDL3 gene on the risk of asthma.Comment: Published in at http://dx.doi.org/10.1214/13-AOAS690 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Generation of spiral bevel gears with zero kinematical errors and computer aided tooth contact analysis

Kinematic errors in spiral bevel gears are a major source of noise and vibrations in transmissions. A method for the generation of Gleason's spiral bevel gears which provides conjugated gear tooth surfaces and an improved bearing contact was developed. A computer program for the simulation of meshing, misalignment, and bearing contact was written

Man-in-the-control-loop simulation of manipulators

A method to achieve man-in-the-control-loop simulation is presented. Emerging real-time dynamics simulation suggests a potential for creating an interactive design workstation with a human operator in the control loop. The recursive formulation for multibody dynamics simulation is studied to determine requirements for man-in-the-control-loop simulation. High speed computer graphics techniques provides realistic visual cues for the simulator. Backhoe and robot arm simulations are implemented to demonstrate the capability of man-in-the-control-loop simulation

Anatomy of Zero-norm States in String Theory

We calculate and identify the counterparts of zero-norm states in the old covariant first quantised (OCFQ) spectrum of open bosonic string in two other quantization schemes of string theory, namely the light-cone DDF zero-norm states and the off-shell BRST zero-norm states (with ghost) in the Witten string field theory (WSFT). In particular, special attention is paid to the inter-particle zero-norm states in all quantization schemes. For the case of the off-shell BRST zero-norm states, we impose the no ghost conditions and recover exactly two types of on-shell zero-norm states in the OCFQ string spectrum for the first few low-lying mass levels. We then show that off-shell gauge transformations of WSFT are identical to the on-shell stringy gauge symmetries generated by two types of zero-norm states in the generalized massive sigma-model approach of string theory. The high energy limit of these stringy gauge symmetries was recently used to calculate the proportionality constants, conjectured by Gross, among high energy scattering amplitudes of different string states. Based on these zero-norm state calculations, we have thus related gauge symmetry of WSFT to the high-energy stringy symmetry of Gross.Comment: 30 page

Decoherence and Recoherence in Model Quantum Systems

We discuss the various manifestations of quantum decoherence in the forms of dephasing, entanglement with the environment, and revelation of "which-path" information. As a specific example, we consider an electron interference experiment. The coupling of the coherent electrons to the quantized electromagnetic field illustrates all of these versions of decoherence. This decoherence has two equivalent interpretations, in terms of photon emission or in terms of Aharonov-Bohm phase fluctuations. We consider the case when the coherent electrons are coupled to photons in a squeezed vacuum state. The time-averaged result is increased decoherence. However, if only electrons which are emitted during selected periods are counted, the decoherence can be suppressed below the level for the photon vacuum. This is the phenomenon of recoherence. This effect is closely related to the quantum violations of the weak energy condition, and is restricted by similar inequalities. We give some estimates of the magnitude of the recoherence effect and discuss prospects for observing it in an electron interferometry experiment.Comment: 8 pages, 3 figures, talk presented at the 7th Friedmann Seminar, Joao Pessoa, Brazil, July 200