A pathway analysis of genome-wide association study highlights novel type 2 diabetes risk pathways.

Genome-wide association studies (GWAS) have been widely used to identify common type 2 diabetes (T2D) variants. However, the known variants just explain less than 20% of the overall estimated genetic contribution to T2D. Pathway-based methods have been applied into T2D GWAS datasets to investigate the biological mechanisms and reported some novel T2D risk pathways. However, few pathways were shared in these studies. Here, we performed a pathway analysis using the summary results from a large-scale meta-analysis of T2D GWAS to investigate more genetic signals in T2D. Here, we selected PLNK and VEGAS to perform the gene-based test and WebGestalt to perform the pathway-based test. We identified 8 shared KEGG pathways after correction for multiple tests in both methods. We confirm previous findings, and highlight some new T2D risk pathways. We believe that our results may be helpful to study the genetic mechanisms of T2D

Giant nonlinearity via breaking parity-time symmetry: a route to low-threshold phonon diodes

Nonreciprocal devices that permit wave transmission in only one direction are indispensible in many fields of science including, e.g., electronics, optics, acoustics, and thermodynamics. Manipulating phonons using such nonreciprocal devices may have a range of applications such as phonon diodes, transistors, switches, etc. One way of achieving nonreciprocal phononic devices is to use materials with strong nonlinear response to phonons. However, it is not easy to obtain the required strong mechanical nonlinearity, especially for few-phonon situations. Here, we present a general mechanism to amplify nonlinearity using $\mathcal{PT}$-symmetric structures, and show that an on-chip micro-scale phonon diode can be fabricated using a $\mathcal{PT}$-symmetric mechanical system, in which a lossy mechanical-resonator with very weak mechanical nonlinearity is coupled to a mechanical resonator with mechanical gain but no mechanical nonlinearity. When this coupled system transits from the $\mathcal{PT}$-symmetric regime to the broken-$\mathcal{PT}$-symmetric regime, the mechanical nonlinearity is transferred from the lossy resonator to the one with gain, and the effective nonlinearity of the system is significantly enhanced. This enhanced mechanical nonlinearity is almost lossless because of the gain-loss balance induced by the $\mathcal{PT}$-symmetric structure. Such an enhanced lossless mechanical nonlinearity is then used to control the direction of phonon propagation, and can greatly decrease (by over three orders of magnitude) the threshold of the input-field intensity necessary to observe the unidirectional phonon transport. We propose an experimentally realizable lossless low-threshold phonon diode of this type. Our study opens up new perspectives for constructing on-chip few-phonon devices and hybrid phonon-photon components.Comment: 13 pages, 9 figure

Quantitative spectroscopic analysis of heterogeneous mixtures: the correction of multiplicative effects caused by variations in physical properties of samples

Spectral measurements of complex heterogeneous types of mixture samples are often affected by significant multiplicative effects resulting from light scattering, due to physical variations (e.g. particle size and shape, sample packing and sample surface, etc.) inherent within the individual samples. Therefore, the separation of the spectral contributions due to variations in chemical compositions from those caused by physical variations is crucial to accurate quantitative spectroscopic analysis of heterogeneous samples. In this work, an improved strategy has been proposed to estimate the multiplicative parameters accounting for multiplicative effects in each measured spectrum, and hence mitigate the detrimental influence of multiplicative effects on the quantitative spectroscopic analysis of heterogeneous samples. The basic assumption of the proposed method is that light scattering due to physical variations has the same effects on the spectral contributions of each of the spectroscopically active chemical component in the same sample mixture. Based on this underlying assumption, the proposed method realizes the efficient estimation of the multiplicative parameters by solving a simple quadratic programming problem. The performance of the proposed method has been tested on two publicly available benchmark data sets (i.e. near-infrared total diffuse transmittance spectra of four-component suspension samples and near infrared spectral data of meat samples) and compared with some empirical approaches designed for the same purpose. It was found that the proposed method provided appreciable improvement in quantitative spectroscopic analysis of heterogeneous mixture samples. The study indicates that accurate quantitative spectroscopic analysis of heterogeneous mixture samples can be achieved through the combination of spectroscopic techniques with smart modeling methodology