We conducted a systematic study of top susceptibility variants from a genome-wide association (GWA) study of Bipolar Disorder to gain insight into the functional consequences of genetic variation influencing disease risk. We report here the results of experiments to explore the effects of these susceptibility variants on DNA methylation and mRNA expression in human cerebellum samples. Among the top susceptibility variants, we identified an enrichment of cis regulatory loci on mRNA expression (eQTLs), and a significant excess of quantitative trait loci for DNA CpG methylation, hereafter referred to as mQTLs. Bipolar Disorder susceptibility variants that cis-regulate both cerebellar expression and methylation of the same gene are a very small proportion of Bipolar Disorder susceptibility variants. This finding suggests that mQTLs and eQTLs provide orthogonal ways of functionally annotating genetic variation within the context of studies of pathophysiology in brain. No lymphocyte mQTL enrichment was found, suggesting that mQTL enrichment was specific to the cerebellum, in contrast to eQTLs. Separately, we found that using mQTL information to restrict the number of SNPs studied enhances our ability to detect a significant association. With this restriction a priori informed by the observed functional enrichment, we identified a significant association (rs12618769, Pbonferroni<0.05) from two other GWA studies (TGen+GAIN; 2,191 cases and 1,434 controls) of Bipolar Disorder, which we replicated in an independent GWA study (WTCCC). Collectively, our findings highlight the importance of integrating functional annotation of genetic variants for gene expression and DNA methylation to advance biological understanding of Bipolar Disorder.

Discrete helical modes have been experimentally observed from implosion to explosion in cylindrical, axially magnetized ultrathin foils (Bz = 0.2 – 2.0 T) using visible self-emission and laser shadowgraphy. The striation angle of the helices, ϕ, was found to increase during the implosion and decrease during the explosion, despite the large azimuthal magnetic field (&gt;40 T). These helical striations are interpreted as discrete, non-axisymmetric eigenmodes that persist from implosion to explosion, obeying the simple relation ϕ = m/kR, where m, k, and R are the azimuthal mode number, axial wavenumber, and radius, respectively. Experimentally, we found that (a) there is only one, or at the most two, dominant unstable eigenmode, (b) there does not appear to be a sharp threshold on the axial magnetic field for the emergence of the non-axisymmetric helical modes, and (c) higher axial magnetic fields yield higher azimuthal modes.

No abstract

A charge sheet model is proposed to study the space charge effect and uniformity of charge separation of an electron pulse train in a drift space. An analytical formula is derived for the charge density limit as a function of gap spacing, injecting energy and pulse separation. To consider the relativistic effects, the theoretical results are verified by numerical solutions up to 80 MeV. This model can be applied to the design of Smith-Purcell radiation, multiple-pulse electron beam for time resolved electron microscopy, and to free electron laser.

High order harmonic generation from solid targets is a compelling route to generating intense attosecond or even zeptosecond pulses. However, the effects of ion motion on the generation of harmonics have only recently started to be considered. Here, we study the effects of ion motion in harmonics production at ultrahigh laser intensities interacting with solid density plasma. Using particle-in-cell simulations, we find that there is an optimum density for harmonic production that depends on laser intensity, which scales linearly with a 0 with no ion motion but with a reduced scaling if ion motion is included. We derive a scaling for this optimum density with ion motion and also find that the background ion motion induces Doppler red-shifts in the harmonic structures of the reflected pulse. The temporal structure of the Doppler shifts is correlated to the envelope of the incident laser pulse. We demonstrate that by introducing a frequency chirp in the incident pulse we are able to eliminate these Doppler shifts almost completely. V C 2015 AIP Publishing LLC.