New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Theory and modeling of ion acceleration from the interaction of ultra-intense lasers with solid density targets

The interaction of a high intensity, short-pulse laser with a thin target can lead to the generation of a highly collimated beam of fast ions off the rear target surface. These ion beams have the potential to impact inertial confinement fusion applications, including their use in diagnostics and fast-ignition. Recent work by the authors in the modeling of ion acceleration, using both full particle-in-cell and hybrid (particle ions, reduced electron physics) models, is leading to improved understanding of the physics governing ion acceleration

Particle-in-cell studies of laser-driven hot spots and a statistical model for mesoscopic properties of Raman backscatter

The authors use explicit particle-in-cell simulations to model stimulated scattering processes in media with both solitary and multiple laser hot spots. These simulations indicate coupling among hot spots, whereby scattered light, plasma waves, and hot electrons generated in one laser hot spot may propagate to neighboring hot spots, which can be destabilized to enhanced backscatter. A nonlinear statistical model of a stochastic beam exhibiting this coupled behavior is described here. Calibration of the model using particle-in-cell simulations is performed, and a threshold is derived for “detonation” of the beam to high reflectivity