In the healthy brain, homeostatic balance between excitation and inhibition maintains neural stability. Reduced inhibition may explain shared symptoms observed in autism and psychosis. Here we review evidence suggesting that altered levels of gamma-aminobutyric acid (GABA) may underlie both disorders, providing a potential cross-diagnostic therapeutic target.

Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy and has the worst prognosis. Hence, there is an urgent need to elucidate targets that sensitize these tumors to chemotherapy and IR. Employing standard assays for viability and sensitization to IR, we identified PRDX1 as a therapeutic target in Group-3 MBL. Specifically, targeting PRDX1 by RNAi or inhibition by Adenanthin led to specific killing and sensitization to IR of Group-3 MBL cells. We rescued sensitization of Daoy and UW228 cells by hypermorphic expression of PRDX1. PRDX1 knockdown caused oxidative DNA damage and induced apoptosis. We correlated PRDX1 expression to patient outcomes in a validated MBL tumor-microarray. Whole genome sequencing identified pathways/genes that were dysregulated with PRDX1 inhibition or silencing. Our in vivo studies in mice employing flank/orthotopic tumors from patient derived xenografts/Group-3 MBL cells confirmed in vitro observations. Animals with tumors in which PRDX1 was targeted by RNAi or Adenanthin (using mini osmotic pumps) showed decreased tumor burden and increased survival when compared to controls. Since, Adenanthin does not cross the blood brain barrier (BBB) we used HAV6 peptide to transiently disrupt the BBB and deliver Adenanthin to the tumor. Immunohistochemistry confirmed that targeting PRDX1 resulted in increased oxidative DNA damage, apoptosis and decreased proliferation. In summary, we have validated PRDX1 as a therapeutic target in group-3 MBL, identified Adenanthin as a potent chemical inhibitor of PRDX1 and confirmed the role of HAV peptide (in the transient modulation of BBB permeability) in an orthotopic model of group-3 MBL.

Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.

3D integration enabled by through-silicon-via (TSV) allows continued performance enhancement and power reduction for semiconductor devices, even without further scaling. For TSV wafers with all Applied Materials unit processes, we evaluate the integrity of oxide liner and copper barrier by capacitance-voltage (C-V) and current-voltage (I-V) measurements, from which oxide capacitance, minimum TSV capacitance, and leakage current are extracted. The capacitance values match well with model predictions. The leakage data also demonstrate good wafer-scale uniformity. The liner and barrier quality are further verified with microanalysis techniques.

Previous studies of the structure of epitaxial Fe/Pt(001) multilayers have shown that the structure of the Fe layers depends on the Fe layer thickness. For small thicknesses (< 12 Å) the Fe is fcc, while for greater thicknesses (> 22 Å) the Fe has a bcc structure. We speculated that this transition of the Fe structure is a result of intermixing with subsequently deposited Pt. We explore this transition further by examining superlattice satellite peaks around the (111) fundamental reflection, and by using grazing incidence x-ray scattering (GIXS) to examine the structure of epitaxial Fe/Pt(001) multilayers during sputter deposition. The GIXS observations show that the initial growth of Fe is in the bcc structure; thin bcc Fe layers are partially transformed to fcc by subsequent deposition of Pt. The transformation is thermodynamically favorable because the intermixed fcc phase has lower epitaxial mismatch and bulk chemical free energy than the bcc phase.

An atomic force microscope (AFM) has been used to reveal residual sub-micron sized decomposition sites in drop weight impacted RDX and laser irradiated AP crystals. In impacted RDX, the small and early reaction sites observed are hemispherical craters, ranging in size from 20–300 nm. The smallest reaction site encompassed about 10,000 molecules with an expected energy evolution of 2 × 10−14 J. On a somewhat larger scale hillocks of 200–800 nm were observed, their shape giving evidence of internal reaction and hot spot melting. Dislocation densities as high as 5 × 1012 per cm2 were observed in sub-ignited RDX. High resolution AFM images of the RDX lattice structure indicate molecular rotation as well as displacements at dislocation sites. In AP, after nanosecond pulsed laser irradiation, reaction sites were trumpet shaped with a smallest size of approximately 50 nm. Most sites contained a crystallographically oriented central square lid formed above the surrounding crystal surface, probably relating to the orthorhombic to cubic phase transition documented in micron scale cracking patterns observed at the laser heated sites.