Investigation of refractory dielectrics for integrated circuits

Pyrolytic silicon nitride dielectric for integrated circuit

A nano-patterned photonic crystal laser with a dye-doped liquid crystal

Covering a nano-patterned titanium dioxide photonic crystal (PC) within a well-oriented film of dye-doped liquid crystal (LC), a distributed feedback laser is constructed whereby the emission characteristics can be manipulated in-situ using an electric field. This hybrid organic-inorganic structure permits simultaneous selectivity of both the beam pattern and laser wavelength by electrical addressing of the LC director. In addition, laser emission is obtained both in the plane and normal to the PC. Along with experimental data, a theoretical model is presented that is based upon an approximate calculation of the band structure of this birefringent, tuneable laser device

Pharmacological and Toxicological Properties of the Potent Oral γ-Secretase Modulator BPN-15606.

Alzheimer's disease (AD) is characterized neuropathologically by an abundance of 1) neuritic plaques, which are primarily composed of a fibrillar 42-amino-acid amyloid-β peptide (Aβ), as well as 2) neurofibrillary tangles composed of aggregates of hyperphosporylated tau. Elevations in the concentrations of the Aβ42 peptide in the brain, as a result of either increased production or decreased clearance, are postulated to initiate and drive the AD pathologic process. We initially introduced a novel class of bridged aromatics referred tγ-secretase modulatoro as γ-secretase modulators that inhibited the production of the Aβ42 peptide and to a lesser degree the Aβ40 peptide while concomitantly increasing the production of the carboxyl-truncated Aβ38 and Aβ37 peptides. These modulators potently lower Aβ42 levels without inhibiting the γ-secretase-mediated proteolysis of Notch or causing accumulation of carboxyl-terminal fragments of APP. In this study, we report a large number of pharmacological studies and early assessment of toxicology characterizing a highly potent γ-secretase modulator (GSM), (S)-N-(1-(4-fluorophenyl)ethyl)-6-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-4-methylpyridazin-3-amine (BPN-15606). BPN-15606 displayed the ability to significantly lower Aβ42 levels in the central nervous system of rats and mice at doses as low as 5-10 mg/kg, significantly reduce Aβ neuritic plaque load in an AD transgenic mouse model, and significantly reduce levels of insoluble Aβ42 and pThr181 tau in a three-dimensional human neural cell culture model. Results from repeat-dose toxicity studies in rats and dose escalation/repeat-dose toxicity studies in nonhuman primates have designated this GSM for 28-day Investigational New Drug-enabling good laboratory practice studies and positioned it as a candidate for human clinical trials

Gravitational Wave Spectrum in Inflation with Nonclassical States

The initial quantum state during inflation may evolve to a highly squeezed quantum state due to the amplification of the time-dependent parameter, $\omega_{phys}(k/a)$, which may be the modified dispersion relation in trans-Planckian physics. This squeezed quantum state is a nonclassical state that has no counterpart in the classical theory. We have considered the nonclassical states such as squeezed, squeezed coherent, and squeezed thermal states, and calculated the power spectrum of the gravitational wave perturbation when the mode leaves the horizon.Comment: 21 page

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

Attraction of the Invasive Halyomorpha halys (Hemiptera: Pentatomidae) to Traps Baited with Semiochemical Stimuli Across the United States

A recent identification of the two-component aggregation pheromone of the invasive stink bug species, Halyomorpha halys (Stål), in association with a synergist, has greatly improved the ability to accurately monitor the seasonal abundance and distribution of this destructive pest. We evaluated the attraction of H. halys to black pyramid traps baited with lures containing the pheromone alone, the synergist methyl (2E,4E,6Z)-decatrienoate (MDT) alone, and the two lures in combination. Traps were deployed around areas of agricultural production including fruit orchards, vegetables, ornamentals, or row crops in Delaware, Maryland, North Carolina, New Jersey, New York, Ohio, Oregon, Pennsylvania, Virginia, and West Virginia from mid-April to mid-October, 2012 and 2013. We confirmed that H. halys adults and nymphs are attracted to the aggregation pheromone season long, but that attraction is significantly increased with the addition of the synergist MDT. H. halys adults were detected in April with peak captures of overwintering adults in mid- to late May. The largest adult captures were late in the summer, typically in early September. Nymphal captures began in late May and continued season long. Total captures declined rapidly in autumn and ceased by mid-October. Captures were greatest at locations in the Eastern Inland region, followed by those in the Eastern Coastal Plain and Pacific Northwest. Importantly, regardless of location in the United States, all mobile life stages of H. halys consistently responded to the combination of H. halys aggregation pheromone and the synergist throughout the entire season, suggesting that these stimuli will be useful tools to monitor for H. halys in managed system

The diagnostic accuracy of high b-value diffusion- and T2-weighted imaging for the detection of prostate cancer: a meta-analysis

Purpose: This study aims to investigate the role of diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) in combination for the detection of prostate cancer, specifically assessing the role of high b-values (> 1000 s/mm2), with a systematic review and meta-analysis of the existing published data.  Methods: The electronic databases MEDLINE, EMBASE, and OpenSIGLE were searched between inception and September 1, 2017. Eligible studies were those that reported the sensitivity and specificity of DWI and T2WI for the diagnosis of prostate cancer by visual assessment using a histopathologic reference standard. The QUADAS-2 critical appraisal tool was used to assess the quality of included studies. A meta-analysis with pooling of sensitivity, specificity, likelihood, and diagnostic odds ratios was undertaken, and a summary receiver-operating characteristics (sROC) curve was constructed. Predetermined subgroup analysis was also performed.  Results: Thirty-three studies were included in the final analysis, evaluating 2949 patients. The pooled sensitivity and specificity were 0.69 (95% CI 0.68–0.69) and 0.84 (95% CI 0.83–0.85), respectively, and the sROC AUC was 0.84 (95% CI 0.81–0.87). Subgroup analysis showed significantly better sensitivity with high b-values (> 1000 s/mm2). There was high statistical heterogeneity between studies.  Conclusion: The diagnostic accuracy of combined DWI and T2WI is good with high b-values (> 1000 s/mm2) seeming to improve overall sensitivity while maintaining specificity. However, further large-scale studies specifically looking at b-value choice are required before a categorical recommendation can be made