Numerical Analysis of a Pulse Detonation Cross Flow Heat Load Experiment

A comparison between experimentally measured and numerically simulated, time-averaged, point heat transfer rates in a pulse detonation (PDE) engine is presented. The comparison includes measurements and calculations for heat transfer to a cylinder in crossflow and to the tube wall itself using a novel spool design. Measurements are obtained at several locations and under several operating conditions. The measured and computed results are shown to be in substantial agreement, thereby validating the modeling approach. The model, which is based in computational fluid dynamics (CFD) is then used to interpret the results. A preheating of the incoming fuel charge is predicted, which results in increased volumetric flow and subsequent overfilling. The effect is validated with additional measurements

Carbon-Carbon Recuperators in Closed-Brayton-Cycle Space Power Systems

The feasibility of using carbon-carbon (C-C) recuperators in conceptual closed-Brayton-cycle space power conversion systems was assessed. Recuperator performance expectations were forecast based on notional thermodynamic cycle state values for potential planetary missions. Resulting thermal performance, mass and volume for plate-fin C-C recuperators were estimated and quantitatively compared with values for conventional offset-strip-fin metallic designs. Mass savings of 30 to 60 percent were projected for C-C recuperators with effectiveness greater than 0.9 and thermal loads from 25 to 1400 kWt. The smaller thermal loads corresponded with lower mass savings; however, 60 percent savings were forecast for all loads above 300 kWt. System-related material challenges and compatibility issues were also discussed

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

De novo and rare inherited mutations implicate the transcriptional coregulator TCF20/SPBP in autism spectrum disorder

BACKGROUND: Autism spectrum disorders (ASDs) are common and have a strong genetic basis, yet the cause of ∼70-80% ASDs remains unknown. By clinical cytogenetic testing, we identified a family in which two brothers had ASD, mild intellectual disability and a chromosome 22 pericentric inversion, not detected in either parent, indicating de novo mutation with parental germinal mosaicism. We hypothesised that the rearrangement was causative of their ASD and localised the chromosome 22 breakpoints. METHODS: The rearrangement was characterised using fluorescence in situ hybridisation, Southern blotting, inverse PCR and dideoxy-sequencing. Open reading frames and intron/exon boundaries of the two physically disrupted genes identified, TCF20 and TNRC6B, were sequenced in 342 families (260 multiplex and 82 simplex) ascertained by the International Molecular Genetic Study of Autism Consortium (IMGSAC). RESULTS: IMGSAC family screening identified a de novo missense mutation of TCF20 in a single case and significant association of a different missense mutation of TCF20 with ASD in three further families. Through exome sequencing in another project, we independently identified a de novo frameshifting mutation of TCF20 in a woman with ASD and moderate intellectual disability. We did not identify a significant association of TNRC6B mutations with ASD. CONCLUSIONS: TCF20 encodes a transcriptional coregulator (also termed SPBP) that is structurally and functionally related to RAI1, the critical dosage-sensitive protein implicated in the behavioural phenotypes of the Smith-Magenis and Potocki-Lupski 17p11.2 deletion/duplication syndromes, in which ASD is frequently diagnosed. This study provides the first evidence that mutations in TCF20 are also associated with ASD

The safety of self-administered allergen immunotherapy during the buildup and maintenance phases

Background—Self-administered allergen immunotherapy is considered controversial. We believe the implementation of a self-administration protocol characterized by patient preselection and a slow buildup phase is safe. Methods—We analyzed 23,614 patient records and associated immunotherapy injections for systemic reactions (SR) during a 1-year period (2011 to 2012). SRs were graded in accordance with the World Allergy Organization (WAO) criteria. Results—Thirty-seven SRs were reported for 23,614 patients who self-administered 2,021,600 injections yielding an annual SR rate of 0.16% (per patient) or 0.002% (per injection). Only 9 of 4643 pediatric (0.19%) and 28 of 18,971 adult patients (0.15%) experienced 1 or more SRs. No deaths (grade V SR) occurred. From 2009 through early 2014, over 90,000 patients received more than 10 million injections in accordance with the United Allergy Services (UAS) protocol without fatalities. Conclusion—We believe this safety profile is due to a preselection of patients to exclude those with a high risk for adverse reactions and a slow immunotherapy buildup phase. In contrast, previous studies documented office-based SRs ranging from approximately 3% to greater than 14%. Thus, the UAS home-immunotherapy SR rate is significantly lower than office-based immunotherapy SR rates (p \u3c 0.0001). The enhanced safety of this protocol results in a decreased frequency and severity of SRs. This safety report, derived from analyses of one of the largest patient cohorts studied, corroborates and expands the observations of previous studies of selfadministered subcutaneous immunotherapy in a low-risk patient population by assessing selfadministered allergen immunotherapy during the buildup and maintenance phases

De novo and rare inherited mutations implicate the transcriptional coregulator TCF20/SPBP in autism spectrum disorder.

BACKGROUND: Autism spectrum disorders (ASDs) are common and have a strong genetic basis, yet the cause of ∼70–80% ASDs remains unknown. By clinical cytogenetic testing, we identified a family in which two brothers had ASD, mild intellectual disability and a chromosome 22 pericentric inversion, not detected in either parent, indicating de novo mutation with parental germinal mosaicism. We hypothesised that the rearrangement was causative of their ASD and localised the chromosome 22 breakpoints. METHODS: The rearrangement was characterised using fluorescence in situ hybridisation, Southern blotting, inverse PCR and dideoxy-sequencing. Open reading frames and intron/exon boundaries of the two physically disrupted genes identified, TCF20 and TNRC6B, were sequenced in 342 families (260 multiplex and 82 simplex) ascertained by the International Molecular Genetic Study of Autism Consortium (IMGSAC). RESULTS: IMGSAC family screening identified a de novo missense mutation of TCF20 in a single case and significant association of a different missense mutation of TCF20 with ASD in three further families. Through exome sequencing in another project, we independently identified a de novo frameshifting mutation of TCF20 in a woman with ASD and moderate intellectual disability. We did not identify a significant association of TNRC6B mutations with ASD. CONCLUSIONS: TCF20 encodes a transcriptional coregulator (also termed SPBP) that is structurally and functionally related to RAI1, the critical dosage-sensitive protein implicated in the behavioural phenotypes of the Smith–Magenis and Potocki–Lupski 17p11.2 deletion/duplication syndromes, in which ASD is frequently diagnosed. This study provides the first evidence that mutations in TCF20 are also associated with ASD