The effects of rigid polyurethane foam as a confinement material on breaching charge detonations

The effects of a rigid polyurethane foam used as a confinement material on four types of breaching explosives were tested, focusing on the changes in shockwave peak pressures, detonation load compression forces, and brisance cratering abilities. The Plate Dent testing procedure was modified to incorporate a load cell force sensor, and two air overpressure sensors were included adjacent to the blast to quantify each test result. The testing variables focused on the polyurethane foam cure times and thickness volumes around the breaching explosives to determine the breaching charges\u27 optimal energy output capabilities when confined by the foam material. The rigid foam confinement increased the compression forces and brisance cratering abilities of all four tested explosives types as the foam cure times were extended and foam confinement radius increased. A reduction in the positive peak blast pressure was noted as the foam confinement material was increased. An increase in the peak blast pressure and compression force occurred when the polyurethane foam cure times were extended. When confined by the polyurethane foam, the average compression force was increased by 483% and the average Plate Dent depths were increased by 26.4%. The average blast peak pressure of a polyurethane foam confined detonation was 10% less than an unconfined detonation. This study\u27s findings show how a breaching charge confined by polyurethane foam would provide a more damaging blast force to a structure while reducing the blast exposure to the breaching team performing the explosive breach --Abstract, page iii

Intra-Arterial Delivery of Radiopharmaceuticals in Oncology: Current Trends and the Future of Alpha-Particle Therapeutics

A paradigm shift is underway in cancer diagnosis and therapy using radioactivity-based agents called radiopharmaceuticals. In the new strategy, diagnostic imaging measures the tumor uptake of radioactive agent X in a patient\u27s specific cancer, and if uptake metrics are realized, the patient can be selected for therapy with radioactive agent Y . The X and Y represent different radioisotopes that are optimized for each application. X-Y pairs are known as radiotheranostics, with the currently approved route of therapy being intravenous administration. The field is now evaluating the potential of intra-arterial dosing of radiotheranostics. In this manner, a higher initial concentration can be achieved at the cancer site, which could potentially enhance tumor-to-background targeting and lead to improved imaging and therapy. Numerous clinical trials are underway to evaluate these new therapeutic approaches that can be performed via interventional radiology. Of further interest is changing the therapeutic radioisotope that provides radiation therapy by β- emission to radioisotopes that also decay by α-particle emissions. Alpha (α)-particle emissions provide high energy transfer to the tumors and have distinct advantages. This review discusses the current landscape of intra-arterially delivered radiopharmaceuticals and the future of α-particle therapy with short-lived radioisotopes

The anatomical distribution of genetic associations

Deeper understanding of the anatomical intermediaries for disease and other complex genetic traits is essential to understanding mechanisms and developing new interventions. Existing ontology tools provide functional, curated annotations for many genes and can be used to develop mechanistic hypotheses; yet information about the spatial expression of genes may be equally useful in interpreting results and forming novel hypotheses for a trait. Therefore, we developed an approach for statistically testing the relationship between gene expression across the body and sets of candidate genes from across the genome. We validated this tool and tested its utility on three applications. First, we show that the expression of genes in associated loci from GWA studies implicates specific tissues for 57 out of 98 traits. Second, we tested the ability of the tool to identify novel relationships between gene expression and phenotypes. Specifically, we experimentally confirmed an underappreciated prediction highlighted by our tool: that white blood cell count – a quantitative trait of the immune system – is genetically modulated by genes expressed in the skin. Finally, using gene lists derived from exome sequencing data, we show that human genes under selective constraint are disproportionately expressed in nervous system tissues

miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.

We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27Kip1) is a direct miR-196b target whose repression enhanced an embryonic stem cell–like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. Conversely, elevation of p27Kip1 significantly reduced MLL-r leukemia self-renewal, promoted monocytic differentiation of leukemic blasts, and induced cell death. Antagonism of miR-196b activity or pharmacologic inhibition of the Cks1-Skp2–containing SCF E3-ubiquitin ligase complex increased p27Kip1 and inhibited human AML growth. This work illustrates that understanding oncogenic miRNA target pathways can identify actionable targets in leukemia

The effect of ice-slushy consumption on plasma vasoactive intestinal peptide during prolonged exercise in the heat

The aim of this study was to determine the effect of exercise in the heat on thermoregulatory responses and plasma vasoactive intestinal peptide concentration (VIP) and whether it is modulated by ice-slushy consumption. Ten male participants cycled at 62% View the MathML sourceV̇O2max for 90 min in 32 °C and 40% relative humidity. A thermoneutral (37 °C) or ice-slushy (−1 °C) sports drink was given at 3.5 ml kg−1 body mass every 15 min during exercise. VIP and rectal temperature increased during exercise (mean±standard deviation: 4.6±4.4 pmol L−1, P=0.005; and 1.3±0.4 °C, P\u3c0.001 respectively) and were moderately associated (r=0.35, P=0.008). While rectal temperature and VIP were not different between trials, ice-slushy significantly reduced heat storage (P=0.010) and skin temperature (timextrial interaction P=0.038). It appears that VIP does not provide the signal linking cold beverage ingestion and lower skin temperature in the heat

Synthesis, Structure and Thermal Properties of Volatile Indium and Gallium Triazenides

Indium and gallium nitride are important semi-conductor materials with desirable properties for high-frequency and power electronics. We have previously demonstrated high quality ALD grown InN and GaN using the hexacoordinated di-isopropyltriazenide In(III) and Ga(III) precursors. Herein we report the structural and thermal properties their analogues employing combinations of isopropyl, sec-butyl and tert-butyltriazenide alkyl groups on the exocyclic nitrogen of the triazenide ligand. The new triazenide compounds were all found to be volatile (80-120 ºC, 0.5 mbar) and showed very good thermal stability (200 and 300 °C). These new triazenide analogues provide a set of precursors whose thermal properties are determined and can be accordingly tailored by strategic choice of exocyclic nitrogen alkyl substituents