The Effect of Reaction Control System Thruster Plume Impingement on Orion Service Module Solar Array Power Production

NASA's new Orion Crew Exploration Vehicle has geometry that orients the reaction control system (RCS) thrusters such that they can impinge upon the surface of Orion's solar array wings (SAW). Plume impingement can cause Paschen discharge, chemical contamination, thermal loading, erosion, and force loading on the SAW surface, especially when the SAWs are in a worst-case orientation (pointed 45 towards the aft end of the vehicle). Preliminary plume impingement assessment methods were needed to determine whether in-depth, timeconsuming calculations were required to assess power loss. Simple methods for assessing power loss as a result of these anomalies were developed to determine whether plume impingement induced power losses were below the assumed contamination loss budget of 2 percent. This paper details the methods that were developed and applies them to Orion's worst-case orientation

Clinical Pharmacokinetics of Triazoles in Pediatric Patients

Triazoles represent an important class of antifungal drugs in the prophylaxis and treatment of invasive fungal disease in pediatric patients. Understanding the pharmacokinetics of triazoles in children is crucial to providing optimal care for this vulnerable population. While the pharmacokinetics is extensively studied in adult populations, knowledge on pharmacokinetics of triazoles in children is limited. New data are still emerging despite drugs already going off patent. This review aims to provide readers with the most current knowledge on the pharmacokinetics of the triazoles: fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole. In addition, factors that have to be taken into account to select the optimal dose are summarized and knowledge gaps are identified that require further research. We hope it will provide clinicians guidance to optimally deploy these drugs in the setting of a life-threatening disease in pediatric patients

Systematic prey preference by introduced mice exhausts the ecosystem on Antipodes Island

For assistance collecting samples in the field the authors thank David Thompson, Erica Sommer, David Boyle and Mark Fraser in summer 2011, Helen Nathan, Terry Greene and Graeme Elliott in winter 2013, Fin Cox in autumn 2016 and Jose Luis Herrera in winter 2016. Thanks to the Department of Conservation, Murihiku, for logistical support, and Hank Haazen and crew of the Tiama for transport. Funding was provided for the summer 2011 expedition by NIWA and winter 2013 expedition by the National Geographic Society (Grant No. 9322-13). Thanks to Stephen Thorpe, Robert Hoare, and John Marris for taxonomic identification of invertebrate samples. Thanks to Surrya Khanam for laboratory sorting, Julie Brown and Anna Kilimnik for stable isotope laboratory analyses and Wendy Nelson for macroalgae identification. JCR is currently funded by the Royal Society of New Zealand Rutherford Discovery Fellowship (Grant No. RDF-UOA1404). TWB is currently funded by the European Union's Horizon 2020 research and innovation programme Marie Skłodowska-Curie Fellowship (Grant No. 747120). Thanks to Katherine Russell and two anonymous reviewers for feedback on the manuscript. This research was conducted under DOC entry (SO-29716-LND 1011/35) and research (SO-29140-FAU 1011/20) permits, and University of Auckland Animal Ethics Committee approval (R845).Peer reviewedPublisher PD

Statistical pairwise interaction model of stock market

Financial markets are a classical example of complex systems as they comprise many interacting stocks. As such, we can obtain a surprisingly good description of their structure by making the rough simplification of binary daily returns. Spin glass models have been applied and gave some valuable results but at the price of restrictive assumptions on the market dynamics or others are agent-based models with rules designed in order to recover some empirical behaviours. Here we show that the pairwise model is actually a statistically consistent model with observed first and second moments of the stocks orientation without making such restrictive assumptions. This is done with an approach based only on empirical data of price returns. Our data analysis of six major indices suggests that the actual interaction structure may be thought as an Ising model on a complex network with interaction strengths scaling as the inverse of the system size. This has potentially important implications since many properties of such a model are already known and some techniques of the spin glass theory can be straightforwardly applied. Typical behaviours, as multiple equilibria or metastable states, different characteristic time scales, spatial patterns, order-disorder, could find an explanation in this picture.Comment: 11 pages, 8 figure

Identification of Candidate Driver Genes in Common Focal Chromosomal Aberrations of Microsatellite Stable Colorectal Cancer

Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Chromosomal instability (CIN) is a major driving force of microsatellite stable (MSS) sporadic CRC. CIN tumours are characterised by a large number of somatic chromosomal copy number aberrations (SCNA) that frequently affect oncogenes and tumour suppressor genes. The main aim of this work was to identify novel candidate CRC driver genes affected by recurrent and focal SCNA. High resolution genome-wide comparative genome hybridisation (CGH) arrays were used to compare tumour and normal DNA for 53 sporadic CRC cases. Context corrected common aberration (COCA) analysis and custom algorithms identified 64 deletions and 32 gains of focal minimal common regions (FMCR) at high frequency (>10%). Comparison of these FMCR with published genomic profiles from CRC revealed common overlap (42.2% of deletions and 34.4% of copy gains). Pathway analysis showed that apoptosis and p53 signalling pathways were commonly affected by deleted FMCR, and MAPK and potassium channel pathways by gains of FMCR. Candidate tumour suppressor genes in deleted FMCR included RASSF3, IFNAR1, IFNAR2 and NFKBIA and candidate oncogenes in gained FMCR included PRDM16, TNS1, RPA3 and KCNMA1. In conclusion, this study confirms some previously identified aberrations in MSS CRC and provides in silico evidence for some novel candidate driver gene

A novel device to measure power grip forces in squirrel monkeys

Understanding the neural bases for grip force behaviors in both normal and neurologically impaired animals is imperative prior to improving treatments and therapeutic approaches. The present paper describes a novel device for the assessment of power grip forces in squirrel monkeys. The control of grasping and object manipulation represents a vital aspect of daily living by allowing the performance of a wide variety of complex hand movements. However, following neurological injury such as stroke, these grasping behaviors are often severely affected, resulting in persistent impairments in strength, grip force modulation and kinematic hand control. While there is a significant clinical focus on rehabilitative strategies to address these issues, there exists the need for translational animal models. In the study presented here, we describe a simple grip force device designed for use in nonhuman primates, which provides detailed quantitative information regarding distal grip force dynamics. Adult squirrel monkeys were trained to exceed a specific grip force threshold, which was rewarded with a food pellet. One of these subjects then received an infarct of the M1 hand representation area. Results suggest that the device provides detailed and reliable information on grip behaviors in healthy monkeys and can detect deficits in grip dynamics in monkeys with cortical lesions (significantly longer release times). Understanding the physiological and neuroanatomical aspects of grasping function following neurological injury may lead to more effective rehabilitative interventions

Reduction in PA28αβ activation in HD mouse brain correlates to increased mHTT aggregation in cell models

Huntington’s disease is an autosomal dominant heritable disorder caused by an expanded CAG trinucleotide repeat at the N-terminus of the Huntingtin (HTT) gene. Lowering the levels of soluble mutant HTT protein prior to aggregation through increased degradation by the proteasome would be a therapeutic strategy to prevent or delay the onset of disease. Native PAGE experiments in HdhQ150 mice and R6/2 mice showed that PA28αβ disassembles from the 20S proteasome during disease progression in the affected cortex, striatum and hippocampus but not in cerebellum and brainstem. Modulating PA28αβ activated proteasomes in various in vitro models showed that PA28αβ improved polyQ degradation, but decreased the turnover of mutant HTT. Silencing of PA28αβ in cells lead to an increase in mutant HTT aggregates, suggesting that PA28αβ is critical for overall proteostasis, but only indirectly affects mutant HTT aggregation

Measuring Differences Among Probability of Detection Curves

Probability of Detection (POD) curves are compared by two statistical methods to quantify system-to-system differences. The first method assesses performance among a group of inspection systems through an adaptation of statistical analysis of variance (ANOVA). The second method uses a chi-squared statistic to test for a difference between two systems. Examples using eddy current data are given for each technique.</p

Magnetic fluctuations in the classical XY model: the origin of an exponential tail in a complex system

We study the probability density function for the fluctuations of the magnetic order parameter in the low temperature phase of the XY model of finite size. In two-dimensions this system is critical over the whole of the low temperature phase. It is shown analytically and without recourse to the scaling hypothesis that, in this case, the distribution is non-Gaussian and of universal form, independent of both system size and critical exponent $\eta$. An exact expression for the generating function of the distribution is obtained, which is transformed and compared with numerical data from high resolution molecular dynamics and Monte Carlo simulations. The calculation is extended to general dimension and an exponential tail is found in all dimensions less than four, despite the fact that critical fluctuations are limited to D=2. These results are discussed in the light of similar behaviour observed in models of interface growth and for dissipative systems driven into a non-equilibrium steady state.Comment: 32 pages, 13 figures, 1 table. Few changes. To appear in Phys. Rev.

A study protocol to investigate the relationship between dietary fibre intake and fermentation, colon cell turnover, global protein acetylation and early carcinogenesis: the FACT study

Background: A number of studies, notably EPIC, have shown a descrease in colorectal cancer risk associated with increased fibre consumption. Whilst the underlying mechanisms are likely to be multifactorial, production of the short-chain fatty-acid butyrate fro butyratye is frequently cited as a major potential contributor to the effect. Butyrate inhibits histone deacetylases, which work on a wide range of proteins over and above histones. We therefore hypothesized that alterations in the acetylated proteome may be associated with a cancer risk phenotype in the colorectal mucosa, and that such alterations are candidate biomarkers for effectiveness of fibre interventions in cancer prevention. Methods an design: There are two principal arms to this study: (i) a cross-sectional study (FACT OBS) of 90 subjects recruited from gastroenterology clinics and; (ii) an intervention trial in 40 subjects with an 8 week high fibre intervention. In both studies the principal goal is to investigate a link between fibre intake, SCFA production and global protein acetylation. The primary measure is level of faecal butyrate, which it is hoped will be elevated by moving subjects to a high fibre diet. Fibre intakes will be estimated in the cross-sectional group using the EPIC Food Frequency Questionnaire. Subsidiary measures of the effect of butyrate on colon mucosal function and precancerous phenotype will include measures of apoptosis, apoptotic regulators cell cycle and cell division. Discussion: This study will provide a new level of mechanistic data on alterations in the functional proteome in response to the colon microenvironment which may underwrite the observed cancer preventive effect of fibre. The study may yield novel candidate biomarkers of fibre fermentation and colon mucosal function