Population-based techniques for the multiple objective optimisation of sandwich materials and structures

Sandwich materials, consisting of two thin, stiff facings separated by a low density core, can be used to produce structures that are both light and flexurally rigid. Such assemblies are attractive for applications in transport and construction. However, their optimisation is rarely straightforward. Not only is this due to the complex equations that govern their mechanics, but also because multiple design variables and objectives are often present. The work in this thesis identifies population-based optimisation techniques as a novel solution to this challenge. Three of these techniques have been developed in MATLAB specifically for this purpose and are based on particle swarm optimisation (sandwichPSO), ant colony optimisation (sandwichACO), and simulated annealing (sandwichSA). To assess their suitability, a benchmark problem considered the application of these techniques to a multiple objective sandwich beam optimisation. Optimised for stiffness mass and cost, a selection of 16 materials for both facing and core were available. Several constraints were also present. The sandwichACO technique demonstrated superior ability as it was able to obtain all optimal solutions in most cases. However, the sandwichPSO and sandwichSA techniques struggled to identify local optimum solutions for the multi-ply, fibre-reinforced polymer sandwich facing laminates. A further case study then applied sandwichACO to the optimisation of a sandwich plate for a rail vehicle floor panel. In addition to the benchmark, the problem was extended to include 40 materials. Also, the material and thickness of the top face was allowed to be different to the bottom. Furthermore, orthotropic fibre-reinforced facing constructions were included, as well as a localised load constraint. A broad range of optimal solutions were identified for the applied minimum mass and cost objectives. Sandwich constructions provided a significant (approximately 40%) saving in both mass and cost compared to the existing plywood design. More significant mass saving designs were also identified (of over 40%), but with a cost premium. Overall, population-based techniques have demonstrated successful application to the design of sandwich materials and structures.EThOS - Electronic Theses Online ServiceNewRail : School of Mechanical and Systems Engineering, Newcastle University : Royal Academy of EngineeringGBUnited Kingdo

First NuSTAR Limits on Quiet Sun Hard X-Ray Transient Events

We present the first results of a search for transient hard X-ray (HXR) emission in the quiet solar corona with the \textit{Nuclear Spectroscopic Telescope Array} (\textit{NuSTAR}) satellite. While \textit{NuSTAR} was designed as an astrophysics mission, it can observe the Sun above 2~keV with unprecedented sensitivity due to its pioneering use of focusing optics. \textit{NuSTAR} first observed quiet Sun regions on 2014 November 1, although out-of-view active regions contributed a notable amount of background in the form of single-bounce (unfocused) X-rays. We conducted a search for quiet Sun transient brightenings on time scales of 100 s and set upper limits on emission in two energy bands. We set 2.5--4~keV limits on brightenings with time scales of 100 s, expressed as the temperature T and emission measure EM of a thermal plasma. We also set 10--20~keV limits on brightenings with time scales of 30, 60, and 100 s, expressed as model-independent photon fluxes. The limits in both bands are well below previous HXR microflare detections, though not low enough to detect events of equivalent T and EM as quiet Sun brightenings seen in soft X-ray observations. We expect future observations during solar minimum to increase the \textit{NuSTAR} sensitivity by over two orders of magnitude due to higher instrument livetime and reduced solar background.Comment: 11 pages, 7 figures; accepted for publication in The Astrophysical Journa

The First Focused Hard X-ray Images of the Sun with NuSTAR

We present results from the the first campaign of dedicated solar observations undertaken by the \textit{Nuclear Spectroscopic Telescope ARray} ({\em NuSTAR}) hard X-ray telescope. Designed as an astrophysics mission, {\em NuSTAR} nonetheless has the capability of directly imaging the Sun at hard X-ray energies ($>$3~keV) with an increase in sensitivity of at least two magnitude compared to current non-focusing telescopes. In this paper we describe the scientific areas where \textit{NuSTAR} will make major improvements on existing solar measurements. We report on the techniques used to observe the Sun with \textit{NuSTAR}, their limitations and complications, and the procedures developed to optimize solar data quality derived from our experience with the initial solar observations. These first observations are briefly described, including the measurement of the Fe K-shell lines in a decaying X-class flare, hard X-ray emission from high in the solar corona, and full-disk hard X-ray images of the Sun.Comment: 11 pages, accepted to Ap

The first X-ray imaging spectroscopy of quiescent solar active regions with NuSTAR

We present the first observations of quiescent active regions (ARs) using NuSTAR, a focusing hard X-ray telescope capable of studying faint solar emission from high temperature and non-thermal sources. We analyze the first directly imaged and spectrally resolved X-rays above 2~keV from non-flaring ARs, observed near the west limb on 2014 November 1. The NuSTAR X-ray images match bright features seen in extreme ultraviolet and soft X-rays. The NuSTAR imaging spectroscopy is consistent with isothermal emission of temperatures 3.1 − 4.4~MK and emission measures 1 – 8 × 10^(46)~cm^(−3). We do not observe emission above 5~MK but our short effective exposure times restrict the spectral dynamic range. With few counts above 6~keV, we can place constraints on the presence of an additional hotter component between 5 and 12~MK of ∼ 10^(46)cm^(−3) and ∼10^(43) cm^(−3), respectively, at least an order of magnitude stricter than previous limits. With longer duration observations and a weakening solar cycle (resulting in an increased livetime), future NuSTAR observations will have sensitivity to a wider range of temperatures as well as possible non-thermal emission

Evidence of significant energy input in the late phase of a solar flare from NuSTAR x-ray observations

We present observations of the occulted active region AR 12222 during the third Nuclear Spectroscopic Telescope ARray (NuSTAR) solar campaign on 2014 December 11, with concurrent Solar Dynamics Observatory (SDO)/AIA and FOXSI-2 sounding rocket observations. The active region produced a medium-size solar flare 1 day before the observations, at ∼18 UT on 2014 December 10, with the post-flare loops still visible at the time of NuSTAR observations. The time evolution of the source emission in the SDO/AIA 335 Å channel reveals the characteristics of an extreme-ultraviolet late-phase event, caused by the continuous formation of new post-flare loops that arch higher and higher in the solar corona. The spectral fitting of NuSTAR observations yields an isothermal source, with temperature 3.8\ndash4.6 MK, emission measure (0.3\ndash1.8) × 10⁴⁶ cm‑3, and density estimated at (2.5\ndash6.0) × 10⁸ cm‑3. The observed AIA fluxes are consistent with the derived NuSTAR temperature range, favoring temperature values in the range of 4.0\ndash4.3 MK. By examining the post-flare loops\rsquo cooling times and energy content, we estimate that at least 12 sets of post-flare loops were formed and subsequently cooled between the onset of the flare and NuSTAR observations, with their total thermal energy content an order of magnitude larger than the energy content at flare peak time. This indicates that the standard approach of using only the flare peak time to derive the total thermal energy content of a flare can lead to a large underestimation of its value

The First Focused Hard X-ray Images of the Sun with NuSTAR

We present results from the the first campaign of dedicated solar observations undertaken by the Nuclear Spectroscopic Telescope ARray (NuSTAR) hard X-ray (HXR) telescope. Designed as an astrophysics mission, NuSTAR nonetheless has the capability of directly imaging the Sun at HXR energies (>3 keV) with an increase in sensitivity of at least two magnitude compared to current non-focusing telescopes. In this paper we describe the scientific areas where NuSTAR will make major improvements on existing solar measurements. We report on the techniques used to observe the Sun with NuSTAR, their limitations and complications, and the procedures developed to optimize solar data quality derived from our experience with the initial solar observations. These first observations are briefly described, including the measurement of the Fe K-shell lines in a decaying X-class flare, HXR emission from high in the solar corona, and full-disk HXR images of the Sun

Monitoring guidance for patients with hypophosphatasia treated with asfotase alfa.

Hypophosphatasia (HPP) is a rare, inherited, systemic, metabolic disorder caused by autosomal recessive mutations or a single dominant-negative mutation in the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). The disease is associated with a broad range of signs, symptoms, and complications, including impaired skeletal mineralization, altered calcium and phosphate metabolism, recurrent fractures, pain, respiratory problems, impaired growth and mobility, premature tooth loss, developmental delay, and seizures. Asfotase alfa is a human, recombinant enzyme replacement therapy that is approved in many countries for the treatment of patients with HPP. To address the unmet need for guidance in the monitoring of patients receiving asfotase alfa, an international panel of physicians with experience in diagnosing and managing HPP convened in May 2016 to discuss treatment monitoring parameters. The panel discussions focused on recommendations for assessing and monitoring patients after the decision to treat with asfotase alfa had been made and did not include recommendations for whom to treat. Based on the consensus of panel members, this review provides guidance on the monitoring of patients with HPP during treatment with asfotase alfa, including recommendations for laboratory, efficacy, and safety assessments and the frequency with which these should be performed during the course of treatment. Recommended assessments are based on patient age and include regular monitoring of biochemistry, skeletal radiographs, respiratory function, growth, pain, mobility and motor function, and quality of life. Because of the systemic presentation of HPP, a coordinated, multidisciplinary, team-based, patient-focused approach is recommended in the management of patients receiving asfotase alfa. Monitoring of efficacy and safety outcomes must be tailored to the individual patient, depending on medical history, clinical manifestations, availability of resources in the clinical setting, and the clinician's professional judgment

Genome-wide meta-analysis of common variant differences between men and women

The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency >0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P < 5 × 10−8) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across ∼115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased trait

A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

J. Kaprio, A. Palotie, A. Raevuori-Helkamaa ja S. Ripatti ovat työryhmän Eating Disorders Working Group of the Psychiatric Genomics Consortium jäseniä. Erratum in: Sci Rep. 2017 Aug 21;7(1):8379, doi: 10.1038/s41598-017-06409-3We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 x 10(-7); OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.Peer reviewe

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202