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Paul O’Brien,1 Ashley Enstone,2 Daisy Bridge,2 Robin Wyn,2 Judit Banhazi3 1Novartis Ireland, Dublin, Ireland; 2Adelphi Values PROVE, Bollington, UK; 3Novartis Pharma AG, Basel, SwitzerlandCorrespondence: Paul O’Brien, Email paul-2.obrien@novartis.comIntroduction: Retinitis pigmentosa (RP) is an inherited retinal pathology associated with “night blindness” and progressive loss of peripheral vision, in some cases leading to complete blindness. Health state utility values are required for activities such as modelling disease burden or the cost-effectiveness of new interventions. The current study aimed to generate utility values for health states of varying levels of functional vision in RP, with members of the general public in the UK.Methods: Five health states were defined according to standard clinical measures of visual ability. Health state descriptions were developed following interviews with patients with RP in the UK (n=5). Further interviews were conducted for confirmation with healthcare professionals with specific experience of managing patients with RP in the UK (n=2). Interviews with members of the general public in the UK were conducted to value health states. A time trade-off (TTO) process based on the established Measurement and Valuation of Health (MVH) protocol was used. Due to the ongoing COVID-19 pandemic, all interviews were web-enabled and conducted 1:1 by a trained moderator.Results: In total, n=110 TTO interviews were conducted with members of the UK general public. Mean TTO utility values followed the logical and expected order, with increasing visual impairment leading to decreased utility. Mean values varied between 0.78 ± 0.20 (“moderate impairment”), and 0.33 ± 0.26 (“hand motion” to “no light perception”). Supplementary visual analogue scale (VAS) scores also followed the logical and expected order: mean VAS values varied between 47.95 ± 15.38 (“moderate impairment”) and 17.22 ± 12.49 in (“hand motion” to “no light perception”).Discussion: These data suggest that individuals living with RP have substantially impaired quality of life. Utility values for RP have been elicited here using a method and sample that is suitable for economic modelling and health technology assessment purposes.Keywords: retinitis pigmentosa, inherited retinal disease, health state utility, health-related quality of life, time trade-off, vignette study

In this paper we describe the potential of the enhanced X-ray Timing and Polarimetry (eXTP) mission for studies related to accretion flows in the strong field gravity regime around both stellar-mass and supermassive black-holes. eXTP has the unique capability of using advanced 'spectral-timing-polarimetry' techniques to analyze the rapid variations with three orthogonal diagnostics of the flow and its geometry, yielding unprecedented insight into the inner accreting regions, the effects of strong field gravity on the material within them and the powerful outflows which are driven by the accretion process., Accepted for publication on Sci. China Phys. Mech. Astron. (2019)

Energy demand has significantly increased in building sectors over the past decade because of population growth, increased indoor activities, and increased energy requirements for controlling the internal environment due to global climate change. The residential sector accounts for 32% of the total energy consumption. Space and water heating account for most of the fossil fuel use in residential buildings. Several studies have been done to optimize the design of heat transfer fins and channels in space and water heating systems to improve their efficiency. In this study the effects of the cross-sectional shape of air-channels on heat transfer from the channels to the air is investigated. Air channels with circular, triangular, rectangular and sinusoidal shaped cross sections are considered. Further, heat transfer to air flowing through beds comprising these air channels are also investigated. Numerical analyses is performed to investigate the dependency of the outlet temperatures to optimize the shape of the air channels and beds. Results show the sinusoidal channel and bed have better performance in relation to the outlet temperature. Considering channels with a length of 100 mm, a surface area of 1770 m2, and a wall-to-air heat transfer rate of 790 W/m2, the air outlet temperature for the sinusoidal channel is about 57°C higher than that of the circular channel. Considering beds with a height of 5 mm and wall-to-air heat transfer rate of 790 W/m2, the outlet temperature of the sinusoidal bed is about 10°C higher than the outlet temperature for a rectangular bed with similar surface area. The results are applicable to the design of thermal energy storage units that could be used directly or indirectly (such as adsorbent beds for thermal energy storages) to supply heat to air within HVAC systems.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0281980 Governments around the world have acknowledged that urgent action is needed to conserve and restore ecological connectivity to help reverse the decline of biodiversity. In this study we tested the hypothesis that functional connectivity for multiple species can be estimated across Canada using a single, upstream connectivity model. We developed a movement cost layer with cost values assigned using expert opinion to anthropogenic land cover features and natural features based on their known and assumed effects on the movement of terrestrial, non-volant fauna. We used Circuitscape to conduct an omnidirectional connectivity analysis for terrestrial landscapes, in which the potential contribution of all landscape elements to connectivity were considered and where source and destination nodes were independent of land tenure. Our resulting map of mean current density provided a seamless estimate of movement probability at a 300 m resolution across Canada. We tested predictions in our map using a variety of independently collected wildlife data. We found that GPS data for individual caribou, wolves, moose, and elk that traveled longer distances in western Canada were all significantly correlated with areas of high current densities. The frequency of moose roadkill in New Brunswick was also positively associated with current density, but our map was not able to predict areas of high road mortality for herpetofauna in southern Ontario. The results demonstrate that an upstream modelling approach can be used to characterize functional connectivity for multiple species across a large study area. Our national connectivity map can help governments in Canada prioritize land management decisions to conserve and restore connectivity at both national and regional scales.

This thesis was scanned from the print manuscript for digital preservation and is copyright the author. Researchers can access this thesis by asking their local university, institution or public library to make a request on their behalf. Monash staff and postgraduate students can use the link in the References field.

Additional file 4. The manual of HIFI-SE package.

Additional file 1: Figure S1. Read counts of the Sanger barcode failed samples. Stars indicate samples of which short amplicon(s) was detected in the HIFI assemblies. Short amplicons are those clusters of abundance > 10 and of length

Additional file 3. Library construction protocol of MGISEQ-2000 SE400 module.

Additional file 5. A note for taxonomy identification issue of sample #035 in plate #4.

Thin films of Cd1−x Zn x S (CZS) were prepared by a novel spin coating/melt method from cadmium ethylxanthato [Cd(C2H5OCS2)2] and zinc ethylxanthato [Zn(C2H5OCS2)2] in x ratios of 0–0.15 and of 1. A solution of the precursor(s) in THF was spin coated onto a glass substrate and then heated at 250 °C for 1 h under N2. The thickness of the film formed can be controlled by varying the solution composition and/or the spin rate of the coating. A total metal precursor solution concentration of 50 mM was used in all cases. The films were characterized by p-XRD, SEM, EDX, ICP-AES, XPS, UV–Vis absorption spectroscopy, Raman spectroscopy and resistivity measurements. The band gaps of the films were between 2.35–2.58 and 3.75 eV (0 ≤ x ≤ 0.15 and at x = 1). The resistivity of Cd1−x Zn x S films was found to vary linearly with zinc contents, and the properties of the films suggest potential application to photovoltaics as window layers. This work is the first study to demonstrate Cd1−x Zn x S thin films by a spin coating/melt method from xanthato precursors.

One of the central scientific goals of the next-generation Cherenkov Telescope Array (CTA) is the detection and characterization of gamma-ray bursts (GRBs). CTA will be sensitive to gamma rays with energies from about 20 GeV, up to a few hundred TeV. The energy range below 1 TeV is particularly important for GRBs. CTA will allow exploration of this regime with a ground-based gamma-ray facility with unprecedented sensitivity. As such, it will be able to probe radiation and particle acceleration mechanisms at work in GRBs. In this contribution, we describe POSyTIVE, the POpulation Synthesis Theory Integrated project for very high-energy emission. The purpose of the project is to make realistic predictions for the detection rates of GRBs with CTA, to enable studies of individual simulated GRBs, and to perform preparatory studies for time-resolved spectral analyses. The mock GRB population used by POSyTIVE is calibrated using the entire 40-year dataset of multi-wavelength GRB observations. As part of this project we explore theoretical models for prompt and afterglow emission of long and short GRBs, and predict the expected radiative output. Subsequent analyses are performed in order to simulate the observations with CTA, using the publicly available ctools and Gammapy frameworks. We present preliminary results of the design and implementation of this project., Comment: 8 pages, Proceedings of the 36th International Cosmic Ray Conference, PoS(ICRC2019)598

The structural dynamics of proteins and other macromolecules typically serve crucial roles for their respective biological function. While rigid protein structures are used in classic “lock and key” descriptions of enzymology and receptor-ligand interactions, more and more evidence suggest that the majority of molecular interactions occur on the spectrum between induced-fit binding and conformational selection binding. This model of biomolecular interaction requires, to differing degrees, conformation plasticity and dynamics of the protein itself. To characterize the determinants and implications of protein dynamics, there exists no more suited biophysical technique than nuclear magnetic resonance (NMR) spectroscopy. This method is capable of probing the individual atomic nuclei of proteins in a site-specific manner. Furthermore, NMR spectroscopy is unique in being able to access timescales from picoseconds to seconds, providing information on events from bond vibration and libration to protein folding and ligand binding. The breadth of biophysical information accessible by NMR spectroscopy has led to its widespread use in the study of protein dynamics. The work presented herein involves i) the use of NMR for investigation of structure and dynamics in two separate biological systems that demonstrate a high degree of flexibility for folded proteins and ii) the improvement of pulse sequences and methodology for better characterizing picosecond to nanosecond backbone and side-chain dynamics. The organizing principle of this work, which is best exemplified in the structural studies of the piRNA-pathway protein Gametocyte-specific factor 1, is the unmatched capability of NMR spectroscopy to decipher molecular details within dynamic protein systems. First, the molecular structure and RNA-binding properties of gametocyte-specific factor 1 (GTSF1) of the piRNA effector pathway were investigated. A partially disordered protein with two Zn finger domains, the work presented here describes the isolation of a GTSF1 protein construct amendable to study by NMR spectroscopy. Chemical shift assignment of GTSF1 allowed site-specific observation of amide correlations, which established the basis for NMR structure calculation of GTSF1 and the evaluation of binding to candidate RNA sequences, with goal of the identification of an in vivo RNA binding partner for GTSF1. The work presents compelling data that indicate GTSF1 Zn finger 1 specifically binds a motif GGUUC(G/A) RNA, which in this study was found in the T-arm loop of transfer RNA. Zn finger 2 is affected by the interaction with RNA, but the available structural and binding data indicate that the second Zn finger is a more dynamic, breathable entity, supported by cysteine chemical shift and structural differences between the two GTSF1 Zn fingers. Although it’s currently speculative, the function of GTSF1 might first require binding of RNA to the more stable Zn finger 1, which then leaves Zn finger 2 poised for binding to another molecular species. tRNA-derived fragments that include the T-arm TC loop have been recently implicated in silencing of transposable elements in mammalian cells. GTSF1, which was identified in a genetic screen for piRNA-pathway proteins as vitally required for gene silencing, might plausibly act as a sensor of transcription of transposable elements and help initiate Piwi-piRISCs-mediated chromatin modification and heterochromatin formation. Next, NMR spectroscopy is used to investigate protein thermostability in psychrophilic (cold-loving) cytochrome c552. Isolated from the bacterium Colwellia psychrerythraea (Cp), previous work has implicated two conserved Cpcyt c552 methionine residues, which are both conserved across psychrophilic and psychrotolerant cytochromes, as acting in dynamical ligand substitution with a third methionine that is the axial heme ligand. It is proposed that elevated backbone dynamics in these methionine residues and the ability for them swap into the axial ligand position accounts for an uncharacteristically high melting temperature (Tm) compared to meso- and thermophile c-type cytochromes. Progress was made in NMR sample preparation and backbone chemical shift assignment of both redox states of Cpcyt c552, and insight from 1D 1H NMR experiments focused on the heme group bound to Cp cytochrome c552 is discussed. Additionally, chemical shifts are used to predict protein dynamics as a first test of a multiple methionine axial ligand hypothesis. Initial data analysis predicts relatively large measures of Random Coil Index for residues surrounding the native axial heme ligand, and shows the hyperfine shifts localized to the residues surrounding the heme. Future experiments will selectively record methyl group dynamics of methionine residues for elucidation of rate constants of methionine substitution and to determine the structural properties of this minor conformation. Finally, two NMR methodology studies are presented in this thesis: a novel simultaneous-acquisition TROSY pulse sequence for measurement of backbone spin relaxation rates (R1 and {1H}-15N heteronuclear NOE) and a side-chain 2H spin relaxation method for using multifield experimental datasets for better sampling of the spectral density function. Together, these pulse sequences represent significant advancements in NMR measurement of microscopic rate constants and more nuanced detail of protein dynamics.

The synthesis of the asymmetric dithiocarbamates of tin(II) with the formula [Sn(S2CNRR׳)2] (where R=Et, R׳=n-Bu (1); R=Me, R׳=n-Bu (2); R=R׳=Et (3)) and their use for the deposition of SnS thin films by aerosol-assisted chemical vapour deposition (AACVD) is described. The effects of temperature and the concentration of the precursors on deposition were investigated. The stoichiometry of SnS was best at higher concentrations of precursors (250mM) and at 450°C. The direct electronic band gap of the SnS produced by this method was estimated from optical absorbance measurements as 1.2eV. The composition of films was confirmed by powder X-ray diffraction (p-XRD) and energy dispersive analysis of X-rays (EDAX) spectroscopy.

In 'Out of Time: Reflections on the Programming Life', Ellen Ullman writes that a senior (male) engineer once asked her why she left full-time engineering for consulting. She replied that she found the engineering culture very 'teenage-boy puerile'. The engineer replied to the effect that such loss of talent was too bad.

X-ray variability in cool stars can be indicative of coronal magnetic field changes and reconfiguration from a variety of phenomena, including flare events (typical timescales of minutes – hours), active-region evolution (hours – days – weeks), rotational modulation (hours – days – weeks), and activity cycles (years – decades). As part of the EXTraS project (Exploring the X-ray transient and variable sky - http://www.extras-fp7.eu/ ), we are performing a survey of ‘long-term’ X-ray variability using the ~decade-long public database of XMM-Newton observations. We are thus focussing here on timescales from ~a day to ~a decade, using average flux values from individual XMM-Newton observations. Though the resulting sampling is often highly non-uniform in time, the light-curves can provide valuable insights into the magnetic activity outside of shorter-term flaring episodes. We have taken a number of stellar samples (Hipparcos-Tycho, Simbad …) and are evaluating the statistical properties of the flux distributions, and comparing these across, for example spectral type, and with previously-published estimates. We are also examining the potential effects of flare events on the apparent long-term variability estimates. We give a preliminary report both on the overall variability distributions and extreme cases, distinguishing between serendipitously-observed stars (yielding, in some sense an unbiased sample) and XMM-Newton target objects (a number of them already reported by other authors).

Context: Nontoxic multinodular goiter (MNG) is frequently observed in the general population, but little is known about the underlying genetic susceptibility to this disease. Familial cases ofMNGhave been reported, and published reports describe 5 families that also contain at least 1 individual with a Sertoli-Leydig cell tumor of the ovary (SLCT). Germline mutations in DICER1, a gene that codes for an RNase III endoribonuclease, have been identified in families affected by pleuropulmonary blastoma (PPB), some of whom include cases of MNG and gonadal tumors such as SLCTs. Objective: To determine whether familial MNG with or without SLCT in the absence of PPB was associated with mutations in DICER1. Design, Setting, and Patients: From September 2009 to September 2010, we screened 53 individuals from 2 MNG and 3 MNG/SLCT families at McGill University for mutations in DICER1. We investigated blood lymphocytes and MNG and SLCT tissue from family members for loss of the wild-type DICER1 allele (loss of heterozygosity), DICER1 expression, and microRNA (miRNA) dysregulation. Main OutcomeMeasure: Detection of germline DICER1 gene mutations in familial MNG with and without SLCT. Results: We identified and characterized germline DICER1 mutations in 37 individuals from 5 families. Two mutations were predicted to be protein truncating, 2 resulted in inframe deletions, and 1 was a missense mutation. Molecular analysis of the 3 SLCTs showed no loss of heterozygosity of DICER1, and immunohistochemical analysis in 2 samples showed strong expression of DICER1 in Sertoli cells but weak staining of Leydig cells. miRNA profiling of RNA from lymphoblastoid cell lines from both affected and unaffected members of the familial MNG cases revealed miRNA perturbations in DICER1 mutation carriers. Conclusions: DICER1 mutations are associated with both familial MNG and MNG with SLCT, independent of PPB. These germline DICER1 mutations are associated with dysregulation of miRNA expression patterns. ©2011 American Medical Association. All rights reserved.

Significant elemental segregation is shown to exist within individual hollow silver–gold (Ag–Au) bimetallic nanoparticles obtained from the galvanic reaction between Ag particles and AuCl4–. Three-dimensional compositional mapping using energy dispersive X-ray (EDX) tomography within the scanning transmission electron microscope (STEM) reveals that nanoparticle surface segregation inverts from Au-rich to Ag-rich as Au content increases. Maximum Au surface coverage was observed for nanoparticles with approximately 25 atom % Au, which correlates to the optimal catalytic performance in a three-component coupling reaction among cyclohexane carboxyaldehyde, piperidine, and phenylacetylene.

Iron chalcogenides have been given much attention due to their exciting electronic and magnetic properties. Iron sulfides exhibits a wide range of phases ranging from the semiconducting non-magnetic pyrite (FeS2) (Eg = 0.8-0.95 eV) to ferromagnetic greigite (Fe3S4) phase. vPotential applications include: information storage devices, catalysis, solar cells, biomedicine, imaging, and sensors. Iron selenide has a direct band gap of 1.23 eV and can be semiconductor, or even superconductor with the characteristics of ferro /ferrimagnetic metals. Herein, We report a simple synthesis of iron chalcogenide nanocrystals in one pot.

This study explores how a group of post-2004 Polish migrants have adapted to life in the UK. Eight participants were interviewed and transcripts were analysed using the qualitative methodology of interpretative phenomenological analysis. Four master themes emerged: relating to Poland; relating to the UK; impact on self; and adaptive ability. Migrants’ relationship with Poland and the UK is considered and the psychological impact of migration on the individual is explored. The findings suggest that migration brings benefits as well as challenges. It is evident that participants are equipped with a range of adaptive characteristics and employ a variety of strategies to cope with difficulties, and these are explored in detail. Exploring identity processes reveals that participants’ adaptation is aided by prior identification with UK and ‘Western culture’, which is understood as a reflection of the socio-economic changes taking place in Poland since 1989. Theoretical implications and relevance of the findings to the field of counselling psychology are considered and further areas of exploration are discussed.

We systematically analyze the prompt emission and the early afterglow data of a sample of 31 GRBs detected by {\em Swift} before September 2005, and estimate the GRB radiative efficiency. BAT's narrow band inhibits a precise determination of the GRB spectral parameters, and we have developed a method to estimate these parameters with the hardness ratio information. The shallow decay component commonly existing in early X-ray afterglows, if interpreted as continuous energy injection in the external shock, suggests that the GRB efficiency previously derived from the late-time X-ray data were not reliable. We calculate two radiative efficiencies using the afterglow kinetic energy E_K derived at the putative deceleration time t_{dec}) and at the break time (t_b) when the energy injection phase ends, respectively. At t_b XRFs appear to be less efficient than normal GRBs. However, when we analyze the data at t_{dec} XRFs are found to be as efficient as GRBs. Short GRBs have similar radiative efficiencies to long GRBs despite of their different progenitors. Twenty-two bursts in the sample are identified to have the afterglow cooling frequency below the X-ray band. Assuming \epsilon_e = 0.1, we find \eta_\gamma(t_b) usually 90%. Nine GRBs in the sample have the afterglow cooling frequency above the X-ray band for a very long time. This suggests a very small \epsilon_B and/or a very low ambient density n., Comment: 43 pages, 10 figures, ApJ, in press

High-velocity outflows from AGN are a well-known phenomena in terms of the Broad Absorption Lines seen in the UV/optical. More recently, similar, possibly related, outflows have been reported in the X-ray. The most extreme example is seen in the nearby, luminous QSO PDS 456, which displays a massive, high velocity (50000 km s-1), high-ionization X-ray outflow of 10 solar masses yr-1. Here we present the UV spectrum of PDS 456 as observed by the Hubble Space Telescope. We find the UV spectrum is also extreme, displaying very broad emission-lines, with CIV 1549 blueshifted by 5000 km s-1 and a broad Ly-alpha absorption trough blueshifted by 14000-24000 km s-1. No strong, broad high-ionization absorption features are seen. We interpret the combined UV and X-ray spectrum of PDS 456 as the signature of a decelerating, cooling outflow, which may be driven by radiation and/or magnetic field. This outflow may be the source of some of the broad emission and absorption-line gas., Comment: Accepted for publication in MNRAS. 6 pages. 6 figures

This White Paper, submitted to the recent ESA call for science themes to define its future large missions, advocates the need for a transformational leap in our understanding of two key questions in astrophysics: 1) How does ordinary matter assemble into the large scale structures that we see today? 2) How do black holes grow and shape the Universe? Hot gas in clusters, groups and the intergalactic medium dominates the baryonic content of the local Universe. To understand the astrophysical processes responsible for the formation and assembly of these large structures, it is necessary to measure their physical properties and evolution. This requires spatially resolved X-ray spectroscopy with a factor 10 increase in both telescope throughput and spatial resolving power compared to currently planned facilities. Feedback from supermassive black holes is an essential ingredient in this process and in most galaxy evolution models, but it is not well understood. X-ray observations can uniquely reveal the mechanisms launching winds close to black holes and determine the coupling of the energy and matter flows on larger scales. Due to the effects of feedback, a complete understanding of galaxy evolution requires knowledge of the obscured growth of supermassive black holes through cosmic time, out to the redshifts where the first galaxies form. X-ray emission is the most reliable way to reveal accreting black holes, but deep survey speed must improve by a factor ~100 over current facilities to perform a full census into the early Universe. The Advanced Telescope for High Energy Astrophysics (Athena+) mission provides the necessary performance (e.g. angular resolution, spectral resolution, survey grasp) to address these questions and revolutionize our understanding of the Hot and Energetic Universe. These capabilities will also provide a powerful observatory to be used in all areas of astrophysics.

International audience; One of the central scientific goals of the next-generation Cherenkov Telescope Array (CTA) is the detection and characterization of gamma-ray bursts (GRBs). CTA will be sensitive to gamma rays with energies from about 20 GeV, up to a few hundred TeV. The energy range below 1 TeV is particularly important for GRBs. CTA will allow exploration of this regime with a ground-based gamma-ray facility with unprecedented sensitivity. As such, it will be able to probe radiation and particle acceleration mechanisms at work in GRBs. In this contribution, we describe POSyTIVE, the POpulation Synthesis Theory Integrated project for very high-energy emission. The purpose of the project is to make realistic predictions for the detection rates of GRBs with CTA, to enable studies of individual simulated GRBs, and to perform preparatory studies for time-resolved spectral analyses. The mock GRB population used by POSyTIVE is calibrated using the entire 40-year dataset of multi-wavelength GRB observations. As part of this project we explore theoretical models for prompt and afterglow emission of long and short GRBs, and predict the expected radiative output. Subsequent analyses are performed in order to simulate the observations with CTA, using the publicly available ctools and Gammapy frameworks. We present preliminary results of the design and implementation of this project.