468 research outputs found

    Early childhood lung function is a stronger predictor of adolescent lung function in cystic fibrosis than early Pseudomonas aeruginosa infection

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    Pseudomonas aeruginosa has been suggested as a major determinant of poor pulmonary outcomes in cystic fibrosis (CF), although other factors play a role. Our objective was to investigate the association of early childhood Pseudomonas infection on differences in lung function in adolescence with CF

    Classifying Severity of Cystic Fibrosis Lung Disease Using Longitudinal Pulmonary Function Data

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    Rationale: The study of genetic modifiers in cystic fibrosis (CF) lung disease requires rigorous phenotyping. One type of genetic association study design compares polymorphisms in patients at extremes of phenotype, requiring accurate classification of pulmonary disease at varying ages

    Determining the Electronic Confinement of a Subsurface Metallic State

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    Dopant profiles in semiconductors are important for understanding nanoscale electronics. Highly conductive and extremely confined phosphorus doping profiles in silicon, known as Si:P δ-layers, are of particular interest for quantum computer applications, yet a quantitative measure of their electronic profile has been lacking. Using resonantly enhanced photoemission spectroscopy, we reveal the real-space breadth of the Si:P δ-layer occupied states and gain a rare view into the nature of the confined orbitals. We find that the occupied valley-split states of the δ-layer, the so-called 1Γ and 2Γ, are exceptionally confined with an electronic profile of a mere 0.40 to 0.52 nm at full width at half-maximum, a result that is in excellent agreement with density functional theory calculations. Furthermore, the bulk-like Si 3pz orbital from which the occupied states are derived is sufficiently confined to lose most of its pz-like character, explaining the strikingly large valley splitting observed for the 1Γ and 2Γ states

    Modulation of cystic fibrosis lung disease by variants in interleukin-8

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    Cystic fibrosis pulmonary disease is characterized by excessive and prolonged inflammation. CF Pulmonary disease severity exhibits considerable variation that, to some extent, appears to be due to the presence of modifier genes. Several components of the inflammatory response are known to have altered regulation in the CF lung. Genetic variants in 52 inflammatory genes were tested for associations with lung disease indices in a CF patient population (n=737) homozygous for the ΔF508 cystic fibrosis transmembrane conductance regulator mutation. Variants in 3 inflammatory genes showed significant genotypic associations with CF lung disease severity, including IL8 and previously reported TGFβ11 (p≤0.05). When analyzed by gender, it was apparent that IL8 variant associations were predominantly due to males. The IL8 variants were tested in an additional CF population (n=385) and the association in males verified (p≤0.01). The IL8 variants were in strong linkage disequilibrium with each other (R2≥0.82), while variants in neighboring genes CXCL6, RASSF6 and PF4V1 did not associate (p≥0.26) and were in weaker LD with each other and with the IL8 variants (0.01≤R2≤0.49). Studies revealed differential expression between the IL8 promoter variant alleles (p<0.001). These results suggest that IL8 variants modify CF lung disease severity and have functional consequences

    A BAC Transgene Expressing Human CFTR under Control of Its Regulatory Elements Rescues Cftr Knockout Mice

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    Small-molecule modulators of cystic fibrosis transmembrane conductance regulator (CFTR) biology show promise in the treatment of cystic fibrosis (CF). A Cftr knockout (Cftr KO) mouse expressing mutants of human CFTR would advance in vivo testing of new modulators. A bacterial artificial chromosome (BAC) carrying the complete hCFTR gene including regulatory elements within 40.1 kb of DNA 5? and 25 kb of DNA 3? to the gene was used to generate founder mice expressing hCFTR. Whole genome sequencing indicated a single integration site on mouse chromosome 8 (8qB2) with ~6 gene copies. hCFTR+ offspring were bred to murine Cftr KO mice, producing hCFTR+/mCftr? (H+/m?) mice, which had normal survival, growth and goblet cell function as compared to wild-type (WT) mice. Expression studies showed hCFTR protein and transcripts in tissues typically expressing mCftr. Functionally, nasal potential difference and large intestinal short-circuit (Isc) responses to cAMP stimulation were similar in magnitude to WT mice, whereas small intestinal cAMP ?Isc responses were reduced. A BAC transgenic mouse with functional hCFTR under control of its regulatory elements has been developed to enable the generation of mouse models of hCFTR mutations by gene editing for in vivo testing of new CF therapies

    The SMILE Soft X-ray Imager (SXI) CCD design and development

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    SMILE, the Solar wind Magnetosphere Ionosphere Link Explorer, is a joint science mission between the European Space Agency and the Chinese Academy of Sciences. The spacecraft will be uniquely equipped to study the interaction between the Earth’s magnetosphere-ionosphere system and the solar wind on a global scale. SMILE’s instruments will explore this science through imaging of the solar wind charge exchange soft X-ray emission from the dayside magnetosheath, simultaneous imaging of the UV northern aurora and in-situ monitoring of the solar wind and magnetosheath plasma and magnetic field conditions. The Soft X-ray Imager (SXI) is the instrument being designed to observe X-ray photons emitted by the solar wind charge exchange process at photon energies between 200 eV and 2000 eV. X-rays will be collected using a focal plane array of two custom-designed CCDs, each consisting of 18 µm square pixels in a 4510 by 4510 array. SMILE will be placed in a highly elliptical polar orbit, passing in and out of the Earth’s radiation belts every 48 hours. Radiation damage accumulated in the CCDs during the mission’s nominal 3-year lifetime will degrade their performance (such as through decreases in charge transfer efficiency), negatively impacting the instrument’s ability to detect low energy X-rays incident on the regions of the CCD image area furthest from the detector outputs. The design of the SMILE-SXI CCDs is presented here, including features and operating methods for mitigating the effects of radiation damage and expected end of life CCD performance. Measurements with a PLATO device that has not been designed for soft X-ray signal levels indicate a temperature-dependent transfer efficiency performance varying between 5 × 10−5 and 9 × 10−4 at expected End of Life for 5.9 keV photons, giving an initial set of measurements from which to extrapolate the performance of the SXI CCDs

    Not just for romance: applications of speed dating in social work education

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    In this article we address how a contemporary adaptation of the \u27speed dating\u27 model was used for educational purposes with two cohorts of social work students. We outline the dimensions of \u27speed dating\u27 as a contemporary social phenomenon, then address how this model relates specifically to groupwork process, and can be used to facilitate social work student learning. The curriculum for two classroom group activities using the \u27speed dating\u27 model are outlined, the first to develop university level study skills, the second for debriefing field placement learning experiences. Finally we examine why the \u27speed dating\u27 metaphor was successful in provoking a playful yet constructively creative space for students to engage in groupwork process.<br /

    Notes on a paper of Mess

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    These notes are a companion to the article "Lorentz spacetimes of constant curvature" by Geoffrey Mess, which was first written in 1990 but never published. Mess' paper will appear together with these notes in a forthcoming issue of Geometriae Dedicata.Comment: 26 page

    Atlantic Bluefin Tuna Tagging Programme in Ireland 2017

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    It is important that stock origin, habitat utilisation and large-scale movement patterns of Atlantic bluefin are characterised in detail to ensure that the population models and concepts used in Atlantic bluefin tuna stock assessment and Management Strategy Evaluation (MSE) are parameterised as accurately as possible. Investigation of the distribution and movements of Atlantic bluefin tuna in Irish waters is now a priority for Ireland. The ocean waters off south Donegal are now regarded by the International Commission for the Conservation of Atlantic Tuna (ICCAT) as an important area for Atlantic bluefin tuna and indications are that significant numbers arrive in the area over the period August to November each year. The Department of Agriculture Food and the Marine (DAFM) requested that the Marine Institute carry out a bluefin tagging programme in autumn 2016 to support the International Commission for the Conservation of Atlantic Tuna (ICCAT) Grand Bluefin Year Programme (GBYP) Atlantic research programme for Bluefin tuna
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