Modeling of Stardust Entry at High Altitude, Part 1: Flowfield Analysis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83562/1/AIAA-37360-273.pd

NACHOS, a CubeSat-Based High-Resolution UV-Visible Hyperspectral Imager for Remote Sensing of Trace Gases: System Overview, Science Objectives, and Preliminary Results

The Nano-satellite Atmospheric Chemistry Hyperspectral Observation System (NACHOS) is a high-throughput (f/2.9), high spectral resolution (1.3 nm optical, 0.57 nm sampling) hyperspectral imager covering the 300-500 nm spectral region with 350 spectral bands. The combined 1.5U instrument payload and 1.5U spacecraft bus comprise a 3U CubeSat. Spectroscopically similar to NASA’s Ozone Monitoring Instrument (OMI), which provides wide-field coverage at ~20 km spatial resolution, NACHOS offers complementary targeted measurements at far higher spatial resolution of ~0.4 km/pixel from 500 km altitude over its 15 ̊ across-track field of view. NACHOS incorporates highly streamlined onboard gas-retrieval algorithms, alleviating the need to routinely downlink massive hyperspectral data cubes. This paper discusses the instrument design, requirements leading to it, preliminary results, and science goals, including monitoring NO2 as a proxy for anthropogenic greenhouse gases, low-level degassing of SO2 and halogen oxides at pre-eruptive volcanoes, and formaldehyde from wildfires. Aiming for an eventual many-satellite constellation providing both high spatial resolution and frequent target revisits, the current NACHOS project is launching two CubeSats, the first already launched to the International Space Station aboard the NG-17 Cygnus vehicle on February 19, 2022 and awaiting deployment to its final orbit in June, and the second launching June 29, 2022

The discovery of potent, selective, and reversible inhibitors of the house dust mite peptidase allergen Der p 1: an innovative approach to the treatment of allergic asthma.

Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma

Molecular Characterization of NRXN1 Deletions from 19,263 Clinical Microarray Cases Identifies Exons Important for Neurodevelopmental Disease Expression

PURPOSE: The purpose of the current study was to assess the penetrance of NRXN1 deletions. METHODS: We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant copy-number variations (CNVs) was used as a proxy to estimate the relative penetrance of NRXN1 deletions. RESULTS: We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability that were significantly greater than in controls (odds ratio (OR) = 8.14; 95% confidence interval (CI): 2.91-22.72; P \u3c 0.0001). Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3\u27 end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5\u27 NRXN1 deletion (OR = 7.47; 95% CI: 2.36-23.61; P = 0.0006). The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (P = 0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV at a prevalence twice as high as that for exonic NRXN1 deletion cases (P = 0.0035). CONCLUSIONS: The results support the importance of exons near the 5\u27 end of NRXN1 in the expression of neurodevelopmental disorders. Intronic NRXN1 deletions do not appear to substantially increase the risk for clinical phenotypes.Genet Med 19 1, 53-61

Attempts to Image the Early Inflammatory Response during Infection with the Lymphatic Filarial Nematode Brugia pahangi in a Mouse Model

Helminth parasites remain a major constraint upon human health and well-being in many parts of the world. Treatment of these infections relies upon a very small number of therapeutics, most of which were originally developed for use in animal health. A lack of high throughput screening systems, together with limitations of available animal models, has restricted the development of novel chemotherapeutics. This is particularly so for filarial nematodes, which are long-lived parasites with a complex cycle of development. In this paper, we describe attempts to visualise the immune response elicited by filarial parasites in infected mice using a non-invasive bioluminescence imaging reagent, luminol, our aim being to determine whether such a model could be developed to discriminate between live and dead worms for in vivo compound screening. We show that while imaging can detect the immune response elicited by early stages of infection with L3, it was unable to detect the presence of adult worms or, indeed, later stages of infection with L3, despite the presence of worms within the lymphatic system of infected animals. In the future, more specific reagents that detect secreted products of adult worms may be required for developing screens based upon live imaging of infected animals

Creative learning conversations: producing living dialogic spaces

publication-status: Publishedtypes: ArticleBackground ‘Creative learning conversations’, are methodological devices developed in two co-participative qualitative research projects exploring creativity and educational futures at the University of Exeter in England. Sources of evidence Framed by Critical Theory, the projects, one on dance education partnership, the other on student voice and transformation, sought to open space between creativity and performativity to initiate emancipatory educational change. This was undertaken over the course of five years in English primary and secondary schools, prioritising humanising, wise creativity (Chappell, 2008; Craft, 2008). Purpose This paper re-analyses data and methodological processes to characterise and theorise creative learning conversations in terms of social spatiality and dialogue. The characteristics are: partiality, emancipation, working from the ‘bottom up’, participation, debate and difference, openness to action, and embodied and verbalised idea exchange. Main argument This re-analysis theoretically adapts Bronfenbrenner’s (1979) ecological model to situate layered engagement. Utilising Lefebvre’s (1991) conceptualisation of Lived space and Bakhtin’s (1984) work on open-ended dialogue, the paper theorises creative learning conversations as producing living dialogic spaces. Conclusions Creative learning conversations are a way of contributing to change which moves us towards an education future fit for the twenty-first century. From a living dialogic space perspective a creative learning conversation is the ongoing process without forced closure of those in the roles of University academic, teachers, artists, students co-participatively researching and developing knowledge of their ‘lived space’ together. Given traditional lethargy in the educational system as a whole commitment to changing education for better futures demands active involvement in living dialogic space, where our humanity both emerges from and guides our shared learning

Long-term eclipse timing of white dwarf binaries: an observational hint of a magnetic mechanism at work

We present a long-term programme for timing the eclipses of white dwarfs in close binaries to measure apparent and/or real variations in their orbital periods. Our programme includes 67 close binaries, both detached and semi-detached and with M-dwarfs, K-dwarfs, brown dwarfs or white dwarfs secondaries. In total, we have observed more than 650 white dwarf eclipses. We use this sample to search for orbital period variations and aim to identify the underlying cause of these variations. We find that the probability of observing orbital period variations increases significantly with the observational baseline. In particular, all binaries with baselines exceeding 10 yr, with secondaries of spectral type K2 – M5.5, show variations in the eclipse arrival times that in most cases amount to several minutes. In addition, among those with baselines shorter than 10 yr, binaries with late spectral type (>M6), brown dwarf or white dwarf secondaries appear to show no orbital period variations. This is in agreement with the so-called Applegate mechanism, which proposes that magnetic cycles in the secondary stars can drive variability in the binary orbits. We also present new eclipse times of NN Ser, which are still compatible with the previously published circumbinary planetary system model, although only with the addition of a quadratic term to the ephemeris. Finally, we conclude that we are limited by the relatively short observational baseline for many of the binaries in the eclipse timing programme, and therefore cannot yet draw robust conclusions about the cause of orbital period variations in evolved, white dwarf binaries

INCITE: A randomised trial comparing constraint induced movement therapy and bimanual training in children with congenital hemiplegia

Background: Congenital hemiplegia is the most common form of cerebral palsy (CP) accounting for 1 in 1300 live births. These children have limitations in capacity to use the impaired upper limb and bimanual coordination deficits which impact on daily activities and participation in home, school and community life. There are currently two diverse intensive therapy approaches. Traditional therapy has adopted a bimanual approach (BIM training) and recently, constraint induced movement therapy (CIMT) has emerged as a promising unimanual approach. Uncertainty remains about the efficacy of these interventions and characteristics of best responders. This study aims to compare the efficacy of CIMT to BIM training to improve outcomes across the ICF for school children with congenital hemiplegia