Laboratory Studies of Solid Carbon Dioxide in Planetary and Interstellar Ices

Laboratory spectra have shown that CO2. is a powerful diagnostic tool for analyzing infrared data from remote observations, as it has been detected on icy moons in the outer solar system as well as dust grain surfaces in the interstellar medium. IR absorption profiles of CO2 wi thin ice mixtures containing H2O and CH30H change with respect to tem perature and mixture ratios. In this particular study, the CO2 stretch mode around 235O cm (exp -1) (4.3 rricrons) is systematically observ ed in different mixtures with H2O and CH30H in temperature ranges from 15K to 150 K, as well as vibrational modes in the near-IR such as th e combination bands near 3700 cm (exp -1) (2.7 microns) and 5080 (exp -1) (2.0 microns). Additionally, some high?temperature deposits (T > 50 K) of H2O, CH30H, and CO2 ice mixtures were performed to determine the maximum temperatures at which CO2 will deposit on the sample win dow. These data may then be used to interpret spectra obtained from remote IR observations. This research was sponsored by Oak Ridge Associ ated Universities (ORAU) through the NASA Postdoctoral Program (NPP) as well as Ames Research Center and the SETI institute who provided fa cilities and equipment

‘It has really amazed me what my body can now do’: boundary work and the construction of a body-positive dance community

Boundaries around normative embodiments in physical cultures can be exclusionary if one’s embodied identity does not ‘fit’. Normative boundaries are particularly marked in codified forms of dance such as ballet. Moves towards body positivity aim to challenge these normative boundaries by redefining what dancers’ bodies can look like and how they should move. This paper stems from an appreciative inquiry undertaken with one such project, a gender-neutral, LGBTQ-friendly adult ballet school in the UK; a subcultural context that marks itself as distinct from broader cultures of dance. Interviews with learners are analysed through a Bourdieuian lens to explore the construction and maintenance of a body-positive subculture. Findings suggest that boundaries of ability were crossed, with celebration of all bodies’ capabilities, and boundaries of normative gender expression were transformed through a commitment to gender-neutrality and LGBTQ-friendly behaviours. However, boundaries around technical and aesthetic norms, while shifted or challenged, ultimately remained in place

“The Original Journals of ‘Kitty’ Wilmot”: manufacturing women’s travel writing in the salon of Helen Maria Williams

This article discusses the implications of a previously unknown Romantic-period manuscript by Anglo-Irish traveler Katherine Wilmot (1773–1824). A later version of Wilmot’s epistolary travelogue of 1801–03 has been valued as an artifact of British experience abroad during the Peace of Amiens for its descriptions of Napoleonic Paris. Yet the newly discovered draft reveals a deeper assimilation within and sympathy towards the radical political and literary networks Wilmot documented, as well as a budding relationship with author and salonnière Helen Maria Williams that is occluded from the later narrative. This article examines the complex choices surrounding authorship for British women abroad in the period by considering a refused invitation that Wilmot submit writing to The English Press, the publishing venture of Williams and her companion John Hurford Stone. The article details Wilmot’s evolving writing in terms of Williams’s influence, outlining how British women travel writers reshaped their experiences to meet the expectations of readers at home while also considering the impact of sedition, gendered agency, and political affinity on the production and reception of their writing

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist