Full-Shell X-Ray Optics Development at NASA Marshall Space Flight Center

NASAs Marshall Space Flight Center (MSFC) maintains an active research program toward the development of high-resolution, lightweight, grazing-incidence x-ray optics to serve the needs of future x-ray astronomy missions such as Lynx. MSFC development efforts include both direct fabrication (diamond turning and deterministic computer-controlled polishing) of mirror shells and replication of mirror shells (from figured, polished mandrels). Both techniques produce full-circumference monolithic (primary + secondary) shells that share the advantages of inherent stability, ease of assembly, and low production cost. However, to achieve high-angular resolution, MSFC is exploring significant technology advances needed to control sources of figure error including fabrication- and coating-induced stresses and mounting-induced distortions

A tale of two lakes: a multi-proxy comparison of Lateglacial and Holocene environmental change in Cappadocia, Turkey

Individual palaeoenvironmental records represent a combination of regional-scale (e.g. climatic) and site-specific local factors. Here we compare multiple climate proxies from two nearby maar lake records, assuming that common signals are due to regional-scale forcing. A new core sequence from Nar Lake in Turkey is dated by varves and U–Th to the last 13.8 ka. Markedly dry periods during the Lateglacial stadial, at 4.3–3.7 and at 3.2–2.6 ka BP, are associated with peaks in Mg/dolomite, positive δ18O, elevated diatom-inferred electrical conductivity, an absence of laminated sediments and low Quercus/chenopod ratios. Wet phases occurred during the early–mid Holocene and 1.5–0.6 ka BP, characterized by negative δ18O, calcite precipitation, high Ca/Sr ratios, a high percentage of planktonic diatoms, laminated sediments and high Quercus/chenopod ratios. Comparison with the record from nearby Eski Acıgöl shows good overall correspondence for many proxies, especially for δ18O. Differences are related to basin infilling and lake ontogeny at Eski Acıgöl, which consequently fails to register climatic changes during the last 2 ka, and to increased flux of lithogenic elements into Nar Lake during the last 2.6 ka, not primarily climatic in origin. In attempting to separate a regional signal from site-specific ‘noise’, two lakes may therefore be better than one

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Tracking the hydro-climatic signal from lake to sediment: a field study from central Turkey

Palaeo-hydrological interpretations of lake sediment proxies can benefit from a robust understanding of the modern lake environment. In this study, we use Nar Gölü, a non-outlet, monomictic maar lake in central Turkey, as a field site for a natural experiment using observations and measurements over a 17-year monitoring period (1997–2014). We compare lake water and sediment trap data to isotopic, chemical and biotic proxies preserved in its varved sediments. Nar Gölü underwent a 3 m lake-level fall between 2000 and 2010. δ18Olakewater is correlated with this lake-level fall, responding to the change in water balance. Endogenic carbonate is shown to precipitate in isotopic equilibrium with lake water and there is a strong relationship between δ18Olakewater and δ18Ocarbonate, which suggests the water balance signal is accurately recorded in the sediment isotope record. Over the same period, sedimentary diatom assemblages also responded, and conductivity inferred from diatoms showed a rise. Shifts in carbonate mineralogy and elemental chemistry in the sediment record through this decade were also recorded. Intra-annual changes in δ18Olakewater and lake water chemistry are used to demonstrate the seasonal variability of the system and the influence this may have on the interpretation of δ18Ocarbonate. We use these relationships to help interpret the sedimentary record of changing lake hydrology over the last 1725 years. Nar Gölü has provided an opportunity to test critically the chain of connection from present to past, and its sedimentary record offers an archive of decadal- to centennial-scale hydro-climatic chang

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

ARIA 2016:Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease

Involvement of the Gut Microbiome in the Local and Systemic Immune Response to Pancreatic Ductal Adenocarcinoma

Simple Summary: One of the reasons that pancreatic cancer is such a deadly disease is that it is able to evade the body’s usual defence system (the immune system). It has been shown that the population of microorganisms in the human gut (the gut microbiome) plays a role in regulating the human immune system. This article outlines the ways in which the gut microbiome influences the immune system in pancreatic cancer both within the bloodstream (systemic) and around the pancreatic tumour itself (local). These are important mechanisms because greater understanding of these will direct the development of future treatments for pancreatic cancer. It is possible that some of these treatment options will target the gut microbiome in order to boost the immune system’s response to pancreatic cancer. Abstract: The systemic and local immunosuppression exhibited by pancreatic ductal adenocarcinoma (PDAC) contributes significantly to its aggressive nature. There is a need for a greater understanding of the mechanisms behind this profound immune evasion, which makes it one of the most challenging malignancies to treat and thus one of the leading causes of cancer death worldwide. The gut microbiome is now thought to be the largest immune organ in the body and has been shown to play an important role in multiple immune-mediated diseases. By summarizing the current literature, this review examines the mechanisms by which the gut microbiome may modulate the immune response to PDAC. Evidence suggests that the gut microbiome can alter immune cell populations both in the peripheral blood and within the tumour itself in PDAC patients. In addition, evidence suggests that the gut microbiome influences the composition of the PDAC tumour microbiome, which exerts a local effect on PDAC tumour immune infiltration. Put together, this promotes the gut microbiome as a promising route for future therapies to improve immune responses in PDAC patients