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    Seasonal H2O and CO2 Ice Cycles at the Mars Phoenix Landing Site: 1. Prelanding CRISM and HiRISE Observations

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    The condensation, evolution, and sublimation of seasonal water and carbon dioxide ices were characterized at the Mars Phoenix landing site from Martian northern midsummer to midspring (Ls ∼ 142° – Ls ∼ 60°) for the year prior to the Phoenix landing on 25 May 2008. Ice relative abundances and grain sizes were estimated using data from the Compact Reconnaissance Imaging Spectrometer for Mars and High Resolution Imaging Science Experiment aboard Mars Reconnaissance Orbiter and a nonlinear mixing model. Water ice first appeared at the Phoenix landing site during the afternoon in late summer (Ls ∼ 167°) as an optically thin layer on top of soil. CO2 ice appeared after the fall equinox. By late winter (Ls ∼ 344°), the site was covered by relatively pure CO2 ice (∼30 cm thick), with a small amount of ∼100 μm diameter water ice and soil. As spring progressed, CO2 ice grain sizes gradually decreased, a change interpreted to result from granulation during sublimation losses. The combined effect of CO2 sublimation and decreasing H2O ice grain sizes allowed H2O ice to dominate spectra during the spring and significantly brightened the surface. CO2 ice disappeared by early spring (Ls ∼ 34°) and H2O ice by midspring (Ls ∼ 59°). Spring defrosting was not uniform and occurred more rapidly over the centers of polygons and geomorphic units with relatively higher thermal inertia values

    Seasonal H2O and CO2 Ice Cycles at the Mars Phoenix Landing Site: 1. Prelanding CRISM and HiRISE Observations

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    The condensation, evolution, and sublimation of seasonal water and carbon dioxide ices were characterized at the Mars Phoenix landing site from Martian northern midsummer to midspring (Ls ∼ 142° – Ls ∼ 60°) for the year prior to the Phoenix landing on 25 May 2008. Ice relative abundances and grain sizes were estimated using data from the Compact Reconnaissance Imaging Spectrometer for Mars and High Resolution Imaging Science Experiment aboard Mars Reconnaissance Orbiter and a nonlinear mixing model. Water ice first appeared at the Phoenix landing site during the afternoon in late summer (Ls ∼ 167°) as an optically thin layer on top of soil. CO2 ice appeared after the fall equinox. By late winter (Ls ∼ 344°), the site was covered by relatively pure CO2 ice (∼30 cm thick), with a small amount of ∼100 μm diameter water ice and soil. As spring progressed, CO2 ice grain sizes gradually decreased, a change interpreted to result from granulation during sublimation losses. The combined effect of CO2 sublimation and decreasing H2O ice grain sizes allowed H2O ice to dominate spectra during the spring and significantly brightened the surface. CO2 ice disappeared by early spring (Ls ∼ 34°) and H2O ice by midspring (Ls ∼ 59°). Spring defrosting was not uniform and occurred more rapidly over the centers of polygons and geomorphic units with relatively higher thermal inertia values

    Effects of Ion Atomic Number on Single-Event Gate Rupture (SEGR) Susceptibility of Power MOSFETs

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    The relative importance of heavy-ion interaction with the oxide, charge ionized in the epilayer, and charge ionized in the drain substrate, on the bias for SEGR failure in vertical power MOSFETs is experimentally investigated. The results indicate that both the charge ionized in the epilayer and the ion atomic number are important parameters of SEGR failure. Implications on SEGR hardness assurance are discussed

    RNA buffers the phase separation behavior of prion-like RNA binding proteins

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    Prion-like RNA binding proteins (RBPs) such as TDP43 and FUS are largely soluble in the nucleus but form solid pathological aggregates when mislocalized to the cytoplasm. What keeps these proteins soluble in the nucleus and promotes aggregation in the cytoplasm is still unknown. We report here that RNAcritically regulates the phase behavior of prion-like RBPs. Low RNA/protein ratios promote phase separation into liquid droplets, whereas high ratios prevent droplet formation in vitro. Reduction of nuclear RNA levels or genetic ablation of RNA binding causes excessive phase separation and the formation of cytotoxic solid-like assemblies in cells. We propose that the nucleus is a buffered system in which high RNA concentrations keep RBPs soluble. Changes in RNA levels or RNA binding abilities of RBPs cause aberrant phase transitions.1125sciescopu

    The Breast Cancer and the Environment Research Centers: Transdisciplinary Research on the Role of the Environment in Breast Cancer Etiology

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    ObjectivesWe introduce and describe the Breast Cancer and the Environment Research Centers (BCERC), a research network with a transdisciplinary approach to elucidating the role of environmental factors in pubertal development as a window on breast cancer etiology. We describe the organization of four national centers integrated into the BCERC network.Data sourcesInvestigators use a common conceptual framework based on multiple levels of biologic, behavioral, and social organization across the life span. The approach connects basic biologic studies with rodent models and tissue culture systems, a coordinated multicenter epidemiologic cohort study of prepubertal girls, and the integration of community members of breast cancer advocates as key members of the research team to comprise the network.Data extractionRelevant literature is reviewed that describes current knowledge across levels of organization. Individual research questions and hypotheses in BCERC are driven by gaps in our knowledge that are presented at genetic, metabolic, cellular, individual, and environmental (physical and social) levels.Data synthesisAs data collection on the cohort, animal experiments, and analyses proceed, results will be synthesized through a transdisciplinary approach.ConclusionCenter investigators are addressing a large number of specific research questions related to early pubertal onset, which is an established risk factor for breast cancer. BCERC research findings aimed at the primary prevention of breast cancer will be disseminated to the scientific community and to the public by breast cancer advocates, who have been integral members of the research process from its inception

    Dermatologist-like explainable AI enhances trust and confidence in diagnosing melanoma

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    Although artificial intelligence (AI) systems have been shown to improve the accuracy of initial melanoma diagnosis, the lack of transparency in how these systems identify melanoma poses severe obstacles to user acceptance. Explainable artificial intelligence (XAI) methods can help to increase transparency, but most XAI methods are unable to produce precisely located domain-specific explanations, making the explanations difficult to interpret. Moreover, the impact of XAI methods on dermatologists has not yet been evaluated. Extending on two existing classifiers, we developed an XAI system that produces text and region based explanations that are easily interpretable by dermatologists alongside its differential diagnoses of melanomas and nevi. To evaluate this system, we conducted a three-part reader study to assess its impact on clinicians' diagnostic accuracy, confidence, and trust in the XAI-support. We showed that our XAI's explanations were highly aligned with clinicians' explanations and that both the clinicians' trust in the support system and their confidence in their diagnoses were significantly increased when using our XAI compared to using a conventional AI system. The clinicians' diagnostic accuracy was numerically, albeit not significantly, increased. This work demonstrates that clinicians are willing to adopt such an XAI system, motivating their future use in the clinic

    Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis

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    SummaryPolycythemia vera (PV), essential thrombocythemia (ET), and myeloid metaplasia with myelofibrosis (MMM) are clonal disorders arising from hematopoietic progenitors. An internet-based protocol was used to collect clinical information and biological specimens from patients with these diseases. High-throughput DNA resequencing identified a recurrent somatic missense mutation JAK2V617F in granulocyte DNA samples of 121 of 164 PV patients, of which 41 had homozygous and 80 had heterozygous mutations. Molecular and cytogenetic analyses demonstrated that homozygous mutations were due to duplication of the mutant allele. JAK2V617F was also identified in granulocyte DNA samples from 37 of 115 ET and 16 of 46 MMM patients, but was not observed in 269 normal individuals. In vitro analysis demonstrated that JAK2V617F is a constitutively active tyrosine kinase

    Anti-Müllerian Hormone Serum Concentrations of Women with Germline BRCA1 or 2 BRCA2 Mutations

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    Study funding/competing interest(s): kConFab is supported by a grant from the Australian National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. KAP is an Australian National Breast Cancer Foundation Practitioner Fellow. JLH is a NHMRC Senior Principal Research Fellow. MH is a NHMRC Practitioner Fellow. RA reports personal fees from Roche Diagnostics & Beckman Coulter outside the submitted work and CS reports other from Melbourne IVF outside the submitted work. The remaining authors have nothing to declare and no conflicts of interest.Study question: Do women with BRCA1 and BRCA2 mutations have reduced ovarian reserve, as measured by circulating anti-müllerian hormone (AMH) concentration?  Summary answer: Women with a germline mutation in BRCA1 have reduced ovarian reserve as measured by AMH.  What is known already: The DNA repair enzymes encoded by BRCA1 and BRCA2 are implicated in reproductive aging. Circulating AMH is a biomarker of ovarian reserve and hence reproductive lifespan.  Study design, size, duration: Cross-sectional study of AMH concentrations of 693 women at the time of enrolment into the Kathleen Cuningham Foundation Consortium for research into Familial Breast Cancer (kConFab) cohort study (recruitment from 19/08/1997 until 18/9/2012). AMH was measured on stored plasma samples between November 2014 and January 2015 using an electrochemiluminescence immunoassay platform.  Participants/materials, setting, methods: Eligible women were from families segregating BRCA1 or BRCA2 mutations and had known mutation status. Participants were aged 25 to 45 years, had no personal history of cancer, retained both ovaries and were not pregnant or breastfeeding at the time of plasma storage. Circulating AMH was measured for 172 carriers and 216 non-carriers from families carrying BRCA1 mutations, and 147 carriers and 158 non-carriers from families carrying BRCA2 mutations. Associations between plasma AMH concentration and carrier status were tested by linear regression, adjusted for age at plasma storage, oral contraceptive use, body mass index and cigarette smoking.  Main results and the role of chance: Mean AMH concentration was negatively associated with age (P < 0.001). Mutation carriers were younger at blood draw than non-carriers (P ≤ 0.031). BRCA1 mutation carriers had, on average, 25% (95% CI: 5% - 41%, P = 0.02) lower AMH concentrations than non-carriers and were more likely to have AMH concentrations in the lowest quartile for age (OR 1.84, 95% CI: 1.11-303, P=0.02). There was no evidence of an association between AMH concentration and BRCA2 mutation status (P = 0.94).  Limitations, reasons for caution: The clinical implications of the lower AMH concentrations seen in BRCA1 mutation carriers cannot be assessed by this study design.  Wider implications of the findings: Women with a germline mutation in BRCA1 may have reduced ovarian reserve. This is consistent with other smaller studies in the literature and has potential implications for fertility and reproductive lifespan. Publisher PDFPeer reviewe
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