High Resolution X-Ray Micro-CT of Ultra-Thin Wall Space Components

A high resolution micro-CT system has been assembled and is being used to provide optimal characterization for ultra-thin wall space components. The Glenn Research Center NDE Sciences Team, using this CT system, has assumed the role of inspection vendor for the Advanced Stirling Convertor (ASC) project at NASA. This article will discuss many aspects of the development of the CT scanning for this type of component, including CT system overview; inspection requirements; process development, software utilized and developed to visualize, process, and analyze results; calibration sample development; results on actual samples; correlation with optical/SEM characterization; CT modeling; and development of automatic flaw recognition software. Keywords: Nondestructive Evaluation, NDE, Computed Tomography, Imaging, X-ray, Metallic Components, Thin Wall Inspectio

South American fires and their impacts on ecosystems increase with continued emissions

Unprecedented fire events in recent years are leading to a demand for improved understanding of how climate change is already affecting fires, and how this could change in the future. Increased fire activity in South America is one of the most concerning of all the recent events, given the potential impacts on local ecosystems and the global climate from the loss of large carbon stores under future socio-environmental change. However, due to the complexity of interactions and feedbacks, and lack of complete representation of fire biogeochemistry in many climate models, there is currently low agreement on whether climate change will cause fires to become more or less frequent in the future, and what impact this will have on ecosystems. Here we use the latest climate simulations from the UK Earth System Model UKESM1 to understand feedbacks in fire, dynamic vegetation, and terrestrial carbon stores using the JULES land surface model, taking into account future scenarios of change in emissions and land use. Based on evaluation of model performance for the present day, we address the specific policy-relevant question: how much fire-induced carbon loss will there be over South America at different global warming levels in the future? We find that burned area and fire emissions are projected to increase in the future due to hotter and drier conditions, which leads to large reductions in carbon storage, especially when combined with increasing land-use conversion. The model simulates a 30% loss of carbon at 4°C under the highest emission scenario, which could be reduced to 7% if temperature rise is limited to 1.5°C. Our results provide a critical assessment of ecosystem resilience under future climate change, and could inform the way fire and land-use is managed in the future to reduce the most deleterious impacts of climate change

Disentangling the Regional Climate Impacts of Competing Vegetation Responses to Elevated Atmospheric CO₂

Biophysical vegetation responses to elevated atmospheric carbon dioxide (CO(2)) affect regional hydroclimate through two competing mechanisms. Higher CO(2) increases leaf area (LAI), thereby increasing transpiration and water losses. Simultaneously, elevated CO(2) reduces stomatal conductance and transpiration, thereby increasing rootzone soil moisture. Which mechanism dominates in the future is highly uncertain, partly because these two processes are difficult to explicitly separate within dynamic vegetation models. We address this challenge by using the GISS ModelE global climate model to conduct a novel set of idealized 2×CO(2) sensitivity experiments to: evaluate the total vegetation biophysical contribution to regional climate change under high CO(2); and quantify the separate contributions of enhanced LAI and reduced stomatal conductance to regional hydroclimate responses. We find that increased LAI exacerbates soil moisture deficits across the sub‐tropics and more water‐limited regions, but also attenuates warming by ∼0.5–1°C in the US Southwest, Central Asia, Southeast Asia, and northern South America. Reduced stomatal conductance effects contribute ∼1°C of summertime warming. For some regions, enhanced LAI and reduced stomatal conductance produce nonlinear and either competing or mutually amplifying hydroclimate responses. In northeastern Australia, these effects combine to exacerbate radiation‐forced warming and contribute to year‐round water limitation. Conversely, at higher latitudes these combined effects result in less warming than would otherwise be predicted due to nonlinear responses. These results highlight substantial regional variation in CO(2)‐driven vegetation responses and the importance of improving model representations of these processes to better quantify regional hydroclimate impacts

Implementation of U.K. Earth system models for CMIP6

We describe the scientific and technical implementation of two models for a core set of experiments contributing to the sixth phase of the Coupled Model Intercomparison Project (CMIP6). The models used are the physical atmosphere-land-ocean-sea ice model HadGEM3-GC3.1 and the Earth system model UKESM1 which adds a carbon-nitrogen cycle and atmospheric chemistry to HadGEM3-GC3.1. The model results are constrained by the external boundary conditions (forcing data) and initial conditions.We outline the scientific rationale and assumptions made in specifying these. Notable details of the implementation include an ozone redistribution scheme for prescribed ozone simulations (HadGEM3-GC3.1) to avoid inconsistencies with the model's thermal tropopause, and land use change in dynamic vegetation simulations (UKESM1) whose influence will be subject to potential biases in the simulation of background natural vegetation.We discuss the implications of these decisions for interpretation of the simulation results. These simulations are expensive in terms of human and CPU resources and will underpin many further experiments; we describe some of the technical steps taken to ensure their scientific robustness and reproducibility

Divergent Regional Climate Consequences of Maintaining Current Irrigation Rates in the 21st Century

There is strong evidence that the expansion and intensification of irrigation over the twentieth century has affected climate in many regions. However, it remains uncertain if these irrigation effects, including buffered warming trends, will weaken or persist under future climate change conditions. Using a 20-member climate model ensemble simulation, we demonstrate that irrigation will continue to attenuate greenhouse gas-forced warming and soil moisture drying in many regions over the 21st century, including Mexico, the Mediterranean, Southwest Asia, and China. Notably, this occurs without any further expansion or intensification of irrigation beyond current levels, even while greenhouse gas forcing steadily increases. However, the magnitude and significance of these moderating irrigation effects vary across regions and are highly sensitive to the background climate state and the degree to which evapotranspiration is supply (moisture) versus demand (energy) limited. Further, limitations on water and land availability may restrict our ability to maintain modern irrigation rates into the future. Nevertheless, it is likely that irrigation, alongside other components of intensive land management, will continue to strongly modulate regional climate impacts in the future. Irrigation should therefore be considered in conjunction with other key regional anthropogenic forcings (e.g., land cover change and aerosols) when investigating the local manifestation of global climate drivers (e.g., greenhouse gases) in model projections

A new strategy for isolating genes controlling dosage compensation in Drosophila using a simple epigenetic mosaic eye phenotype

<p>Abstract</p> <p>Background</p> <p>The <it>Drosophila </it>Male Specific Lethal (MSL) complex contains chromatin modifying enzymes and non-coding <it>roX </it>RNA. It paints the male X at hundreds of bands where it acetylates histone H4 at lysine 16. This epigenetic mark increases expression from the single male X chromosome approximately twofold above what gene-specific factors produce from each female X chromosome. This equalises X-linked gene expression between the sexes. Previous screens for components of dosage compensation relied on a distinctive male-specific lethal phenotype.</p> <p>Results</p> <p>Here, we report a new strategy relying upon an unusual male-specific mosaic eye pigmentation phenotype produced when the MSL complex acts upon autosomal <it>roX1 </it>transgenes. Screening the second chromosome identified at least five loci, two of which are previously described components of the MSL complex. We focused our analysis on the modifier alleles of MSL1 and MLE (for 'maleless'). The MSL1 lesions are not simple nulls, but rather alter the PEHE domain that recruits the MSL3 chromodomain and MOF ('males absent on first') histone acetyltransferase subunits to the complex. These mutants are compromised in their ability to recruit MSL3 and MOF, dosage compensate the X, and support long distance spreading from <it>roX1 </it>transgenes. Yet, paradoxically, they were isolated because they somehow increase MSL complex activity immediately around <it>roX1 </it>transgenes in combination with wild-type MSL1 subunits.</p> <p>Conclusions</p> <p>We propose that these diverse phenotypes arise from perturbations in assembly of MSL subunits onto nascent <it>roX </it>transcripts. This strategy is a promising alternative route for identifying previously unknown components of the dosage compensation pathway and novel alleles of known MSL proteins.</p

Teaching behaviors in the cardiac surgery simulation environment

OBJECTIVE: To understand how teaching behaviors contribute to simulation-based learning, we used a 7-category educational framework to assess the teaching behaviors used in basic skills training. METHODS: Twenty-four first-year cardiothoracic surgery residents and 20 faculty participated in the Boot Camp vessel anastomosis sessions. A portable chest model with synthetic graft and target vessels and a tissue-based porcine model simulated coronary artery anastomosis. After each 2-hour session on days 1 and 2, residents assessed teaching behaviors of faculty using a 20-item questionnaire based on the 5-point Likert scale. After session on day 1, faculty completed a self-assessment questionnaire. At 3 months, faculty completed self-assessment questionnaires regarding teaching behaviors in simulation and clinical settings. Each questionnaire item represents 1 or more teaching categories: "learning climate," "control of session," "communication of goals," "promoting understanding and retention," "evaluation," "feedback," and "self-directed learning." RESULTS: Generally, resident ratings indicated that faculty showed positive teaching behaviors. Faculty self-assessment ratings were all lower (P < .025) than those assigned to them by the residents except for 1 component representative of "feedback," which approached significance (P = .04); 2 items, representative of "promoting understanding and retention" and "evaluation", had mean scores of less than 3. At 3 months, compared with self-assessment at Boot Camp, faculty ratings suggested improved teaching behaviors in their simulation settings in the following: "learning climate," "control of session," "communication of goals," "promoting understanding and retention," and "evaluation." The simulation environment was perceived as more positive for technical skills training in certain aspects compared with clinical setting: instructor reviewed function and operation of equipment with learner before session (representative of "promoting understanding and retention") and instructor allowed the learner ample time to practice (representative of "control of session" and "promoting understanding and retention") (P < .025). CONCLUSIONS: Simulation-based skills training is perceived by residents to be associated with positive teaching behaviors. Faculty self-ratings indicate that they do not always use many of these teaching behaviors and that their performance can be improved. The simulation setting may provide greater opportunity for positive teaching behaviors compared with the clinical environment

Cost-utility of revisions for cervical deformity correction warrants minimization of reoperations.

Background: Cervical deformity (CD) surgery has become increasingly more common and complex, which has also led to reoperations for complications such as distal junctional kyphosis (DJK). Cost-utility analysis has yet to be used to analyze CD revision surgery in relation to the cost-utility of primary CD surgeries. The aim of this study was to determine the cost-utility of revision surgery for CD correction. Methods: Retrospective review of a multicenter prospective CD database. CD was defined as at least one of the following: C2-C7 Cobb \u3e10°, cervical lordosis (CL) \u3e10°, cervical sagittal vertical axis (cSVA) \u3e4 cm, chin-brow vertical angle (CBVA) \u3e25°. Quality-adjusted life year (QALY) were calculated by EuroQol Five-Dimensions questionnaire (EQ-5D) and Neck Disability Index (NDI) mapped to SF-6D index and utilized a 3% discount rate to account for residual decline to life expectancy (men: 76.9 years, women: 81.6 years). Medicare reimbursement at 30 days assigned costs for index procedures (9+ level posterior fusion, 4-8 level posterior fusion with anterior fusion, 2-3 level posterior fusion with anterior fusion, 4-8 level anterior fusion) and revision fusions (2-3 level, 4-8 level, or 9+ level posterior refusion). Cost per QALY gained was calculated. Results: Eighty-nine CD patients were included (61.6 years, 65.2% female). CD correction for these patients involved a mean 7.7±3.7 levels fused, with 34% combined approach surgeries, 49% posterior-only and 17% anterior-only, 19.1% three-column osteotomy. Costs for index surgeries ranged from $20,001-55,205, with the average cost for this cohort of$44,318 and cost per QALY of $27,267. Eleven revision surgeries (mean levels fused 10.3) occurred up to 1-year, with an average cost of$41,510. Indications for revisions were DJK (5/11), neurologic impairment [4], infection [1], prominent/painful instrumentation [1]. Average QALYs gained was 1.62 per revision patient. Cost was $28,138 per QALY for reoperations. Conclusions: CD revisions had a cost of$28,138 per QALY, in addition to the $27,267 per QALY for primary CD surgeries. For primary CD patients, CD surgery has the potential to be cost effective, with the caveats that a patient livelihood extends long enough to have the benefits and durability of the surgery is maintained. Efforts in research and surgical technique development should emphasize minimization of reoperation causes just as DJK that significantly affect cost utility of these surgeries to bring cost-utility to an acceptable range

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Modeling the mitochondrial cardiomyopathy of Barth syndrome with iPSC and heart-on-chip technologies

Studying monogenic mitochondrial cardiomyopathies may yield insights into mitochondrial roles in cardiac development and disease. Here, we combine patient-derived and genetically engineered iPSCs with tissue engineering to elucidate the pathophysiology underlying the cardiomyopathy of Barth syndrome (BTHS), a mitochondrial disorder caused by mutation of the gene Tafazzin (TAZ). Using BTHS iPSC-derived cardiomyocytes (iPSC-CMs), we defined metabolic, structural, and functional abnormalities associated with TAZ mutation. BTHS iPSC-CMs assembled sparse and irregular sarcomeres, and engineered BTHS “heart on chip” tissues contracted weakly. Gene replacement and genome editing demonstrated that TAZ mutation is necessary and sufficient for these phenotypes. Sarcomere assembly and myocardial contraction abnormalities occurred in the context of normal whole cell ATP levels. Excess levels of reactive oxygen species mechanistically linked TAZ mutation to impaired cardiomyocyte function. Our study provides new insights into the pathogenesis of Barth syndrome, suggests new treatment strategies, and advances iPSC-based in vitro modeling of cardiomyopathy