2,171 research outputs found

    High-Resolution Patterned Cellular Constructs by Droplet-Based 3D Printing.

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    Bioprinting is an emerging technique for the fabrication of living tissues that allows cells to be arranged in predetermined three-dimensional (3D) architectures. However, to date, there are limited examples of bioprinted constructs containing multiple cell types patterned at high-resolution. Here we present a low-cost process that employs 3D printing of aqueous droplets containing mammalian cells to produce robust, patterned constructs in oil, which were reproducibly transferred to culture medium. Human embryonic kidney (HEK) cells and ovine mesenchymal stem cells (oMSCs) were printed at tissue-relevant densities (10(7) cells mL(-1)) and a high droplet resolution of 1 nL. High-resolution 3D geometries were printed with features of ≤200 μm; these included an arborised cell junction, a diagonal-plane junction and an osteochondral interface. The printed cells showed high viability (90% on average) and HEK cells within the printed structures were shown to proliferate under culture conditions. Significantly, a five-week tissue engineering study demonstrated that printed oMSCs could be differentiated down the chondrogenic lineage to generate cartilage-like structures containing type II collagen

    Allocating the Burdens of Climate Action: Consumption-Based Carbon Accounting and the Polluter-Pays Principle

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    Action must be taken to combat climate change. Yet, how the costs of climate action should be allocated among states remains a question. One popular answer—the polluter-pays principle (PPP)—stipulates that those responsible for causing the problem should pay to address it. While intuitively plausible, the PPP has been subjected to withering criticism in recent years. It is timely, following the Paris Agreement, to develop a new version: one that does not focus on historical production-based emissions but rather allocates climate burdens in proportion to each state’s annual consumption-based emissions. This change in carbon accounting results in a fairer and more environmentally effective principle for distributing climate duties

    Selecting Forecasting Methods

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    I examined six ways of selecting forecasting methods: Convenience, “what’s easy,” is inexpensive, but risky. Market popularity, “what others do,” sounds appealing but is unlikely to be of value because popularity and success may not be related and because it overlooks some methods. Structured judgment, “what experts advise,” which is to rate methods against prespecified criteria, is promising. Statistical criteria, “what should work,” are widely used and valuable, but risky if applied narrowly. Relative track records, “what has worked in this situation,” are expensive because they depend on conducting evaluation studies. Guidelines from prior research, “what works in this type of situation,” relies on published research and offers a low-cost, effective approach to selection. Using a systematic review of prior research, I developed a flow chart to guide forecasters in selecting among ten forecasting methods. Some key findings: Given enough data, quantitative methods are more accurate than judgmental methods. When large changes are expected, causal methods are more accurate than naive methods. Simple methods are preferable to complex methods; they are easier to understand, less expensive, and seldom less accurate. To select a judgmental method, determine whether there are large changes, frequent forecasts, conflicts among decision makers, and policy considerations. To select a quantitative method, consider the level of knowledge about relationships, the amount of change involved, the type of data, the need for policy analysis, and the extent of domain knowledge. When selection is difficult, combine forecasts from different methods

    Subcellular heterogeneity of ryanodine receptor properties in ventricular myocytes with low T-tubule density

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    Rationale: In ventricular myocytes of large mammals, not all ryanodine receptor (RyR) clusters are associated with T-tubules (TTs); this fraction increases with cellular remodeling after myocardial infarction (MI). Objective: To characterize RyR functional properties in relation to TT proximity, at baseline and after MI. Methods: Myocytes were isolated from left ventricle of healthy pigs (CTRL) or from the area adjacent to a myocardial infarction (MI). Ca2+ transients were measured under whole-cell voltage clamp during confocal linescan imaging (fluo-3) and segmented according to proximity of TTs (sites of early Ca2+ release, F>F50 within 20 ms) or their absence (delayed areas). Spontaneous Ca2+ release events during diastole, Ca2+ sparks, reflecting RyR activity and properties, were subsequently assigned to either category. Results: In CTRL, spark frequency was higher in proximity of TTs, but spark duration was significantly shorter. Block of Na+/Ca2+ exchanger (NCX) prolonged spark duration selectively near TTs, while block of Ca2+ influx via Ca2+ channels did not affect sparks properties. In MI, total spark mass was increased in line with higher SR Ca2+ content. Extremely long sparks (>47.6 ms) occurred more frequently. The fraction of near-TT sparks was reduced; frequency increased mainly in delayed sites. Increased duration was seen in near-TT sparks only; Ca2+ removal by NCX at the membrane was significantly lower in MI. Conclusion: TT proximity modulates RyR cluster properties resulting in intracellular heterogeneity of diastolic spark activity. Remodeling in the area adjacent to MI differentially affects these RyR subpopulations. Reduction of the number of sparks near TTs and reduced local NCX removal limit cellular Ca2+ loss and raise SR Ca2+ content, but may promote Ca2+ waves

    Risk of Childhood Cancers Associated with Residence in Agriculturally Intense Areas in the United States

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    Background: The potential for widespread exposure to agricultural pesticides through drift during application raises concerns about possible health effects to exposed children living in areas of high agricultural activity. Objectives: We evaluated whether residence in a county with greater agricultural activity was associated with risk of developing cancer in children \u3c 15 years of age. Methods: Incidence data for U.S. children 0–14 years of age diagnosed with cancer between 1995 and 2001 were provided by member registries of the North American Association of Central Cancer Registries. We determined percent cropland for each county using agricultural census data, and used the overall study distribution to classify agriculturally intense counties. We estimated odds ratios and 95% confidence intervals for all ages and 5-year age groups for total cancers and selected cancer sites using logistic regression. Results: Our study results showed statistically significant increased risk estimates for many types of childhood cancers associated with residence at diagnosis in counties having a moderate to high level of agricultural activity, with a remarkably consistent dose–response effect seen for counties having ≥ 60% of the total county acreage devoted to farming. Risk for different cancers varied by type of crop. Conclusions: Although interpretation is limited by the ecologic design, in this study we were able to evaluate rarer childhood cancers across a diverse agricultural topography. The findings of this exploratory study support a continued interest in the possible impact of long-term, low-level pesticide exposure in communities located in agriculturally intense areas

    Growth and dislocation studies of β-HMX

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    Background: The defect structure of organic materials is important as it plays a major role in their crystal growth properties. It also can play a subcritical role in “hot-spot” detonation processes of energetics and one such energetic is cyclotetramethylene-tetranitramine, in the commonly used beta form (β-HMX). Results: The as-grown crystals grown by evaporation from acetone show prismatic, tabular and columnar habits, all with {011}, {110}, (010) and (101) faces. Etching on (010) surfaces revealed three different types of etch pits, two of which could be identified with either pure screw or pure edge dislocations, the third is shown to be an artifact of the twinning process that this material undergoes. Examination of the {011} and {110} surfaces show only one type of etch pit on each surface; however their natural asymmetry precludes the easy identification of their Burgers vector or dislocation type. Etching of cleaved {011} surfaces demonstrates that the etch pits can be associated with line dislocations. All dislocations appear randomly on the crystal surfaces and do not form alignments characteristic of mechanical deformation by dislocation slip. Conclusions: Crystals of β-HMX grown from acetone show good morphological agreement with that predicted by modelling, with three distinct crystal habits observed depending upon the supersaturation of the growth solution. Prismatic habit was favoured at low supersaturation, while tabular and columnar crystals were predominant at higher super saturations. The twin plane in β-HMX was identified as a (101) reflection plane. The low plasticity of β-HMX is shown by the lack of etch pit alignments corresponding to mechanically induced dislocation arrays. On untwinned {010} faces, two types of dislocations exist, pure edge dislocations with b = [010] and pure screw dislocations with b = [010]. On twinned (010) faces, a third dislocation type exists and it is proposed that these pits are associated with pure screw dislocations with b = [010]
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