It has been argued that climate change is the biggest global health threat of the 21st century. The extreme high temperatures of the summer of 2003 were associated with up to seventy thousand excess ...deaths across Europe. Previous studies have attributed the meteorological event to the human influence on climate, or examined the role of heat waves on human health. Here, for the first time, we explicitly quantify the role of human activity on climate and heat-related mortality in an event attribution framework, analysing both the Europe-wide temperature response in 2003, and localised responses over London and Paris. Using publicly-donated computing, we perform many thousands of climate simulations of a high-resolution regional climate model. This allows generation of a comprehensive statistical description of the 2003 event and the role of human influence within it, using the results as input to a health impact assessment model of human mortality. We find large-scale dynamical modes of atmospheric variability remain largely unchanged under anthropogenic climate change, and hence the direct thermodynamical response is mainly responsible for the increased mortality. In summer 2003, anthropogenic climate change increased the risk of heat-related mortality in Central Paris by ∼70% and by ∼20% in London, which experienced lower extreme heat. Out of the estimated ∼315 and ∼735 summer deaths attributed to the heatwave event in Greater London and Central Paris, respectively, 64 ( 3) deaths were attributable to anthropogenic climate change in London, and 506 ( 51) in Paris. Such an ability to robustly attribute specific damages to anthropogenic drivers of increased extreme heat can inform societal responses to, and responsibilities for, climate change.
The use of lipid nanocapsules (LNCs) has enabled an improvement of the oral bioavailability of paclitaxel (Ptx). However, mechanisms that support this recent observation are not yet understood. By ...focusing on the well defined
in vitro Caco-2 model, the purpose of this study was to evaluate the transport of LNCs across a model intestinal barrier. Firstly, four sizes of paclitaxel or dye (Nile Red)-loaded LNCs were formulated and LNCs with sizes between 26.3
±
2.7
nm and 132.7
±
5.5
nm were obtained. Different transport and uptake experiments were then performed across a Caco-2 cells culture model using these LNCs. Paclitaxel-loaded LNCs improved permeability of Ptx across intestinal epithelium compared with free Ptx or Taxol
® by a factor of 3.5. At 37
°C particle size did not influence transport efficiency. However, at 4
°C a decrease in Ptx transport was observed with increasing size of LNCs. Thus, with LNCs of 25
nm size, the apparent permeability coefficient (
P
app) was 5.3
±
1.1
cm s
−
1
at 37
°C and 2.2
±
0.4
cm s
−
1
at 4
°C. In comparison in LNCs of 130
nm size, the
P
app decreased from 5.8
±
0.8
cm s
−
1
at 37
°C to 0.5
±
0.1
cm s
−
1
at 4
°C. The uptake of LNCs by Caco-2 cells and the incapacity of LNCs to open tight junctions were also demonstrated. Furthermore, experiment transports were performed in the presence of different inhibitors of endocytosis. Findings indicated a reduction of Ptx transport of 30
±
6% when cell cholesterol was depleted, 65
±
12% when caveolae-mediated endocytosis was inhibited and 20
±
8% when clathrin-mediated endocytosis was inhibited. Finally, transmission electronic microscopy showed the presence of nano-objects on the basolateral side of the Caco-2 cell monolayers when LNCs were applied on the apical side.
LNCs were transported across the intestinal barrier via clathrin- and caveolae-mediated pathways that allow transcytosis.
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Soil moisture impacts on precipitation have been strongly debated. Recent observational evidence of afternoon rain falling preferentially over land parcels that are drier than the surrounding areas ...(negative spatial effect), contrasts with previous reports of a predominant positive temporal effect. However, whether spatial effects relating to soil moisture heterogeneity translate into similar temporal effects remains unknown. Here we show that afternoon precipitation events tend to occur during wet and heterogeneous soil moisture conditions, while being located over comparatively drier patches. Using remote-sensing data and a common analysis framework, spatial and temporal correlations with opposite signs are shown to coexist within the same region and data set. Positive temporal coupling might enhance precipitation persistence, while negative spatial coupling tends to regionally homogenize land surface conditions. Although the apparent positive temporal coupling does not necessarily imply a causal relationship, these results reconcile the notions of moisture recycling with local, spatially negative feedbacks.
Laboratory-based research is resource intensive in terms of financial costs and its carbon footprint. Research laboratories require immense amounts of energy to power equipment, as well as large ...volumes of materials, particularly of single-use item consumption. In fact, many laboratories have essentially become reliant on single-use plastics. Understanding the full carbon footprint of consumable usage is increasingly important as many research institutes commit to carbon neutrality. To date, no carbon footprint assessment has been conducted to detail the differences between single-use plastics, and reusable glass in a laboratory setting. Here, we analyse the CO2 equivalent (CO2e) footprint of utilising single-use plastics, and re-use of glass or plastic items within laboratory environments. We focused our assessment on four commonly utilised consumables for mammalian cell and bacterial culture, and found that re-use scenarios resulted in substantial reduction in CO2e footprint up to 11-fold. In addition, we estimated the long-term financial costs of re-use and single-use scenarios, and found that re-use had either similar or much lower running costs even when including technical staff wage. We concluded that research facilities must foster re-use in laboratory consumables, while reserving single-use items for select, defined cases. Our study highlights the need to account for indirect CO2e footprint in designing a carbon-neutral lab and promotes circular economy principles.
Abstract
Hematopoietic stem cells differentiate into a broad range of specialized blood cells. This process is tightly regulated and depends on transcription factors, micro-RNAs, and long non-coding ...RNAs. Recently, also circular RNA (circRNA) were found to regulate cellular processes. Their expression pattern and their identity is however less well defined. Here, we provide the first comprehensive analysis of circRNA expression in human hematopoietic progenitors, and in differentiated lymphoid and myeloid cells. We here show that the expression of circRNA is cell-type specific, and increases upon maturation. CircRNA splicing variants can also be cell-type specific. Furthermore, nucleated hematopoietic cells contain circRNA that have higher expression levels than the corresponding linear RNA. Enucleated blood cells, i.e. platelets and erythrocytes, were suggested to use RNA to maintain their function, respond to environmental factors or to transmit signals to other cells via microvesicles. Here we show that platelets and erythrocytes contain the highest number of circRNA of all hematopoietic cells, and that the type and numbers of circRNA changes during maturation. This cell-type specific expression pattern of circRNA in hematopoietic cells suggests a hithero unappreciated role in differentiation and cellular function.
When we grasp and manipulate an object, populations of tactile nerve fibers become activated and convey information about the shape, size, and texture of the object and its motion across the skin. ...The response properties of tactile fibers have been extensively characterized in single-unit recordings, yielding important insights into how individual fibers encode tactile information. A recurring finding in this extensive body of work is that stimulus information is distributed over many fibers. However, our understanding of population-level representations remains primitive. To fill this gap, we have developed a model to simulate the responses of all tactile fibers innervating the glabrous skin of the hand to any spatiotemporal stimulus applied to the skin. The model first reconstructs the stresses experienced by mechanoreceptors when the skin is deformed and then simulates the spiking response that would be produced in the nerve fiber innervating that receptor. By simulating skin deformations across the palmar surface of the hand and tiling it with receptors at their known densities, we reconstruct the responses of entire populations of nerve fibers. We show that the simulated responses closely match their measured counterparts, down to the precise timing of the evoked spikes, across a wide variety of experimental conditions sampled from the literature. We then conduct three virtual experiments to illustrate how the simulation can provide powerful insights into population coding in touch. Finally, we discuss how the model provides a means to establish naturalistic artificial touch in bionic hands.
•The load resisting mechanisms and failure modes noticeably varied between different corner reinforcement configurations.•The applied load was mainly transferred to edge columns adjacent to the ...removed corner column.•The risk of progressive collapse can be reduced with the existence of overhangs surrounding a removed corner column.•Yield line theory can be used to estimate the slab flexural capacities under corner column removal scenarios in this study.
Reinforced concrete (RC) flat plate structures are broadly used in car parks, residential and office buildings due to their economic and architectural advantages. However, this structural system is inherently prone to punching shear failure, which may propagate horizontally and vertically, ultimately leading to the progressive collapse of the entire structure or of a large portion of it. This paper presents the experimental results from two quasi-static large-displacement tests performed on a 1/3 scale, 2 × 2-bay, RC flat plate substructure subjected to corner column removal scenarios. The specimen was tested twice with different corner reinforcement configurations: (i) firstly, one corner column, with torsional strips, was removed and the Uniformly Distributed Load (UDL) on the bay adjacent to the removed column was increased to failure (Test T1), and (ii) secondly, as the damage was concentrated in the vicinity of removed corner column in (i), the corner column diagonally opposite to the first removed one, without torsional strips, was removed. The UDL on the bay adjacent to the second removed column was also increased to failure (Test T2). Different failure and post-failure behaviours, failure modes, and collapse resisting mechanisms between the two tests were witnessed, presented and analysed. Results show that 80% to 110% of the applied load is transferred to the two edge columns adjacent to the removed corner column throughout the entire two tests. The ultimate load carrying capacity for T1 is found to be 1.7 times smaller than the one for T2.
•Punching shear failure was observed in both tests.•The majority of the applied loads transferred to the columns nearest to the removed one(s).•The post-failure stages largely enabled the slab to ...resist collapse.•Two column removal reduced load capacity but increased the deformation cpacity.
Existing studies on progressive collapse of reinforced concrete (RC) flat plate structures have mainly focused on single column loss scenarios. However, accidental events, such as earthquakes, blasts or vehicle collisions, may cause a more severe initial damage beyond the loss of only one column. To fill this gap in knowledge, this study reports two quasi-static large-displacement experimental tests on two nominally identical 1/3-scale, 2 × 2-bay RC flat plate substructures under an edge-column (S-E) and an edge-interior-column (S-EI) removal scenarios. Two types of uniformly distributed loads (UDLs) were applied to the slab in the two tests: (1) an increased UDL during the tests on the bays adjacent to the removed column(s) and (2) a constant 5 kPa UDL elsewhere to simulate the design live load. In both tests, punching shear failures were observed and led to the first peak loads (FPLs) which were all followed by a sharp load drop. Subsequently, the load increased again to reach the post-failure peak loads (PPLs). The experimental results showed that the PPL was 9.6% higher than the FPL in S-E and 81.9% higher in S-EI. Relative to S-E at the PPL, S-EI presented a more ductile structural behaviour, in which the applied load at the PPL was 26.9% lower, but with a 112% larger displacement, than S-E. In both tests, tensile membrane actions were observed at large deformations and found to be essential in developing post-failure capacities. Such resisting mechanism cannot be neglected when investigating progressive collapse of RC flat plate structures. The yield line theory was found to overestimate the flexural capacity of the two tests.
The building construction sector contributes to a quarter of the total Australian Greenhouse gas emissions. These emissions are mainly attributed to the use of energy intensive materials. To achieve ...better environmental benefits and cost saving, the utilisation of wood-based construction materials is currently attracting attention. However, the manufacturing of engineered wood products consumes large quantities of chemicals and energy, which may have adverse environmental impacts. Therefore, a life cycle study was conducted to compare various materials for constructing the structural frame of a 4-storey apartment building compliant with the Australian building codes. Five alternatives were assessed: Laminated Veneer Lumber (LVL) manufactured from early to mid-rotation hardwood plantation logs (LVLm), LVL manufactured from mature hardwood plantations (LVLh), LVL manufactured from mature softwood plantations (LVLs), concrete and steel. The functional unit was defined as the whole building structural frame. Global Warming Potential (GWP), Acidification, Eutrophication, Fossil Depletion, Human-toxicity Potential (HTP) and Life Cycle Cost (LCC) were evaluated. The LVL generally performed better than concrete and steel structural products. Particularly, LVLm had the lowest GWP (2.84E4±233 kg-CO2-eq) and LCC ($128,855 ± 2797), which were less than a quarter of the concrete option. However, the usage of chemical preservatives and phenol-formaldehyde adhesive during the LVL production and treatment caused the HTP impact to be higher than the steel option. Monte Carlo Analysis showed that while the LVL options presented a higher sensitivity to the combined uncertainties, the overall ranking of the five options remained the same. Therefore, the inclusion of wood-based material in structural elements may significantly contribute to reduce the environmental impacts and the LCC of the construction sector.
•Five alternatives for multi-storey residential building frame construction were assessed.•Life cycle assessment and life cycle costing analysis were conducted.•Low material cost and labour demand led to economic saving in the LVL options.•Chemical consumption was a major contributor to the environmental impacts of LVL.•LVL from hardwood thinning had the best environmental and economic performance.
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