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Background and purpose:The contribution of endothelin‐1 (ET‐1) to vascular hyper‐reactivity associated with chronic ethanol intake, a major risk factor in several cardiovascular diseases, remains to be investigated.Experimental approach:The biphasic haemodynamic responses to ET‐1 (0.01–0.1 nmol kg−1, i.v.) or to the selective ETB agonist, IRL1620 (0.001–1.0 nmol kg−1, i.v.), with or without ETA or ETB antagonists (BQ123 (c(DTrp‐Dasp‐Pro‐Dval‐Leu)) at 1 and 2.5 mg kg−1 and BQ788 (N‐cis‐2,6‐dimethyl‐piperidinocarbonyl‐L‐γ‐methylleucyl1‐D‐1methoxycarbonyltryptophanyl‐D‐norleucine) at 0.25 mg kg−1, respectively) were tested in anaesthetized rats, after 2 weeks' chronic ethanol treatment. Hepatic parameters and ET receptor protein levels were also determined.Key results:The initial hypotensive responses to ET‐1 or IRL1620 were unaffected by chronic ethanol intake, whereas the subsequent pressor effects induced by ET‐1, but not by IRL1620, were potentiated. BQ123 at 2.5 but not 1 mg kg−1 reduced the pressor responses to ET‐1 in ethanol‐treated rats. Conversely, BQ788 (0.25 mg kg−1) potentiated ET‐1‐induced increases in mean arterial blood pressure in control as well as in ethanol‐treated rats. Interestingly, in the latter group, increases in heart rate, induced by ET‐1 at a dose of 0.025 mg kg−1 were enhanced following ETB receptor blockade. Finally, we observed higher levels of ETA receptor in the heart and mesenteric artery and a reduction of ETB receptor protein levels in the aorta and kidney from rats chronically treated with ethanol.Conclusions and implications:Increased vascular reactivity to ET‐1 and altered protein levels of ETA and ETB receptors could play a role in the pathogenesis of cardiovascular complications associated with chronic ethanol consumption.British Journal of Pharmacology (2008) 154, 971–981; doi:10.1038/bjp.2008.157; published online 12 May 2008

AbstractBackgroundBinge alcohol exposure during adolescence results in long‐lasting alterations in the brain and behavior. For example, adolescent intermittent ethanol (AIE) exposure in rodents results in long‐term loss of functional connectivity among prefrontal cortex (PFC) and striatal regions as well as a variety of neurochemical, molecular, and epigenetic alterations. Interneurons in the PFC and striatum play critical roles in behavioral flexibility and functional connectivity. For example, parvalbumin (PV) interneurons are known to contribute to neural synchrony and cholinergic interneurons contribute to strategy selection. Furthermore, extracellular perineuronal nets (PNNs) that surround some interneurons, particularly PV+ interneurons, further regulate cellular plasticity. The effect of AIE exposure on the expression of these markers within the PFC is not well understood.MethodsThe present study tested the hypothesis that AIE exposure reduces the expression of PV+ and choline acetyltransferase (ChAT)+ interneurons in the adult PFC and striatum and increases the related expression of PNNs (marked by binding of Wisteria floribunda agglutinin lectin) in adulthood. Male rats were exposed to AIE (5 g/kg/day, 2‐days‐on/2‐days‐off, i.e., P25 to P54) or water (CON), and brain tissue was harvested in adulthood (>P80). Immunohistochemistry and co‐immunofluorescence were used to assess the expression of ChAT, PV, and PNNs within the adult PFC and striatum following AIE exposure.ResultsChAT and PV interneuron densities in the striatum and PFC were unchanged after AIE exposure. However, PNN density in the PFC of AIE‐exposed rats was greater than in CON rats. Moreover, significantly more PV neurons were surrounded by PNNs in AIE‐exposed subjects than controls in both PFC subregions assessed: orbitofrontal cortex (CON = 34%; AIE = 40%) and medial PFC (CON = 10%; AIE = 14%).ConclusionsThese findings indicate that, following AIE exposure, PV interneuron expression in the adult PFC and striatum is unaltered, while PNNs surrounding these neurons are increased. This increase in PNNs may restrict the plasticity of the ensheathed neurons, thereby contributing to impaired microcircuitry in frontostriatal connectivity and related behavioral impairments.

Abstract:While the need to update EPA benefit-cost analysis to reflect the most recent science is broadly acknowledged, little work has been done examining how well ex ante BCAs estimate the actual benefits and costs of regulations. This paper adds to the existing literature on ex post cost analyses by examining EPA’s analysis of the 1998 Locomotive Emission Standards. Due to data limitations and minimal ability to construct a reasonable counterfactual for each component of the cost analysis, the assessment relies mainly on industry expert opinion, augmented with ex post information from publicly available data sources when possible. The paper finds that the total cost of bringing line-haul locomotives into compliance with the 1998 Locomotive Emission Standards rule remains uncertain. Even though the initial per-unit locomotive compliance costs were higher than predicted by EPA, total costs also depend on the number of locomotives affected by the regulation. Over 2000–2009, the number of newly built line-haul locomotives was higher but the number of remanufactured line-haul locomotives was lower than EPA’s estimate.

Abstract Globally, three-quarter of a billion people live without electricity. Besides, hundreds of million use a solar lantern for less than 4 h a day. Most of the access-deprived are in the Global South, predominantly in Sub-Saharan Africa and South Asia. The United Nations framed the seventh Sustainable Development Goal to improve access. Solar photovoltaic powered mini-grids are increasingly extending better service to deprived regions. However, poor load-factor and expensive storage adversely affect viability. Also, these mini-grids do not support infrequent large loads to avoid further loss of load-factor. Electric cooking is efficient and non-polluting; water treatment facilities can save millions from contaminant and pathogen by providing clean water. Besides, both electric cooking and water treatment are less expensive than alternatives. But mini-grids frequently do not support these. Indeed, the presence of sustained productive loads favourably influences the mini-grid economy. This study investigates the role of critical household loads to deliver similar bearing on the mini-grid economy. Results underscore realisation of desirable impact with household collaboration under a demand-response program. Collaborative consumption can lower initial investment by 62% and reduce the unit energy cost to $0.23. Also, cooperation improves the mini-grid load factor and promotes viability. Additionally, fast deployment needs during and after Covid-19 remains inherently supported while mitigating the pandemic induced financial stress of both consumer and mini-grid operator. This study of 88 nation-states underscores that demand response in a mini-grid can not only improve affordability for all consumers, but it can also bring 186 million people within affordable access.

Twenty-minute neighbourhoods highlight the importance of well-connected and mixed-used neighbourhoods and communities with proximate access to employment, essential services, public transport, and open spaces. Shorter distances together with re-prioritised public spaces encourage more active transport choices, resulting in public health benefits and reduced environmental pollution. Higher liveability brought about by mixed-use developments enables people to have equitable access to local facilities, amenities, and employment opportunities, promoting vibrancy, social cohesion, and intergenerational connections. The attributes of 20-minute neighbourhoods also combine to create places, that are acknowledged as friendly for all ages, address changing needs across the life course, and provide better support for the ageing population. Furthermore, there are indications that 20-minute neighbourhoods may be more resilient against many of the negative impacts of stringent public health protocols such as those implemented in periods of lockdown during the Covid-19 pandemic. In this article, we evaluate and compare planning policies and practices aimed at establishing 20-minute neighbourhoods in Melbourne (Australia) and Scotland (the UK). Using case studies, we discuss similarities and differences involved in using place-based approaches of 20-minute neighbourhoods to address 21st-century challenges in key areas of health and wellbeing, equity, environmental sustainability, and community resilience.

ABSTRACTA novel design for a high temperature SOFC, based on lamellar electrode-electrolyte segments obtained by solidification of an oxidic eutectic melt on an electrolyte substrate is presented. Such “composite” electrodes contain NiO or MnO - 8Y-ZrO2 lamellae, which after reduction / oxidation yield electrode-electrolyte lamellae with 1–2 μm width and a vertical dimension of> 100 μm, depending upon the amount of eutectic melt solidified on a polycrystalline substrate. The nucleation of the eutectic on a polycrystalline substrate followed by a semi-directional crystallization of the two phases yields a gradient of 3-phase boundaries over the height of such an electrode, with the number of 3-phase boundaries increasing towards the substrate.

Abstract As the part of a study to develop buparvaquone (BPQ) formulations for the treatment of cutaneous leishmaniasis, the topical delivery of BPQ and one of its prodrugs from a range of formulations was evaluated. In previous studies, BPQ and its prodrugs were shown to be potent antileishmanials in-vitro, with ED50 values in the nanomolar range. 3-Phosphono-oxymethyl-buparvaquone (3-POM-BPQ) was the most potent antileishmanial and was chosen, together with the parent drug, for further investigation. The ability of the parent and prodrug formulations to cross human and murine skin was tested in-vitro using the Franz diffusion cells. Formulations intended for topical application containing either BPQ or 3-POM-BPQ were developed using excipients that were either acceptable for topical use (GRAS or FDA inactive ingredients) or currently going through the regulatory process. BPQ was shown to penetrate both human epidermal membranes and full thickness BALB/c skin from a range of formulations (gels, emulsions). Similarly, 3-POM-BPQ penetrated full-thickness BALB/c skin from several gel formulations. In-vitro binding studies showed that BPQ bound melanin in a dose-dependent manner and preferably bound to delipidized skin over untreated BALB/c skin (on a weight to weight basis). The results confirm that BPQ and its prodrug 3-POM-BPQ can penetrate the skin from several formulations, making them potentially interesting candidates for further investigation of topical formulations using in-vivo models of cutaneous leishmaniasis.

Abstract One approach to creating physics-based reduced-order models (ROMs) of battery-cell dynamics requires first generating linearized Laplace-domain transfer functions of all cell internal electrochemical variables of interest. Then, the resulting infinite-dimensional transfer functions can be reduced by various means in order to find an approximate low-dimensional model. These methods include Pade approximation or the Discrete-Time Realization algorithm. In a previous article, Lee and colleagues developed a transfer function of the electrolyte concentration for a porous-electrode pseudo-two-dimensional lithium-ion cell model. Their approach used separation of variables and Sturm–Liouville theory to compute an infinite-series solution to the transfer function, which they then truncated to a finite number of terms for reasons of practicality. Here, we instead use a variation-of-parameters approach to arrive at a different representation of the identical solution that does not require a series expansion. The primary benefits of the new approach are speed of computation of the transfer function and the removal of the requirement to approximate the transfer function by truncating the number of terms evaluated. Results show that the speedup of the new method can be more than 3800.