1,093 research outputs found
Estimating the maximum rise in temperature according to climate models using abstract interpretation
Current climate models are complex computer programs that are typically iterated time-step by time-step to predict the next set of values of the climate-related variables. Since these iterative methods are necessarily computed only for a fixed number of iterations, they are unable to answer the natural question whether there is a limit to the rise of global temperature. In order to answer that question we propose to combine climate models with software verification techniques that can find invariant conditions for the set of program variables. In particular, we apply the constraint database approach to software verification to find that the rise in global temperature is bounded according to the common Java Climate Model that implements the Wigely/Raper Upwelling-Diffusion Energy Balance Model climate model
Project SHOES: Secondary heat opportunities from electrical substations
Through the mechanism of stepping up and stepping down voltages with electrical power transformers, losses in the form of heat occur and are dissipated to the atmosphere. These losses have the opportunity to be recovered and upgraded to help support the thermal demands of buildings as allow carbon secondary heat source. The electrification of heat facilitates the uptake of electrically driven heat pumps that are efficient means of upgrading low temperature heat sources to commonly used temperatures and the employment of district heating networks enables the transition of these alternative heat sources into the economy. This paper describes the results discovered from an initial investigation on the contribution available from a transformer energy recovery scheme using the Southampton Bulk Supply Point substation and District Heating Scheme as a case study. Benefits to the heat sector and asset owner are analysed from the results considering the techno-economic, environmental and social performance with the aim to provide guidance to the engineering community for further in-depth feasibility studies on this waste energy recovery concep
The Biases of Risk Tradeoff Analysis: Towards Parity in Environmental and Health-and-Safety Regulation
Risk tradeoff analysis is in the process of transforming the practice of regulation. Its core idea is simple and intuitively appealing: Regulations undertaken to minimize or eliminate certain health risks often have the perverse effect of promoting other risks. A serious analysis of the impact of a regulation should pay attention not only to its primary effects in reducing the so-called target risk, but also to the secondary effects of the regulation in bringing about ancillary risks. In this way, risk tradeoff analysis promises a more rational technique for the evaluation of regulation. Risk tradeoff analysis, however, focuses exclusively on the negative secondary effects of risk regulation, but systematically ignores the phenomenon of ancillary benefits, the reductions in risk that take place in addition to--and as a direct or indirect result of--reductions in the target risk. The resulting conclusions are therefore consistently biased against regulation. This methodological bias is, in turn, reinforced by an institutional bias that emerges when risk tradeoff analysis is applied in the administrative state. Agency inattention to ancillary effects gives rise to iterative processes of administrative oversight and judicial review that privilege the opponents of regulation. This Article sheds light on these biases and proposes a solution: ancillary benefit analysis. This technique would direct the attention of administrative decisionmakers to the positive byproducts of regulation designed to promote health, safety, and the environment. At a time when risk tradeoff analysis enjoys ever-growing support in the courts and the academy, this Article proposes an approach through which to counteract its one-sidedness
External iliac artery dissection secondary to endofibrosis in a cyclist
Endofibrosis of the external iliac artery is an uncommon disease affecting primarily young, otherwise healthy, endurance athletes. Thigh pain during maximal exercise with quick resolution postexercise is characteristic of the so-called cyclist's iliac syndrome. We report an unusual case in which the typical endofibrotic plaque was accompanied by dissection of the external iliac artery. The patient was treated surgically with excision of the affected artery segment and placement of an interposition graft. This case highlights an unusual finding in association with external iliac artery endofibrosis and provides an opportunity to briefly review the literature on the subject
Performance Enhancement of Urban Ground Source Heat Pumps through Interactions with Underground Railway Tunnels
Ground source heat pumps (GSHPs) can provide an efficient way of heating and cooling buildings due to their high operating efficiencies. The implementation of these systems in urban environments could have further benefits. In such locations the ground source heat is potentially more accessible via alternative sources such as through underground railways (URs). This paper investigates to what extent the heat in the soil surrounding an UR tunnel could enhance the operation of urban GSHPs installations. To address this, a numerical investigation was set out which included a parametric study considering a number of geometrical options of the systems. The results showed that heat extraction rates of GSHPs installed near UR tunnels can be significantly improved by up to ~ 43%
The presence of heterogeneous nuclear ribonucleoproteins in frontotemporal lobar degeneration with FUS positive inclusions
Frontotemporal lobar degeneration with fused in sarcoma–positive inclusions (FTLD-FUS) is a disease with unknown cause. Transportin 1 is abundantly found in FUS-positive inclusions and responsible for the nuclear import of the FET proteins of which FUS is a member. The presence of all FET proteins in pathological inclusions suggests a disturbance of transportin 1–mediated nuclear import. FUS also belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) protein family. We investigated whether hnRNP proteins are associated with FUS pathology implicating dysfunctional nuclear export in the pathogenesis of FTLD-FUS. hnRNP proteins were investigated in affected brain regions in FTLD-FUS using immunohistochemistry, biochemical analysis, and the expression analysis. We demonstrated the presence of several hnRNP proteins in pathological inclusions including neuronal cytoplasmic inclusions and dystrophic neurites. The biochemical analysis revealed a shift in the location of hnRNP A1 from the nucleus to the cytoplasm. The expression analysis revealed an increase in several hnRNP proteins in FTLD-FUS. These results implicate a wider dysregulation of movement between intracellular compartments, than mechanisms only affecting the nuclear import of FUS proteins
Tau Isoform-Driven CBD Pathology Transmission in Oligodendrocytes in Humanized Tau Mice
The aggregation of abnormally phosphorylated tau protein in neurons and glia is a neuropathological hallmark of several neurodegenerative disorders, collectively known as tauopathies. They are further subclassified based on the preferential pathological aggregation of three carboxyl-terminal repeat domains (3R) and/or 4R tau. Corticobasal degeneration (CBD) is a rare neurodegenerative disorder classified as a 4R tauopathy. In the present study, we extend analysis of CBD-tau cell-type specific pathology transmission with 3R and 4R tau isoform distinguishable changes. We use a humanized tau (hTau) mouse line, which overexpress all six human tau isoforms in a murine tau knockout background and perform intrastriatal inoculation of control and CBD-tau enriched human brain homogenate. We show that CBD-tau causes hyperphosphorylation of tau at Ser202 predominantly in oligodendrocytes. Next, we demonstrate the spread of tau pathology from striatum to the overlaying corpus callosum and further to the contralateral side. Finally, we demonstrate that the almost exclusive oligodendrocyte-based transmission of hyperphosphorylated tau is reflected in the endogenous 4R tau isoform expression and corresponds to subclassification of CBD as a 4R tauopathy. Additionally, we identify functional changes in oligodendrocytes reflected by myelin basic protein abnormalities upon CBD-tau inoculation. These changes are not observed in murine tau knockout mice lacking both human and murine tau. Our study presents not only in vivo tau isoform–driven region- and cell-specific tau pathology, but also underlines that tau pathology seeding and transmission might be oligodendrocyte-based. These results, which need to be extended to more cases, give new insights into why tauopathies might vary greatly in both histopathological and neuroanatomical patterns
Comprehensive thermal analysis of a high stability Cu-Zr-Al bulk metallic glass subjected to high-pressure torsion
Bulk metallic glass of Cu38Zr54Al8 nominal composition was synthesized by copper mold casting into 6 mm diameter rods. Disks of the as-cast glass were subjected to severe plastic deformation by high-pressure torsion for different number of revolutions. The microstructure and the thermal behavior of the as-cast, isothermally annealed and deformed glass have been investigated by X-ray diffraction and differential scanning calorimetry, respectively. Continuous heating experiments revealed a two-stage devitrification event with excellent glass forming parameters, such as glass transition (T-g = 671 K), supercooled liquid region ( increment T-x = 80 K), reduced glass transition (T-r = 0.57) and gamma parameter (gamma = 0.41). Power law crystal growth during diffusion-controlled homogeneous nucleation was observed for isothermal annealings. Glassy state was preserved almost in the entire sample volume of the as-cast alloy during the high-pressure torsion process, corresponding to the extreme stability of the Cu38Zr54Al8 alloy against deformation-induced devitrification. This is in accordance with the transition of the reversible specific heat from the glassy to supercooled liquid state measured by modulated calorimetry. It was also concluded that glassy structure is more ordered in the severely deformed state
Association of clusterin with the BRI2-derived amyloid molecules ABri and ADan
Familial British and Danish dementias (FBD and FDD) share striking neuropathological similarities with Alzheimer's disease (AD), including intraneuronal neurofibrillary tangles as well as parenchymal and vascular amyloid deposits. Multiple amyloid associated proteins with still controversial role in amyloidogenesis colocalize with the structurally different amyloid peptides ABri in FBD, ADan in FDD, and Aβ in AD. Genetic variants and plasma levels of one of these associated proteins, clusterin, have been identified as risk factors for AD. Clusterin is known to bind soluble Aβ in biological fluids, facilitate its brain clearance, and prevent its aggregation. The current work identifies clusterin as the major ABri- and ADan-binding protein and provides insight into the biochemical mechanisms leading to the association of clusterin with ABri and ADan deposits. Mirroring findings in AD, the studies corroborate clusterin co-localization with cerebral parenchymal and vascular amyloid deposits in both disorders. Ligand affinity chromatography with downstream Western blot and amino acid sequence analyses unequivocally identified clusterin as the major ABri- and ADan-binding plasma protein. ELISA highlighted a specific saturable binding of clusterin to ABri and ADan with low nanomolar Kd values within the same range as those previously demonstrated for the clusterin-Aβ interaction. Consistent with its chaperone activity, thioflavin T binding assays clearly showed a modulatory effect of clusterin on ABri and ADan aggregation/fibrillization properties. Our findings, together with the known multifunctional activity of clusterin and its modulatory activity on the complex cellular pathways leading to oxidative stress, mitochondrial dysfunction, and the induction of cell death mechanisms – all known pathogenic features of these protein folding disorders – suggests the likelihood of a more complex role and a translational potential for the apolipoprotein in the amelioration/prevention of these pathogenic mechanisms
The novel MAPT mutation K298E:mechanisms of mutant tau toxicity, brain pathology and tau expression in induced fibroblast-derived neurons
Frontotemporal lobar degeneration (FTLD) consists of a group of neurodegenerative diseases characterized by behavioural and executive impairment, language disorders and motor dysfunction. About 20-30 % of cases are inherited in a dominant manner. Mutations in the microtubule-associated protein tau gene (MAPT) cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17T). Here we report a novel MAPT mutation (K298E) in exon 10 in a patient with FTDP-17T. Neuropathological studies of post-mortem brain showed widespread neuronal loss and gliosis and abundant deposition of hyperphosphorylated tau in neurons and glia. Molecular studies demonstrated that the K298E mutation affects both protein function and alternative mRNA splicing. Fibroblasts from a skin biopsy of the proband taken at post-mortem were directly induced into neurons (iNs) and expressed both 3-repeat and 4-repeat tau isoforms. As well as contributing new knowledge on MAPT mutations in FTDP-17T, this is the first example of the successful generation of iNs from skin cells retrieved post-mortem
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