Szilard-Chalmers recoil studies in Zeolite L, offretite and erionite

Imperial Users onl

Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that is associated with repetitive head impacts or exposure to blast waves. First described as punch-drunk syndrome and dementia pugilistica in retired boxers1-3, CTE has since been identified in former participants of other contact sports, ex-military personnel and after physical abuse4-7. No disease-modifying therapies currently exist, and diagnosis requires an autopsy. CTE is defined by an abundance of hyperphosphorylated tau protein in neurons, astrocytes and cell processes around blood vessels8,9. This, together with the accumulation of tau inclusions in cortical layers II and III, distinguishes CTE from Alzheimer's disease and other tauopathies10,11. However, the morphologies of tau filaments in CTE and the mechanisms by which brain trauma can lead to their formation are unknown. Here we determine the structures of tau filaments from the brains of three individuals with CTE at resolutions down to 2.3 Å, using cryo-electron microscopy. We show that filament structures are identical in the three cases but are distinct from those of Alzheimer's and Pick's diseases, and from those formed in vitro12-15. Similar to Alzheimer's disease12,14,16-18, all six brain tau isoforms assemble into filaments in CTE, and residues K274-R379 of three-repeat tau and S305-R379 of four-repeat tau form the ordered core of two identical C-shaped protofilaments. However, a different conformation of the β-helix region creates a hydrophobic cavity that is absent in tau filaments from the brains of patients with Alzheimer's disease. This cavity encloses an additional density that is not connected to tau, which suggests that the incorporation of cofactors may have a role in tau aggregation in CTE. Moreover, filaments in CTE have distinct protofilament interfaces to those of Alzheimer's disease. Our structures provide a unifying neuropathological criterion for CTE, and support the hypothesis that the formation and propagation of distinct conformers of assembled tau underlie different neurodegenerative diseases

Microstructural Development in As Built and Heat Treated IN625 Component Additively Manufactured by Laser Powder Bed Fusion

The RL10 engine program is exploring the use of IN625 Ni-base superalloy components that are additively manufactured using laser powder bed fusion (LPBF). IN625 alloy powders are commercially available for LPBF to produce dense, complex parts/components. In this study, IN625 components, with both simple and complex geometries with overhangs, were manufactured via LPBF, and subjected to a heat-treatment consisting of a stress relief, hot isostatic pressing (HIP), and a solution anneal. The microstructure was examined with optical, scanning electron, and transmission electron microscopy. Changes in phase constituents and microstructure were documented as a function of heat treatment and component geometry (i.e., bulk section built on support structure versus thin, overhang section built on top of the previous powder bed). The as-built microstructural features included large columnar grains, a sub-grain cellular-solidification structure, approximately ~ 1 µm in diameter, and solute enriched cell boundaries decorated with A2B Laves phases. After heat treatment, the bulk section consisted of recrystallized equiaxed grains with annealing twins, and the sub-grain cellular-solidification structure was found to be completely dissolved. However, in the thin, overhang section, the sub-grain cellular-solidification structure persisted within columnar grain structure, which exhibited no recrystallization. An alternate HIP cycle with a higher temperature was employed to produce desired microstructure (i.e., recrystallized grains without sub-grain cells and Laves phases) in components with geometrical complexity for successful testing of RL10 engine

Optimization of Ameristar's Montage department: Senior design project report

In the Montage department at Ameristar, orders are being scheduled in a way where there are excessive daily changeovers. There is also a lack of communication between the production floor and scheduling department as to what sequence the orders should run in each day. This is a problem because there are significant productivity losses. An updated scheduling system is needed for this department to improve output of standard and custom-sized fence orders

Mapping pneumonia research: a systematic analysis of UK investments and published outputs 1997–2013

BackgroundThe burden of pneumonia continues to be substantial, particularly among the poorest in global society. We describe here the trends for UK pneumonia R&D investment and published outputs, and correlate with 2013 global mortality.MethodsData related to awards to UK institutions for pneumonia research from 1997 to 2013 were systematically sourced and categorised by disease area and type of science. Investment was compared to mortality figures in 2010 and 2013 for pneumonia, tuberculosis and influenza. Investment was also compared to publication data.ResultsOf all infectious disease research between 2011 and 2013 (£917.0 million), £28.8 million (3.1%) was for pneumonia. This was an absolute and proportionate increase from previous time periods. Translational pneumonia research (33.3%) received increased funding compared with 1997–2010 where funding was almost entirely preclinical (87.5%, here 30.9%), but high-burden areas such as paediatrics, elderly care and antimicrobial resistance received little investment. Annual investment remains volatile; publication temporal trends show a consistent increase. When comparing investment to global burden with a novel ‘investment by mortality observed’ metric, tuberculosis (£48.36) and influenza (£484.21) receive relatively more funding than pneumonia (£43.08), despite investment for pneumonia greatly increasing in 2013 compared to 2010 (£7.39). Limitations include a lack of private sector data and the need for careful interpretation of the comparisons with burden, plus categorisation is subjective.ConclusionsThere has been a welcome increase for pneumonia funding awarded to UK institutions in 2011–2013 compared with 1997–2010, along with increases for more translational research. Published outputs relating to pneumonia rose steadily from 1997 to 2013. Investment relative to mortality for pneumonia has increased, but it remains low compared to other respiratory infections and clear inequities remain. Analyses that measure investments in pneumonia can provide an insight into funding trends and research gaps.Research in contextPneumonia continues to be a high-burden illness around the globe. This paper shows that although research funding is increasing in the UK (between 1997 and 2013), it remains poorly funded compared to other important respiratory infectious diseases such as tuberculosis and influenza. Publications about pneumonia have been steadily increasing over time, indicating continuing academic and clinical interest in the topic. Though global mortality of pneumonia is declining, it should still be an area of high priority for funders, policymakers and researchers

Echocardiographic assessment of patients with infectious endocarditis: Prediction of risk for complications

AbstractTo enhance the echocardiographic identification of high risk lesions in patients with infectious endocarditis, the medical records and two-dimensional echocardiograms of 204 patients with this condition were analyzed. The occurrence of specific clinical complications was recorded and vegetations were assessed with respect to predetermined morphologic characteristics.The overall complication rates were roughly equivalent for patients with mitral (53%), aortic (62%), tricuspid (77%) and prosthetic valve (61%) vegetations, as well as for those with nonspecific valvular changes but no discrete vegetations (57%), although the distribution of specific complications varied considerably among these groups. There were significantly fewer complications in patients without discernible valvular abnormalities (27%).In native left-sided valve endocarditis, vegetation size, extent, mobility and consistency were all found to be significant univariate predictors of complications. In multivariate analysis, vegetation size, extent and mobility emerged as optimal predictors and an echocardiographic score based on these factors predicted the occurrence of complications with 70% sensitivity and 92% specificity in mitral valve endocarditis and with 76% sensitivity and 62% specificity in aortic valve endocarditis

A method-centric 'User Manual' for the mitigation of diffuse water pollution from agriculture

We describe the development of a manual of methods for mitigating diffuse water pollution from agriculture and its important influence on policy and practice in England and Wales. The objective of the ‘User Manual’ was to provide policy makers and those implementing policies with information about the cost, effectiveness and applicability of potential methods in a form that would be readily understood by non-specialists. The ‘User Manual’ was based on earlier reports synthesizing available research data and, where data were unavailable, used expert elicitation. The outcome generated 44 potential methods (under the broad categories of land use, soil management, livestock management, fertilizer management, manure management and farm infrastructure) and described the simultaneous impact of applying each method on losses of nitrate, phosphorus and faecal indicator organisms relative to baseline losses. Estimates of cost and effectiveness were presented at the whole-farm level for seven model farm types. Methods differed widely in their cost-effectiveness and applicability to the different model farms. Advantages and limitations of the approach are discussed and subsequent developments of the original ‘User Manual’ are described, together with the opinions of catchment officers who have used the ‘User Manual’ to implement mitigation methods on farms