How cholesterol interacts with membrane proteins: an exploration of cholesterol-binding sites including CRAC, CARC, and tilted domains

The plasma membrane of eukaryotic cells contains several types of lipids displaying high biochemical variability in both their apolar moiety (e.g., the acyl chain of glycerolipids) and their polar head (e.g., the sugar structure of glycosphingolipids). Among these lipids, cholesterol is unique because its biochemical variability is almost exclusively restricted to the oxidation of its polar −OH group. Although generally considered the most rigid membrane lipid, cholesterol can adopt a broad range of conformations due to the flexibility of its isooctyl chain linked to the polycyclic sterane backbone. Moreover, cholesterol is an asymmetric molecule displaying a planar α face and a rough β face. Overall, these structural features open up a number of possible interactions between cholesterol and membrane lipids and proteins, consistent with the prominent regulatory functions that this unique lipid exerts on membrane components. The aim of this review is to describe how cholesterol interacts with membrane lipids and proteins at the molecular/atomic scale, with special emphasis on transmembrane domains of proteins containing either the consensus cholesterol-binding motifs CRAC and CARC or a tilted peptide. Despite their broad structural diversity, all these domains bind cholesterol through common molecular mechanisms, leading to the identification of a subset of amino acid residues that are overrepresented in both linear and three-dimensional membrane cholesterol-binding sites.Fil: Fantini, J.. Aix-Marseille Université. Interactions Moléculaires et Systèmes Membranaires; FranciaFil: Barrantes, Francisco Jose. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

FROM THE GENERAL DOCUMENTATION OF HADRIAN'S VILLA TO DESIGN ANALYSIS OF COMPLEX CUPOLAS: A PROCEDURAL APPROACH

Abstract. The paper illustrates the progress of Hadrian's Villa digital documentation with special emphasis on a series of modelling issues emerged while studying vaults and cupolas of the site. Together with the more general problem of giving scientific coherence to both active and passive sensor outputs – systematically gathered from 2013 – a methodological problem concerning data interpretation of complex opus caementicium vaults have become dramatically important for the interdisciplinary research team. A methodology for improving the understanding the original shapes of Hadrianic cupolas was designed to provide scholars and professionals operating at the Villa with reliable and easy to use outputs, for interpretation, restoration, maintenance practice. Sensors integration played a fundamental role since allowed researchers a global understanding of intrados and extrados surfaces using reverse modelling applications. Features and 2D primitives extracted from high-resolution models were analysed in order to create flexible procedural models of reconstruction hypothesis/completion of cupolas. Due to the very nature of these shapes (apparently irregular), but with a solid geometric conception, we applied the last achievements of Catmull-Clark bicubic surfaces in combination with Visual Programming Language (VPL).</p

30-day in-hospital mortality after acute myocardial infarction in Tuscany (Italy): An observational study using hospital discharge data

Abstract Background: Coronary heart disease is the leading cause of mortality in the world. One of the outcome indicators recently used to measure hospital performance is 30-day mortality after acute myocardial infarction (AMI). This indicator has proven to be a valid and reproducible indicator of the appropriateness and effectiveness of the diagnostic and therapeutic process for AMI patients after hospital admission. The aim of this study was to examine the determinants of inter-hospital variability on 30-day in-hospital mortality after AMI in Tuscany. This indicator is a proxy of 30-day mortality that includes only deaths occurred during the index or subsequent hospitalizations. Methods: The study population was identified from hospital discharge records (HDRs) and included all patients with primary or secondary ICD-9-CM codes of AMI (ICD-9 codes 410.xx) that were discharged between January 1, 2009 and November 30, 2009 from any hospital in Tuscany. The outcome of interest was 30-day all-cause in-hospital mortality, defined as a death occurring for any reason in the hospital within 30 days of the admission date. Because of the hierarchical structure of the data, with patients clustered into hospitals, random-effects (multilevel) logistic regression models were used. The models included patient risk factors and random intercepts for each hospital. Results: The study included 5,832 patients, 61.90% male, with a mean age of 72.38 years. During the study period, 7.99% of patients died within 30 days of admission. The 30-day in-hospital mortality rate was significantly higher among patients with ST segment elevation myocardial infarction (STEMI) compared with those with non-ST segment elevation myocardial infarction (NSTEMI). The multilevel analysis which included only the hospital variance showed a significant inter-hospital variation in 30-day in-hospital mortality. When patient characteristics were added to the model, the hospital variance decreased. The multilevel analysis was then carried out separately in the two strata of patients with STEMI and NSTEMI. In the STEMI group, after adjusting for patient characteristics, some residual inter-hospital variation was found, and was related to the presence of a cardiac catheterisation laboratory. Conclusion: We have shown that it is possible to use routinely collected administrative data to predict mortality risk and to highlight inter-hospital differences. The distinction between STEMI and NSTEMI proved to be useful to detect organisational characteristics, which affected only the STEMI subgroup. Keywords: Myocardial infarction, Mortality, Cardiovascular risk, Medical record

Case Report: Coexistence of SUNCT and Hypnic Headache in the Same Patient

Background: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and hypnic headache (HH) are two exceedingly rare and distinctly classified primary headaches. The hypothalamus seems to be a crucial region involved in the pathophysiology of both conditions, but no cases of SUNCT and HH co-occurrence have been described so far. Case results: A 49-year-old woman who has been suffering from SUNCT for years, with alternation of symptomatic periods and remissions, developed a new headache with different clinical features, presenting exclusively during sleep and with a dramatic responsiveness to caffeine, that met the diagnostic criteria for HH. Conclusions: The available literature suggests that SUNCT and HH are different conditions but the association in the same patient that we describe supports the concept that they are not mutually exclusive. Further studies are needed to establish if they share a common pathophysiological mechanism

Raman excitation spectroscopy of carbon nanotubes: effects of pressure medium and pressure

Raman excitation and emission spectra for the radial breathing mode (RBM) are reported, together with a preliminary analysis. From the position of the peaks on the two-dimensional plot of excitation resonance energy against Raman shift, the chiral indices (m, n) for each peak are identified. Peaks shift from their positions in air when different pressure media are added - water, hexane, sulphuric acid - and when the nanotubes are unbundled in water with surfactant and sonication. The shift is about 2 - 3 cm-1 in RBM frequency, but unexpectedly large in resonance energy, being spread over up to 100meV for a given peak. This contrasts with the effect of pressure. The shift of the peaks of semiconducting nanotubes in water under pressure is orthogonal to the shift from air to water. This permits the separation of the effects of the pressure medium and the pressure, and will enable the true pressure coefficients of the RBM and the other Raman peaks for each (m, n) to be established unambiguously.Comment: 6 pages, 3 Figures, Proceedings of EHPRG 2011 (Paris

3D MODELLING OF THE NEGRO TOWER FOR ITS COMPREHENSIVE ANALYSIS AND A CONSERVATION PROPOSAL

Abstract. The Negro Tower, in El Algar, Cartagena (Region of Murcia, Spain), is a building which dates to 1585. It is a tower built in a rural environment, inland from the coast, to alert and protect the population from pirate attacks. It was part of the network of watchtowers and defense posts along the coast of Murcia built between the sixteenth and seventeenth centuries. The tower is protected as a historical monument, but its state of conservation is very poor. For this reason, a comprehensive study has been carried out to ensure its correct restoration and future conservation. Historical and constructive analysis has allowed us to discover the social, cultural and architectural characteristics of the tower. Digital photogrammetry and 3D laser scanning compatible with classic topography have been used for the graphic survey of the tower. All this information has permitted the elaboration of thorough three-dimensional modelling and the proposal of a volumetric recomposition of the tower. The presentation will set out the working methodology followed as well as the important results achieved. This research work aims to contribute to the recognition and correct conservation of the Tower. The graphic survey and the three-dimensional model obtained will allow the recovery of the tower and its integration into the natural environment

The CloudSME Simulation Platform and its Applications: A Generic Multi-cloud Platform for Developing and Executing Commercial Cloud-based Simulations

Simulation is used in industry to study a large variety of problems ranging from increasing the productivity of a manufacturing system to optimizing the design of a wind turbine. However, some simulation models can be computationally demanding and some simulation projects require time consuming experimentation. High performance computing infrastructures such as clusters can be used to speed up the execution of large models or multiple experiments but at a cost that is often too much for Small and Medium-sized Enterprises (SMEs). Cloud computing presents an attractive, lower cost alternative. However, developing a cloud-based simulation application can again be costly for an SME due to training and development needs, especially if software vendors need to use resources of different heterogeneous clouds to avoid being locked-in to one particular cloud provider. In an attempt to reduce the cost of development of commercial cloud-based simulations, the CloudSME Simulation Platform (CSSP) has been developed as a generic approach that combines an AppCenter with the workflow of the WS-PGRADE/gUSE science gateway framework and the multi-cloud-based capabilities of the CloudBroker Platform. The paper presents the CSSP and two representative case studies from distinctly different areas that illustrate how commercial multi-cloud-based simulations can be created

Enabling Cloud-based Computational Fluid Dynamics with a Platform-as-a-Service Solution

Computational Fluid Dynamics (CFD) is widely used in manufacturing and engineering from product design to testing. CFD requires intensive computational power and typically needs high performance computing to reduce potentially long experimentation times. Dedicated high performance computing systems are often expensive for small-to-medium enterprises (SMEs). Cloud computing claims to enable low cost access to high performance computing without the need for capital investment. The CloudSME Simulation Platform aims to provide a flexible and easy to use cloud-based Platform-as-a-Service (PaaS) technology that can enable SMEs to realize the benefits of high performance computing. Our Platform incorporates workflow management and multi-cloud implementation across various cloud resources. Here we present the components of our technology and experiences in using it to create a cloud-based version of the TransAT CFD software. Three case studies favourably compare the performance of a local cluster and two different clouds and demonstrate the viability of our cloud-based approach

Couples living with type 1 diabetes : an integrative review of the impacts on health and wellbeing

Impacts of type 1 diabetes and relationship factors on health and wellbeing of both persons with diabetes and partners (T1D partners) have not been investigated. Integrative review methods evaluated the evidence. From 323 titles, we included 24 studies involving 16,083 persons with diabetes and 1020 T1D partners. Studies were quantitative (n = 13), qualitative (n = 9) and mixed methods (n = 2). Maintaining resilient, good quality, intimate relationships optimises physical and psychological outcomes for persons with diabetes. Partners experience disturbed sleep and while general psychological health is maintained, distress surrounding hypoglycaemia is overwhelming for over a third of partners. Nurturing quality relationships could reap significant health benefits

Patterns of amenable child mortality over time in 34 member countries of the Organisation for Economic Co-operation and Development (OECD): Evidence from a 15-year time trend analysis (2001-2015)

Objectives To analyse the trends of amenable mortality rates (AMRs) in children over the period 2001-2015. Design Time trend analysis. Setting Thirty-four member countries of the Organisation for Economic Co-operation and Development (OECD). Participants Midyear estimates of the resident population aged 6414 years. Primary and secondary outcome measures Using data from the WHO Mortality Database and Nolte and McKee's list, AMRs were calculated as the annual number of deaths over the population/100 000 inhabitants. The rates were stratified by age groups (&lt;1, 1-4, 5-9 and 10-14 years). All data were summarised by presenting the average rates for the years 2001/2005, 2006/2010 and 2011/2015. Results There was a significant decline in children's AMRs in the &lt;1 year group in all 34 OECD countries from 2001/2005 to 2006/2010 (332.78 to 295.17/100 000; %\u394-11.30%; 95% CI -18.75% to -3.85%) and from 2006/2010 to 2011/2015 (295.17 to 240.22/100 000; %\u394-18.62%; 95% CI -26.53% to -10.70%) and a slow decline in the other age classes. The only cause of death that was significantly reduced was conditions originating in the early neonatal period for the &lt;1 year group. The age-specific distribution of causes of death did not vary significantly over the study period. Conclusions The low decline in amenable mortality rates for children aged 651 year, the large variation in amenable mortality rates across countries and the insufficient success in reducing mortality from all causes suggest that the heath system should increase its efforts to enhance child survival. Promoting models of comanagement between primary care and subspecialty services, encouraging high-quality healthcare and knowledge, financing universal access to healthcare and adopting best practice guidelines might help reduce amenable child mortality