Method for Computing Short-Range Forces between Solid-Liquid Interfaces Driving Grain Boundary Premelting

We present a molecular dynamics based method for computing accurately short-range structural forces resulting from the overlap of spatially diffuse solid-liquid interfaces at wetted grain boundaries close to the melting point. The method is based on monitoring the fluctuations of the liquid layer width at different temperatures to extract the excess interfacial free-energy as a function of this width. The method is illustrated for a high energy Sigma 9 twist boundary in pure Ni. The short-range repulsion driving premelting is found to be dominant in comparison to long-range dispersion and entropic forces and consistent with previous experimental findings that nanometer-scale layer widths may only be observed very close to the melting point.Comment: 5 pages, four figure

CALPHAD formalism for Portland clinker: thermodynamic models and databases

International audienceThe so-called CALPHAD method is widely used in metallurgy to predict phase diagrams of multi-component systems. The application of the method to oxide systems is much more recent, because of the difficulty of modelling the ionic liquid phase. Since the 1980s, several models have been proposed by various communities. Thermodynamic databases for oxides are available and still under development. The purpose of this article is to discuss the distinct approaches of the method for the calculation of multi-component systems for Portland cement elaboration. The article gives a state of the art of the most recent experimental data and the various calculations for the CaO-Al2O3-SiO2 phase diagram. A literature review of the three binary sub-systems leads to main conclusions: (i) discrepancies are found in the literature for the selected experimental data, (ii) the phase diagram data in the reference books are not complete and up to date and (iii) the two-sublattices model and the modified quasichemical model can be equally used for the modelling of the aluminates liquid. The predictive feature of the CALPHAD method is illustrated using the CaO-Al2O3-SiO2 system with the two-sublattices model: extrapolated (predicted) and fully-assessed phase diagrams are compared in the clinkering zone of interest. The recent application of the predictive method for the calculations of high-order systems (taking into account Fe2O3, SO3, CaF2, P2O5) shows that the databases developed with the two-sublattices model and the modified quasichemical model are no longer equivalent

Unconventional MBE Strategies from Computer Simulations for Optimized Growth Conditions

We investigate the influence of step edge diffusion (SED) and desorption on Molecular Beam Epitaxy (MBE) using kinetic Monte-Carlo simulations of the solid-on-solid (SOS) model. Based on these investigations we propose two strategies to optimize MBE growth. The strategies are applicable in different growth regimes: During layer-by-layer growth one can exploit the presence of desorption in order to achieve smooth surfaces. By additional short high flux pulses of particles one can increase the growth rate and assist layer-by-layer growth. If, however, mounds are formed (non-layer-by-layer growth) the SED can be used to control size and shape of the three-dimensional structures. By controlled reduction of the flux with time we achieve a fast coarsening together with smooth step edges.Comment: 19 pages, 7 figures, submitted to Phys. Rev.

Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)

The neuronal ceroid lipofuscinoses are a group of lysosomal storage disorders that comprise the most common, genetically heterogeneous, fatal neurodegenerative disorders of children. They are characterised by childhood onset, visual failure, epileptic seizures, psychomotor retardation and dementia. CLN3 disease, also known as Batten disease, is caused by autosomal recessive mutations in the CLN3 gene, 80–85% of which are a ~1 kb deletion. Currently no treatments exist, and after much suffering, the disease inevitably results in premature death. The aim of this study was to generate a zebrafish model of CLN3 disease using antisense morpholino injection, and characterise the pathological and functional consequences of Cln3 deficiency, thereby providing a tool for future drug discovery. The model was shown to faithfully recapitulate the pathological signs of CLN3 disease, including reduced survival, neuronal loss, retinopathy, axonopathy, loss of motor function, lysosomal storage of subunit c of mitochondrial ATP synthase, and epileptic seizures, albeit with an earlier onset and faster progression than the human disease. Our study provides proof of principle that the advantages of the zebrafish over other model systems can be utilised to further our understanding of the pathogenesis of CLN3 disease and accelerate drug discovery

In pursuit of humane and sustainable housing patterns on the island of Cyprus

The newly developed urban environment often shows extensive neglect of local values and a lack of design promoting environmental quality in our cities and towns within the ‘economic’ concept of a city. Most housing environments, particularly those produced on the basis of mass production systems, are missing vital aspects of sustainability and lack environmental and humane qualities, both at urban and architectural levels. It is essential to focus on the requirements of sustainable development, both as a philosophy of planning and design and during the process of making and managing our environments. Current urban and architectural development practices in Cyprus cannot be considered sustainable. However, traditional settlements on Cyprus, such as the vernacular patterns, are excellent examples to learn from as they represent a long-established culture and good use of local values and resources, matched with local skills meeting people’s needs. This paper first focuses on what sustainability means in terms of housing environments by highlighting the qualities of traditional housing patterns in Cypriot settlements. Second, it provides a critical evaluation of newly developed housing patterns on the island in terms of the environment and traditions. Finally, it proposes principles of sustainable planning and design whose main aim is to create buildings that are sensitive to people and the environment and are culturally specific.International Journal of Sustainable Development & World Ecology 15(3), 179-188. (2008

Direct Computation of the Superionic Conductivity in Caf2 by Constant-Temperature Equilibrium and Nonequilibrium Molecular-Dynamics

Europhysics Letter

Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives

Colistin; Phramacokinetic; Technique of nebulizationColistina; Farmacocinètica; Tècnica de nebulitzacióColistina; Farmacocinético; Técnica de nebulizaciónClinical evidence suggests that nebulized colistimethate sodium (CMS) has benefits for treating lower respiratory tract infections caused by multidrug-resistant Gram-negative bacteria (GNB). Colistin is positively charged, while CMS is negatively charged, and both have a high molecular mass and are hydrophilic. These physico-chemical characteristics impair crossing of the alveolo-capillary membrane but enable the disruption of the bacterial wall of GNB and the aggregation of the circulating lipopolysaccharide. Intravenous CMS is rapidly cleared by glomerular filtration and tubular excretion, and 20–25% is spontaneously hydrolyzed to colistin. Urine colistin is substantially reabsorbed by tubular cells and eliminated by biliary excretion. Colistin is a concentration-dependent antibiotic with post-antibiotic and inoculum effects. As CMS conversion to colistin is slower than its renal clearance, intravenous administration can lead to low plasma and lung colistin concentrations that risk treatment failure. Following nebulization of high doses, colistin (200,000 international units/24h) lung tissue concentrations are > five times minimum inhibitory concentration (MIC) of GNB in regions with multiple foci of bronchopneumonia and in the range of MIC breakpoints in regions with confluent pneumonia. Future research should include: (1) experimental studies using lung microdialysis to assess the PK/PD in the interstitial fluid of the lung following nebulization of high doses of colistin; (2) superiority multicenter randomized controlled trials comparing nebulized and intravenous CMS in patients with pandrug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis; (3) non-inferiority multicenter randomized controlled trials comparing nebulized CMS to intravenous new cephalosporines/ß-lactamase inhibitors in patients with extensive drug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis.This research received no external funding

Effects of artificially‐induced iPEEP and post‐inspiratory pause on dead space and slope of capnographic phase III in acute respiratory failure

According to a previous report (Brandolese et al., 1993), artificially-induced intrinsic positive end-expiratory pressure (iPEEP) causes a deterioration of gas exchange in mechanically-ventilated patients with acute respiratory failure, presumably because of a less homogeneous distribution of inspired gas. Objectives This hypothesis was investigated indirectly by measuring the slope of phase III, anatomic and physiologic dead space using volumetric capnography. Methods Measurements were obtained in 11 sedated, mechanically-ventilated paralyzed acute respiratory failure patients with iPEEP<3 cmH2O assessed at zero end-expiratory pressure, and without a known diagnosis of chronic obstructive pulmonary disease. In all experimental conditions, respiratory rate, ventilation and total PEEP (PEEPtot) were the same, but the same PEEPtot was obtained either by applying external PEEP (ePEEP condition) or by shortening the duration of expiration to produce iPEEP. iPEEP was induced either by reducing the inspiratory flow (Fins) and increasing the duration of the inflation (TI) (iPEEP with long TI, iPEEPlongTI condition), or by keeping constant Fins and TI, and introducing a long post-inspiratory pause (pIp) (iPEEP with long pause, iPEEPlongP condition). Results PEEPtot was not significantly different in the three experimental conditions (6.6±1.3, 6.4±1.5 and 6.4±1.2 cmH2O, P=0.474, for ePEEP, iPEEPlongTI and iPEEPlongP, respectively), as was the corresponding end-expiratory volume above equilibrium volume, measured during a deflation to ZEEP (P=0.158). iPEEP was not different between iPEEPlongTI and iPEEPlongP (4.9±1.1 and 5.1±0.9 cmH2O, P=0.453, respectively), but substantially greater than in the ePEEP condition (0.6±0.3 cmH2O, P<0.001). PaO2 was not significantly different among the three conditions (P=0.262), while PaCO2 was lower at iPEEPlongP (35.2±4.7 mmHg) than at ePEEP (38.4±5.2 mmHg, P<0.001) and iPEEPlongTI (38.3±4.2 mmHg, P=0.019). Relative to ePEEP, slope of phase III, anatomic, physiologic and alveolar dead space were not different at iPEEPlongTI (Δ -0.7±1.8 %CO2/L, P=0.655; 1±7 ml, P=1.000, 2±22, P=1.000 and 1±17 ml, P=1.000, respectively). In contrast, the same parameters were significantly lower at iPEEPlongP (Δ -1.6±1.1 %CO2/L, P<0.002, -18±9 ml, P<0.001, -32±19 ml, P<0.001, and -14±13 ml, P=0.017, respectively). Conclusions In these patients, no difference in slope of phase III, anatomic and physiologic dead space were detected between ePEEP and iPEEPlongTI, suggesting that during iPEEPlongTI the effect of iPEEP-induced alterations of ventilation distribution, if any, were completely compensated by the increase of inspiratory duration (Åström et al., 2008). In contrast, prolongation of pIp led to a significant reduction of heterogeneity as indexed by slope of phase III in the iPEEPlongP condition, despite the presence of iPEEP. References Brandolese R, Broseghini C, Polese G, Bernasconi M, Brandi G, Milic-Emili J, Rossi A. Effects of intrinsic PEEP on pulmonary gas exchange in mechanically-ventilated patients. Eur Respir J. 1993 Mar;6(3):358-63. PMID: 8472826. Aström E, Niklason L, Drefeldt B, Bajc M, Jonson B. Partitioning of dead space--a method and reference values in the aw ake human. Eur Respir J. 2000 Oct;16(4):659-64. doi: 10.1034/j.1399-3003.2000.16d16.x. PMID: 11106209