Micromechanical finite element analyses of fire retardant woven fabric composites at elevated temperatures using unit cells at multiple length scales

This paper presents a micromechanical Finite Element (FE) model developed to predict the effective mechanical properties of glass fibre-reinforced (woven fabric) polymer composites with/without fire retardant particulate additives at elevated temperatures. The elevated mechanical properties of glass fibre-reinforced epoxy composites with/without fire retardants were predicted using three unit cells of varying length scales in micromechanical FE analysis. Theoretically predictions of flexural behaviour of these fibre-reinforced polymer composites at elevated temperatures were satisfactorily validated against experimentally measured data. The numerical model developed herein was then used for the prediction of other mechanical properties of fibre-reinforced polymer composites that would have been difficult to collect at elevated temperatures. Micromechanical FE models such as the one contained in this paper are useful to architectural engineers as they can be used to guide the design and qualification of new engineering composites that satisfy stringent Building codes in fire prone engineering applications

Alpha-Synuclein Oligomers Interact with Metal Ions to Induce Oxidative Stress and Neuronal Death in Parkinson's Disease

Protein aggregation and oxidative stress are both key pathogenic processes in Parkinson's disease, although the mechanism by which misfolded proteins induce oxidative stress and neuronal death remains unknown. In this study, we describe how aggregation of alpha-synuclein (α-S) from its monomeric form to its soluble oligomeric state results in aberrant free radical production and neuronal toxicity

Single-Molecule Imaging of Individual Amyloid Protein Aggregates in Human Biofluids.

The misfolding and aggregation of proteins into amyloid fibrils characterizes many neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. We report here a method, termed SAVE (single aggregate visualization by enhancement) imaging, for the ultrasensitive detection of individual amyloid fibrils and oligomers using single-molecule fluorescence microscopy. We demonstrate that this method is able to detect the presence of amyloid aggregates of α-synuclein, tau, and amyloid-β. In addition, we show that aggregates can also be identified in human cerebrospinal fluid (CSF). Significantly, we see a twofold increase in the average aggregate concentration in CSF from Parkinson's disease patients compared to age-matched controls. Taken together, we conclude that this method provides an opportunity to characterize the structural nature of amyloid aggregates in a key biofluid, and therefore has the potential to study disease progression in both animal models and humans to enhance our understanding of neurodegenerative disorders.This research study was funded in part by the Wellcome Trust/MRC Joint Call in Neurodegeneration award (WT089698) to the UK Parkinson's Disease Consortium (UKPDC) and the NIHR rare disease translational research collaboration and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. We are also grateful to the Augustus Newman and Wolfson Foundations for their support. We thank the Royal Society for the University Research Fellowship of Dr. Steven F. Lee (UF120277).This is the final version of the article. It first appeared from ACS via http://dx.doi.org/10.1021/acschemneuro.5b00324

Fabrication and characterization of dual function nanoscale pH-scanning ion conductance microscopy (SICM) probes for high resolution pH mapping

The easy fabrication and use of nanoscale dual function pH-scanning ion conductance microscopy (SICM) probes is reported. These probes incorporate an iridium oxide coated carbon electrode for pH measurement and an SICM barrel for distance control, enabling simultaneous pH and topography mapping. These pH-SICM probes were fabricated rapidly from laser pulled theta quartz pipets, with the pH electrode prepared by in situ carbon filling of one of the barrels by the pyrolytic decomposition of butane, followed by electrodeposition of a thin layer of hydrous iridium oxide. The other barrel was filled with an electrolyte solution and Ag/AgCl electrode as part of a conductance cell for SICM. The fabricated probes, with pH and SICM sensing elements typically on the 100 nm scale, were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and various electrochemical measurements. They showed a linear super-Nernstian pH response over a range of pH (pH 2–10). The capability of the pH-SICM probe was demonstrated by detecting both pH and topographical changes during the dissolution of a calcite microcrystal in aqueous solution. This system illustrates the quantitative nature of pH-SICM imaging, because the dissolution process changes the crystal height and interfacial pH (compared to bulk), and each is sensitive to the rate. Both measurements reveal similar dissolution rates, which are in agreement with previously reported literature values measured by classical bulk methods

Kinetic model of the aggregation of alpha-synuclein provides insights into prion-like spreading.

The protein alpha-synuclein (αS) self-assembles into small oligomeric species and subsequently into amyloid fibrils that accumulate and proliferate during the development of Parkinson's disease. However, the quantitative characterization of the aggregation and spreading of αS remains challenging to achieve. Previously, we identified a conformational conversion step leading from the initially formed oligomers to more compact oligomers preceding fibril formation. Here, by a combination of single-molecule fluorescence measurements and kinetic analysis, we find that the reaction in solution involves two unimolecular structural conversion steps, from the disordered to more compact oligomers and then to fibrils, which can elongate by further monomer addition. We have obtained individual rate constants for these key microscopic steps by applying a global kinetic analysis to both the decrease in the concentration of monomeric protein molecules and the increase in oligomer concentrations over a 0.5-140-µM range of αS. The resulting explicit kinetic model of αS aggregation has been used to quantitatively explore seeding the reaction by either the compact oligomers or fibrils. Our predictions reveal that, although fibrils are more effective at seeding than oligomers, very high numbers of seeds of either type, of the order of 10(4), are required to achieve efficient seeding and bypass the slow generation of aggregates through primary nucleation. Complementary cellular experiments demonstrated that two orders of magnitude lower numbers of oligomers were sufficient to generate high levels of reactive oxygen species, suggesting that effective templated seeding is likely to require both the presence of template aggregates and conditions of cellular stress.We thank Dr. Nadia Shivji and Beata Blaszczyk for ɑS protein expression, Dr. Peter Jönsson for help with preliminary TIRFM imaging experiments, Chris Taylor for help with preliminary autodilution experiments and Prof. Michel Goedert for critical reading of the manuscript. M.I. is funded by Dr. Tayyeb-Hussain Scholarship. G.A.G. is funded by the Schiff Foundation . S.G. is funded through a Wellcome Trust Intermediate Clinical Fellowship. Funding from the Frances and Augustus Newman Foundation, the European Research Council and the Biothechnology and Biophysical Sciences Research Council is gratefully acknowledged.This is the author accepted manuscript. The final version is available from the National Academy of Sciences via http://dx.doi.org/10.1073/pnas.152412811

Detecting RNA base methylations in single cells by in situ hybridization.

Methylated bases in tRNA, rRNA and mRNA control a variety of cellular processes, including protein synthesis, antimicrobial resistance and gene expression. Currently, bulk methods that report the average methylation state of ~104-107 cells are used to detect these modifications, obscuring potentially important biological information. Here, we use in situ hybridization of Molecular Beacons for single-cell detection of three methylations (m62A, m1G and m3U) that destabilize Watson-Crick base pairs. Our method-methylation-sensitive RNA fluorescence in situ hybridization-detects single methylations of rRNA, quantifies antibiotic-resistant bacteria in mixtures of cells and simultaneously detects multiple methylations using multicolor fluorescence imaging

The Masaya Triple Layer: a 2100 year old basaltic multi-episodic Plinian eruption from the Masaya Caldera Complex (Nicaragua)

The Masaya Caldera Complex has been the site of three highly explosive basaltic eruptions within the last six thousand years. A Plinian eruption ca. 2 ka ago formed the widespread deposits of the Masaya Triple Layer. We distinguish two facies within the Masaya Triple Layer from each other: La Concepción facies to the south and Managua facies to the northwest. These two facies were previously treated as two separated deposits (La Concepción Tephra and the Masaya Triple Layer of Pérez and Freundt, 2006) because of their distinct regional distribution and internal architectures. However, chemical compositions of bulk rock, matrix and inclusion glasses and mineral phases demonstrate that they are the product of a single basaltic magma batch. Additionally, a marker bed containing fluidal-shaped vesicular lapilli allowed us to make a plausible correlation between the two facies, also supported by consistent lateral changes in lithologic structure and composition, thickness and grain size. We distinguish 10 main subunits of the Masaya Triple Layer (I to X), with bulk volumes ranging between 0.02 and 0.22 km3, adding up to 0.86 km3 (0.4 km3 DRE) for the entire deposit. Distal deposits identified in two cores drilled offshore Nicaragua, at a distance of ∼ 170 km from the Masaya Caldera Complex, increase the total tephra volume to 3.4 km3 or ∼ 1.8 km3 DRE of erupted basaltic magma. Isopleth data of five major fallout subunits indicate mass discharges of 106 to 108 kg/s and eruption columns of 21 to 32 km height, affected by wind speeds of < 2 m/s to ∼ 20 m/s which increased during the course of the multi-episodic eruption. Magmatic Plinian events alternated with phreatoplinian eruptions and phreatomagmatic explosions generating surges that typically preceded breaks in activity. While single eruptive episodes lasted for few hours, the entire eruption probable lasted weeks to months. This is indicated by changes in atmospheric conditions and ash-layer surfaces that had become modified during the breaks in activity. The Masaya Triple Layer has allowed to reconstruct in detail how a basaltic Plinian eruption develops in terms of duration, episodicity, and variable access of external water to the conduit, with implications for volcanic hazard assessment

Structure in 6D and 4D N=1 supergravity theories from F-theory

We explore some aspects of 4D supergravity theories and F-theory vacua that are parallel to structures in the space of 6D theories. The spectrum and topological terms in 4D supergravity theories correspond to topological data of F-theory geometry, just as in six dimensions. In particular, topological axion-curvature squared couplings appear in 4D theories; these couplings are characterized by vectors in the dual to the lattice of axion shift symmetries associated with string charges. These terms are analogous to the Green-Schwarz terms of 6D supergravity theories, though in 4D the terms are not generally linked with anomalies. We outline the correspondence between F-theory topology and data of the corresponding 4D supergravity theories. The correspondence of geometry with structure in the low-energy action illuminates topological aspects of heterotic-F-theory duality in 4D as well as in 6D. The existence of an F-theory realization also places geometrical constraints on the 4D supergravity theory in the large-volume limit.Comment: 63 page

Ambient-aware continuous care through semantic context dissemination

Background: The ultimate ambient-intelligent care room contains numerous sensors and devices to monitor the patient, sense and adjust the environment and support the staff. This sensor-based approach results in a large amount of data, which can be processed by current and future applications, e. g., task management and alerting systems. Today, nurses are responsible for coordinating all these applications and supplied information, which reduces the added value and slows down the adoption rate. The aim of the presented research is the design of a pervasive and scalable framework that is able to optimize continuous care processes by intelligently reasoning on the large amount of heterogeneous care data. Methods: The developed Ontology-based Care Platform (OCarePlatform) consists of modular components that perform a specific reasoning task. Consequently, they can easily be replicated and distributed. Complex reasoning is achieved by combining the results of different components. To ensure that the components only receive information, which is of interest to them at that time, they are able to dynamically generate and register filter rules with a Semantic Communication Bus (SCB). This SCB semantically filters all the heterogeneous care data according to the registered rules by using a continuous care ontology. The SCB can be distributed and a cache can be employed to ensure scalability. Results: A prototype implementation is presented consisting of a new-generation nurse call system supported by a localization and a home automation component. The amount of data that is filtered and the performance of the SCB are evaluated by testing the prototype in a living lab. The delay introduced by processing the filter rules is negligible when 10 or fewer rules are registered. Conclusions: The OCarePlatform allows disseminating relevant care data for the different applications and additionally supports composing complex applications from a set of smaller independent components. This way, the platform significantly reduces the amount of information that needs to be processed by the nurses. The delay resulting from processing the filter rules is linear in the amount of rules. Distributed deployment of the SCB and using a cache allows further improvement of these performance results

The repulsive lattice gas, the independent-set polynomial, and the Lov\'asz local lemma

We elucidate the close connection between the repulsive lattice gas in equilibrium statistical mechanics and the Lovasz local lemma in probabilistic combinatorics. We show that the conclusion of the Lovasz local lemma holds for dependency graph G and probabilities {p_x} if and only if the independent-set polynomial for G is nonvanishing in the polydisc of radii {p_x}. Furthermore, we show that the usual proof of the Lovasz local lemma -- which provides a sufficient condition for this to occur -- corresponds to a simple inductive argument for the nonvanishing of the independent-set polynomial in a polydisc, which was discovered implicitly by Shearer and explicitly by Dobrushin. We also present some refinements and extensions of both arguments, including a generalization of the Lovasz local lemma that allows for "soft" dependencies. In addition, we prove some general properties of the partition function of a repulsive lattice gas, most of which are consequences of the alternating-sign property for the Mayer coefficients. We conclude with a brief discussion of the repulsive lattice gas on countably infinite graphs.Comment: LaTex2e, 97 pages. Version 2 makes slight changes to improve clarity. To be published in J. Stat. Phy