Computational Modelling of Atherosclerosis

Atherosclerosis is one of the principle pathologies of cardiovascular disease with blood cholesterol a significant risk factor. The World Health Organisation estimates that approximately 2.5 million deaths occur annually due to the risk from elevated cholesterol with 39% of adults worldwide at future risk. Atherosclerosis emerges from the combination of many dynamical factors, including haemodynamics, endothelial damage, innate immunity and sterol biochemistry. Despite its significance to public health, the dynamics that drive atherosclerosis remain poorly understood. As a disease that depends on multiple factors operating on different length scales, the natural framework to apply to atherosclerosis is mathematical and computational modelling. A computational model provides an integrated description of the disease and serves as an in silico experimental system from which we can learn about the disease and develop therapeutic hypotheses. Although the work completed in this area to-date has been limited, there are clear signs that interest is growing and that a nascent field is establishing itself. This paper discusses the current state of modelling in this area, bringing together many recent results for the first time. We review the work that has been done, discuss its scope and highlight the gaps in our understanding that could yield future opportunities.Comment: in Briefings in Bioinformatics (2015

A radial mode ultrasonic horn for the inactivation of <i>Escherichia coli</i> K12

Tuned cylindrical radial mode ultrasonic horns offer advantages over ultrasonic probes in the design of flow-through devices for bacterial inactivation. This study presents a comparison of the effectiveness of a radial horn and probe in the inactivation of Escherichia coli K12. The radial horn is designed using finite element analysis and the predicted modal parameters are validated using experimental modal analysis. A validated finite element model of the probe is also presented. Visual studies of the cavitation fields produced by the radial horn and probe are carried out using luminol and also backlighting to demonstrate the advantages of radial horns in producing a more focused cavitation field with widely dispersed streamers. Microbiological studies show that, for the same power density, better inactivation of E. coli K12 is achieved using the radial horn and, also, the radial horn offers greater achievable power density resulting in further improvements in bacterial inactivation. The radial horn is shown to be more effective than the probe device and offers opportunities to design in-line flow-through devices for processing applications

The relation between hemispheric lateralisation and measures of immune competence and adherence in Human Immunodeficiency Virus Type 1 (HIV-1)

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited - Copyright © 2012 Sumner et al

Regulated internalization of caveolae

Caveolae are specialized invaginations of the plasma membrane which have been proposed to play a role in diverse cellular processes such as endocytosis and signal transduction. We have developed an assay to determine the fraction of internal versus plasma membrane caveolae. The GPI-anchored protein, alkaline phosphatase, was clustered in caveolae after antibody-induced crosslinking at low temperature and then, after various treatments, the relative amount of alkaline phosphatase on the cell surface was determined. Using this assay we were able to show a time- and temperature-dependent decrease in cell-surface alkaline phosphatase activity which was dependent on antibody-induced clustering. The decrease in cell surface alkaline phosphatase activity was greatly accelerated by the phosphatase inhibitor, okadaic acid, but not by a protein kinase C activator. Internalization of clustered alkaline phosphatase in the presence or absence of okadaic acid was blocked by cytochalasin D and by the kinase inhibitor staurosporine. Electron microscopy confirmed that okadaic acid induced removal of caveolae from the cell surface. In the presence of hypertonic medium this was followed by the redistribution of groups of caveolae to the center of the cell close to the microtubule-organizing center. This process was reversible, blocked by cytochalasin D, and the centralization of the caveolar clusters was shown to be dependent on an intact microtubule network. Although the exact mechanism of internalization remains unknown, the results show that caveolae are dynamic structures which can be internalized into the cell. This process may be regulated by kinase activity and require an intact actin network

Problem-based Learning: A Critical Rationalist Perspective

Although problem-based learning is being adopted by many institutions around the world as an effective model of learning in higher education, there is a surprising lack of critique in the problem-based learning literature in relation to its philosophical characteristics. This paper explores epistemology as a starting point for investigating the theoretical underpinnings of problem-based learning as a learning model. Criticisms of empiricism are analysed in terms of the perceived learning outcomes of learners undertaking a problem-based learning curriculum. It is argued that models of empiricism theorised by philosophers such as Bacon, Locke and Hume cannot fully account for the learning model found in problem-based learning curricula. It is proposed that an alternative epistemological approach is needed. The work of Karl Popper is discussed, whose critical rationalist epistemology emphasises the generation of bold conjectures and criticism. Popper's work shows a positive contribution to the demands of higher education, characterised by learners who are serious about making professional progress. The paper concludes by critically analysing the tensions and contradictions of problem-based learning in light of Popper's epistemological theory of critical rationalism. It is argued that a critical rationalist perspective has educational benefits for students as it creates an environment rich in critical thinking, reading and writing and values disjunction and challenge

Supply Chain Performance Indicators for Australian Beef Industry: An Empirical Analysis

Abstract: This research presents and analyses supply chain performance indicators for Australian beef producers, processors and retailers/wholesalers based on an empirical approach. The survey results showed that: 1. for producers, competitive advantage was significantly influenced by the supply chain performance components food quality, flexibility and responsiveness 2. for processors, competitive advantage was significantly influenced by the supply chain performance components food quality and responsiveness 3. at the retail/wholesale level, competitive advantage was significantly influenced by food quality, flexibility, responsiveness and efficiency 4. a significant problem affecting the overall performance of the Australian beef supply chain was unskilled and inexperienced staff. Various statistical tests confirmed the validity and reliability of the results. Keywords: supply chain performance indicators, food quality, flexibility, responsiveness, efficiency

An endosomal beta COP is involved in the pH-dependent formation of transport vesicles destined for late endosomes

In this paper, we show that beta COP is present on endosomes and is required for the formation of vesicles which mediate transport from early to late endosomes. Both the association of beta COP to endosomal membranes as well as transport vesicle formation depend on the lumenal pH. We find that epsilon COP, but not gamma COP, is also associated to endosomes, and that this association is also lumenal pH dependent. Our data, thus, indicate that a subset of COPs is part of the mechanism regulating endosomal membrane transport, and that membrane association of these COPs is controlled by the acidic properties of early endosomes, presumably via a trans-membrane pH sensor

Food Price Policy in Indonesia

Agricultural and Food Policy,

Annexin XIIIb: a novel epithelial specific annexin is implicated in vesicular traffic to the apical plasma membrane

The sorting of apical and basolateral proteins into vesicular carriers takes place in the trans-Golgi network (TGN) in MDCK cells. We have previously analyzed the protein composition of immunoisolated apical and basolateral transport vesicles and have now identified a component that is highly enriched in apical vesicles. Isolation of the encoding cDNA revealed that this protein, annexin XIIIb, is a new isoform of the epithelial specific annexin XIII sub-family which includes the previously described intestine-specific annexin (annexin XIIIa; Wice, B. M., and J. I, Gordon. 1992. J. Cell Biol. 116:405-422). Annexin XIIIb differs from annexin XIIIa in that it contains a unique insert of 41 amino acids in the NH2 terminus and is exclusively expressed in dog intestine and kidney, Immunofluorescence microscopy demonstrated that annexin XIIIb was localized to the apical plasma membrane and underlying punctate structures. Since annexins have been suggested to play a role in membrane-membrane interactions in exocytosis and endocytosis, we investigated whether annexin XIIIb, is involved in delivery to the apical cell surface. To this aim we used permeabilized MDCK cells and a cytosol-dependent in vitro transport assay. Antibodies specific for annexin XIIIb significantly inhibited the transport of influenza virus hemagglutinin from the TGN to the apical plasma membrane while the transport of vesicular stomatitis virus glycoprotein to the basolateral cell surface was unaffected. We propose that annexin XIIIb, plays a role in vesicular transport to the apical plasma membrane in MDCK cells