Differential expression of chemokine and matrix re-modelling genes is associated with contrasting schistosome-induced hepatopathology in murine models

The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we investigated the contribution of variations in host gene expression to the contrasting hepatic pathology observed between two inbred mouse strains following Schistosoma japonicum infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in S. japonicum-infected BALB/c and CBA mice. We show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with the significantly greater accumulation of neutrophils at granulomatous regions seen in histological sections of hepatic tissue. In contrast, up-regulated expression of the eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the more pronounced hepatic damage in these mice. Profibrotic genes showed similar levels of expression in both mouse strains, as did genes associated with Th1 and Th2 responses. However, imbalances in expression of matrix metalloproteinases (e.g. MMP12, MMP13) and tissue inhibitors of metalloproteinases (TIMP1) may contribute to the contrasting pathology observed in the two strains. Overall, these results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. This improved understanding of the immunopathogenesis in the murine model schistosomiasis provides the basis for a better appreciation of the complexities associated with chronic human schistosomiasis.

Stability and convergence of implicit numerical methods for a class of fractional advection-dispersion models

In this paper, a class of fractional advection-dispersion models (FADM) is investigated. These models include five fractional advection-dispersion models: the immobile, mobile/immobile time FADM with a temporal fractional derivative 0 < γ < 1, the space FADM with skewness, both the time and space FADM and the time fractional advection-diffusion-wave model with damping with index 1 < γ < 2. They describe nonlocal dependence on either time or space, or both, to explain the development of anomalous dispersion. These equations can be used to simulate regional-scale anomalous dispersion with heavy tails, for example, the solute transport in watershed catchments and rivers. We propose computationally effective implicit numerical methods for these FADM. The stability and convergence of the implicit numerical methods are analyzed and compared systematically. Finally, some results are given to demonstrate the effectiveness of our theoretical analysis.

A general method to determine sampling windows for nonlinear mixed effects models with an application to population pharmacokinetic studies

Optimal design methods have been proposed to determine the best sampling times when sparse blood sampling is required in clinical pharmacokinetic studies. However, the optimal blood sampling time points may not be feasible in clinical practice. Sampling windows, a time interval for blood sample collection, have been proposed to provide flexibility in blood sampling times while preserving efficient parameter estimation. Because of the complexity of the population pharmacokinetic models, which are generally nonlinear mixed effects models, there is no analytical solution available to determine sampling windows. We propose a method for determination of sampling windows based on MCMC sampling techniques. The proposed method attains a stationary distribution rapidly and provides time-sensitive windows around the optimal design points. The proposed method is applicable to determine sampling windows for any nonlinear mixed effects model although our work focuses on an application to population pharmacokinetic models.

Using process models to support design of airport terminals

The complex design process of airport terminal needs to support a wide range of changes in operational facilities for both usual and unusual/emergency events. Process model describes how activities within a process are connected and also states logical information flow of the various activities. The traditional design process overlooks the necessity of information flow from the process model to the actual building design, which needs to be considered as a integral part of building design. The current research introduced a generic method to obtain design related information from process model to incorporate with the design process. Appropriate integration of the process model prior to the design process uncovers the relationship exist between spaces and their relevant functions, which could be missed in the traditional design approach. The current paper examines the available Business Process Model (BPM) and generates modified Business Process Model(mBPM) of check-in facilities of Brisbane International airport. The information adopted from mBPM then transform into possible physical layout utilizing graph theory.

Identification of vitronectin as a novel insulin-like growth factor-II binding protein

We have previously reported the presence of a 70 kDa insulin-like growth factor (IGF)-II-specific binding protein in chicken serum using Western ligand blotting approaches. In order to ascertain the identity of this 70 kDa IGF-II binding species, the protein has been purified from chicken serum using a combination of ion-exchange and gel-permeation chromatography. Interestingly, amino acid sequencing of the purified protein revealed that it has the same N-terminal sequence as chicken vitronectin (VN). The protein has the ability to specifically bind IGF-II and not IGF-I as determined by ligand blotting, cross-linking and competitive binding assay approaches. In addition, the protein binds 125I-des(l-6)-IGF-II, suggesting that the interaction with IGF-II is different to those with other characterized IGF-binding proteins. Importantly, we have ascertained that both human and bovine VN also specifically bind IGF-II. These results are particularly relevant in the light of the recent report that the urokinase-type plasminogen activator receptor, a protein that also binds VN, has been shown to associate with the cation-independent mannose-6-phosphate/GF-II receptor and suggest a possible role for IGF-II in cell adhesion and invasion.

The development of ground impact models for the analysis of the risks associated with Unmanned Aircraft Operations over inhabited areas

With the emergence of Unmanned Aircraft Systems (UAS) there is a growing need for safety standards and regulatory frameworks to manage the risks associated with their operations. The primary driver for airworthiness regulations (i.e., those governing the design, manufacture, maintenance and operation of UAS) are the risks presented to people in the regions overflown by the aircraft. Models characterising the nature of these risks are needed to inform the development of airworthiness regulations. The output from these models should include measures of the collective, individual and societal risk. A brief review of these measures is provided. Based on the review, it was determined that the model of the operation of an UAS over inhabited areas must be capable of describing the distribution of possible impact locations, given a failure at a particular point in the flight plan. Existing models either do not take the impact distribution into consideration, or propose complex and computationally expensive methods for its calculation. A computationally efficient approach for estimating the boundary (and in turn area) of the impact distribution for fixed wing unmanned aircraft is proposed. A series of geometric templates that approximate the impact distributions are derived using an empirical analysis of the results obtained from a 6-Degree of Freedom (6DoF) simulation. The impact distributions can be aggregated to provide impact footprint distributions for a range of generic phases of flight and missions. The maximum impact footprint areas obtained from the geometric template are shown to have a relative error of typically less than 1% compared to the areas calculated using the computationally more expensive 6DoF simulation. Computation times for the geometric models are on the order of one second or less, using a standard desktop computer. Future work includes characterising the distribution of impact locations within the footprint boundaries.

An authorization framework using building information models

A building information model (BIM) is an electronic repository of structured, three-dimensional data that captures both the physical and dynamic functional characteristics of a facility. In addition to its more traditional function as a tool to aid design and construction, a BIM can be used throughout the life cycle of a facility, functioning as a living database that places resources contained within the building in their spatial and temporal context. Through its comprehension of spatial relationships, a BIM can meaningfully represent and integrate previously isolated control and management systems and processes, and thereby provide a more intuitive interface to users. By placing processes in a spatial context, decision-making can be improved, with positive flow-on effects for security and efficiency. In this article, we systematically analyse the authorization requirements involved in the use of BIMs. We introduce the concept of using a BIM as a graphical tool to support spatial access control configuration and management (including physical access control). We also consider authorization requirements for regulating access to the structured data that exists within a BIM as well as to external systems and data repositories that can be accessed via the BIM interface. With a view to addressing these requirements we present a survey of relevant spatiotemporal access control models, focusing on features applicable to BIMs and highlighting capability gaps. Finally, we present a conceptual authorization framework that utilizes BIMs.