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.

Scenes, quarters and clusters : new experiments in the formation and governance of creative places in China

This thesis examines the formation and governance patterns of the social and spatial concentration of creative people and creative business in cities. It develops a typology for creative places, adding the terms 'scene' and 'quarter' to 'clusters', to fill in the literature gap of partial emphasis on the 'creative clusters' model as an organising mechanism for regional and urban policy. In this framework, a cluster is the gathering of firms with a core focus on economic benefits; a quarter is the urban milieu usually driven by a growth coalition consisting of local government, real estate agents and residential communities; and a scene is the spontaneous assembly of artists, performers and fans with distinct cultural forms. The framework is applied to China, specifically to Hangzhou – a second-tier city in central eastern China that is ambitious to become a 'national cultural and creative industries centre'. The thesis selects three cases – Ideal & Silian 166 Creative Industries Park, White-horse Lake Eco-creative City and LOFT49 Creative Industries Park – to represent scene, quarter and cluster respectively. Drawing on in-depth interviews with initiators, managers and creative professionals of these places, together with extensive documentary analysis, the thesis investigates the composition of actors, characteristics of the locality and the diversity of activities. The findings illustrate that, in China, planning and government intervention is the key to the governance of creative space; spontaneous development processes exist, but these need a more tolerant environment, a greater diversity of cultural forms and more time to develop. Moreover, the main business development model is still real estate based: this model needs to incorporate more mature business models and an enhanced IP protection system. The thesis makes a contribution to literature on economic and cultural geography, urban planning and creative industries theory. It advocates greater attention to self-management, collaborative governance mechanisms and business strategies for scenes, quarters and clusters. As intersections exist in the terms discussed, a mixed toolkit of the three models is required to advance the creative city discourse in China.