Biofunctionalised electrospun scaffolds for cartilage tissue engineering

The field of tissue engineering has advanced and evolved to focus on biomimetic strategies to meet the rise in demands of tissue replacements for surgical reconstruction. One of the key strategies focuses on developing growth factor delivery systems, by incorporating growth factors into tissue scaffolds. While growth factors are crucial cell-inducing components, their limitations such as short half-lives and dose related adverse effects remain a challenge. To overcome these challenges, this thesis is focused on the development of a novel biomimetic tissue scaffold concept incorporating cell-mediated activation of growth factors for cartilage regeneration. The latent transforming growth factor-β1 (TGF-β1) was selected as a model latent protein due to its well established effects on cartilage as well as its ubiquity in many other tissue types. The thesis first focused on the development and characterisation of the tissue scaffold. A non-woven fibrous scaffold was fabricated by electrospinning, surface modified using ammonia plasma, followed by scaffold surface biofunctionalisation with the latent TGF-β1. Physiochemical characterisation revealed that: (1) the scaffold architecture closely resembled that of the native cartilage extracellular matrix; (2) the scaffold surface was chemically modified for subsequent biofunctionalisation reaction; and (3) the latent TGF-β1 was incorporated onto the scaffold and the active TGF-β1 was detected upon acid and enzymatic activation. Biological effects of the biofunctionalised scaffold were assessed using human nasal chondrocytes in a serum free environment and compared with conventional TGF-β1 supplementation on non-biofunctionalised scaffolds (as control). The biofunctionalised scaffold group induced a lower cell metabolic activity and significantly higher gene expression of cartilage specific transcription factor Sox9 after 14 days. The second part of the thesis evaluated the chondrogenic efficacy of the biofunctionalised scaffolds, using the aforementioned chondrocytes and human mesenchymal stem cells (MSC), in an in-vivo rat model. Cell-scaffold constructs were implanted into subcutaneous pockets of athymic rats for six weeks. Gene expression and immunohistochemistry showed that the biofunctionalised group induced significant chondrogenic differentiation in chondrocytes and type II collagen production when compared to controls. Interestingly, a converse response was observed in MSC where the control group induced relatively higher chondrogenic potentials that the biofunctionalised group. This thesis demonstrates that the latent TGF-β1 biofunctionalised scaffolds induced chondrocytic differentiation in chondrocytes and more importantly the proof of concept of cell-mediated activation of growth factors as a novel approach for functional tissue regeneration

The Design of Multiyear Crop Insurance Contracts

Crop Production/Industries, Risk and Uncertainty,

Point pattern matching by heuristic methods : a genetic algorithm and simulated annealing

The problem we consider is to find a subset of points in a pattern that best match to a subset of points in another pattern through a transformation in an optimal sense. Exhaustive search to find the best assignment mapping one set of points to another set is, if the number of points that are to be matched is large, computationally expensive. We propose two stochastic searching techniques - a genetic algorithm and simulated annealing to search for the best ( almost the best ) assignment efficiently. To make the comparison between GA and SA fair, we introduce a piece-wise linear cooling schedule for the SA. As compared to conventional searching techniques such as simple hill climbing and random search techniques, the proposed methods are able to attain better solutions much faster. The proposed methods can be applied to n-dimensional point patterns and any transformation, but we only present results for two-dimensional point patterns and similarity transformations

An Economic Critique of Birch and Cobb’s The Liberation of Life

The discussion concerning humans and the environment has intensified in recent years. Now, more than ever, we must ask how we as economists can engage in a conversation regarding environmentalism when the participants come from a myriad of disciplines. I posit that it is only through an understanding of the other disciplines’ ethics and values that the economist can meaningfully engage in the conversation. This paper is an exercise in this interdisciplinary understanding. First, Charles Birch and John B. Cobb Jr.’s ecological viewpoint is presented. This is followed by the economic prescriptions arising from the ecological viewpoint. A subsequent critique and refutation of these economic prescriptions is made from an economic perspective

Group cohesiveness of Home Economics Improvement Clubs in Taiwan

The Home Improvement Clubs are one of the most important kinds of voluntary educational and social groups in rural Taiwan. The operating effectiveness of these groups is influential to the success of home economics extension work. This study examines the group cohesiveness of Home Economics Improvement Clubs and analyzes the factors affecting group cohesiveness and the cohesiveness-performance effect. This examination aims to provide some useful recommendations to the home economics extension work;One hundred and eight club leaders and 216 club members were asked to express their thoughts about some of the group characteristics of Home Economics Improvement Clubs to which they belong, including group cohesiveness, group performance, club leadership, leadership of extension workers, degree of organizational support, degree of family support, group members\u27 homogeneity, members\u27 learning motivation, and members\u27 interaction. Thirty-six extension workers were also interviewed;The findings show that the subjects gave very positive evaluations about all items measuring group cohesiveness. The results from structural equation modeling demonstrate that extension workers\u27 leadership, group age, members\u27 interaction, and learning motivation have significant positive effects on group cohesiveness. However, the cohesiveness-performance effect is not significant;Based on the research findings this study proposes four recommendations for home economics extension work: (1) to strengthen the vertical and horizontal linkages between related organizations; (2) to carry out more activities and programs for group member participation, (3) to enhance training programs for extension workers; (4) to enhance training programs for club leaders. The limitations of this study and some directions for future research are also discussed

Destabilizing the autoinhibitory conformation of Zap70 induces up-regulation of inhibitory receptors and T cell unresponsiveness.

Zap70 plays a critical role in normal T cell development and T cell function. However, little is known about how perturbation of allosteric autoinhibitory mechanisms in Zap70 impacts T cell biology. Here, we analyze mice with a hypermorphic Zap70 mutation, W131A, which destabilizes the autoinhibitory conformation of Zap70, rendering the kinase in a semiactive state. W131A mutant mice with wild-type T cell receptor (TCR) repertoires exhibited relatively normal T cell development. However, crossing the W131A mutant mice to OTII TCR transgenic mice resulted in increased negative selection of OTII+ thymocytes and in increased thymic and peripheral T regulatory cells. Strikingly, increased basal TCR signaling was associated with a marked increase in inhibitory receptor expression and with T cells that were relatively refractory to TCR stimulation. PD-1 inhibitory receptor blockade partially reversed T cell unresponsiveness. Collectively, disruption of normal Zap70 autoinhibition engaged negative feedback mechanisms by which negative selection and inhibitory receptors restrain TCR signaling to enforce both central and peripheral tolerance

Dip-coated La2Ti2O7 as a buffer layer for growth of Bi3.25La0.75Ti3O12 films with enhanced (0 1 1) orientation

Thin-films of La2Ti2O7 were obtained by dip-coating process using a precursor salt in nitric acid solution. The effects of solution concentration, withdrawal speed, post-annealing duration and temperature were investigated both on grain size and orientation of the La2Ti2O7 thin layers. In addition, a target with the required stoichiometry for PVD deposition of La-substituted Bi4Ti3O12 (BLT) was successfully sintered by spark plasma sintering (SPS) at 750 ◦C. Finally (0 1 1)-oriented BLT ferroelectric films have been grown by RF sputtering on (1 1 0)-oriented La2Ti2O7 polycrystalline thin-film. A preferential orientation of BLT thin films has been obtained after annealing at a temperature lower than 650 ◦C