As the information technology develops rapidly, the software industry also keep growing and growing. Huge amount of capital and intelligence are being invested in developing the new software. However, it has been such a big negative impact on all software developers caused by the illegal reproduction and distribution. Therefore, besides the copyright regulations, software companies have always been concentrated on how to prevent their software from being illegally reproduced by adding protection codes. As most of the companies are not willing to reveal their protection methods, it is hard to have any chance to learn from each other's techniques and experiences. As a result, this thesis is really concentrated on collecting and categorizing as many as possible the protection coding technologies and in the end, analyzing and applying those to our own programs.

Cell adhesion to extracellular matrices (ECM) is essential to numerous physiological and pathological processes. Cell adhesion is initiated by binding of the transmembrane integrin family of receptors to an ECM ligand such as fibronectin (FN). Once bound, integrins cluster together and form focal adhesions (FA). FAs serve as structural links and signal transduction elements between the cell and its extracellular environment. While a great deal of progress has been made in identifying the biochemical components that comprise focal adhesions and the roles they play in migration, cell spreading, and signaling, the contributions of these proteins to mechanical interactions between the cell and its environment remain poorly understood. A FA adhesion protein of particular importance is vinculin. When localized to focal adhesions, vinculin forms a ternary complex with talin and 1-integrin. This 1-integrin-talin-vinculin complex plays a central role in the regulation of FA assembly and cell spreading and migration. Nevertheless, the specific contribution to adhesive force generation of the 1-integrin-talin-vinculin complex remains poorly understood. The objective of this project was to analyze the role of vinculin in the cell adhesion strengthening process. Our central hypothesis is that vinculin modulates adhesion strength via regulating the size and/or composition of the integrin-talin-vinculin complex. We used a novel combination of biochemical reagents and engineering techniques along with quantitative and sensitive adhesion strength measurements to provide new insights into how the structure of vinculin contributes to cell adhesion strength.

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 149-163). Also available online.

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 149-163). Also available in print.

The Spin-Transfer Torque Magnetoresistive Random Access Memory (STT-MRAM) has opened new doors as an emerging technology with high potential to replace traditional CMOS-based memory technology. This has come true due to the density, speed and non- volatility that have been demonstrated. The STT-MRAM uses Magnetic Tunnel Junction (MTJ) elements as non-volatile memory storage devices because of the recent discovery of spin-torque phenomenon for switching the magnetization states. The magnetization of the free layer in STT-MRAM can be switched from logic "1" to logic "0" by the use of a spin-transfer torque. However, the STT-MRAMs have till now only been used as universal memory. As a result, STT-MRAMs are not yet commercially used as computing elements, though they have the potential to be used as Logic-In-Memory computation applications. In order to advance this STT-MRAM technology for computation, we have used different MRAM devices that are available as memory elements with different geometries, to use it as computing elements. This dissertation presents design and implementation of such devices using different multilayer magnetic material stacks for computation. Currently, the design of STT-MRAMs is limited to only memory architectures, and there have been no proposals on the viability of STT-MRAMs as computational devices. In the present work, we have developed a design, which could be implemented for universal logic computation. We have utilized the majority gate architecture, which uses the magneto-static interaction between the freelayers of the multilayer nanomagnets, to perform computation. Furthermore, the present work demonstrates the study of dipolar interaction between nanomagnetic disks, where we observed multiple magnetization states for a nanomagnetic disk with respect to its interaction energy with its neighboring nanomagnets. This was achieved by implementing a single layer nanomagnetic disk with critical dimension selected from the phase plot of single domain state (SDS) and vortex state (VS). In addition, we found that when the interaction energy between the nanomagnetic disks with critical dimension decreases (increase in center-to-center distance) the magnetization state of the nanomagnetic disks changes from single domain state to vortex state within the same dimension. We were able to observe this effect due to interaction between the neighboring nanomagnets. Finally, we have presented the design and implementation of a Spin-Torque driven Re- configurable Array of Nanomagnets (STRAN) that could perform Boolean and non-Boolean computation. The nanomagnets are located at every intersection of a very large crossbar array structure. We have placed these nanomagnets in such a way that the ferromagnetic free layers couple with each other. The reconfigurable array design consists of an in-plane (IP) free layer and a fixed polarizer [magnetized out-of-plane (OP)]. The cells that need to be deselected from the array are taken to a non-computing oscillating state.

published_or_final_version / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy

Upon aging, the intervertebral disc (IVD) inevitably undergoes degeneration characterized by biochemical and morphologic changes. IVD degeneration can lead to multiple clinical disorders such as back and neck pain, and myelopathy. Low back pain can disable up to 85% of the adult population and results in a significant restriction of social activities and inability to work. Such disorder incurs billions of dollars in medical expenditures each year. Despite advances in the detection and treatment of the degeneration, the regeneration of the IVD remains low because current therapies are limited by exogenous curing approaches. New strategies for the reversal of IVD degeneration, including gene, cytokine, and stem cell therapies that can influence the anabolic and catabolic pathways in disc cells have been under investigation. These therapies aim to rejuvenate or replace diminished nucleus pulposus cells in the degenerative IVD. Recent reports have put forth a proposal of “endogenous disc stem cells”, suggesting that cells derived from the degenerative IVD tissue possess stem cell properties. These putative stem cells are believed to regulate the development and homeostasis of the IVD tissue. In this study, we identified and characterized a stem cell population from the IVD of healthy Rhesus monkey, termed disc stem/progenitor cells (DSCs). We show that the DSCs possess clonogenicity, multipotency and self-renewal capacity. The DSCs are phenotypically similar to bone marrow mesenchymal stem cells (BMSCs) but they are not identical. The DSCs show a faster growth rate under hypoxia than normoxia. DSCs derived from nucleus pulposus (DSCNP) show a stable expression level of hypoxia inducible factor-1 alpha (Hif-1ａ) in response to hypoxia. DSCs derived from annulus fibrosus (DSCAF) are more resistant to apoptosis under hypoxia than DSCNP. More importantly, small leucine-rich proteoglycans (SLRPs) are identified as important DSC niche components. We show that biglycan (bgn) and decorin (dcn) reduce the susceptibility of DSCs to hypoxia-induced apoptosis by promoting the expression of hypoxia inducible factors (HIFs). Our findings suggest that DSCs rely on the unique niche components for survival. In summary, our findings propose the existence of endogenous stem cells in IVD. Further study of the DSCs may provide new insights into the biology of IVD and facilitate the design of new strategies to treat disc degeneration in future. / published_or_final_version / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy

Degenerative disc disease (DDD) is a medical condition whereby the intervertebral discs (IVD) of the human spine degenerates and may cause pain which significantly affects the quality of one掇 life. Its prevalence has sparked off much research in deciphering its causes and developing new treatments. Recently, attempts to treat this degenerative problem have turned to seeking answers from regenerative medicine. One approach is to deliver mesenchymal stem cells (MSCs) with or without carriers to the nucleus pulposus (NP) in degenerative disc to restore both its structural and functional properties. However, the optimal conditions and signals for inducing MSCs differentiation toward NP-like phenotype have not been identified. This work aimed to develop injectable microspheres with matrix microenvironment mimicking that of native NP tissue for MSCs delivery. Firstly, it was aimed to establish a collagen microencapsulation based 3D culture system for maintenance of the phenotype of nucleus pulposus cells (NPCs) and remodeling of the collagen matrix to one that was similar to the native NP. Secondly, it was aimed to optimize a decellularization protocol for complete removal of the encapsulated NPCs with minimal loss of remodeled extracellular matrix. Thirdly, it was aimed to investigate whether this acellular matrix produced by NPCs was inductive for MSCs discogenic differentiation. Finally, it was aimed to evaluate the efficacy of the MSC-seeded acellular matrix microspheres in a pilot rabbit disc degeneration model. It demonstrated that NPCs maintained their phenotype, survived within the collagen microspheres and produced NP-like ECM such as glycosaminoglycan (GAG) and collagen type II. GAG production of NPCs was found to positively correlate with the dosage of TGF-? within a short period, initial collagen concentration and cell seeding density. An optimized decellularization protocol with 50mM SB-10, 0.6mM SB-16 and 0.14% Triton X-200 was established to completely remove the encapsulated NPCs with partial retention of the GAG-rich matrix. The decellularized microspheres were able to be repopulated with human MSCs (hMSCs) or rabbit MSCs (rMSCs). Within the NPC-derived acellular matrix, the repopulated hMSCs were able to partially exhibit NPC phenotype with upregulated expression of a few NPC markers and NP-like ECM according to histological, biochemical, immunohistological and real-time PCR results. In the pilot in vivo evaluation study, preliminary results showed that intra-discal injection of MSCs reseeded acellular NPC-matrix microspheres maintained a better water content than the control MSC-microspheres without the NPC-derived acellular matrix. This work reconstituted in vitro a NP-like 3D matrix and provided preliminary evidence on discogenic differentiation of MSCs in such a matrix environment. This work laid down the foundation to future development of stem cell-based therapies for DDD. Further studies should focus on deciphering the soluble and insoluble composition of such a NP-like matrix environment and understanding the molecular mechanism of the cell-matrix interactions involved. / published_or_final_version / Mechanical Engineering / Doctoral / Doctor of Philosophy

The need for the development of a rigorous analytical model of the lumbar spine to clarify the role of mechanical factors in low-back disorders has long been recognized. In response to this need, a general three dimensional nonlinear finite element program has been developed as part of this work and has been applied to the analysis of a lumbar L(,2-3) joint including the posterior elements. The analysis accounts for both the material and geometric nonlinearities and is based on a representation of the nucleus as an incompressible inviscid fluid and of the annulus as a composite of collagenous fibres embedded in a matrix of ground substance. The facet articulation has been accounted for by treating it as a general moving contact problem. The ligaments have been modelled as a collection of nonlinear axial elements. The geometry of the finite element model is based on in-vitro measurements. / The response of the joint under single compression, single flexion, single extension and also under flexion or extension combined with compression and sagittal shear has been analyzed for both the normal and degenerated states of the nucleus. Validity of the model has then been established by a comparison of those predictions which are also amenable to direct measurements. The states of strain and stress in different components of the lumbar joint have been thoroughly studied under all the foregoing loading conditions. / Those elements of the joint predicted to be vulnerable to mechanical failure or damage under the above types of loading have been identified. These results have been correlated with the lumbar joint injuries reported clinically. Furthermore, some joint injury mechanisms and degeneration processes have been proposed and the supporting clinical evidences have been presented.

No description available.