Activator Protein-1 (AP-1) is an oncogenic transcription factor that is dysregulated in numerous human cancers, making it an attractive therapeutic target. AP-1 forms via interaction of cJun and cFos proteins, which intertwine to generate a ‘coiled coil’ (CC) structure. Thus, the cJun/cFos α-helical CC domains responsible for dimerisation are appealing targets for inhibiting AP-1 formation and activity. Helical peptide antagonists that sequester cJun can be derived from the cFos CC domain by selection of more optimal amino acids for increased binding affinity. Peptides can then be downsized and modified to improve therapeutic potential. Two approaches aimed to identify novel short peptides against cJun. The first was to covalently cyclise amino acid side chains in existing cFos-derived peptide “FosW”, with the aim of constraining FosW into a stable helix to allow downsizing without significant loss of binding structure and affinity. Using circular dichroism spectroscopy and isothermal titration calorimetry, a series of helix constrained peptides were characterised, from which a peptide was identified that retained 88 % of FosW binding affinity whilst being 22 % shorter, and which entered breast cancer cells in vitro, with preliminary data suggesting potential ability to inhibit AP-1 in cellulo. The second approach was to combine two existing high-throughput peptide selection systems, with the aim of benefitting from overlap in their strengths and weaknesses. Combination of in vitro CIS display and in cellulo Protein-fragment Complementation Assay successfully isolated a high affinity peptide from a hugely diverse library, and future refinements to further exploit this approach, particularly for short peptide selection, were formulated. Thus, molecules and techniques derived here may expedite the future development of therapies for cancers featuring AP-1 dysregulation.

<p>Abstract</p><p>The purpose of this study is to reach conclusions that pertain to the key steps involved in the development of a system of innovation. Once identifiable procedures have been reached, then the research seeks to address the characteristics, or roles, that the actors must adhere to in order to keep the system sustainable. When these two areas of research have been concluded, not only will the research question be addressed, but the general applicability of the system of innovation theories will also be challenged in a scientifically relevant way. The main theoretical concepts that will guide the study are Triple Helix, Sustainability, and Innovation.</p><p>The research approach used is deductive, where the information gathered will deem the study as being qualitative. In order to gather the information, six interviews were conducted with various individuals representing actors within the Triple Helix model, and that information was analyzed through interpretism. Due to the social relations occurring in the study, a hermeneutic positioning will derive an underlying positioning in the approach to theory. Once this approach is used, the empirical information gathered from the interviews will be analyzed versus that of the theoretical framework where the conclusions for the study will be generated.</p><p>The practical issue that inspired this study is the Mountain Pine Beetle epidemic occurring in British Columbia, Canada. The timber industry is being decimated due to an increase in the number of beetles, and the result is unusable wood. Because of the resource-reliance in certain milieus that are being effected by the beetle, this study seeks an alternative system for economic stability through a system of innovation.</p><p>The conclusions for the study have very pragmatic characteristics about them. The development of an innovation system begins with the identification of a system leader to mediate the process. The findings suggest that mediation will harmonize the agendas of the actors in the system and work towards a consensus. In addition, contextual issues in the form of knowledge and communication create cultural roadblocks in the implementation process; therefore need to be overcome in order to divert the actors from strict resource dependency. Sustainability in this system involves exclusive responsibilities between the actors involved, but the fundamental challenge rests in routinization of the process. Routinization encompasses micro-level procedures each actor must adhere to, and once this challenge has been overcome, the innovation system will remain sustained.</p>

Abstract The purpose of this study is to reach conclusions that pertain to the key steps involved in the development of a system of innovation. Once identifiable procedures have been reached, then the research seeks to address the characteristics, or roles, that the actors must adhere to in order to keep the system sustainable. When these two areas of research have been concluded, not only will the research question be addressed, but the general applicability of the system of innovation theories will also be challenged in a scientifically relevant way. The main theoretical concepts that will guide the study are Triple Helix, Sustainability, and Innovation. The research approach used is deductive, where the information gathered will deem the study as being qualitative. In order to gather the information, six interviews were conducted with various individuals representing actors within the Triple Helix model, and that information was analyzed through interpretism. Due to the social relations occurring in the study, a hermeneutic positioning will derive an underlying positioning in the approach to theory. Once this approach is used, the empirical information gathered from the interviews will be analyzed versus that of the theoretical framework where the conclusions for the study will be generated. The practical issue that inspired this study is the Mountain Pine Beetle epidemic occurring in British Columbia, Canada. The timber industry is being decimated due to an increase in the number of beetles, and the result is unusable wood. Because of the resource-reliance in certain milieus that are being effected by the beetle, this study seeks an alternative system for economic stability through a system of innovation. The conclusions for the study have very pragmatic characteristics about them. The development of an innovation system begins with the identification of a system leader to mediate the process. The findings suggest that mediation will harmonize the agendas of the actors in the system and work towards a consensus. In addition, contextual issues in the form of knowledge and communication create cultural roadblocks in the implementation process; therefore need to be overcome in order to divert the actors from strict resource dependency. Sustainability in this system involves exclusive responsibilities between the actors involved, but the fundamental challenge rests in routinization of the process. Routinization encompasses micro-level procedures each actor must adhere to, and once this challenge has been overcome, the innovation system will remain sustained.

Uniform lying helix(ULH) is a cholesteric LC structure with helical axix lying on the substrate. This structure has a periodic refractive index profile characteristics, so that it can be used as a phase grating. The ULH period can be tuned with different electric fields which provide with various applications. However, ULH is not a steady state in general, once the electric field shutdown, ULH texture will transform to planar texture. Generally, the ULH exist only under a few conditions: well homogeneous alignment and cell the ratio of gap to pitch smaller than 2 , in case the ratio more than 2, the ULH won¡¦t align well. We use two methods to make ULH align well at large cell gap pitch ratio; cooling down from isotropic temperature under electric field and putting mechanical stress on the sample, therefore we can get a well alignment and more stable ULH. We discuss the influence of different boundary conditions to the stability of ULH, and we discover that when d/p large than 10, the stability of ULH improved significantly. Then we study the influence in different alignment anchoring, we find stronger anchoring energy makes ULH transform to planar easily. So we use photo alignment to get weaker anchoring energy, and the ULH using photo alignment stable more than 24 hours. Finally we use a large d/p ULH as tunable phase grating, the pitch length can be tuned about 380nm with low power consumption, and it still have grating function when the field shutdown . Keyword: cholesteric liquid crystal¡Buniform lying helix¡Bgrating

The numbers of atoms in a protein molecule are large, from 103 to 104. If we try to solve the positions of all atoms in a protein molecule, we usually can¡¦t get the result due to tremendous degrees of freedom. Here, we use the uniform cylinders to replace the helixes found in most protein molecules, and reduce the degrees of freedom dramatically. We also adapt Su¡¦s method to avoid the ¡§X-ray phase problem¡¨. In this thesis, we simulate the small angle X-ray diffraction data of atoms which uniformly confined in cylinders, and then using trying cylinders to simulate the real cylinders. Our study shows that we can find the cylinders¡¦ positions quite successfully and efficiently. Our approach provides a promising way to find out the helix structure of proteins.

This study was carried out to examine how innovation can support sustainability and why these two concepts are important for agriculture. To do this, it was necessary to explore the meaning of sustainability and innovation for sustainability, the barriers and opportunities in building a local innovation system by identifying learning interactions, and the role of higher education institutions in achieving sustainability. Since there has been no empirical study of innovation and sustainability in agriculture from a bottom-up perspective, a qualitative case study with multi-methods approach was conducted. The field study took place in Yucatán, México, in the Conkal community over a period of three months in 2013. This research was comprised of in-depth interviews with stakeholders involved in habanero chile farming to identify their perceptions, challenges, and the nature of their willingness and practice of innovation and sustainability. Both Strengths, Weaknesses, Opportunities, Threats (SWOT) and document analysis were used to complement the interview evidence. The results highlight the interpretations of sustainability principles (economic, ecological, and social) and the flow of knowledge and learning interactions that are occurring in the habanero chile product system. To increase innovation capacity, the integration of multiple local players is important to create local innovation systems that can also achieve sustainability principles. The study suggests that learning interactions and knowledge networks at the local level can be used to develop and disseminate technological and non-technological innovation for social, economic, and ecological improvement in farming. Such improvements should be supported by higher education institutions by generating, transferring, and applying ideas, resources, and programs to local communities. Higher education institutions should work towards the integration of various types of knowledge and increase engagement with local farming needs. However, the willingness and trust of individuals as well as the lack of leveraging opportunities to innovate for sustainability were perceived as barriers. The key contribution of this study is to highlight and promote how innovation systems at small scales can support sustainability that may lead to a quintuple helix model (one that integrates the following five components: university, government, industry, civil society, and natural environment). The most important aspect of this study is the suggestion that the integration of social, ecological, and economic goals in innovation systems can help shape an approach that can reorganize innovation for sustainability. Such suggestions are described in the results and discussion sections.

No description available.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed on June 26, 2009). Includes bibliographical references.

Thesis (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2005. / Embargoed. Vita. Bibliography: 97-112.

Universiẗat, Diss., 2002--Potsdam.