A recent shift towards proteomics has seen many structural genomics initiatives set up for high-throughput structure determination using traditional methods of x-ray crystallography and NMR. The next step in the proteomic revolution focuses on the interplay of multi-protein complexes and transient protein-protein interactions, which are involved in many cellular functions. Greater understanding of protein-protein interactions will inevitably lead to better comprehension of the regulation of cellular process, which has implications in biomedical sciences and biotechnology. Even though many high-resolution initiatives focus on proteins and protein complexes, their structure-determination success rates are still low. An emerging approach uses chemical cross-linking and mass spectrometry to derive a set of sparse distance constrains, which can be used for building models of proteins and to map out residues in protein interaction interface based on partial structural information. This technique allows low-resolution identification of protein structures and their interactions in cases where traditional structure determination techniques did not produce results. Chemical cross-linkers have been successfully used for many years in identifying interacting proteins. However, recent advances in mass spectrometry have allowed the identification of exact insertion points of low-abundance cross-links and hence has opened up a new perspective on the use of cross-linkers in combination with computational structure prediction. For protein interaction studies, the approach uses chemical cross-linking information with molecular docking, so that the cross-links are treated as explicit constraints in the calculations. This study focuses on a low-cost and rapid approach to structure prediction, where partial structural information and distance constraints can be used to obtain the relative orientation of interacting proteins and domains, specifically as a rescue strategy where traditional high resolution structure determination methods were unsuccessful. This hybrid biochemical/bioinformatics approach was applied in the determination of structure of the latexin:carboxypeptidase A complex, and succeeded in achieving 4 Å rmsd compared to the crystal structure determined subsequently (Mouradov et al., 2006). Application of the bioinformatics/biochemical approach to multi-domain proteins was carried out on murine acyl-CoA thioesterase 7 (Acot7). X-ray crystallography provided structures of the two separate domains of Acot7, however the full length protein did not crystalise. Combining chemical cross-linking, mass spectrometry, molecular docking and homology modeling we were able to reconstruct how the two domains are arranged in the full length protein (Forwood et al., 2007). Limitations of this technique caused by the enormous complexity of the cross-linking reaction mixtures were identified and emphasized by analysing a large (four protein) complex of DNA polymerase III, where only one inter-protein cross-link was identified. A rapid and cost-effective method for identification of cross-linked peptides using a commercially available cross-linker was developed as part of the overall aim of streamlining the hybrid biochemical/bioinformatics in order for it to become a generally applicable technique for rapid protein structure characterisation (King et al., 2008). Finally an in-house software package was developed for assignment of cross-linked peptides based on m/z values.

Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 4 uppsatser.

Thesis (Ph.D. in Toxicology) -- University of Colorado at Denver and Health Sciences Center, 2005. / Typescript. Includes bibliographical references (leaves 128-138).

Thesis (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2006. / Not embargoed. Vita. Bibliography: 129-137.

Project management (PM) plays a significant role in achieving the company’s goal and objectives. Due to its significant role, it is essential that the project managers use processes which remain focussed on the company’s business strategy. However, some implementations of the company’s business strategy have led to failures as a result of misalignment between project management and the company’s business strategy. Such misalignment has an impact on both the project management and business strategy and may lead to problems in the overall functioning of the business, including the implementation of the company’s business strategy through the projects. This research was undertaken to investigate the problem of aligning project management process with the company’s business strategy which has not been fully investigated to-date. This investigation aims to provide a deeper understanding and more holistic analysis of the key factors, such as stakeholders and contextual factors (AF), which enable or inhibit this alignment in order to develop a conceptual framework that addresses this research gap. This study examines and analyses the alignment process, by considering the key factors at the early planning phase of project management. To address the research gap, the study employs a qualitative, multiple case study approach in the interpretive paradigm. Data was collected via interviews of senior personnel (executives and project managers), mainly from three managerial levels of the organisation, including corporate, business, and functional levels in four telecommunication companies of the private sector in Saudi Arabia. The investigation was carried out by collecting data through semi-structured interviews to critically explore collectively the perspectives of the executives and the project managers on their experience of managing and executing the company’s business strategy and the projects. Written and electronic documentations as well as non-participant observations also served as important triangulation and complementary sources in understanding the phenomenon being studied and as a means of gaining additional perspectives and further insights on key issues. This study provides a novel contribution to the alignment process of project management to business strategy. The original contribution and findings of this study contribute to the growing body of knowledge of project management by developing a practical framework to benefit both academics and practitioners and to increase awareness of the alignment process. This holistic conceptual framework includes two sets of factors that impact the alignment process. Additionally, it provides a unique prescriptive standard and a code of practice for practitioners seeking to realise efficient and effective alignment.

abstract: Treatment of cerebral aneurysms using non-invasive methods has existed for decades. Since the advent of modern endovascular techniques, advancements to embolic materials have largely focused on improving platinum coil technology. However, the recent development of Onyx®, a liquid-delivery precipitating polymer system, has opened the door for a new class of embolic materials--liquid-fill systems. These liquid-fill materials have the potential to provide better treatment outcomes than platinum coils. Initial clinical use of Onyx has proven promising, but not without substantial drawbacks, such as co-delivery of angiotoxic compounds and an extremely technical delivery procedure. This work focuses on formulation, characterization and testing of a novel liquid-to-solid gelling polymer system, based on poly(propylene glycol) diacrylate (PPODA) and pentaerythritol tetrakis(3-mercaptopropionate) (QT). The PPODA-QT system bypasses difficulties associated with Onyx embolization, yet still maintains non-invasive liquid delivery--exhibiting the properties of an ideal embolic material for cerebral aneurysm embolization. To allow for material visibility during clinical delivery, an embolic material must be radio-opaque. The PPODA-QT system was formulated with commercially available contrast agents and the gelling kinetics were studied, as a complete understanding of the gelling process is vital for clinical use. These PPODA-QT formulations underwent in vitro characterization of material properties including cytotoxicity, swelling, and degradation behaviors. Formulation and characterization tests led to an optimized PPODA-QT formulation that was used in subsequent in vivo testing. PPODA-QT formulated with the liquid contrast agent ConrayTM was used in the first in vivo studies. These studies employed a swine aneurysm model to assess initial biocompatibility and test different delivery strategies of PPODA-QT. Results showed good biocompatibility and a suitable delivery strategy, providing justification for further in vivo testing. PPODA-QT was then used in a small scale pilot study to gauge long-term effectiveness of the material in a clinically-relevant aneurysm model. Results from the pilot study showed that PPODA-QT has the capability to provide successful, long-term treatment of model aneurysms as well as facilitate aneurysm healing. / Dissertation/Thesis / Ph.D. Bioengineering 2011

Doctor of Philosophy / Department of Biological and Agricultural Engineering / Donghai Wang / The depletion of petroleum feedstock along with significant concerns about health and environment lead to an interest in alternative green products. Soy protein (SP) adhesives have great potential as a renewable material for wood industries. The obstacle of applying SP-based adhesives is its relatively low water resistance. The overall objective was to enhance the water resistance of SP adhesives through protein and lignin interaction. An improvement of adhesion performance, flowability, and thermal properties of SP adhesives was achieved through the protein and lignin interaction and formation of protein and lignin copolymer. pH adjustment is a simple process to change protein folding and lignin properties. Cleavage of β-O-4 linkage was observed at pH 8.5 and pH 12, resulting in an increase in lignin active groups and the changes in lignin particle size and thermal properties. Cross-linking of protein with lignin took place via carbonyl, amino, and hydroxyl groups. Multiple-point and non-specific interactions between lignin and protein resulted in stronger lignin-protein networks and changes in properties, which improved wet adhesion strength of protein adhesives. In addition, lignin was depolymerized by laccase enzyme with the presence of mediator, TEMPO, to induce a formation of the strong lignin-protein network. The formation of the strong lignin-protein network increased the wet adhesion strength by 106% and the partial wood failure was observed after the three-layer wood test. A better performance was also observed on the three-cycle soaking test. The adhesion performance of SP adhesives was also greatly affected by lignin particle size and the protein to lignin ratio at pH 4.5. The wet adhesion strength of SP adhesives increased as lignin particle size decreased. The protein-lignin adhesive with protein to lignin ratio of 10:2 (w/w) at 12% solid content had the lowest contact angle and the highest wet adhesion strength of 4.66 MPa, which is 53.3% higher than that of 10% pure SP adhesive. Lignin-protein interactions, water resistance property, and glue line pattern had strong influences on an adhesion performance. Lignin and soy protein were modified at pH 4.5, 8.5 and 12. The maximum increase (620%) in water resistance was found at pH 12 with an addition of lignin. After the protein was unfolded (pH 8.5) and denatured (pH 12), it was refolded by shifting pH to 4.5. The better-wet adhesion performance was obtained at pH 4.5, 8.5-4.5 and 12 with rigid glue line. Shifting pH from 8.5 to 4.5 promoted lignin-protein interaction and increased adhesion performance. The protein-lignin adhesives using absolutely renewable materials and practical processes showed an excellent potential to replace the petroleum-based adhesives and fulfill the global demand for green products and technologies.

Memoria (licenciado en ciencias jurídicas y sociales) / El presente trabajo tiene como objetivo analizar la práctica del linking y sus consecuencias jurídicas en el marco de la legislación chilena y extrajera. Se procederá a identificar esta práctica que se presenta como el acto de proporcionar hipervínculos, en el contexto de una página web de enlaces, que destinen al usuario hacia contenido protegido por derecho de autor puesto a disposición por un tercero en un servidor o página web distinta de la primera y sin autorización del titular de aquellos derechos. En base a esto, se realizará un estudio de las posibles responsabilidades de los distintos actores que se ven involucrados en esta práctica. Palabras Clave: linking, comunicación pública, puesta a disposición, responsabilidad de terceros

[pt] Com o surgimento da Linked (Open) Data, uma série de novos e importantes desafios de pesquisa vieram à tona. A abertura de dados, como muitas vezes a Linked Data é conhecida, oferece uma oportunidade para integrar e conectar, de forma homogênea, fontes de dados heterogêneas na Web. Como diferentes fontes de dados, com recursos em comum ou relacionados, são publicados por diferentes editores, a sua integração e consolidação torna-se um verdadeiro desafio. Outro desafio advindo da Linked Data está na criação de um grafo denso de dados na Web. Com isso, a identificação e interligação, não só de recursos idênticos, mas também dos recursos relacionadas na Web, provê ao consumidor (data consumer) uma representação mais rica dos dados e a possibilidade de exploração dos recursos conectados. Nesta tese, apresentamos três abordagens para enfrentar os problemas de integração, consolidação e interligação de dados. Nossa primeira abordagem combina técnicas de informação mútua e programação genética para solucionar o problema de alinhamento complexo entre fontes de dados, um problema raramente abordado na literatura. Na segunda e terceira abordagens, adotamos e ampliamos uma métrica utilizada em teoria de redes sociais para enfrentar o problema de consolidação e interligação de dados. Além disso, apresentamos um aplicativo Web chamado Cite4Me que fornece uma nova perspectiva sobre a pesquisa e recuperação de conjuntos de Linked Open Data, bem como os benefícios da utilização de nossas abordagens. Por fim, uma série de experimentos utilizando conjuntos de dados reais demonstram que as nossas abordagens superam abordagens consideradas como estado da arte. / [en] With the emergence of Linked (Open) Data, a number of novel and notable research challenges have been raised. The openness that often characterises Linked Data offers an opportunity to homogeneously integrate and connect heterogeneous data sources on the Web. As disparate data sources with overlapping or related resources are provided by different data publishers, their integration and consolidation becomes a real challenge. An additional challenge of Linked Data lies in the creation of a well-interlinked graph of Web data. Identifying and linking not only identical Web resources, but also lateral Web resources, provides the data consumer with richer representation of the data and the possibility of exploiting connected resources. In this thesis, we present three approaches that tackle data integration, consolidation and linkage problems. Our first approach combines mutual information and genetic programming techniques for complex datatype property matching, a rarely addressed problem in the literature. In the second and third approaches, we adopt and extend a measure from social network theory to address data consolidation and interlinking. Furthermore, we present a Web-based application named Cite4Me that provides a new perspective on search and retrieval of Linked Open Data sets, as well as the benefits of using our approaches. Finally, we validate our approaches through extensive evaluations using real-world datasets, reporting results that outperform state of the art approaches.

Doctor of Philosophy / Department of Chemical Engineering / Mary E. Rezac / Catalytic membrane reactors are a class of reactors that utilize a membrane to selectively deliver reactants to catalysts integrated in the membrane. The focus of this research has been on developing and characterizing polymeric catalytic membranes for three-phase hydrogenation reactions, where the membrane functions as a gas/liquid phase contactor allowing selective delivery of hydrogen through the membrane to reach catalytic sites located on the liquid side of the membrane. The benefit of conducting three-phase reactions in this manner is that delivering hydrogen through the membrane to reach catalytic sites avoids the necessity of hydrogen dissolution and diffusion in the liquid phase, which are both inherently low and often described as causing mass-transfer and reaction rate limitations for the reactive system. This work examines two types of membrane reactor systems, porous polytetrafluoroethylene and asymmetric Matrimid membranes, respectively, for the ruthenium catalyzed aqueous phase hydrogenation of levulinic acid. The highly hydrophobic PTFE material provides an almost impermeable barrier to the liquid phase while allowing hydrogen gas to freely transport through the pores to reach catalytic sites located at the liquid/membrane interface. Catalytic rates as a function of hydrogen pressure over the range 0.07 to 5.6 bar are presented and shown to be higher than those of a packed bed reactor under similar reaction conditions. An increasing catalytic benefit was obtained operating at temperatures up to 90 °C, which is attributed to increased hydrogen permeability and avoidance of the decreasing solubility of hydrogen in water with increasing temperature. The membrane reactor was shown to be stable with no decrease in catalytic activity over 200 hours of operation. The Matrimid membrane reactor work demonstrates the feasibility of applying an integrally-skinned asymmetric membrane for an aqueous phase hydrogenation reaction and focuses on the impact that membrane hydrogen permeance and catalyst loading have on catalytic activity. The non-porous nature of the separating layer in the Matrimid membrane allowed successful operation up to 150 °C. The overall catalytic rates were approximately an order of magnitude lower than those achieved in the PTFE membrane reactor system due primarily to significantly lower hydrogen permeances, nevertheless rates were still higher than control experiments. This work also focuses on characterizing Matrimid/solvent thermodynamic relationships for a variety of organic solvents, looking at sorption, diffusion, and polymer relaxation behavior in thin films ranging from 0.1 to 2.0 µm in thickness using quartz crystal microbalance techniques. Diffusion coefficients at infinite dilution for water and C1-C6 alcohols are given as a function of van der Waals molar volume and a clear dependency is shown ranging from 2E-11 to 6.5E-13 cm²/s for water and hexanol, respectively, for 0.26 µm thick films. Diffusion coefficients for all studied vapor penetrants displayed a marked dependence on thickness spanning approximately two orders of magnitude for each respective vapor penetrant over the range 0.1 to 1.0 µm. Chemically cross-linking Matrimid is a method to mitigate some of the relatively high sorption and swelling behavior exhibited in the presence of sorbing species. An in-depth analysis on the vapor phase ethylenediamine cross-linking of Matrimid films and its impact on diffusion, sorption, and relaxation is also described.