Multiscale analysis of protein functions and stochastic modelling of gene transcriptional regulatory networks

Genomic and proteomic analyses have attracted a great deal of interests in biological research in recent years. Many methods have been applied to discover useful information contained in the enormous databases of genomic sequences and amino acid sequences. The results of these investigations inspire further research in biological fields in return. These biological sequences, which may be considered as multiscale sequences, have some specific features which need further efforts to characterise using more refined methods. This project aims to study some of these biological challenges with multiscale analysis methods and stochastic modelling approach. The first part of the thesis aims to cluster some unknown proteins, and classify their families as well as their structural classes. A development in proteomic analysis is concerned with the determination of protein functions. The first step in this development is to classify proteins and predict their families. This motives us to study some unknown proteins from specific families, and to cluster them into families and structural classes. We select a large number of proteins from the same families or superfamilies, and link them to simulate some unknown large proteins from these families. We use multifractal analysis and the wavelet method to capture the characteristics of these linked proteins. The simulation results show that the method is valid for the classification of large proteins. The second part of the thesis aims to explore the relationship of proteins based on a layered comparison with their components. Many methods are based on homology of proteins because the resemblance at the protein sequence level normally indicates the similarity of functions and structures. However, some proteins may have similar functions with low sequential identity. We consider protein sequences at detail level to investigate the problem of comparison of proteins. The comparison is based on the empirical mode decomposition (EMD), and protein sequences are detected with the intrinsic mode functions. A measure of similarity is introduced with a new cross-correlation formula. The similarity results show that the EMD is useful for detection of functional relationships of proteins. The third part of the thesis aims to investigate the transcriptional regulatory network of yeast cell cycle via stochastic differential equations. As the investigation of genome-wide gene expressions has become a focus in genomic analysis, researchers have tried to understand the mechanisms of the yeast genome for many years. How cells control gene expressions still needs further investigation. We use a stochastic differential equation to model the expression profile of a target gene. We modify the model with a Gaussian membership function. For each target gene, a transcriptional rate is obtained, and the estimated transcriptional rate is also calculated with the information from five possible transcriptional regulators. Some regulators of these target genes are verified with the related references. With these results, we construct a transcriptional regulatory network for the genes from the yeast Saccharomyces cerevisiae. The construction of transcriptional regulatory network is useful for detecting more mechanisms of the yeast cell cycle.

Integrating information literacy into higher education curricula : an IL curricular integration model

This study investigates a way to systematically integrate information literacy (IL) into an undergraduate academic programme and develops a model for integrating information literacy across higher education curricula. Curricular integration of information literacy in this study means weaving information literacy into an academic curriculum. In the associated literature, it is also referred to as the information literacy embedding approach or the intra-curricular approach. The key findings identified from this study are presented in 4 categories: the characteristics of IL integration; the key stakeholders in IL integration; IL curricular design strategies; and the process of IL curricular integration. Three key characteristics of the curricular integration of IL are identified: collaboration and negotiation, contextualisation and ongoing interaction with information. The key stakeholders in the curricular integration of IL are recognised as the librarians, the course coordinators and lecturers, the heads of faculties or departments, and the students. Some strategies for IL curricular design include: the use of IL policies and standards in IL curricular design; the combination of face to face and online teaching as an emerging trend; the use of IL assessment tools which play an important role in IL integration. IL can be integrated into the intended curriculum (what an institution expects its students to learn), the offered curriculum (what the teachers teach) and the received curriculum (what students actually learn). IL integration is a process of negotiation, collaboration and the implementation of the intended curriculum. IL can be integrated at different levels of curricula such as: institutional, faculty, departmental, course and class curriculum levels. Based on these key findings, an IL curricular integration model is developed. The model integrates curriculum, pedagogy and learning theories, IL theories, IL guidelines and the collaboration of multiple partners. The model provides a practical approach to integrating IL into multiple courses across an academic degree. The development of the model was based on the IL integration experiences of various disciplines in three universities and the implementation experience of an engineering programme at another university; thus it may be of interest to other disciplines. The model has the potential to enhance IL teaching and learning, curricular development and to implement graduate attributes in higher education. Sociocultural theories are applied to the research process and IL curricular design of this study. Sociocultural theories describe learning as being embedded within social events and occurring as learners interact with other people, objects, and events in a collaborative environment. Sociocultural theories are applied to explore how academic staff and librarians experience the curricular integration of IL; they also support collaboration in the curricular integration of IL and the development of an IL integration model. This study consists of two phases. Phase I (2007) was the interview phase where both academic staff and librarians at three IL active universities were interviewed. During this phase, attention was paid specifically to the practical process of curricular integration of IL and IL activity design. Phase II, the development phase (2007-2008), was conducted at a fourth university. This phase explores the systematic integration of IL into an engineering degree from Year 1 to Year 4. Learning theories such as sociocultural theories, Bloom’s Taxonomy and IL theories are used in IL curricular development. Based on the findings from both phases, an IL integration model was developed. The findings and the model contribute to IL education, research and curricular development in higher education. The sociocultural approach adopted in this study also extends the application of sociocultural theories to the IL integration process and curricular design in higher education.

Knowledge integration within Japanese firms : the Fujitsu way

The paper analyses knowledge integration processes at Fujitsu from a multi-level and systemic perspective. The focus is on team-building capability, capturing and utilising individual tacit knowledge, and communication networks for integrating dispersed specialist knowledge required in the development of new products and services. The analysis shows how knowledge integration is performed by Fujitsu at different layers of the company.

Maintenance chain integration using Petri-net enabled multiagent system modeling and implementation approach

Engineering asset management (EAM) is a broad discipline and the EAM functions and processes are characterized by its distributed nature. However, engineering asset nowadays mostly relies on self-maintained experiential rule bases and periodic maintenance, which is lacking a collaborative engineering approach. This research proposes a collaborative environment integrated by a service center with domain expertise such as diagnosis, prognosis, and asset operations. The collaborative maintenance chain combines asset operation sites, service center (i.e., maintenance operation coordinator), system provider, first tier collaborators, and maintenance part suppliers. Meanwhile, to realize the automation of communication and negotiation among organizations, multiagent system (MAS) technique is applied to enhance the entire service level. During the MAS design processes, this research combines Prometheus MAS modeling approach with Petri-net modeling methodology and unified modeling language to visualize and rationalize the design processes of MAS. The major contributions of this research include developing a Petri-net enabled Prometheus MAS modeling methodology and constructing a collaborative agent-based maintenance chain framework for integrated EAM.

Functional role of cell surface CUB domain-containing protein 1 in tumour cell dissemination

The function of CUB domain-containing protein 1 (CDCP1), a recently described transmembrane protein expressed on the surface of hematopoietic stem cells and normal and malignant cells of different tissue origin, is not well defined. The contribution of CDCP1 to tumor metastasis was analyzed by using HeLa carcinoma cells overexpressing CDCP1 (HeLa-CDCP1) and a high-disseminating variant of prostate carcinoma PC-3 naturally expressing high levels of CDCP1 (PC3-hi/diss). CDCP1 expression rendered HeLa cells more aggressive in experimental metastasis in immunodeficient mice. Metastatic colonization by HeLa-CDCP1 was effectively inhibited with subtractive immunization-generated, CDCP1-specific monoclonal antibody (mAb) 41-2, suggesting that CDCP1 facilitates relatively late stages of the metastatic cascade. In the chick embryo model, time- and dose-dependent inhibition of HeLa-CDCP1 colonization by mAb 41-2 was analyzed quantitatively to determine when and where CDCP1 functions during metastasis. Quantitative PCR and immunohistochemical analyses indicated that CDCP1 facilitated tumor cell survival soon after vascular arrest. Live cell imaging showed that the function-blocking mechanism of mAb 41-2 involved enhancement of tumor cell apoptosis, confirmed by attenuation of mAb 41-2–mediated effects with the caspase inhibitor z-VAD-fmk. Under proapoptotic conditions in vitro, CDCP1 expression conferred HeLa-CDCP1 cells with resistance to doxorubicin-induced apoptosis, whereas ligation of CDCP1 with mAb 41-2 caused additional enhancement of the apoptotic response. The functional role of naturally expressed CDCP1 was shown by mAb 41-2–mediated inhibition of both experimental and spontaneous metastasis of PC3-hi/diss. These findings confirm that CDCP1 functions as an antiapoptotic molecule and indicate that during metastasis CDCP1 facilitates tumor cell survival likely during or soon after extravasation.