Research-based spin-offs as agents of knowledge dissemination: evidence from the analysis of innovation networks

The paper addresses the role played by research-based spin-offs (RBSOs) as knowledge dissemination mechanisms, through their position in knowledge networks. For this purpose the paper analyses the formal networks established by the Portuguese RBSOs in the context of publicly funded research, technology and pre-commercial product development projects, and investigates their configuration along two levels. At organisational level, in order to understand whether RBSOs extend their reach beyond the academic sphere; and if they do, whether they relate with similar firms or connect to organisations located downstream in the knowledge value chain, and which is their position in networks involving both research organisations and other firms. At spatial level, in order to understand whether RBSOs extend their reach beyond the region where they are created, thus potentially acting as connectors between diverse regions. The analysis starts from the population of RBSOs created in Portugal until 2007 (387) and identifies those that have established formal technological relationships as part of projects funded by all the programmes launched in the period 1993-2012. As a result, the analysis encompasses 192 collaborative projects and involves 82 spin-offs and 281 partners, of which only 20% are research organisations, the remaining being other firms and a variety of other user organisations. The results, although still preliminary, provide some insights into the knowledge networking behaviour of the RBSOs. As expected, research organisations are a central actor in spin-offs’ networks, being the sole partner for some of them. But half of the RBSOs have moved beyond the academic sphere, being frequently a central element in tripartite technological relationships between research and other organisations and occupying an intermediation position in the network, thus potentially acting as facilitators in knowledge circulation and transformation. Also as expected, RBSOs are predominantly located in the main metropolitan areas and tend to relate with organisations similarly located. But while geographical proximity emerges as important in the choice of partners, in about half of the cases, RBSOs knowledge networks have extended beyond regional boundaries. Given their central position in the network this suggests a role as connectors across regions that will be explored in subsequent research.

Research-based spin-offs as agents of knowledge dissemination: evidence from the analysis of innovation networks

The paper addresses the role played by research-based spin-offs (RBSOs) as knowledge dissemination mechanisms, through their position in knowledge networks. For this purpose the paper analyses the formal networks established by Portuguese RBSOs, in the context of publicly funded research, technology and pre-commercial product development projects, and investigates their configuration across two levels. At organisational level, in order to understand whether RBSOs extend their reach beyond the academic sphere; and if they do, whether they connect to organisations located downstream in the knowledge value chain, and which is their position in networks involving both research organisations and other firms. At spatial level, in order to understand whether RBSOs extend their reach beyond the region where they are created, thus potentially acting as connectors between diverse regions. The analysis starts from the population of RBSOs created in Portugal until 2007 (327 firms) and identifies those that have established formal technological relationships, as part of projects funded by all the relevant programmes launched in the period 1993-2012. As a result, the analysis encompasses 192 collaborative projects and involves 82 spin-offs and 281 partners, of which only 20% are research organisations, the remaining being other firms and a variety of other downstream organisations. The results, although still preliminary, provide some insights into the knowledge networking behaviour of the RBSOs. As expected, research organisations are a central actor in spin-offs’ networks, being the sole partner for some of them. But half of the RBSOs have moved beyond the academic sphere, being frequently a central element in tripartite technological relationships between research and other organisations, and occupying an intermediation position in the network, thus potentially acting as facilitators in knowledge circulation and transformation. Also as expected, RBSOs are predominantly located in the main metropolitan areas and tend to relate with organisations similarly located. But while geographical proximity emerges as important in the choice of partners, in about half of the cases, RBSOs knowledge networks have extended beyond regional boundaries. Given their central position in the network, this suggests a role as connectors across regions that will be explored in subsequent research.

ROLE OF ENTERPRISE ARCHITECTURE IN HEALTHCARE ORGANIZATIONS AND KNOWLEDGE-BASED MEDICAL DIAGNOSIS SYSTEM

Enterprise architecture (EA) is a tool that aligns organization’s business-process with application and information technology (IT) through EAmodels. This EA model allows the organization to cut off unnecessary IT expenses and determines the future and current IT requirements and boosts organizational performance. Enterprise architecture may be employed in every firm where the firm or organization requires configurations between information technology and business functions. This research investigates the role of enterprise architecture in healthcare organizations and suggests the suitable EA framework for knowledge-based medical diagnostic system for EA modeling by comparing the two most widely used EA frameworks. The results of the comparison identified that the proposed EA has a better framework for knowledge-based medical diagnostic system.

Microfluidics-based single-cell functional proteomics microchip for portraying protein signal transduction networks within the framework of physicochemical principles, with applications in fundamental and translational cancer research

Single-cell functional proteomics assays can connect genomic information to biological function through quantitative and multiplex protein measurements. Tools for single-cell proteomics have developed rapidly over the past 5 years and are providing unique opportunities. This thesis describes an emerging microfluidics-based toolkit for single cell functional proteomics, focusing on the development of the single cell barcode chips (SCBCs) with applications in fundamental and translational cancer research.

The microchip designed to simultaneously quantify a panel of secreted, cytoplasmic and membrane proteins from single cells will be discussed at the beginning, which is the prototype for subsequent proteomic microchips with more sophisticated design in preclinical cancer research or clinical applications. The SCBCs are a highly versatile and information rich tool for single-cell functional proteomics. They are based upon isolating individual cells, or defined number of cells, within microchambers, each of which is equipped with a large antibody microarray (the barcode), with between a few hundred to ten thousand microchambers included within a single microchip. Functional proteomics assays at single-cell resolution yield unique pieces of information that significantly shape the way of thinking on cancer research. An in-depth discussion about analysis and interpretation of the unique information such as functional protein fluctuations and protein-protein correlative interactions will follow.

The SCBC is a powerful tool to resolve the functional heterogeneity of cancer cells. It has the capacity to extract a comprehensive picture of the signal transduction network from single tumor cells and thus provides insight into the effect of targeted therapies on protein signaling networks. We will demonstrate this point through applying the SCBCs to investigate three isogenic cell lines of glioblastoma multiforme (GBM).

The cancer cell population is highly heterogeneous with high-amplitude fluctuation at the single cell level, which in turn grants the robustness of the entire population. The concept that a stable population existing in the presence of random fluctuations is reminiscent of many physical systems that are successfully understood using statistical physics. Thus, tools derived from that field can probably be applied to using fluctuations to determine the nature of signaling networks. In the second part of the thesis, we will focus on such a case to use thermodynamics-motivated principles to understand cancer cell hypoxia, where single cell proteomics assays coupled with a quantitative version of Le Chatelier's principle derived from statistical mechanics yield detailed and surprising predictions, which were found to be correct in both cell line and primary tumor model.

The third part of the thesis demonstrates the application of this technology in the preclinical cancer research to study the GBM cancer cell resistance to molecular targeted therapy. Physical approaches to anticipate therapy resistance and to identify effective therapy combinations will be discussed in detail. Our approach is based upon elucidating the signaling coordination within the phosphoprotein signaling pathways that are hyperactivated in human GBMs, and interrogating how that coordination responds to the perturbation of targeted inhibitor. Strongly coupled protein-protein interactions constitute most signaling cascades. A physical analogy of such a system is the strongly coupled atom-atom interactions in a crystal lattice. Similar to decomposing the atomic interactions into a series of independent normal vibrational modes, a simplified picture of signaling network coordination can also be achieved by diagonalizing protein-protein correlation or covariance matrices to decompose the pairwise correlative interactions into a set of distinct linear combinations of signaling proteins (i.e. independent signaling modes). By doing so, two independent signaling modes – one associated with mTOR signaling and a second associated with ERK/Src signaling have been resolved, which in turn allow us to anticipate resistance, and to design combination therapies that are effective, as well as identify those therapies and therapy combinations that will be ineffective. We validated our predictions in mouse tumor models and all predictions were borne out.

In the last part, some preliminary results about the clinical translation of single-cell proteomics chips will be presented. The successful demonstration of our work on human-derived xenografts provides the rationale to extend our current work into the clinic. It will enable us to interrogate GBM tumor samples in a way that could potentially yield a straightforward, rapid interpretation so that we can give therapeutic guidance to the attending physicians within a clinical relevant time scale. The technical challenges of the clinical translation will be presented and our solutions to address the challenges will be discussed as well. A clinical case study will then follow, where some preliminary data collected from a pediatric GBM patient bearing an EGFR amplified tumor will be presented to demonstrate the general protocol and the workflow of the proposed clinical studies.

The role of microcomputer-based laboratory display in supporting the construction of new understanding in kinematics

Teachers' failure to utilise MBL activities more widely may be due to not recognising their capacity to transform the nature of laboratory activities to be more consistent with contemporary constructivist theories of learning. This research aimed to increase understanding of how MBL activities specifically designed to be consistent with a constructivist theory of learning support or constrain student construction of understanding. The first author conducted the research with his Year 11 physics class of 29 students. Dyads completed nine tasks relating to kinematics using a Predict-Observe-Explain format. Data sources included video and audio recordings of students and teacher during four 70-minute sessions, students' display graphs and written notes, semi-structured student interviews, and the teacher's journal. The study identifies the actors and describes the patterns of interactions in the MBL. Analysis of students' discourse and actions identified many instances where students' initial understanding of kinematics were mediated in multiple ways. Students invented numerous techniques for manipulating data in the service of their emerging understanding. The findings are presented as eight assertions. Recommendations are made for developing pedagogical strategies incorporating MBL activities which will likely catalyse student construction of understanding.