International investment law and media disputes: a complement to WTO law

The author suggests that international investment law is a potentially powerful legal tool to protect freedom of expression, at least for foreign-owned media companies

Genome-Wide Characterization of the Effects of Nucleic Acid Modifying Enzymes: Cytidine Deaminases and DNA Methylation

Activation-induced cytidine deaminase (AID) is essential for two processes of immunoglobulin diversification in germinal center B cells: somatic hypermutation (SHM), in which mutations are introduced into immunoglobulin (Ig) genes, and class-switch recombination (CSR), in which genomic constant regions are recombined to encode antibodies of different isotypes. Both of these processes require AID-catalyzed C-to-U lesions at the Ig loci, which are resolved to generate point mutations or double-stranded DNA breaks in the cases of SHM and CSR, respectively. Despite over a decade of intense study, a number of open issues remain surrounding AID. The diversity of findings regarding AID’s role in DNA demethylation raises the question of the scope of its involvement in this process. Additionally, while it is clear that AID-mediated damage occurs, the effects of this damage on the average B cell have not been characterized. Finally, the issue of whether AID is able to edit RNA in vivo has never been rigorously addressed in the literature. In each of these cases, the advent of high-throughput sequencing provides methods for genome-wide characterization of AID’s effects. This thesis presents the application of a number of genome-scale, sequencing-based methods to characterize the effects of AID deficiency and overexpression on the activated B cell: mRNA-Seq and miRNA-Seq allow for measurements of RNA expression and editing, while reduced-representation bisulfite sequencing (RRBS) assays DNA methylation. These analyses confirmed AID’s known role in immunoglobulin isotype switching, while also demonstrating that it has little other effect on gene expression. Additionally, no evidence of AID-dependent mRNA or miRNA editing could be detected. Finally, RRBS data failed to support a role for AID in the regulation of DNA methylation. Thus, despite evidence of its additional activities in other systems, antibody diversification appears to be AID’s sole physiological function in activated B cells. Following the conclusion of my studies of AID’s effects in B cells, I applied similar genomics tools to two amenable topics in nucleic acid modifications. First, I used mRNA-Seq to attempt to determine the substrate of the orphan cytidine deaminase Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide 2 (APOBEC2). Next, I used whole-genome bisulfite sequencing to explore the distribution of 5-methylcytosine in Trypanosoma brucei. In both of these cases, results were inconclusive but suggest future directions for investigation

Conditions and Constraints of Collaborative Designerly Work

As the problems we face today become more complex and larger scale, designers need to investigate what people actually do, what they value, and how they understand things. This human-centred approach to solving complex problems requires greater breadth and depth of expertise, than any single designer can possess. Therefore it becomes necessary for designers to work in collaborative situations to share knowledge with different stakeholders and understand the interaction between people and their environments. Drawing on a recent series of interviews (n=14), this paper provides insight into what collaboration means from the point of view of professional designers. The paper focuses on designers’ experiences of the conditions and challenges of new product development

Three's company: Situation-problem-solution co-evolution

This paper reports the results of a study examining the co-evolution of design situations, problems, and solutions. The research method is a longitudinal study tracking the creative problem-solving processes of 4 MSc student design teams on an industrial design project. The data includes observations, interviews, field notes, and documents. Visual mapping and temporal bracketing analysis techniques reveal insights into the teams' design processes. The results provide evidence that integrating effectuation enabled some teams to pivot their projects by co-evolving the situation, problem, and solution spaces simultaneously. This finding suggests designers can shape situations through effectuation, rather than just passively respond to environmental cues. These exploratory results indicate the potential value of expanding design theory to consider triadic co-evolution of situation, problem, and solution. The implications highlight opportunities for design education to cultivate designer entrepreneurs skilled in strategic pivoting through situation-problem-solution co-evolution

Investigating the Significance of Informal Interactions within Interdisciplinary Design Activity

Designing is an activity that integrates knowledge from many different domains to create something new or to solve a problem. However, the innovative power that interdisciplinary approaches bring adds an additional layer of complexity. Additional factors come into play when stakeholders with specialist skills and diverse worldviews must create shared understanding to meet high-level goals. The paper presents results from an empirical study of interdisciplinary collaborative design activity in industry. Ethnographic case studies of three companies were conducted and twenty-seven (n=27) semi-structured interviews were recorded. The study used the DRM approach (Blessing and Chakrabarti, 2009) and using NVivo CAQDAS software supported theory construction. I identified twenty influencing factors and illustrated their dynamic interaction within a model of the collaborative design process. The study found that the innovative power of interdisciplinary collaborative design is underpinned by informal interactions. Consequently, I argue that developing design methods should take into account the significant role that informal interactions play within interdisciplinary collaborative design activity

Epistemological Positions Informing Theories of Design Research: Implications for the Design Discipline and Design Practice

Design research is not simply concerned with speculations regarding the relationship of theory and practice. Design research also brings out significant questions regarding the nature of research and the position of the doctorate in university education. This paper presents analyses of examples of objectivist, constructionist, and subjectivist theories of design research. The assumptions that underpin their perspectives are outlined, their powers of generalisation considered. The implications for the position of the design discipline in relation to the greater academic community, and the characterisations of design practice that they contain, are drawn out. The paper concludes by considering the pedagogical implications of the role of disciplines in the knowledge building cycle between research and professional practice

Creating Organisational Knowledge Through Strategic Business Model Design

Innovation requires teams to create knowledge through integrating insights from different domains. However, the innovative power that interdisciplinary approaches bring can also increase complexity. Consequently, collaboration is required to support design activity. I take the position that while Horst Rittel’s argumentative approach provides a crucial point of departure for understanding collaborative design, the tools and methods developed within this research stream have remained focused on capturing design decisions to act as a memory aid. In contrast, I argue that the argumentative approach to design should aim to create organisational knowledge through critical inquiry.Drawing on insights from a recent empirical study of interdisciplinary collaborative design activity in industry, this paper highlights the essential role of organisational knowledge creation within collaborative design activity. I show that the organisational knowledge creation cycle can be usefully supported at a strategic level through business model design. However, business model design has historically been undertaken as a tool to represent structure rather than as technique for critical inquiry and investigation. In this paper I show that recasting business model design through a collaborative argumentative approach presents a new technique for designers to create knowledge at the strategic level