Design Thinking: Project Portfolio Management and Simulation – A Creative Mix for Research

This paper takes de Bono’s explanation of ‘design thinking’ as the starting point for a report on a doctoral research project that began with a conventional ‘why?’ question, and then, instead of looking for an ‘explanation’, chose to look forward in time to establish an understanding of ‘how to’ think differently about a recurring problem. The catalyst for this work was observation of otherwise competent managers making desperately wrong decisions when good decision making was crucial to their company’s future. The initial choice to ‘look forward’ when designing the research strategy was made well before there was a clear understanding of what was being observed. Given that trajectory, this paper explores the process by which a simulation was created and then used in conjunction with a comparatively new approach to data collection (Explanation looks backwards and design looks forward [1].)

Inactivation of promoter 1B of APC causes partial gene silencing: evidence for a significant role of the promoter in regulation and causative of familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is caused by germline mutations in the adenomatous polyposis coli (APC) gene. Two promoters, 1A and 1B, have been recognized in APC, and 1B is thought to have a minor role in the regulation of the gene. We have identified a novel deletion encompassing half of this promoter in the largest family (Family 1) of the Swedish Polyposis Registry. The mutation leads to an imbalance in allele-specific expression of APC, and transcription from promoter 1B was highly impaired in both normal colorectal mucosa and blood from mutation carriers. To establish the significance of promoter 1B in normal colorectal mucosa (from controls), expression levels of specific transcripts from each of the promoters, 1A and 1B, were examined, and the expression from 1B was significantly higher compared with 1A. Significant amounts of transcripts generated from promoter 1B were also determined in a panel of 20 various normal tissues examined. In FAP-related tumors, the APC germline mutation is proposed to dictate the second hit. Mutations leaving two or three out of seven 20-amino-acid repeats in the central domain of APC intact seem to be required for tumorigenesis. We examined adenomas from mutation carriers in Family 1 for second hits in the entire gene without any findings, however, loss of the residual expression of the deleterious allele was observed. Three major conclusions of significant importance in relation to the function of APC can be drawn from this study; (i) germline inactivation of promoter 1B is disease causing in FAP; (ii) expression of transcripts from promoter 1B is generated at considerable higher levels compared with 1A, demonstrating a hitherto unknown importance of 1B; (iii) adenoma formation in FAP, caused by impaired function of promoter 1B, does not require homozygous inactivation of APC allowing for alternative genetic models as basis for adenoma formation

Understanding the rift, the (still) uneasy bedfellows of History and Organization Studies

Although the use of History has become increasingly discussed and more widely applied within Organization Studies (OS), its relevance for OS still remains far from centrally accepted. This article historicizes the relationship between Sociology and History as a means of better understanding the tensions, perceived and real, that exist between History and Organization Studies. In particular we analyse three differences of epistemological standpoint (method, objectivity and usefulness) that are commonly seen as the foundation stones to incompatibility. Perhaps surprisingly for an analysis of apparent disciplinary differences, we find that these distinctions in terms of approach, once closely examined, are rarely clear-cut and historians and OS scholars are frequently closer in intention and method than they are distant. However, despite their large intersection of interests, we argue that important distinctions between the two fields should be acknowledged. Our contribution to the debates over the need for more historical approaches within OS therefore centrally rests on abandoning aspirations for fully integrative models of working together, in favour of cooperative modes that concede the fields’ differences. This subtle shift of emphasis will, we believe, greatly benefit OS scholars who hope to include historical perspectives in their work

The Earth: Plasma Sources, Losses, and Transport Processes

This paper reviews the state of knowledge concerning the source of magnetospheric plasma at Earth. Source of plasma, its acceleration and transport throughout the system, its consequences on system dynamics, and its loss are all discussed. Both observational and modeling advances since the last time this subject was covered in detail (Hultqvist et al., Magnetospheric Plasma Sources and Losses, 1999) are addressed