The organization and management of nuclear power plants

The explanation of aggregate and sectoral investment behavior has been one of the less successful endeavors in empirical economics. Existing econometric models have had little success in explaining or predicting investment spending. This may be because most such models fail to account for the irreversibility of most investment spending. With irreversibility, changes in the riskiness of future cash flows or interest rates should in theory dramatically affect the decision to invest - more so than, say, a change in the levels of interest rates. Here I survey some of the empirical support for this proposition, and discuss the implications for investment modelling.Nuclear power plants are a controversial technology. The future of the industry depends on the ability to manage efficiently and safely, and to effectively manage organizational change as new technologies and practices are introduced and disseminated. This paper provides a conceptual framework and discussion of the management and organization of nuclear power plants around three questions: (1) How should nuclear power plants be organized and managed to ensure that they are operated most safely and efficiently? (2) What does an understanding of the organization and management of nuclear power plants tell us about how they change or resist change? and (3) What indicators or measures of various characteristics and processes of nuclear power plants are needed in order to address the above questions? We review existing literature on the organization and management of nuclear power plants, and suggest how we would structure a research project to address the above questions.Supported by the Center for Energy Policy Research at M.I.T

Whole-genome landscapes of major melanoma subtypes

Melanoma of the skin is a common cancer only in Europeans, whereas it arises in internal body surfaces (mucosal sites) and on the hands and feet (acral sites) in people throughout the world. Here we report analysis of whole-genome sequences from cutaneous, acral and mucosal subtypes of melanoma. The heavily mutated landscape of coding and non-coding mutations in cutaneous melanoma resolved novel signatures of mutagenesis attributable to ultraviolet radiation. However, acral and mucosal melanomas were dominated by structural changes and mutation signatures of unknown aetiology, not previously identified in melanoma. The number of genes affected by recurrent mutations disrupting non-coding sequences was similar to that affected by recurrent mutations to coding sequences. Significantly mutated genes included BRAF, CDKN2A, NRAS and TP53 in cutaneous melanoma, BRAF, NRAS and NF1 in acral melanoma and SF3B1 in mucosal melanoma. Mutations affecting the TERT promoter were the most frequent of all; however, neither they nor ATRX mutations, which correlate with alternative telomere lengthening, were associated with greater telomere length. Most melanomas had potentially actionable mutations, most in components of the mitogen-activated protein kinase and phosphoinositol kinase pathways. The whole-genome mutation landscape of melanoma reveals diverse carcinogenic processes across its subtypes, some unrelated to sun exposure, and extends potential involvement of the non-coding genome in its pathogenesis

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Measured Success: Innovation management in Australia

This book conducts an in-depth analysis of eleven cases of high-technology innovation in Australia. While all eleven cases were potential world-beaters, only three or four were truly successful. By contrasting the successful and unsuccessful cases, the book provides insights into the limited success which Australian innovators achieve. The eleven cases include a project within a large corporation, a joint venture between a large corporation and some Australian academic institutions, and nine start-ups. They are drawn from domains such as software, minerals exploration and smelting, scientific instruments, ship building and biotechnology. Most of the ventures are over ten years old, so they have enough history to allow us to draw useful lessons. While they have not been particularly successful, they are definitely more successful than the vast majority of Australian high-technology attempts. In addition, the book contains commentaries from five Australian leaders with an interest in innovation. The book makes two distinct contributions. On one hand, there is a shortage of well documented cases of Innovation in Australia. Consequently, the cases give people with an interest in the subject a glimpse into the goings on within Australian high technology ventures, and the problems they face. On the other hand, the analysis, combined with the commentaries, provide valuable directions for both a research and policy agenda for innovation in Australia

The missing link : organizational behavior as a key element in energy/environment regulation and university energy management

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Civil Engineering, 1990.Vita.Includes bibliographical references (p. 251-255).by Peter B. Cebon.M.S

Submission to the review of the national innovation system

This submission takes the findings of Measured Success: Innovation Management in Australia and applies them to the problem of creating an effective innovation system in Australia

Corporate Governance as a repeated game prisoners\u27 dilemma - and the push to the defect-defect cell

Governance of strategic risk can be understood as a repeated-game prisoners’ dilemma. In the cooperate-cooperate cell, boards and managers work together in a trusting, highly communicative relationship to make sense of the environment and to create and enact a strategy. In the defect-defect cell, the board distrusts the CEO and is concerned with monitoring and incentive alignment. Organisations with a focused strategy built on innovation-like actions benefit from being in the cooperate-cooperate cell. However, various internal and institutional forces push organisations, and particularly listed corporations, to the defect-defect cell

When the chemistry is right : a study of work organization and change in two chemical plants

Thesis (Ph. D.)--Massachusetts Institute of Technology, Sloan School of Management, 1995.Includes bibliographical references (p. 247-252).by Peter Bernard Cebon.Ph.D