BeWith: A Between-Within Method to Discover Relationships between Cancer Modules via Integrated Analysis of Mutual Exclusivity, Co-occurrence and Functional Interactions

The analysis of the mutational landscape of cancer, including mutual exclusivity and co-occurrence of mutations, has been instrumental in studying the disease. We hypothesized that exploring the interplay between co-occurrence, mutual exclusivity, and functional interactions between genes will further improve our understanding of the disease and help to uncover new relations between cancer driving genes and pathways. To this end, we designed a general framework, BeWith, for identifying modules with different combinations of mutation and interaction patterns. We focused on three different settings of the BeWith schema: (i) BeME-WithFun in which the relations between modules are enriched with mutual exclusivity while genes within each module are functionally related; (ii) BeME-WithCo which combines mutual exclusivity between modules with co-occurrence within modules; and (iii) BeCo-WithMEFun which ensures co-occurrence between modules while the within module relations combine mutual exclusivity and functional interactions. We formulated the BeWith framework using Integer Linear Programming (ILP), enabling us to find optimally scoring sets of modules. Our results demonstrate the utility of BeWith in providing novel information about mutational patterns, driver genes, and pathways. In particular, BeME-WithFun helped identify functionally coherent modules that might be relevant for cancer progression. In addition to finding previously well-known drivers, the identified modules pointed to the importance of the interaction between NCOR and NCOA3 in breast cancer. Additionally, an application of the BeME-WithCo setting revealed that gene groups differ with respect to their vulnerability to different mutagenic processes, and helped us to uncover pairs of genes with potentially synergetic effects, including a potential synergy between mutations in TP53 and metastasis related DCC gene

From Social Simulation to Integrative System Design

As the recent financial crisis showed, today there is a strong need to gain "ecological perspective" of all relevant interactions in socio-economic-techno-environmental systems. For this, we suggested to set-up a network of Centers for integrative systems design, which shall be able to run all potentially relevant scenarios, identify causality chains, explore feedback and cascading effects for a number of model variants, and determine the reliability of their implications (given the validity of the underlying models). They will be able to detect possible negative side effect of policy decisions, before they occur. The Centers belonging to this network of Integrative Systems Design Centers would be focused on a particular field, but they would be part of an attempt to eventually cover all relevant areas of society and economy and integrate them within a "Living Earth Simulator". The results of all research activities of such Centers would be turned into informative input for political Decision Arenas. For example, Crisis Observatories (for financial instabilities, shortages of resources, environmental change, conflict, spreading of diseases, etc.) would be connected with such Decision Arenas for the purpose of visualization, in order to make complex interdependencies understandable to scientists, decision-makers, and the general public.Comment: 34 pages, Visioneer White Paper, see http://www.visioneer.ethz.c

Multiple testing for SNP-SNP interactions

Most genetic diseases are complex, i.e. associated to combinations of SNPs rather than individual SNPs. In the last few years, this topic has often been addressed in terms of SNP-SNP interaction patterns given as expressions linked by logical operators. Methods for multiple testing in high-dimensional settings can be applied when many SNPs are considered simultaneously. However, another less well-known multiple testing problem arises within a fixed subset of SNPs when the logic expression is chosen optimally. In this article, we propose a general asymptotic approach for deriving the distribution of the maximally selected chi-square statistic in various situations. We show how this result can be used for testing logic expressions - in particular SNP-SNP interaction patterns - while controlling for multiple comparisons. Simulations show that our method provides multiple testing adjustment when the logic expression is chosen such as to maximize the statistic. Its benefit is demonstrated through an application to a real dataset from a large population-based study considering allergy and asthma in KORA. An implementation of our method is available from the Comprehensive R Archive Network (CRAN) as R package 'SNPmaxsel'

Brain matters…in social sciences

Here we offer a general introduction to cognitive neuroscience and provide examples relevant to psychology, healthcare and bioethics, law and criminology, information studies, of how brain studies have influenced, are influencing or show the potential to influence the social sciences. We argue that social scientists should read, and be enabled to understand, primary sources of evidence in cognitive neuroscience. We encourage cognitive neuroscientists to reflect upon the resonance that their work may have across the social sciences and to facilitate a mutually enriching interdisciplinary dialogue

Complementary or Conflictual? Formal Participation, Informal Participation, and Organizational Performance

Most studies of worker participation examine either formal participatory structures or informal participation. Yet, increasingly, works councils and other formal participatory bodies are operating in parallel with collective bargaining or are filling the void left by its decline. Moreover, these bodies are sprouting in workplaces in which workers have long held a modicum of influence, authority, and production- or service-related information. This study leverages a case from the healthcare sector to examine the interaction between formal and informal worker participation. Seeking to determine whether or not these two forces—each independently shown to benefit production or service delivery—complement or undermine one another, we find evidence for the latter. In the case of the 27 primary care departments that we study, formal structures appeared to help less participatory departments improve their performance. However, these same structures also appeared to impede those departments with previously high levels of informal participation. While we remain cautious with respect to generalizability, the case serves as a warning to those seeking to institute participation in an environment in which some workers have long felt they had the requisite authority, influence, and information necessary to perform their jobs effectively

Design Mechanism as Territorial Strategic Capability

The current exigencies that a territory must faced in order to its’ optimal positioning in future regional competition requires the ability to design the appropriate mechanism which better valorize the territory capability. Such a construct is vital for territorial sustainable development and supposes the creation of a specific body of knowledge from distinctive local resource exploitation and unique value creation and allocation. Territorial mechanism design is a typical management decision about identification, ownership and control of specific strategic capabilities and their combination in a distinctive territorial portfolio. The most difficult responsibility is to allocate the territorial value added which is a source of conflict among territorial components. Our current paper research covers the basics of two complementary territorial pillars-rural and tourism potential and proves the lack of specific design mechanisms which explain the current diminishing value of Galati Braila region. The proposed management system, relying upon territorial control mechanism, will ensure knowledge sharing process via collaborative learning, with the final role of appropriate territorial attractivity signals, reinforcing identity as key factor of territorial attractability. Our paper is fully documented on there years of data analyzing from territorial area of interest. This offers us the necessary empiric contrasting for our proposed solution.territorial disruptive typicity, coordination design mechanism, sustainable development, collaborative learning, territorial change

Action learning as an enabler for successful technology transfer with construction SMEs

There is an increasing demand for construction companies to adopt and use new technologies. At the same time universities are increasingly being called upon to assist with ‘technology transfer’ through positive engagement with industry. However, there is little literature investigating technology transfer from the perspective of small construction companies which make up the overwhelming majority of firms in the sector. This paper contributes to this developing area by providing a literature review of technology transfer and proposing a holistic system required for success. Building upon this review it assesses the potential use of action learning as a means of providing this holistic solution and, in so doing, promoting technology transfer and improving the links between higher education institutions (HEIs) and the construction industry. The assessment is made through a literature review of action learning in construction and an analysis of results from the national Construction Knowledge Exchange (CKE) initiative which uses an action learning methodology to assist HEIs in supporting local construction small and medium-sized enterprises (SMEs). The initial results show that this innovative approach, has been successful in creating synergies between academic and business worlds, helping HEIs to communicate more effectively with businesses and vice versa. However, the results indicate that innovations which small construction companies tend to more successfully adopt are those which can contribute to the business in a quick, tangible fashion, and which can be dovetailed into existing rganisational capabilities. This is found to be in marked contrast to the relevant literature which depict large companies operating in more complex networks, drawing upon them for new tacit and explicit technologies which support more long term, formal technology strategies, and which often complement some form of specialised internal research and development capability. The implication for policy is that any technology transfer initiatives need to appreciate and actively manage the different motivations and capabilities of small and large construction companies to absorb and use new technology

Supplementary skills guides for built environment researchers

Deepening specialised knowledge-base and wider skills of researchers in a wider variety of disciplines are prerequisite for developing successful leadership in higher education, the public sector and industry. In response to this repeated calls for enhancing supplementary skills of the built environment researchers, TG53 (Postgraduate Research Training in Building and Construction) initiated steps to develop and nurture understanding of supplementary skills and providing a common frame of reference for use and further discourse and has developed 6 good practice examples highlighting skills for researchers within the built environment. Accordingly, this TG53 publication is in response to the repeated calls for enhancing supplementary skills of the built environment researchers