Considering a whole-of-community approach to integrating nature in cities, an international case study of Vauban, Germany

Globally, cities face a convergence of complex and rapidly evolving challenges, including climate change, resource shortages, population growth and urbanization, and financial pressures. Biophilic urbanism is an emerging design principle capable of considering the multidimensional and interdependent complexities of urban systems and infrastructure, which through the use of natural design features, can meet society’s inherent need for contact with nature, and assist efforts to respond to these growing challenges. Considering the imperative for addressing these challenges, this paper proposes that significant lessons can be learned from existing examples of biophilic urbanism, avoiding ‘re-invention of the wheel’ and facilitating accelerated innovation in other areas. Vauban is a 38-hectare brownfield development located 3 kilometers from the centre of Germany’s ‘ecological capital’ of Freiburg city. It was developed using an innovative process with strong community participation and reinterpreted developer roles to produce an example of integrated sustainability. Innovation in transport, energy, housing, development and water treatment has enabled a relatively high-density, mixed-use development that integrates a considerable amount of nature. This paper discusses Vauban in light of research undertaken over the last two years through the Sustainable Built Environment National Research Centre in Australia, to investigate emerging elements of ‘biophilic urbanism’ (nature-loving cities), and their potential to be mainstreamed within urban environments. The paper considers the interplay between the policies, community dynamics and innovations in Vauban, within the context of the culture, history and practice of sustainability in Germany, and how these have enabled nature to be integrated into the urban environment of Vauban while achieving other desirable goals for urban areas. It highlights potential applications from Vauban for Australian cities.

Controlling microencapsulation and release of micronized proteins using poly(ethylene glycol) and electrospraying

The fabrication of tailored microparticles for delivery of therapeutics is a challenge relying upon a complex interplay between processing parameters and materials properties. The emerging use of electrospraying allows better tailoring of particle morphologies and sizes than current techniques, critical to reproducible release profiles. While dry encapsulation of proteins is essential for the release of active therapeutics from microparticles, it is currently uncharacterized in electrospraying. To this end, poly(ethylene glycol) (PEG) was assessed as a micronizing and solubilizing agent for dry protein encapsulation and release from electrosprayed particles made from polycaprolactone (PCL). The physical effect of PEG in protein-loaded poly(lactic-co-glycolic acid) (PLGA) particles was also studied, for comparison. The addition of 5–15 wt% PEG 6 kDa or 35 kDa resulted in reduced PCL particle sizes and broadened distributions, which could be improved by tailoring the electrospraying processing parameters, namely by reducing polymer concentration and increasing flow rate. Upon micronization, protein particle size was reduced to the micrometer domain, resulting in homogenous encapsulation in electrosprayed PCL microparticles. Microparticle size distributions were shown to be the most determinant factor for protein release by diffusion and allowed specific control of release patterns.

Direct repression of MYB by ZEB1 suppresses proliferation and epithelial gene expression during epithelial-to-mesenchymal transition of breast cancer cells

Introduction Epithelial-to-mesenchymal transition (EMT) promotes cell migration and is important in metastasis. Cellular proliferation is often downregulated during EMT, and the reverse transition (MET) in metastases appears to be required for restoration of proliferation in secondary tumors. We studied the interplay between EMT and proliferation control by MYB in breast cancer cells. Methods MYB, ZEB1, and CDH1 expression levels were manipulated by lentiviral small-hairpin RNA (shRNA)-mediated knockdown/overexpression, and verified with Western blotting, immunocytochemistry, and qRT-PCR. Proliferation was assessed with bromodeoxyuridine pulse labeling and flow cytometry, and sulforhodamine B assays. EMT was induced with epidermal growth factor for 9 days or by exposure to hypoxia (1% oxygen) for up to 5 days, and assessed with qRT-PCR, cell morphology, and colony morphology. Protein expression in human breast cancers was assessed with immunohistochemistry. ZEB1-MYB promoter binding and repression were determined with Chromatin Immunoprecipitation Assay and a luciferase reporter assay, respectively. Student paired t tests, Mann–Whitney, and repeated measures two-way ANOVA tests determined statistical significance (P < 0.05). Results Parental PMC42-ET cells displayed higher expression of ZEB1 and lower expression of MYB than did the PMC42-LA epithelial variant. Knockdown of ZEB1 in PMC42-ET and MDA-MB-231 cells caused increased expression of MYB and a transition to a more epithelial phenotype, which in PMC42-ET cells was coupled with increased proliferation. Indeed, we observed an inverse relation between MYB and ZEB1 expression in two in vitro EMT cell models, in matched human breast tumors and lymph node metastases, and in human breast cancer cell lines. Knockdown of MYB in PMC42-LA cells (MYBsh-LA) led to morphologic changes and protein expression consistent with an EMT. ZEB1 expression was raised in MYBsh-LA cells and significantly repressed in MYB-overexpressing MDA-MB-231 cells, which also showed reduced random migration and a shift from mesenchymal to epithelial colony morphology in two dimensional monolayer cultures. Finally, we detected binding of ZEB1 to MYB promoter in PMC42-ET cells, and ZEB1 overexpression repressed MYB promoter activity. Conclusions This work identifies ZEB1 as a transcriptional repressor of MYB and suggests a reciprocal MYB-ZEB1 repressive relation, providing a mechanism through which proliferation and the epithelial phenotype may be coordinately modulated in breast cancer cells.

Urban knowledge and innovation spaces : concepts, conditions, and contexts

Innovation is one of the key determinants of growth in the globalised knowledge economy, and ‘urban knowledge and innovation spaces’ form the spatial foci for sustained innovation. This paper aims to explore concepts, conditions and contexts that substantiate the development of these spaces of innovation. The paper seeks to identify the foundational elements of knowledge- based urban development to outline the concept of urban knowledge and innovation spaces, and justify its meaning, unique characteristics and growing influence in the contemporary cities. It rationalises the relevance of the three underlying conditions—namely policy, place, and people— to better understand their contribution in the development of such spaces. This paper sheds light over the varied contexts shaping each urban knowledge and innovation space uniquely. The paper reveals the interplay between design and policies that is required for the creation of spaces of innovation that are economically strong, socially connected, spatially stimulating, and environmentally sustainable.

The 3rd Knowledge Cities World Summit Proceedings

FROM KCWS 2010 Ch airs and Summit Proceeding Ed ito rs ‘Knowledge’ is a resource, which relies on the past for a better future. In the 21st century, more than ever before, cities around the world depend on the knowledge of their citizens, their institutions and their firms and enterprises. The knowledge image, the human competence and the reputation of their public and private institutions and corporations profiles a city. It attracts investment, qualified labour and professionals, as well as students and researchers. And it creates local life spaces and professional milieus, which offer the quality of life to the citizens that are seeking to cope with the challenges of modern life in a competitive world. Integrating knowledge-based development in urban strategies and policies, beyond the provision of schools and locations for higher education, has become a new ambitious arena of city politics. Coming from theory to practice, and bringing together the manifold knowledge stakeholders in a city and preparing joint visions for the knowledge city is a new challenge for city managers, urban planners and leaders of the civic society . It requires visionary power, creativity, holistic thinking, the willingness to cooperate with all groups of the local civil society, and the capability to moderate communication processes to overcome conflicts and to develop joint action for a sustainable future. This timely Melbourne 2010 – The Third Knowledge City World Summit makes an important reminder that ‘knowledge’ is the key notion in the 21st Century development. Considering this notion, the summit aims to shed light on the multi-faceted dimensions and various scales of building the ‘knowledge city’ and on ‘knowledge-based development’ paradigms. At this summit, the theoretical and practical maturing of knowledge-based development paradigms will be advanced through the interplay between the world’s leading academic’s theories and the practical models and strategies of practitioners’ and policy makers’ drawn from around the world. As chairs of The Melbourne 2010 Summit, we have compiled this summit proceeding in order to disseminate the knowledge generated and shared in Melbourne with the wider research, governance, and practice communities. The papers in the proceedings reflect the broad range of contributions to the summit. They report on recent developments in planning and managing knowledge cities and ICT infrastructure, they assess the role of knowledge institutions in regional innovation systems and of the intellectual capital of cities and regions; they describe the evolution of knowledge-based approaches to urban development in differing cultural environments; they finally bridge the discourse on the knowledge city to other urban development paradigms such as the creative city, the ubiquitous city or the compact city. The diversity of papers presented shows how different scholars from planning cultures around the world interpret the knowledge dimension in urban and regional development. All papers of this proceeding have gone through a double-blind peer review process and been reviewed by our summit editorial review and advisory board members. We cordially thank the members of the Summit Proceeding Editorial Review and Advisory Board for their diligent work in the review of the papers. We hope the papers in this proceeding will inspire and make a significant contribution to the research, governance, and practice circles.

The 4th Knowledge Cities World Summit Proceedings

FROM KCWS 2011 CHAIRS AND SUMMIT PROCEEDING EDITORS In recent years, with the impact of global knowledge economy, a more comprehensive development approach has gained significant popularity. This new development approach, so called ‘knowledgebased development’, is different from its traditional predecessor. With a much more balanced focus on all of the four key development domains – economic, enviro-urban, institutional, and sociocultural – this contemporary approach, aims to bring economic prosperity, environmental sustainability and local institutional competence with a just socio-spatial order to our cities and regions. The ultimate goal of knowledge-based development is to produce a city purposefully designed to encourage the continuous production, circulation and commercialisation of social and scientific knowledge – this will in turn establish a ‘knowledge city’. A city following the ‘knowledge city’ concept embarks on a strategic mission to firmly encourage and nurture locally focussed innovation, science and creativity within the context of an expanding knowledge economy and society. In this regard a ‘knowledge city’ can be seen as an integrated city, which physically and institutionally combines the functions of a science and technology park with civic and residential functions and urban amenities. It also offers one of the effective paradigms for the sustainable cities of our time. This fourth edition of KCWS – The 4th Knowledge Cities World Summit 2011 – makes an important reminder that the 'knowledge city' concept is a key notion in the 21st Century development. Considering this notion, the Summit sheds light on the multi-faceted dimensions and various scales of building a ‘knowledge city’ via 'knowledge-based development' paradigm by particularly focusing on the overall Summit theme of ‘Knowledge Cities for Future Generations’. At this summit, the theoretical and practical maturing of knowledge-based development paradigms are advanced through the interplay between the world’s leading academics’ theories and the practical models and strategies of practitioners’ and policy makers’ drawn from around the world. This summit proceeding is compiled in order to disseminate the knowledge generated and shared in KCWS 2011 with the wider research, governance, and practice communities the knowledge cocreated in this summit. All papers of this proceeding have gone through a double-blind peer review process and been reviewed by our summit editorial review and advisory board members. We, organisers of the summit, cordially thank the members of the Summit Proceeding Editorial Review and Advisory Board for their diligent work in the review of the papers. We hope the papers in this proceeding will inspire and make a significant contribution to the research, governance, and practice circles.

Conceptualising, evaluating and reporting social resilience in vulnerable regional and remote communities facing climate change in tropical Queensland : marine and tropical sciences research facility transition project final report

Regional and remote communities in tropical Queensland are among Australia’s most vulnerable in the face of climate change. At the same time, these socially and economically vulnerable regions house some of Australia’s most significant biodiversity values. Past approaches to terrestrial biodiversity management have focused on tackling biophysical interventions through the use of biophysical knowledge. An equally important focus should be placed on building regional-scale community resilience if some of the worst biodiversity impacts of climate change are to be avoided or mitigated. Despite its critical need, more systemic or holistic approaches to natural resource management have been rarely trialed and tested in a structured way. Currently, most strategic interventions in improving regional community resilience are ad hoc, not theory-based and short term. Past planning approaches have not been durable, nor have they been well informed by clear indicators. Research into indicators for community resilience has been poorly integrated within adaptive planning and management cycles. This project has aimed to resolve this problem by: * Reviewing the community and social resilience and adaptive planning literature to reconceptualise an improved framework for applying community resilience concepts; * Harvesting and extending work undertaken in MTSRF Phase 1 to identifying the learnings emerging from past MTSRF research; * Distilling these findings to identify new theoretical and practical approaches to the application of community resilience in natural resource use and management; * Reconsidering the potential interplay between a region’s biophysical and social planning processes, with a focus on exploring spatial tools to communicate climate change risk and its consequent environmental, economic and social impacts, and; * Trialling new approaches to indicator development and adaptive planning to improve community resilience, using a sub-regional pilot in the Wet Tropics. In doing so, we also looked at ways to improve the use and application of relevant spatial information. Our theoretical review drew upon the community development, psychology and emergency management literature to better frame the concept of community resilience relative to aligned concepts of social resilience, vulnerability and adaptive capacity. Firstly, we consider community resilience as a concept that can be considered at a range of scales (e.g. regional, locality, communities of interest, etc.). We also consider that overall resilience at higher scales will be influenced by resilience levels at lesser scales (inclusive of the resilience of constituent institutions, families and individuals). We illustrate that, at any scale, resilience and vulnerability are not necessarily polar opposites, and that some understanding of vulnerability is important in determining resilience. We position social resilience (a concept focused on the social characteristics of communities and individuals) as an important attribute of community resilience, but one that needs to be considered alongside economic, natural resource, capacity-based and governance attributes. The findings from the review of theory and MTSRF Phase 1 projects were synthesized and refined by the wider project team. Five predominant themes were distilled from this literature, research review and an expert analysis. They include the findings that: 1. Indicators have most value within an integrated and adaptive planning context, requiring an active co-research relationship between community resilience planners, managers and researchers if real change is to be secured; 2. Indicators of community resilience form the basis for planning for social assets and the resilience of social assets is directly related the longer term resilience of natural assets. This encourages and indeed requires the explicit development and integration of social planning within a broader natural resource planning and management framework; 3. Past indicator research and application has not provided a broad picture of the key attributes of community resilience and there have been many attempts to elicit lists of “perfect” indicators that may never be useful within the time and resource limitations of real world regional planning and management. We consider that modeling resilience for proactive planning and prediction purposes requires the consideration of simple but integrated clusters of attributes; 4. Depending on time and resources available for planning and management, the combined use of well suited indicators and/or other lesser “lines of evidence” is more flexible than the pursuit of perfect indicators, and that; 5. Index-based, collaborative and participatory approaches need to be applied to the development, refinement and reporting of indicators over longer time frames. We trialed the practical application of these concepts via the establishment of a collaborative regional alliance of planners and managers involved in the development of climate change adaptation strategies across tropical Queensland (the Gulf, Wet Tropics, Cape York and Torres Strait sub-regions). A focus on the Wet Tropics as a pilot sub-region enabled other Far North Queensland sub-region’s to participate and explore the potential extension of this approach. The pilot activities included: * Further exploring ways to innovatively communicate the region’s likely climate change scenarios and possible environmental, economic and social impacts. We particularly looked at using spatial tools to overlay climate change risks to geographic communities and social vulnerabilities within those communities; * Developing a cohesive first pass of a State of the Region-style approach to reporting community resilience, inclusive of regional economic viability, community vitality, capacitybased and governance attributes. This framework integrated a literature review, expert (academic and community) and alliance-based contributions; and * Early consideration of critical strategies that need to be included in unfolding regional planning activities with Far North Queensland. The pilot assessment finds that rural, indigenous and some urban populations in the Wet Tropics are highly vulnerable and sensitive to climate change and may require substantial support to adapt and become more resilient. This assessment finds that under current conditions (i.e. if significant adaptation actions are not taken) the Wet Tropics as a whole may be seriously impacted by the most significant features of climate change and extreme climatic events. Without early and substantive action, this could result in declining social and economic wellbeing and natural resource health. Of the four attributes we consider important to understanding community resilience, the Wet Tropics region is particularly vulnerable in two areas; specifically its economic vitality and knowledge, aspirations and capacity. The third and fourth attributes, community vitality and institutional governance are relatively resilient but are vulnerable in some key respects. In regard to all four of these attributes, however, there is some emerging capacity to manage the possible shocks that may be associated with the impacts of climate change and extreme climatic events. This capacity needs to be carefully fostered and further developed to achieve broader community resilience outcomes. There is an immediate need to build individual, household, community and sectoral resilience across all four attribute groups to enable populations and communities in the Wet Tropics region to adapt in the face of climate change. Preliminary strategies of importance to improve regional community resilience have been identified. These emerging strategies also have been integrated into the emerging Regional Development Australia Roadmap, and this will ensure that effective implementation will be progressed and coordinated. They will also inform emerging strategy development to secure implementation of the FNQ 2031 Regional Plan. Of most significance in our view, this project has taken a co-research approach from the outset with explicit and direct importance and influence within the region’s formal planning and management arrangements. As such, the research: * Now forms the foundations of the first attempt at “Social Asset” planning within the Wet Tropics Regional NRM Plan review; * Is assisting Local government at regional scale to consider aspects of climate change adaptation in emerging planning scheme/community planning processes; * Has partnered the State government (via the Department of Infrastructure and Planning and Regional Managers Coordination Network Chair) in progressing the Climate Change adaptation agenda set down within the FNQ 2031 Regional Plan; * Is informing new approaches to report on community resilience within the GBRMPA Outlook reporting framework; and * Now forms the foundation for the region’s wider climate change adaptation priorities in the Regional Roadmap developed by Regional Development Australia. Through the auspices of Regional Development Australia, the outcomes of the research will now inform emerging negotiations concerning a wider package of climate change adaptation priorities with State and Federal governments. Next stage research priorities are also being developed to enable an ongoing alliance between researchers and the region’s climate change response.

Temperature-dependent properties of nc-Si thin films synthesized in low-pressure, thermally nonequilibrium, high-density inductively coupled plasmas

Silicon thin films were synthesized simultaneously on single-crystal silicon and glass substrates by lowpressure, thermally nonequilibrium, high-density inductively coupled plasma-assisted chemical vapor deposition from the silane precursor gas without any additional hydrogen dilution in a broad range of substrate temperatures from 100 to 500 °C. The effect of the substrate temperature on the morphological, structural and optical properties of the synthesized silicon thin films is systematically studied by X-ray diffractometry, Raman spectroscopy, UV-vis spectroscopy, and scanning electron microscopy. It is shown that the formation of nanocrystalline silicon (nc-Si) occurs when the substrate temperature is higher than 200 °C and that all the deposited nc-Si films have a preferential growth along the (111) direction. However, the mean grain size of the (111) orientation slightly and gradually decreases while the mean grain size of the (220) orientation shows a monotonous increase with the increased substrate temperature from 200 to 500 °C. It is also found that the crystal volume fraction of the synthesized nc-Si thin films has a maximum value of ∼69.1% at a substrate temperature of 300 rather than 500 °C. This rather unexpected result is interpreted through the interplay of thermokinetic surface diffusion and hydrogen termination effects. Furthermore, we have also shown that with the increased substrate temperature from 100 to 500 °C, the optical bandgap is reduced while the growth rates tend to increase. The maximum rates of change of the optical bandgap and the growth rates occur when the substrate temperature is increased from 400 to 500 °C. These results are highly relevant to the development of photovoltaic thin-film solar cells, thin-film transistors, and flat-panel displays.

Solo3

Solo3 is and evening of solo works collaboratively created by Jenny Roche and choreographers John Jasperse (US), Jodi Melnick (US) and Liz Roche (Ireland). It was commissioned by the Dublin Dance Festival 2008 for the culmination of Jenny Roche's residency as an artist with the festival. The three works address the role of the dancer as co-creator within choreographic practice and further examine how the dancer can inhabit multiple embodiments across various choreographies leading to a plurality of selfhood in line with post-modern and poststructuralist notions of subjectivity (Deleuze and Guattari 1987). Furthermore, the oscillation of real and imagined subjectivities in performance (Emilyn Claid 2006) and the interplay of intercorporeal and intersubjective relations between choreographer and dancer (Sally Gardner 2007) are highlighted in these works.

A simulation modeling approach to understanding information technology value cocreation

The business value of information technology (IT) is increasingly being cocreated by multiple parties, opening opportunities for new research initiatives. Previous studies on IT value cocreation mainly focus on analyzing sources of cocreated IT value, yet inadequately accommodating the influence of competition relationships in IT value cocreation activities. To fill the gap, this in-progress paper suggests an agent-based modeling (also simulation) approach to investigating potential influences of the dynamic interplay between cooperation and competition relationships in IT value cocreation settings. In particular, the research proposes a high-level conceptual framework to position general IT value cocreation processes. A relational network view is offered, aiming at decomposing and systemizing several typical cooperation and competition scenarios in practical IT value cocreation settings. The application of a simulation approach to analytical insights and to theory building is illustrated.

The Politics of Urban Cultural Policy : Global Perspectives

The Politics of Urban Cultural Policy brings together a range of international experts to critically analyze the ways that governmental actors and non-governmental entities attempt to influence the production and implementation of urban policies directed at the arts, culture, and creative activity. Presenting a global set of case studies that span five continents and 22 cities, the essays in this book advance our understanding of how the dynamic interplay between economic and political context, institutional arrangements, and social networks affect urban cultural policy-making and the ways that these policies impact urban development and influence urban governance. The volume comparatively studies urban cultural policy-making in a diverse set of contexts, analyzes the positive and negative outcomes of policy for different constituencies, and identifies the most effective policy directions, emerging political challenges, and most promising opportunities for building effective cultural policy coalitions. The volume provides a comprehensive and in-depth engagement with the political process of urban cultural policy and urban development studies around the world. It will be of interest to students and researchers interested in urban planning, urban studies and cultural studies.

The Habitual Rhythms of Becoming-Involved: Insights into Participation Experiences in Urban Spaces by Children with Diverse Mobility

This chapter reports on a study that reveals the essence of participation in urban spaces by ten children who live with various physical conditions: Muscular Dystrophy, Cerebral Palsy, and Autoimmune Rheumatic Diseases. These conditions affect muscle and movement differently resulting in diverse ways in which children move through space (personal mobility). The children at the time of the research were 9-12 years of age residing in South-east Queensland, Australia. The approach and methods selected for this study, interpretive phenomenological inquiry and grounded theory, were chosen for their capacity to capture the complexity and multiple interactions of the child’s urban living. The confronting and poignant accounts by children and their families of their experiences produced a new way of understanding the concept of participation, as a ‘journey of becoming involved.’ Their accounts of performing everyday routines (e.g. leaving home, getting in and out of the car, and entering places) in urban spaces (neighbourhood streets, schools, open spaces, shopping centres, and hospitals) revealed differences in the way settings were experienced. These differences were associated with the interplay between the body, space and context. Where interplays were problematic, explicit decisions about children’s involvement were made. These decisions were described in terms of ‘avoid going’, ‘pick and choose’, ‘discontinue’, ‘accept’, or ‘contest.’ What these decisions mean is some spaces are avoided, some journeys are discontinued, and some barriers encountered in journeys are normalised as everyday experiences, i.e. ‘tolerable discrimination’. These actions resulted in experiences of non-participation or partial–tokenistic participation. The key substantive contribution of the research lies in the identification of points in children’s journeys that shape participation experience. These points identify where future interventions in policy, programming and design can be made to make real and sustaining changes to lives of children and their families in geographies crucial to urban living.

Literacy, poverty and schooling : what matters in young people's education?

This paper draws upon several decades of literacy research in schools in high poverty environments to explore what matters in young people’s education. In dialogue with themes from Kevin Marjoribanks’ work, such as student aspirations, family environments, and teacher expectations, key insights are summarised. Referring to longitudinal case studies and a current ethnographic project, the interplay between literacy, poverty and schooling, and, young people’s aspirations and education outcomes is explored. While the work of educators in high poverty communities continues to be highly demanding, there are some schools and teachers making a durable positive difference to learner dispositions and literate repertoires. Teacher expectations and discursive practices are crucial in this process.

Epigenetic mechanisms mediating vulnerability and resilience to psychiatric disorders

The impact that stressful encounters have upon long-lasting behavioural phenotypes is varied. Whereas a significant proportion of the population will develop "stress-related" conditions such as post-traumatic stress disorder or depression in later life, the majority are considered "resilient" and are able to cope with stress and avoid such psychopathologies. The reason for this heterogeneity is undoubtedly multi-factorial, involving a complex interplay between genetic and environmental factors. Both genes and environment are of critical importance when it comes to developmental processes, and it appears that subtle differences in either of these may be responsible for altering developmental trajectories that confer vulnerability or resilience. At the molecular level, developmental processes are regulated by epigenetic mechanisms, with recent clinical and pre-clinical data obtained by ourselves and others suggesting that epigenetic differences in various regions of the brain are associated with a range of psychiatric disorders, including many that are stress-related. Here we provide an overview of how these epigenetic differences, and hence susceptibility to psychiatric disorders, might arise through exposure to stress-related factors during critical periods of development.

Bridging experiments, models and simulations : an integrative approach to validation in computational cardiac electrophysiology

Computational models in physiology often integrate functional and structural information from a large range of spatio-temporal scales from the ionic to the whole organ level. Their sophistication raises both expectations and scepticism concerning how computational methods can improve our understanding of living organisms and also how they can reduce, replace and refine animal experiments. A fundamental requirement to fulfil these expectations and achieve the full potential of computational physiology is a clear understanding of what models represent and how they can be validated. The present study aims at informing strategies for validation by elucidating the complex interrelations between experiments, models and simulations in cardiac electrophysiology. We describe the processes, data and knowledge involved in the construction of whole ventricular multiscale models of cardiac electrophysiology. Our analysis reveals that models, simulations, and experiments are intertwined, in an assemblage that is a system itself, namely the model-simulation-experiment (MSE) system. Validation must therefore take into account the complex interplay between models, simulations and experiments. Key points for developing strategies for validation are: 1) understanding sources of bio-variability is crucial to the comparison between simulation and experimental results; 2) robustness of techniques and tools is a pre-requisite to conducting physiological investigations using the MSE system; 3) definition and adoption of standards facilitates interoperability of experiments, models and simulations; 4) physiological validation must be understood as an iterative process that defines the specific aspects of electrophysiology the MSE system targets, and is driven by advancements in experimental and computational methods and the combination of both.