Fibroblast nemosis in malignant progression of epithelial cells

Paracrine regulation between the components of the tumour microenvironment cancer cells, activated fibroblasts, immune and endothelial cells is under intense investigation. The signals between the different cell types are mediated by soluble factors, such as growth factors, proinflammatory cytokines and proteolytic enzymes. Nemosis is an experimental in vitro model of fibroblast activation, leading to increased production of such mediators. Nemotic activation of fibroblasts occurs as they are forced to cluster thereby forming a multicellular spheroid. The aim of the present studies was to elucidate the mechanisms underlying the nemotic response of cancer-associated fibroblasts (CAF) and the role of nemosis in paracrine regulation between activated fibroblasts and benign and malignant epithelial cells. The results presented in this thesis demonstrate that the nemotic response of CAFs and normal fibroblasts differs, and inter-individual variations exist between fibroblast populations. In co-culture experiments, fibroblasts increased colony formation of squamous cell carcinoma (SCC) cells, and CAFs further augmented this, highlighting the tumour-evolving properties of CAFs. Furthermore, fibroblast monolayers in those co-cultures started to cluster spontaneously. This kind of spontaneous nemosis response might take place also in vivo, although more direct evidence of this still needs to be obtained. The HaCaT skin carcinoma progression model was used to study the effects of benign and malignant keratinocytes on fibroblast nemosis. Benign HaCaT cells inhibited fibroblast nemosis, observed as inhibition of cyclooxygenase 2 (COX-2) induction in nemotic spheroids. In contrast, malignant HaCaTs further augmented the nemotic response by increasing expression of COX-2 and the growth factors hepatocyte growth factor / scatter factor (HGF/SF) and vascular endothelial growth factor (VEGF), as well as causing a myofibroblastic differentiation of nemotic fibroblasts into fibroblasts resembling CAFs. On the other side of this reciprocal signalling, factors secreted into conditioned medium by the nemotic fibroblasts promoted proliferation and motility of the HaCaT cell lines. Notably, the nemotic fibroblast medium increased the expression of p63, a transcription factor linked to carcinogenesis, also in the highly metastatic HaCaT cells. These results emphasize the paracrine role of factors secreted by activated fibroblasts in driving tumour progression. We also investigated the epithelial-mesenchymal transition (EMT) of the HaCaT clones in response to transforming growth factor β (TGF-β), which is a well-characterized inducer of EMT. TGF-β caused growth arrest and loss of epithelial cell junctions in the HaCaT derivatives, but mesenchymal markers were not induced, suggesting a partial, but not complete EMT response. Inflammation induced by COX-2 has been proposed to be a key mechanism in EMT of benign cells. Corroborating this notion, COX-2 was induced only in benign, not in malignant HaCaT derivatives. Furthermore, in cells in which TGF-β caused COX-2 induction, migration was clearly augmented. The concept of treating cancer is changing from targeting solely the cancer cells to targeting the whole microenvironment. The results of this work emphasise the role of activated fibroblasts in cancer progression and that CAFs should also be taken into consideration in the treatment of cancer. The results from these studies suggests that nemosis could be used as a diagnostic tool to distinguish in vitro activated fibroblasts from tumour stroma and also in studying the paracrine signalling that is mediated to other cell types via soluble factors.

Regenerative sustainability for the built environment – from vision to reality: An introductory chapter

Regenerative sustainability is emerging as an alternative discourse around the transition from a ‘mechanistic’ to an ‘ecological’ or living systems worldview. This view helps us to re-conceptualize relationships among humans’ technological, ecological, economic, social and political systems. Through exploration of ‘net positive’ or ‘regenerative’ development lenses and the traditional sustainability literature, the conceptualization and approaches to achieve sustainable development and ecological modernization are expanded to articulate and to explore the evolving sustainability discourse, ‘regenerative sustainability’. This Special Volume of Journal of Cleaner Production (SV) is focused upon various dimensions of regenerative sustainability (e.g. regenerative design, regenerative development, and positive development) applied to the urban built environment at scales, which range from individual buildings, neighborhoods, and urban developments to integrated regional sustainable development. The main focus is on how these approaches and developments are evolving, how they can help us to prevent or adapt to climate change and how these approaches are likely to evolve in the next two to three decades. These approaches are addressed in four themes: (1) reviewing the theoretical development of the discourse of regenerative sustainability, its emerging principles and practices, (2) explaining how it can be measured and monitored, (3) providing encouraging practical pathways and examples of its implementation in multiple cultural and climatic contexts, and (4) mapping obstacles and enablers that must be addressed to help to ensure that more rapid progress is made in implementing the transitions towards an urban built environment that supports genuinely sustainable societies.

The disruptive technologies that will shape business in the years ahead

Regardless of your industry, the marketplace is continually evolving. The reason, increasingly, is the evolution of disruptive technology. Disruptive technologies are enhanced or new technological innovations that essentially displace conventional and established technology, rendering it obsolete. They can create opportunities for new products, new markets, and new ways of conducting business. In 2016, business models will again change as businesses adapt. The enhancement of current technology and the development of new technological innovations will undeniably transform how new businesses are established, and how existing businesses compete. For small and medium-sized firms, technology will also enable significant leaps forward in terms of innovation, efficiency and competitiveness. Adapting quickly will be essential, so here’s the top six we think you should be prepared for.

A case study on the economics of overhead irrigation in the lower Burdekin

Converting from an existing irrigation system is often seen as high risk by the land owner. The significant financial investment and the long period over which the investment runs is also complicated by the uncertainty associated with long term input costs (such as energy), crop production, and the continually evolving natural resource management rules and policy. Irrigation plays a pivotal part in the Burdekin sugarcane farming system. At present the use of furrow irrigation is by far the most common form due to the ease of use, relatively low operating cost and well established infrastructure currently in place. The Mulgrave Area Farmer Integrated Action (MAFIA) grower group, located near Clare in the lower Burdekin region, identified the need to learn about sustainable farming systems with a focus on the environment, social and economic implications. In early 2007, Hesp Faming established a site to investigate the use of overhead irrigation as an alternative to furrow irrigation and its integration with new farming system practices, including Green Cane Trash Blanketing (GCTB). Although significant environmental and social benefits exist, the preliminary investment analysis indicates that the Overhead Low Pressure (OHLP) irrigation system is not adding financial value to the Hesp Farming business. A combination of high capital costs and other offsetting factors resulted in the benefits not being fully realised. A different outcome is achieved if Hesp Farming is able to realise value on the water saved, with both OHLP irrigation systems displaying a positive NPV. This case study provides a framework to further investigate the economics of OHLP irrigation in sugarcane and it is anticipated that with additional data a more definitive outcome will be developed in the future.

Government entity contribution to an effective partnership privatisation

The partnership form of privatisation is increasingly being used, in particular to carry out complex and evolving bundles of services. These have not previously been privatised because of incomplete contracts and contract management difficulties. Improved performance of the government entity as contract administrator and member of the partnership is crucial to modern service delivery expectations yet the privatisation literature has focused on other aspects of partnerships leaving the understanding of factors impacting the effectiveness of the government entity underdeveloped. This paper proposes the development of knowledge as to the range of factors which impact the effectiveness of the government entity. There is limited data available as to the operation of trust in the partnership relationship, and as to the capability of a range of privatisation forms to achieve stewardship of infrastructure. This research will utilise the findings from that research to build a tentative framework which will be utilised in staged research interrogating first the privatization literature and then the literature of other disciplines and sectors. The combined data will be analysed to provide government and practitioners such as government entity CEO’s with a complete listing of the operation of the factors which impact the effectiveness of the government entity in contributing to improved service delivery.

Circulating tumor cells: Isolation, expansion, characterization and translation to clinic

Circulating tumor cells (CTCs) are the seeds for cancer metastases development, which is responsible for >90% of cancer-related deaths. Accurate quantification of CTCs in human fluids could be an invaluable tool for understanding cancer prognosis, delivering personalized medicine to prevent metastasis and finding cancer therapy effectiveness. Although CTCs were first discovered more than 200 years ago, until now it has been a nightmare for clinical practitioners to capture and diagnose CTCs in clinical settings. Our society needs rapid, sensitive, and reliable assays to identify the CTCs from blood in order to help save millions of lives. Due to the phenotypic EMT transition, CTCs are undetected for more than one-third of metastatic breast cancer patients in clinics. To tackle the above challenges, the first volume in “Circulating Tumor Cells (CTCs): Detection Methods, Health Impact and Emerging Clinical Challenges discusses recent developments of different technologies, which have the capability to target and elucidate the phenotype heterogenity of CTCS. It contains seven chapters written by world leaders in this area, covering basic science to possible device design which can have beneficial applications in society. This book is unique in its design and content, providing an in-depth analysis to elucidate biological mechanisms of cancer disease progression, CTC detection challenges, possible health effects and the latest research on evolving technologies which have the capability to tackle the above challenges. It describes the broad range of coverage on understanding CTCs biology from early predictors of the metastatic spread of cancer, new promising technology for CTC separation and detection in clinical environment and monitoring therapy efficacy via finding the heterogeneous nature of CTCs. (Imprint: Nova Biomedical)

Dreiundsechzig 1933-2005

Irene Runge wrote 14 books so far. This one was written for the occasion of her 63rd birthday - instead of a speech, it was printed and delivered to 63 of her friends. The book is a memoir, and jumps back and forth in time. It consists mostly of personal memories and anecdotes, but there is also an essay-style to it, with very reflective passages and analyses. It is divided into many chapters, which also resemble diary entries. Irene Runge is a member of the "second generation". She was born in the New York exile, but her parents moved back to Germany after the war, during a climate in the USA, which made it very difficult for sympathisers with the communist party. Her memories give rich insight into the life as an emigrant in New York, but also as re-emigrant in Germany. She writes about the their disappointments with the evolving German Democratic Republic (GDR), Eastern Germany, experiences, which repeated again in 1989/1990, when the reunification with West Germany took place. The year 1989 had practical consequences for her private life--she lost her job at the university, because her past seemed not compatible. She discusses the PDS, the party which evolved from the communist party of Eastern Germany, Berlin after the "Wende" (reunification), and life in Berlin after the reunification. At one point she asks whether the current Turkish-Muslim community in Berlin could be comparable to the living conditions of the Jewish community in the 1930. This is a rare memoir documenting many recent aspects of German-speaking Jewry.

APSIM – Evolution towards a new generation of agricultural systems simulation

Agricultural systems models worldwide are increasingly being used to explore options and solutions for the food security, climate change adaptation and mitigation and carbon trading problem domains. APSIM (Agricultural Production Systems sIMulator) is one such model that continues to be applied and adapted to this challenging research agenda. From its inception twenty years ago, APSIM has evolved into a framework containing many of the key models required to explore changes in agricultural landscapes with capability ranging from simulation of gene expression through to multi-field farms and beyond. Keating et al. (2003) described many of the fundamental attributes of APSIM in detail. Much has changed in the last decade, and the APSIM community has been exploring novel scientific domains and utilising software developments in social media, web and mobile applications to provide simulation tools adapted to new demands. This paper updates the earlier work by Keating et al. (2003) and chronicles the changing external challenges and opportunities being placed on APSIM during the last decade. It also explores and discusses how APSIM has been evolving to a “next generation” framework with improved features and capabilities that allow its use in many diverse topics.

The plasticity of NBS resistance genes in sorghum is driven by multiple evolutionary processes

Background Increased disease resistance is a key target of cereal breeding programs, with disease outbreaks continuing to threaten global food production, particularly in Africa. Of the disease resistance gene families, the nucleotide-binding site plus leucine-rich repeat (NBS-LRR) family is the most prevalent and ancient and is also one of the largest gene families known in plants. The sequence diversity in NBS-encoding genes was explored in sorghum, a critical food staple in Africa, with comparisons to rice and maize and with comparisons to fungal pathogen resistance QTL. Results In sorghum, NBS-encoding genes had significantly higher diversity in comparison to non NBS-encoding genes and were significantly enriched in regions of the genome under purifying and balancing selection, both through domestication and improvement. Ancestral genes, pre-dating species divergence, were more abundant in regions with signatures of selection than in regions not under selection. Sorghum NBS-encoding genes were also significantly enriched in the regions of the genome containing fungal pathogen disease resistance QTL; with the diversity of the NBS-encoding genes influenced by the type of co-locating biotic stress resistance QTL. Conclusions NBS-encoding genes are under strong selection pressure in sorghum, through the contrasting evolutionary processes of purifying and balancing selection. Such contrasting evolutionary processes have impacted ancestral genes more than species-specific genes. Fungal disease resistance hot-spots in the genome, with resistance against multiple pathogens, provides further insight into the mechanisms that cereals use in the “arms race” with rapidly evolving pathogens in addition to providing plant breeders with selection targets for fast-tracking the development of high performing varieties with more durable pathogen resistance.

Cultural safety and diversity: Refocusing our energies in mental health nursing practice, education and research

INTRODUCTION AND BACKGROUND: This presentation draws on a body of work assessing cultural safety's potential to generate change in mental health nursing research (Cox and Simpson 2015), in education and in clinical practice (Cox and Taua 2013, 2016; Happell, Cowin, Roper, Lakeman & Cox 2013). It presents evidence to suggest that cultural safety could resolve the conceptual confusion surrounding culture and diversity in nursing curricular, in clinical and in research practice. The history and nature of mental health work recommend cultural safety to focus attention on diversity, power imbalance, racism, cultural dominance, and structural inequality, identified as barriers and tensions in clinical practice and in service user participation. Cultural safety gives mental health nursing a well theorized and articulated model, which is evolving to improve practice into the future. DESCRIPTION: This work involved an immersion in the literature on cultural safety and the Service User Research movement. It draws on 5 months' work with a service users' research group in the UK and reflections on 9 years of cultural safety teaching. POLICY/PRACTICE CHANGE: This work provokes a crucial change of emphasis from locating the source of issues in the diversity of people to locating it in how society responds to diversity: a change from individualistic to systemic concerns. IMPLICATIONS FOR MENTAL HEALTH NURSING: Cultural safety in clinical practice, education, and research is specifically concerned with awareness of the impact of systemic workplace cultures and with staff cultural self-awareness to bring about cultural change and person-centred care of individuals' unique needs and aspirations within their life context.

Two distinct classes of QTL determine rust resistance in sorghum

Background: Agriculture is facing enormous challenges to feed a growing population in the face of rapidly evolving pests and pathogens. The rusts, in particular, are a major pathogen of cereal crops with the potential to cause large reductions in yield. Improving stable disease resistance is an on-going major and challenging focus for many plant breeding programs, due to the rapidly evolving nature of the pathogen. Sorghum is a major summer cereal crop that is also a host for a rust pathogen which occurs in almost all sorghum growing areas of the world, causing direct and indirect yield losses in sorghum worldwide, however knowledge about its genetic control is still limited. In order to further investigate this issue, QTL and association mapping methods were implemented to study rust resistance in three bi-parental populations and an association mapping set of elite breeding lines in different environments. Results: In total, 64 significant or highly significant QTL and 21 suggestive rust resistance QTL were identified representing 55 unique genomic regions. Comparisons across populations within the current study and with rust QTL identified previously in both sorghum and maize revealed a high degree of correspondence in QTL location. Negative phenotypic correlations were observed between rust, maturity and height, indicating a trend for both early maturing and shorter genotypes to be more susceptible to rust. Conclusions: The significant amount of QTL co-location across traits, in addition to the consistency in the direction of QTL allele effects, has provided evidence to support pleiotropic QTL action across rust, height, maturity and stay-green, supporting the role of carbon stress in susceptibility to rust. Classical rust resistance QTL regions that did not co-locate with height, maturity or stay-green QTL were found to be significantly enriched for the defence-related NBS-encoding gene family, in contrast to the lack of defence-related gene enrichment in multi-trait effect rust resistance QTL. The distinction of disease resistance QTL hot-spots, enriched with defence-related gene families from QTL which impact on development and partitioning, provides plant breeders with knowledge which will allow for fast-tracking varieties with both durable pathogen resistance and appropriate adaptive traits.

Developing an evolutionary/ecological approach in enterprise education

This paper presents an ecological/evolutionary approach to enterprise education. Ecological approaches are used at the University of Tasmania to heighten the awareness of students to a raft of difficult to observe environmental factors associated with developing enterprising ideas. At Sheffield University, the discovery and exploitation of entrepreneurial opportunities is viewed as a co-evolving system of emerging business ideas, and routines/heuristics respectively. It is argued that using both approaches enables students to develop a greater awareness of their situated environment, and ultimately the degree of fit between their learning process and a changing external world. The authors argue that in order to improve the chances of longer-term survival what is needed is a new level of organisation where the individual is capable of developing a representation of the external world that he or she can use to sense the appropriateness of local decisions. This reinterpretation of events allows individuals to step back and examine the broader consequences of their actions through the interpretation and anticipation of feedback from the environment. These approaches thus seek to develop practice-based heuristics which individuals can use to make sense of their lived experiences, as they learn to evolve in an increasingly complex world.

A Decentralized Session Management Framework for Heterogeneous Ad-Hoc and Fixed Networks

Wireless technologies are continuously evolving. Second generation cellular networks have gained worldwide acceptance. Wireless LANs are commonly deployed in corporations or university campuses, and their diffusion in public hotspots is growing. Third generation cellular systems are yet to affirm everywhere; still, there is an impressive amount of research ongoing for deploying beyond 3G systems. These new wireless technologies combine the characteristics of WLAN based and cellular networks to provide increased bandwidth. The common direction where all the efforts in wireless technologies are headed is towards an IP-based communication. Telephony services have been the killer application for cellular systems; their evolution to packet-switched networks is a natural path. Effective IP telephony signaling protocols, such as the Session Initiation Protocol (SIP) and the H 323 protocol are needed to establish IP-based telephony sessions. However, IP telephony is just one service example of IP-based communication. IP-based multimedia sessions are expected to become popular and offer a wider range of communication capabilities than pure telephony. In order to conjoin the advances of the future wireless technologies with the potential of IP-based multimedia communication, the next step would be to obtain ubiquitous communication capabilities. According to this vision, people must be able to communicate also when no support from an infrastructured network is available, needed or desired. In order to achieve ubiquitous communication, end devices must integrate all the capabilities necessary for IP-based distributed and decentralized communication. Such capabilities are currently missing. For example, it is not possible to utilize native IP telephony signaling protocols in a totally decentralized way. This dissertation presents a solution for deploying the SIP protocol in a decentralized fashion without support of infrastructure servers. The proposed solution is mainly designed to fit the needs of decentralized mobile environments, and can be applied to small scale ad-hoc networks or also bigger networks with hundreds of nodes. A framework allowing discovery of SIP users in ad-hoc networks and the establishment of SIP sessions among them, in a fully distributed and secure way, is described and evaluated. Security support allows ad-hoc users to authenticate the sender of a message, and to verify the integrity of a received message. The distributed session management framework has been extended in order to achieve interoperability with the Internet, and the native Internet applications. With limited extensions to the SIP protocol, we have designed and experimentally validated a SIP gateway allowing SIP signaling between ad-hoc networks with private addressing space and native SIP applications in the Internet. The design is completed by an application level relay that permits instant messaging sessions to be established in heterogeneous environments. The resulting framework constitutes a flexible and effective approach for the pervasive deployment of real time applications.

Longitudinal cohort study of horse owners

This report summarises the findings of a three-year mixed methods research study designed to capture factors that influence horse owner Hendra virus (HeV) risk mitigation practices. The research project focuses on horse owners; their knowledge, attitudes, and risk mitigation practices, i.e. uptake of vaccination, property management, and biosecurity practices. A flexible research methodology enabled the tracking of core subject areas over time whilst also responding to new or evolving shifts in the HeV landscape, e.g. new HeV cases, event management, and issues arising in the vaccine roll-out. By tracking relationships within the data and engaging with stakeholders and the horse owner population, it is hoped that findings from the study will help to identify important linkages and effective strategies for communication/information and policy implementation.

Reinventing Nordic Openness : Transparency and State Information in Finland

The study explores new ideational changes in the information strategy of the Finnish state between 1998 and 2007, after a juncture in Finnish governing in the early 1990s. The study scrutinizes the economic reframing of institutional openness in Finland that comes with significant and often unintended institutional consequences of transparency. Most notably, the constitutional principle of publicity (julkisuusperiaate), a Nordic institutional peculiarity allowing public access to state information, is now becoming an instrument of economic performance and accountability through results. Finland has a long institutional history in the publicity of government information, acknowledged by law since 1951. Nevertheless, access to government information became a policy concern in the mid-1990s, involving a historical narrative of openness as a Nordic tradition of Finnish governing Nordic openness (pohjoismainen avoimuus). International interest in transparency of governance has also marked an opening for institutional re-descriptions in Nordic context. The essential added value, or contradictory term, that transparency has on the Finnish conceptualisation of governing is the innovation that public acts of governing can be economically efficient. This is most apparent in the new attempts at providing standardised information on government and expressing it in numbers. In Finland, the publicity of government information has been a concept of democratic connotations, but new internationally diffusing ideas of performance and national economic competitiveness are discussed under the notion of transparency and its peer concepts openness and public (sector) information, which are also newcomers to Finnish vocabulary of governing. The above concepts often conflict with one another, paving the way to unintended consequences for the reforms conducted in their name. Moreover, the study argues that the policy concerns over openness and public sector information are linked to the new drive for transparency. Drawing on theories of new institutionalism, political economy, and conceptual history, the study argues for a reinvention of Nordic openness in two senses. First, in referring to institutional history, the policy discourse of Nordic openness discovers an administrative tradition in response to new dilemmas of public governance. Moreover, this normatively appealing discourse also legitimizes the new ideational changes. Second, a former mechanism of democratic accountability is being reframed with market and performance ideas, mostly originating from the sphere of transnational governance and governance indices. Mobilizing different research techniques and data (public documents of the Finnish government and international organizations, some 30 interviews of Finnish civil servants, and statistical time series), the study asks how the above ideational changes have been possible, pointing to the importance of nationalistically appealing historical narratives and normative concepts of governing. Concerning institutional developments, the study analyses the ideational changes in central steering mechanisms (political, normative and financial steering) and the introduction of budget transparency and performance management in two cases: census data (Population Register Centre) and foreign political information (Ministry for Foreign Affairs). The new policy domain of governance indices is also explored as a type of transparency. The study further asks what institutional transformations are to be observed in the above cases and in the accountability system. The study concludes that while the information rights of citizens have been reinforced and recalibrated during the period under scrutiny, there has also been a conversion of institutional practices towards economic performance. As the discourse of Nordic openness has been rather unquestioned, the new internationally circulating ideas of transparency and the knowledge economy have entered this discourse without public notice. Since the mid 1990s, state registry data has been perceived as an exploitable economic resource in Finland and in the EU public sector information. This is a parallel development to the new drive for budget transparency in organisations as vital to the state as the Population Register Centre, which has led to marketization of census data in Finland, an international exceptionality. In the Finnish Ministry for Foreign Affairs, the post-Cold War rhetorical shift from secrecy to performance-driven openness marked a conversion in institutional practices that now see information services with high regards. But this has not necessarily led to the increased publicity of foreign political information. In this context, openness is also defined as sharing information with select actors, as a trust based non-public activity, deemed necessary amid the global economic competition. Regarding accountability system, deliberation and performance now overlap, making it increasingly difficult to identify to whom and for what the public administration is accountable. These evolving institutional practices are characterised by unintended consequences and paradoxes. History is a paradoxical component in the above institutional change, as long-term institutional developments now justify short-term reforms.