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.

Requiem for a beast : a case study in controversy

In 2008, Matt Ottley’s Requiem for a Beast: A Work for Image, Word and Music was awarded the Book of the Year: Picture Book by the Children’s Book Council of Australia (CBCA). Ottley’s book is challenging in its form and content: it uses words, illustrations, and music to tell a sustained, multi-layered narrative about one young man’s attempts to reconcile his family’s and his nation’s shameful history of violence against Aboriginal Australians, while also coming to terms with his own attempts to commit suicide. Given the ways in which the CBCA’s annual book awards are used by teachers, librarians, and parents to select the “best” books for young readers, it is unsurprising that the prizing of Requiem for a Beast stirred up controversy. Responses to the book proliferated across professional and popular outlets—it even received coverage on an Australian tabloid television program—and initiated a variety of conversations about what constitutes appropriate reading for young people. Perhaps more significantly, the controversy over Requiem winning picture book of the year forced the CBCA, teacher librarians, and caregivers to examine (and, often, defend) their roles and responsibilities in the circulation and promotion of children’s literature. This paper reads the Requiem controversies as a case study for understanding the complementary and contradictory roles of institutions and individuals in the ethical circulation of children’s literature in contemporary Australia and beyond.

Onset of Mediterranean outflow into the North Atlantic

Sediments cored along the southwestern Iberian margin during Integrated Ocean Drilling Program Expedition 339 provide constraints on Mediterranean Outflow Water (MOW) circulation patterns from the Pliocene epoch to the present day. After the Strait of Gibraltar opened (5.33 million years ago), a limited volume of MOW entered the Atlantic. Depositional hiatuses indicate erosion by bottom currents related to higher volumes of MOW circulating into the North Atlantic, beginning in the late Pliocene. The hiatuses coincide with regional tectonic events and changes in global thermohaline circulation (THC). This suggests that MOW influenced Atlantic Meridional Overturning Circulation (AMOC), THC, and climatic shifts by contributing a component of warm, saline water to northern latitudes while in turn being influenced by plate tectonics.

Critical dependence of blood-borne biomarker concentrations on the half-lives of their carrier proteins

Until recently, the low-abundance (LA) range of the serum proteome was an unexplored reservoir of diagnostic information. Today it is increasingly appreciated that a diagnostic goldmine of LA biomarkers resides in the blood stream in complexed association with more abundant higher molecular weight carrier proteins such as albumin and immunoglobulins. As we now look to the possibility of harvesting these LA biomarkers more efficiently through engineered nano-scale particles, mathematical approaches are needed in order to reveal the mechanisms by which blood carrier proteins act as molecular 'mops' for LA diagnostic cargo, and the functional relationships between bound LA biomarker concentrations and other variables of interest such as biomarker intravasation and clearance rates and protein half-lives in the bloodstream. Here we show, by simple mathematical modeling, how the relative abundance of large carrier proteins and their longer half-lives in the bloodstream work together to amplify the total blood concentration of these tiny biomarkers. The analysis further suggests that alterations in the production of biomarkers lead to gradual rather than immediate changes in biomarker levels in the blood circulation. The model analysis also points to the characteristics of artificial nano-particles that would render them more efficient harvesters of tumor biomarkers in the circulation, opening up possibilities for the early detection of curable disease, rather than simply better detection of advanced disease.

The amplified peptidome : the new treasure chest of candidate biomarkers

Mass spectrometric analysis of the low-molecular weight (LMW) range of the serum/plasma proteome is revealing the existence of large numbers of previously unknown peptides and protein fragments predicted to be derived from low- abundance proteins. This raises the question of why such low abundance molecules would be retained at detectable levels in the circulation, instead of being rapidly cleared and excreted. Theoretical models of biomarker production and association with serum carrier proteins have been developed to elucidate the mechanisms governing biomarker half-life in the bloodstream. These models predict that the vast majority of LMW biomarkers exist in association with circulating high molecular mass carrier proteins. Moreover, the total serum/ plasma concentration of the biomarker is largely determined by the clearance rate of the carrier protein, not the free-phase biomarker clearance itself. These predictions have been verified experimentally using molecular mass fractionation of human serum before mass spectrometry sequence analysis. These principles have profound implications for biomarker discovery and measurement.

Visions and values : the Children’s Book Council of Australia’s prizing of picture books in the twenty-first century

The Children’s Book Council of Australia (CBCA) administers the oldest national prize for children’s literature in Australia. Each year, the CBCA confers “Book of the Year” awards to literature for young people in five categories. In 2001, the establishment of an “Early Childhood” category opened up the venerable “Picture Book” category (first awarded in 1955) to books with an implied readership up to 18 years of age. As a result, this category has emerged in recent years as a highly visible space within which the CBCA can contest discourses of cultural marginalisation insofar as Australian (“colonial”) literature is constructed as inferior or adjunct to the major Anglophone literary traditions, and the consistent identification of children’s literature (and, indeed, of children) as lesser than its ‘adult’ counterparts. The CBCA is engaged in defining, evaluating, and legitimising a tradition of Australian children’s literature which is underpinned by a canonical impulse, and is a reflexive practice of self-definition, self-evaluation and self-legitimisation for the CBCA itself. While it is obviously problematic to identify award winners as a canon, it is equally obvious that literary prizing is a cultural practice derived from the logic of canonicity. In his discussion of the United States’s Newbery Medal, Kenneth Kidd notes that “Medal books are instant classics, the selection process an ostensible simulation of the test of time” (169) and that “the Medal is part of the canonical architecture of children's literature” (169). Thus, it is instructive to consider the visions and values of the national, of the social, and of the literary-aesthetic, in the picture books chosen by the Children’s Book Council of Australia (CBCA) as the “best” of the early twenty-first century. These books not only constitute a kind of canon for contemporary Australian children’s literature, but may well come to define what contemporary Australian children’s literature means in the wider literary field. The Book of the Year: Picture Book awards given by the CBCA since 2001 demonstrate that it is not only true of the Booker Prize that, “The choices of winning books reflect not only on the books themselves, then, but also back on the Prize, affecting its reputation and creating journalistic capital which is vital for the Prize to achieve its prominence and impact.” (81). Many of the twenty-first century CBCA award-winning picture books complicate traditional or comfortable understanding of Australianness, children’s literature, or “appropriate” modes of form and content, reminding us that “moments when texts resist or complicate recuperation into national discourses offer fruitful points for exploring the relationships between text and celebratory context” (Roberts 6). The CBCA has taken the opportunities offered by the liberation of the Picture Book category from an implied readership to challenge dominant constructions of children’s literature in Australia, and in so doing, are engaged in overt practices of canonicity with potentially long-lasting effects. Works Cited: Kidd, Kenneth. “Prizing Children’s Literature: The Case of Newbery Gold.” Children's Literature 35 (2007): 166-190. Roberts, Gillian. Prizing Literature: The Celebration and Circulation of National Culture. Toronto: U Toronto P, 2011. Squires, Claire. “Book Marketing and the Booker Prize.” Judging a Book by Its Cover: Fans, Publishers, Designers, and the Marketing of Fiction. Eds. Nicole Matthews and Nickianne Moody. Aldershot: Ashgate, 2007. 71-82.

Tetraspanins as regulators of the tumour microenvironment : implications for metastasis and therapeutic strategies

One of the hallmarks of cancer is the ability to activate invasion and metastasis (Hanahan et al., 2011). Cancer morbidity and mortality are largely related to the spread of the primary, localised tumour to adjacent and distant sites (Pantel et al., 2004). Appropriate management and treatment decisions of predicting metastatic disease at the time of diagnosis is thus crucial, which supports better understanding of the metastatic process. There are common events that occur during metastasis: dissociation from the primary tumour mass, reorganisation/remodelling of extracellular matrix, cell migration, recognition and transversal of endothelial cells and the vascular circulation and lodgement and proliferation within ectopic stroma (Wells, 2006). One of the key and initial events is the increased capability of cancer cells to move, escaping the regulation of normal physiological control. The cellular cytoskeleton plays an important role in cancer cell motility and active cytoskeletal rearrangement can result in metastatic disease. This active change in cytoskeletal dynamics results in manipulation of plasma membrane and cellular balance between cellular adhesion and motility which in turn determines cancer cell movement. Members of the tetraspanins play important roles in regulation of cancer migration and cancer-endothelial cell interactions, which are critical for cancer invasion and metastasis. Their involvements in active cytoskeletal dynamics, cancer metastasis and potential clinical application will be discussed in this review. In particular, tetraspanin member, CD151, is highlighted for its major role in cancer invasion and metastasis

Circulating fragments of N-Terminal Pro-B-Type Natriuretic Peptides in plasma of heart failure patients

BACKGROUND: The use of nonstandardized N-terminal pro-B-type natriuretic peptide (NT-proBNP) assays can contribute to the misdiagnosis of heart failure (HF). Moreover, there is yet to be established a common consensus regarding the circulating forms of NT-proBNP being used in current assays. We aimed to characterize and quantify the various forms of NT-proBNP in the circulation of HF patients. METHODS: Plasma samples were collected from HF patients (n = 20) at rest and stored at -80 degrees C. NT-proBNP was enriched from HF patient plasma by use of immunoprecipitation followed by mass spectrometric analysis. Customized homogeneous sandwich AlphaLISA (R) immunoassays were developed and validated to quantify 6 fragments of NT-proBNP. RESULTS: Mass spectrometry identified the presence of several N- and C-terminally processed forms of circulating NT-proBNP, with physiological proteolysis between Pro2-Leu3, Leu3-Gly4, Pro6-Gly7, and Pro75-Arg76. Consistent with this result, AlphaLISA immunoassays demonstrated that antibodies targeting the extreme N or C termini measured a low apparent concentration of circulating NT-proBNP. The apparent circulating NT-proBNP concentration was increased with antibodies targeting nonglycosylated and nonterminal epitopes (P < 0.05). CONCLUSIONS: In plasma collected from HF patients, immunoreactive NT-proBNP was present as multiple N- and C-terminally truncated fragments of the full length NT-proBNP molecule. Immunodetection of NT-proBNP was significantly improved with the use of antibodies that did not target these terminal regions. These findings support the development of a next generation NT-proBNP assay targeting nonterminal epitopes as well as avoiding the central glycosylated region of this molecule. (c) 2013 American Association for Clinical Chemistry

Demographics and survivial of a cohort of blood and breast cancer patients who developed heart failure following cancer treatment

Background/Aim: Cardiotoxicity resulting in heart failure is a devastating complication of cancer therapy. It is possible that a patient may survive cancer only to develop heart failure (HF), which is more deadly than cancer. The aim of this project was to profile the characteristics of patients at risk of cancer treatment induced heart failure. Methods: Linked Health Data Analysis of Queensland Cancer Registry (QCR) from 1996-2009, Death Registry and Hospital Administration records for HF and chemotherapy admissions were reviewed. Index heart failure admission must have occurred after the date of cancer registry entry. Results: A total of 15,987 patients were included in this analysis; 1,062 (6.6%) had chemotherapy+HF admission (51.4% Female) and 14,925 (93.4%) chemotherapy_no HF admission. Median age of chemotherapy+HF patients was 67 years (IQR 58 to 75) vs. 54 years (IQR 44 to 64) for chemotherapy_no HF admission. Chemotherapy+HF patients had increased risk of all cause mortality (HR 2.79 [95% CI 2.58-3.02] and 1.67 [95% CI, 1.54 to 1.81] after adjusting for age, sex, marital status, country of birth, cancer site and chemotherapy dose). Index HF admission occurred within one year of cancer diagnosis in 47% of HF patients with 80% of patinets having there index admission with 3 years. The number of chemotherapy cycles was not associated with significant reduction in survival time in chemotherapy+HF patients. Mean survival for heart failure patients was 5.3 years (95% CI, 4.99 - 5.62) vs.9.57 years (95% CI, 9.47-9.68) for chemotherapy_no HF admission patients. Conclusion: All-cause mortality was 67% higher in patients diagnosed with HF following chemotherapy in adjusted analysis for covariates. Methods to improve and better coordinate of the interdisciplinary care for cancer patients with HF involving cardiologists and oncologists are required, including evidence-based guidelines for the comprehensive assessment, monitoring and management of this cohort.

Circulating antibodies against Plasmodium falciparum histidine-rich proteins 2 interfere with antigen detection by rapid diagnostic tests

Background Rapid diagnostic tests (RDTs) for detection of Plasmodium falciparum infection that target P. falciparum histidine-rich protein 2 (PfHRP2), a protein that circulates in the blood of patients infected with this species of malaria, are widely used to guide case management. Understanding determinants of PfHRP2 availability in circulation is therefore essential to understanding the performance of PfHRP2-detecting RDTs. Methods The possibility that pre-formed host anti-PfHRP2 antibodies may block target antigen detection, thereby causing false negative test results was investigated in this study. Results Anti-PfHRP2 antibodies were detected in 19/75 (25%) of plasma samples collected from patients with acute malaria from Cambodia, Nigeria and the Philippines, as well as in 3/28 (10.7%) asymptomatic Solomon Islands residents. Pre-incubation of plasma samples from subjects with high-titre anti-PfHRP2 antibodies with soluble PfHRP2 blocked the detection of the target antigen on two of the three brands of RDTs tested, leading to false negative results. Pre-incubation of the plasma with intact parasitized erythrocytes resulted in a reduction of band intensity at the highest parasite density, and a reduction of lower detection threshold by ten-fold on all three brands of RDTs tested. Conclusions These observations indicate possible reduced sensitivity for diagnosis of P. falciparum malaria using PfHRP2-detecting RDTs among people with high levels of specific antibodies and low density infection, as well as possible interference with tests configured to detect soluble PfHRP2 in saliva or urine samples. Further investigations are required to assess the impact of pre-formed anti-PfHRP2 antibodies on RDT performance in different transmission settings.