Scleral matrix metalloproteinases, serine proteinase activity and hydrational capacity are increased in myopia induced by retinal image degradation

In the avian model of myopia, retinal image degradation quickly leads to ocular enlargement. We now give evidence that regionally specific changes in ocular size are correlated with both biomechanical indices of scleral remodeling, e.g. hydration capacity and with biochemical changes in proteinase activities. The latter include a 72 kDa matrix metalloproteinase (putatively MMP-2), other gelatin-binding MMPs, an acid pH MMP and a serine protease. Specifically, we have found that increases in scleral hydrational capacity parallel increases in collagen degrading activities. Gelatin zymography reveals that eyes with 7 days of retinal image degradation have elevated levels (1.4-fold) of gelatinolytic activities at 72 and 67 kDa M(r) in equatorial and posterior pole regions of the sclera while, after 14 days of treatment, increases are no longer apparent. Lower M(r) zymographic activities at 50, 46 and 37 kDa M(r) are collectively increased in eyes treated for both 7 and 14 days (1.4- and 2.4-fold respectively) in the equator and posterior pole areas of enlarging eyes. Western blot analyses of scleral extracts with an antibody to human MMP-2 reveals immunoreactive bands at 65, 30 and 25 kDa. Zymograms incubated under slightly acidic conditions reveal that, in enlarging eyes, MMP activities at 25 and 28 kDa M(r) are increased in scleral equator and posterior pole (1.6- and 4.5-fold respectively). A TIMP-like protein is also identified in sclera and cornea by Western blot analysis. Finally, retinal-image degradation also increases (~2.6-fold) the activity of a 23.5 kDa serine proteinase in limbus, equator and posterior pole sclera that is inhibited by aprotinin and soybean trypsin inhibitor. Taken together, these results indicate that eye growth induced by retinal-image degradation involves increases in the activities of multiple scleral proteinases that could modify the biomechanical properties of scleral structural components and contribute to tissue remodeling and growth.

Frizzled-7 receptor ectodomain expression in a colon cancer cell line induces morphological change and attenuates tumor growth

Frizzled (FZD) receptors have a conserved N-terminal extracellular cysteine-rich domain that interacts with Wnts and co-expression of the receptor ectodomain can antagonize FZD-mediated signalling. Using the ectodomain as an antagonist we have modulated endogenous FZD7 signalling in the moderately differentiated colon adenocarcinoma cell line, SK-CO-1. Unlike the parental cell line, which grows as tightly associated adherent cell clusters, the FZD7 ectodomain expressing cells display a spread out morphology and grow as a monolayer in tissue culture. This transition in morphology was associated with decreased levels of plasma membrane-associated E-cadherin and β-catenin, localized increased levels of vimentin and redistribution of α6 integrin to cellular processes in the FZD7 ectodomain expressing cells. The morphological and phenotype changes induced by FZD7 ectodomain expression in SK-CO-1 cells is thus consistent with the cells undergoing an epithelial-to-mesenchymal-like transition. Furthermore, initiation of tumor formation in a xenograft tumor growth assay was attenuated in the FZD7 ectodomain expressing cells. Our results indicate a pivotal role for endogenous FZD7 in morphology transitions that are associated with colon tumor initiation and progression.

Progression of human breast cancer cells from hormone-dependent to hormone-independent growth both in vitro and in vivo

We have isolated a series of sublines of the hormone-dependent MCF-7 human breast cancer cell line after selection both in vivo and in vitro for growth in the presence of subphysiological concentrations of estrogens. These sublines represent a model system for study of the processes leading to hormonal autonomy. The cells form growing tumors in ovariectomized athymic nude mice in the absence of estrogen supplementation but retain some responsivity to estrogen as determined by stimulation of the rate of tumor growth in vivo and by induction of progesterone receptor. An ovarian-independent but hormone-responsive phenotype may occur early in the natural progression to hormone-independent and unresponsive growth in breast cancer. We observed no change in the affinity or decrease in the level of expression of estrogen receptors and progesterone receptors among the sublines and the parental cells. Epidermal growth factor receptors are not overexpressed in ovarian-independent cells. Thus, altered hormone receptor expression may be a late event in the acquisition of a hormone-independent and unresponsive phenotype. Sublines isolated by in vivo but not in vitro selection are more invasive than the parental cells both in vivo and across an artificial basement membrane in vitro. Thus, as yet unknown tumor-host interactions may be important in the development of an invasive phenotype. Furthermore, acquisition of the ovarian-independent and invasive phenotypes can occur independently.

Epithelial mesenchymal transition traits in human breast cancer cell lines parallel the CD44HI/CD24lO/-stem cell phenotype in human breast cancer

We review here the recently emerging relationship between epithelial-mesenchymal transition (EMT) and breast cancer stem cells (BCSC), and provide analyses of published data on human breast cancer cell lines, supporting their utility as a model for the EMT/BCSC state. Genome-wide transcriptional profiling of these cell lines has confirmed the existence of a subgroup with mesenchymal tendencies and enhanced invasive properties ('Basal B'/Mesenchymal), distinct from subgroups with either predominantly luminal ('Luminal') or mixed basal/luminal ('Basal A') features (Neve et al. Cancer Cell, 2006). A literature-derived EMT gene signature has shown specific enrichment within the Basal B subgroup of cell lines, consistent with their over-expression of various EMT transcriptional drivers. Basal B cell lines are found to resemble BCSC, being CD44highCD24low. Moreover, gene products that distinguish Basal B from Basal A and Luminal cell lines (Basal B Discriminators) showed close concordance with those that define BCSC isolated from clinical material, as reported by Shipitsin et al. (Cancer Cell, 2007). CD24 mRNA levels varied across Basal B cell lines, correlating with other Basal B Discriminators. Many gene products correlating with CD24 status in Basal B cell lines were also differentially expressed in isolated BCSC. These findings confirm and extend the importance of the cellular product of the EMT with Basal B cell lines, and illustrate the value of analysing these cell lines for new leads that may improve breast cancer outcomes. Gene products specific to Basal B cell lines may serve as tools for the detection, quantification, and analysis of BCSC/EMT attributes.

Regulation of proliferation, invasion and growth factor synthesis in breast cancer by steroids

Endogenous ovarian estrogens and progestins appear to play a critical role in the development and progression of breast cancer. Local productions of growth factors probably also contribute to malignant proliferation, while production and activation of collagenolytic enzymes may be equally critical for local invasive processes. The current review focusses on characterization of growth factor-receptor systems operant in normal and malignant breast epithelium. In addition, the determinants of local invasion are reviewed: attachment, modality, and proteose secretion. Finally, data are discussed concerning the regulation of both proliferation and invasion by hormones and antihormonal agents in hormone-dependent breast cancer. The results suggest new potential pharmacologic targets to explore to suppress onset and progression of breast cancer.

Capital cost model for Robert evaporators

ROBERT EVAPORATORS in Australian sugar factories are traditionally constructed with 44.45 mm outside diameter stainless steel tubes of ~2 m length for all stages of evaporation. There are a few vessels with longer tubes (up to 2.8 m) and smaller and larger diameters (38.1 and 50.8 mm). Queensland University of Technology is undertaking a study to investigate the heat transfer performance of tubes of different lengths and diameters for the whole range of process conditions typically encountered in the evaporator set. Incorporation of these results into practical evaporator designs requires an understanding of the cost implications for constructing evaporator vessels with calandrias having tubes of different dimensions. Cost savings are expected for tubes of smaller diameter and longer length in terms of material, labour and installation costs in the factory. However these savings must be considered in terms of the heat transfer area requirements for the evaporation duty, which will likely be a function of the tube dimensions. In this paper a capital cost model is described which provides a relative cost of constructing and installing Robert evaporators of the same heating surface area but with different tube dimensions. Evaporators of 2000, 3000, 4000 and 5000 m2 are investigated. This model will be used in conjunction with the heat transfer efficiency data (when available) to determine the optimum tube dimensions for a new evaporator at a specified evaporation duty. Consideration is also given to other factors such as juice residence time (and implications for sucrose degradation and control) and droplet de-entrainment in evaporators of different tube dimensions.

Space within the surface : the patterned surfaces of Florence Broadhurst and Jim Thompson

The Woods Bagot 2007 refurbishment of the Qantas and British Airways Bangkok Business lounge in the Survarnabhumi Airport features wall finishes designed by wallpaper designer, Florence Broadhurst (1899-1977) and Thai Silk trader, Jim Thompson (1906-1967). This distinctive selection, which is proclaimed on the airport’s website, of patterned wall surfaces side by side draws attention to their striking similarities and their defining differences . Thompson and Broadhurst would appear to be worlds apart, but here in the airport their work brings them together. Thompson, the son of a wealthy cotton family in America, worked as an architect before joining the army. He moved to Bangkok to start The Thai Silk Company in 1948. Broadhurst was born on a farm in Mt. Perry, Queensland. She began her career as a performance artist, as part of an Australian troupe in Shanghai, moving onto pursue a career in fashion design, catering to the middle and upper classes in London. Upon her return to Australia, Broadhurst started a print design company in 1959. Both Broadhurst and Thompson pursued multiple careers, lived many lives, and died under mysterious circumstances. Broadhurst was murdered in 1977 at her Sydney print warehouse, which remains an unsolved crime. Thompson disappeared in Malaysia in 1967 and his body has never been found. This chapter investigates the parallels between Thompson and Broadhurst and what lead them to design such popular patterns for wall surfaces towards the end of their careers. While neither designer was a household name, their work is familiar to most, seen in the costume and set design of films, on the walls of restaurants and cafes and even in family homes. The reason for the popularity of their patterns has not previously been analysed. However, this chapter suggests that the patterns are intriguing because they contain something of their designers’ identities. It suggests that the coloured surface provides a way of camouflaging and hiding its subjects’ histories, such that Broadhurst and Thompson, consciously or unconsciously, used the patterned surface as a plane in which their past lives could be buried. The revealing nature of the stark white wall, compared with the forgiveness provided by the pattern in which to hide, is elaborated by painter and advocate for polychromatic architecture, Fernand Léger in his essay, “The Wall, The Architect, The Painter (1965).” Léger writes that, “the modern architect has gone too far in his magnificent attempts to cleanse through emptiness,” and that the resultant white walls of modernity create ‘an impalpability of air, of slick, brilliant new surfaces where nothing can be hidden any longer …even shadows don’t dare to enter’. To counter the exposure produced by the white wall, Thompson and Broadhurst designed patterned surfaces that could harbour their personal histories. Broadhurst and Thompson’s works share a number of commonalities in their design production, even though their work in print design commenced a decade apart. Both designers opted to work more with traditional methods of pattern making. Broadhurst used hand-operated screens, and Thompson outsourced work to local weavers and refrained from operating out of a factory. Despite humble beginnings, Broadhurst and Thompson enjoyed international success with their wall patterns being featured in a number of renowned international hotels in Bahrain, Singapore, Sydney, and London in the 1970s and 1980s. Their patterns were also transferred to fabric for soft furnishings and clothing. Thompson’s patterns were used for costumes in films including the King and I and Ben Hur. Broadhurst’s patterns were also widely used by fashion designers and artists, such as Akira Isogowa‘s costume design for Salome, a 1998 production by the Sydney Dance Company. Most recently her print designs have been used by skin illustrator Emma Hack, in a series of works painting female bodies into Broadhurst’s patterns. Hack’s works camouflage the models’ bodies into the patterned surface, assimilating subject and surface, hinting at there being something living within the patterned wall. More than four decades after Broadhurst’s murder and five decades since Thompson’s disappearance, their print designs persist as more than just a legacy. They are applied as surface finishes with the same fervour as when the designs were first released. This chapter argues that the reason for the ongoing celebration of their work is that there is the impalpable presence of the creator in the patterns. It suggests that the patterns blur the boundary between subject and surface.

Mice behaviorally selected for high Pavlovian fear memory exhibit fear generalization, HPA-axis alterations and increased basal activity in cortico-limbic circuits

Biological factors underlying individual variability in fearfulness and anxiety have important implications for stress-related psychiatric illness including PTSD and major depression. Using an advanced intercross line (AIL) derived from C57BL/6 and DBA/2J mouse strains and behavioral selection over 3 generations, we established two lines exhibiting High or Low fear behavior after fear conditioning. Across the selection generations, the two lines showed clear differences in training and tests for contextual and conditioned fear. Before fear conditioning training, there were no differences between lines in baseline freezing to a novel context. However, after fear conditioning High line mice demonstrated pronounced freezing in a new context suggestive of poor context discrimination. Fear generalization was not restricted to contextual fear. High fear mice froze to a novel acoustic stimulus while freezing in the Low line did not increase over baseline. Enhanced fear learning and generalization are consistent with transgenic and pharmacological disruption of the hypothalamic-pituitary-adrenal axis (HPA-axis) (Brinks, 2009, Thompson, 2004, Kaouane, 2012). To determine whether there were differences in HPA-axis regulation between the lines, morning urine samples were collected to measure basal corticosterone. Levels of secreted corticosterone in the circadian trough were analyzed by corticosterone ELISA. High fear mice were found to have higher basal corticosterone levels than low line animals. Examination of hormonal stress response components by qPCR revealed increased expression of CRH mRNA and decreased mRNA for MR and CRHR1 in hypothalamus of high fear mice. These alterations may contribute to both the behavioral phenotype and higher basal corticosterone in High fear mice. To determine basal brain activity in vivo in High and Low fear mice we used manganese-enhanced magnetic resonance imaging (MEMRI). Analysis revealed a pattern of basal brain activity made up of amygdala, cortical and hippocampal circuits that was elevated in the High line. Ongoing studies also seek to determine the relative balance of excitatory and inhibitory tone in the amygdala and hippocampus and the neuronal structure of its neurons. While these heterogeneous lines are selected on fear memory expression, HPA-axis alterations and differences in hippocampal activity segregate with the behavioral phenotypes. These differences are detectable in a basal state strongly suggesting these are biological traits underlying the behavioral phenotype (Johnson et al, 2011).

‘Only a pawn in their game’ : crime, risk and politics in the case of Robert Fardon

In 2003 Robert Fardon was the first prisoner to be detained under the Dangerous Prisoners (Sexual Offenders) Act 2003 (Qld), the first of the new generation preventive detention laws enacted in Australia and directed at keeping sex offenders in prison or under supervision beyond the expiry of their sentences where a court decides, on the basis of psychiatric assessments, that unconditional release would create an unacceptable risk to the community. A careful examination of Fardon’s case shows the extent to which the administration of the regime was from the outset governed by politics and political calculation rather than the logic of risk management and community protection. In 2003 Robert Fardon was the first person detained under the Dangerous Prisoners (Sexual Offenders) Act 2003 (Qld) (hereafter DPSOA), a newly enacted Queensland law aimed at the preventive detention of sex offenders. It was the first of a new generation of such laws introduced in Australia, now also in force in NSW, Western Australia and Victoria. The laws have been widely criticized by lawyers, academics and others (Keyzer and McSherry 2009; Edgely 2007). In this article I want to focus on the details of how the Queensland law was administered in Fardon’s case, he being perhaps the most well-known prisoner detained under such laws and certainly the longest held. It will show, I hope, that seemingly abstract rule of law principles invoked by other critics are not simply abstract: they afford a crucial practical safeguard against the corruption of criminal justice in which the ends both of community protection and of justice give way to opportunistic exploitation of ‘the mythic resonance of crime and punishment for electoral purposes’ (Scheingold 1998: 888).

The life of data: Evolving national testing

To this point, the collection has provided research-based, empirical accounts of the various and multiple effects of the National Assessment Program – Literacy and Numeracy (NAPLAN) in Australian schooling as a specific example of the global phenomenon of national testing. In this chapter, we want to develop a more theoretical analysis of national testing systems, globalising education policy and the promise of national testing as adaptive, online tests. These future moves claim to provide faster feedback and more useful diagnostic help for teachers. There is a utopian testing dream that one day adaptive, online tests will be responsive in real time providing an integrated personalised testing, pedagogy and intervention for each student. The moves towards these next generation assessments are well advanced, including the work of Pearson’s NextGen Learning and Assessment research group, the Organization for Economic Co-operation and Development’s (OECD) move into assessing affective skills and the Australian Curriculum, Assessment and Reporting Authority’s (ACARA) decision to phase in NAPLAN as an online, adaptive test from 2017...

National testing from an Australian perspective

Introduction This book examines a pressing educational issue: the global phenomenon of national testing in schooling and its vernacular development in Australia. The Australian National Assessment Program – Literacy and Numeracy (NAPLAN), introduced in 2008, involves annual census testing of students in Years 3, 5, 7 and 9 in nearly all Australian schools. In a variety of ways, NAPLAN affects the lives of Australia’s 3.5 million school students and their families, as well as more than 350,000 school staff and many other stakeholders in education. This book is organised in relation to a simple question: What are the effects of national testing for systems, schools and individuals? Of course, this simple question requires complex answers. The chapters in this edited collection consider issues relating to national testing policy, the construction of the test, usages of the testing data and various effects of testing in systems, schools and classrooms. Each chapter examines an aspect of national testing in Australia using evidence drawn from research. The final chapter by the editors of this collection provides a broader reflection on this phenomenon and situates developments in testing globally...

Local experiences, global similarities: Teacher perceptions of the impacts of national testing

Since 2008, Australian schoolchildren in Years 3, 5, 7 and 9 have sat a series of tests each May designed to assess their attainment of basic skills in literacy and numeracy. These tests are known as the National Assessment Program – Literacy and Numeracy (NAPLAN). In 2010, individual school NAPLAN data were first published on the MySchool website which enables comparisons to be made between individual schools and statistically like schools across Australia. NAPLAN represents the increased centrality of the federal government in education, particularly in regards to education policy. One effect of this has been a recast emphasis of education as an economic, rather than democratic, good. As Reid (2009) suggests, this recasting of education within national productivity agendas mobilises commonsense discourses of accountability and transparency. These are common articles of faith for many involved in education administration and bureaucracy; more and better data, and holding people to account for that data, must improve education...

The influence of Lord Robert Baden-Powell on the development of the Boy Scout Movement with observations on its operation in Queensland 1907-1937

The purpose of the Boy Scout Movement was to create boys who were honest, obedient to constituted authority and loyal to the King and the British Empire. This thesis examines the influence that Scouting's founder, Lord Robert Baden-Powell, had on the development of Scouting in Queensland in the period 1907 to 1937, and concludes that that influence was profound. Baden-Powell conceived the Boy Scout Movement, and its non-formal educative method as an answer to some of the social, economic, and political problems at the beginning of the twentieth century – a paradigm recognised and acknowledged by educators of the day.

Relocating the American Dream : The America of the 1960s as Portrayed by the New Journalists Norman Mailer, Hunter S. Thompson, and Tom Wolfe

The concept of the American Dream was subject to a strong re-evaluation process in the 1960s, as counterculture became a prominent force in American society. A massive generation of young people, moved by the Vietnam War, the hippie movement, and psychedelic experimentation, created substantial social turbulence in their efforts to break out of conventional patterns and to create a new kind of society. This thesis outlines and analyses the concept of the American Dream in popular imagination through three works of new journalism. My primary data consists of Tom Wolfe’s The Electric Kool-Aid Acid Test (1967), Hunter S. Thompson’s Fear and Loathing in Las Vegas: A Savage Journey to the Heart of the American Dream (1971), and Norman Mailer’s Armies of the Night: History as a Novel, the Novel as History (1968). In defining the American Dream, I discuss the history of the concept as well as its manifestations in popular culture. Because of its elusive and amorphous nature, the concept of the American Dream can only be examined in cultural texts that portray the values, sentiments, and customs of a certain era. I have divided the analytical section of my thesis into three parts. In the first part I examine how the authors discuss the American society of their time in relation to ideology, capitalism, and the media. In the second part I focus on the Vietnam War and the controversy it creates in relation to the notions of freedom and patriotism. In the third part I discuss how the authors portray the countercultural visions of a better America that challenged the traditional interpretations of the American Dream. I also discuss the dark side of the new dream: the problems and disillusions that came with the effort to change the world. This thesis is an effort to trace the relocation of the American Dream in the context of the 1960s counterculture and new journalism. It hopes to provide a valuable addition to the cultural history of the sixties and to the effort of conceptualizing the American Dream.