Organic and acquisitive employment growth : re-examining,testing and extending Penrose's Growth Theory.

Edith Penrose’s theory of firm growth postulates that a firm’s current growth rate will be influenced by the adjustment costs of, and changes to a firm’s productive opportunity set arising from, previous growth. Although she explicitly considered the impact of previous organic growth on current organic growth, she was largely silent about the impact of previous acquisitive growth. In this paper we extend Penrose’s work to examine that the relative impact of organic and acquisitive growth on the adjustment costs and productive opportunity set of the firm. Employing a panel of commercially active enterprises in Sweden over a 10 year period our results suggest the following. First, previous organic growth acts as a constraint on current organic growth. Second, previous acquisitive growth has a positive effect on current organic growth. We conclude that organic growth and acquisitive growth constitute two distinct strategic options facing the firm, which have a differential impact on the future organic growth of the firm.

The genetic basis of human height : the role of estrogen

Height is a complex physical trait that displays strong heritability. Adult height is related to length of the long bones, which is determined by growth at the epiphyseal growth plate. Longitudinal bone growth occurs via the process of endochondral ossification, where bone forms over the differentiating cartilage template at the growth plate. Estrogen plays a major role in regulating longitudinal bone growth and is responsible for inducing the pubertal growth spurt and fusion of the epiphyseal growth plate. However, the mechanism by which estrogen promotes epiphyseal fusion is poorly understood. It has been hypothesised that estrogen functions to regulate growth plate fusion by stimulating chondrocyte apoptosis, angiogenesis and bone cell invasion in the growth plate. Another theory has suggested that estrogen exposure exhausts the proliferative capacity of growth plate chondrocytes, which accelerates the process of chondrocyte senescence, leading to growth plate fusion. The overall objective of this study was to gain a greater understanding of the molecular mechanisms behind estrogen-mediated growth and height attainment by examining gene regulation in chondrocytes and the role of some of these genes in normal height inheritance. With the heritability of height so well established, the initial hypothesis was that genetic variation in candidate genes associated with longitudinal bone growth would be involved in normal adult height variation. The height-related genes FGFR3, CBFA1, ER and CBFA1 were screened for novel polymorphisms using denaturing HPLC and RFLP analysis. In total, 24 polymorphisms were identified. Two SNPs in ER (rs3757323 C>T and rs1801132 G>C) were strongly associated with adult male height and displayed an 8 cm and 9 cm height difference between homozygous genotypes, respectively. The TC haplotype of these SNPs was associated with a 6 cm decrease in height and remarkably, no homozygous carriers of the TC haplotype were identified in tall subjects. No significant associations with height were found for polymorphisms in the FGFR3, CBFA1 or VDR genes. In the epiphyseal growth plate, chondrocyte proliferation, matrix synthesis and chondrocyte hypertrophy are all major contributors to long bone growth. As estrogen plays such a significant role in both growth and final height attainment, another hypothesis of this study was that estrogen exerted its effects in the growth plate by influencing chondrocyte proliferation and mediating the expression of chondrocyte marker genes. The examination of genes regulated by estrogen in chondrocyte-like cells aimed to identify potential regulators of growth plate fusion, which may further elucidate mechanisms involved in the cessation of linear growth. While estrogen did not dramatically alter the proliferation of the SW1353 cell line, gene expression experiments identified several estrogen regulated genes. Sixteen chondrocyte marker genes were examined in response to estrogen concentrations ranging from 10-12 M to 10-8 M over varying time points. Of the genes analysed, IHH, FGFR3, collagen II and collagen X were not readily detectable and PTHrP, GHR, ER, BMP6, SOX9 and TGF1 mRNAs showed no significant response to estrogen treatments. However, the expression of MMP13, CBFA1, BCL-2 and BAX genes were significantly decreased. Interestingly, the majority of estrogen regulated genes in SW1353 cells are expressed in the hypertrophic zone of the growth plate. Estrogen is also known to regulate systemic GH secretion and local GH action. At the molecular level, estrogen functions to inhibit GH action by negatively regulating GH signalling. GH treated SW1353 cells displayed increases in MMP9 mRNA expression (4.4-fold) and MMP13 mRNA expression (64-fold) in SW1353 cells. Increases were also detected in their respective proteins. Treatment with AG490, an established JAK2 inhibitor, blocked the GH mediated stimulation of both MMP9 and MMP13 mRNA expression. The application of estrogen and GH to SW1353 cells attenuated GH-stimulated MMP13 levels, but did not affect MMP9 levels. Investigation of GH signalling revealed that SW1353 cells have high levels of activated JAK2 and exposure to GH, estrogen, AG490 and other signalling inhibitors did not affect JAK2 phosphorylation. Interestingly, AG490 treatment dramatically decreased ERK2 signalling, although GH did stimulate ERK2 phosphorylation above control levels. AG490 also decreased CBFA1 expression, a transcription factor known to activate MMP9 and MMP13. Finally, GH and estrogen treatment increased expression of SOCS3 mRNA, suggesting that SOCS3 may regulate JAK/STAT signalling in SW1353 cells. The modulation of GH-mediated MMP expression by estrogen in SW1353 cells represents a potentially novel mechanism by which estrogen may regulate longitudinal bone growth. However, further investigation is required in order to elucidate the precise mechanisms behind estrogen and GH regulation of MMP13 expression in SW1353 cells. This study has provided additional evidence that estrogen and the ER gene are major factors in the regulation of growth and the determination of adult height. Newly identified polymorphisms in the ER gene not only contribute to our understanding of the genetic basis of human height, but may also be useful in association studies examining other complex traits. This study also identified several estrogen regulated genes and indicated that estrogen modifies the expression of genes which are primarily expressed in the hypertrophic region of the epiphyseal growth plate. Furthermore, synergistic studies incorporating GH and estrogen have revealed the ability of estrogen to attenuate the effects of GH on MMP13 expression, revealing potential pathways by which estrogen may modulate growth plate fusion, longitudinal bone growth and even arthritis.

Tests of the elaborated intrusion theory of craving and desire : features of alcohol craving during treatment for an alcohol disorder

Objectives. We tested predictions from the elaborated intrusion (EI) theory of desire, which distinguishes intrusive thoughts and elaborations, and emphasizes the importance of imagery. Secondarily, we undertook preliminary evaluations of the Alcohol Craving Experience (ACE) questionnaire, a new measure based on EI Theory. Methods. Participants (N ¼ 232) were in correspondence-based treatment trials for alcohol abuse or dependence. The study used retrospective reports obtained early in treatment using the ACE, and daily self-monitoring of urges, craving, mood and alcohol consumption. Results. The ACE displayed high internal consistency and test – retest reliability and sound relationships with self-monitored craving, and was related to Baseline alcohol dependence, but not to consumption. Imagery during craving was experienced by 81%,with 2.3 senses involved on average. More frequent imagery was associated with longer episode durations and stronger craving. Transient intrusive thoughts were reported by 87% of respondents, and were more common if they frequently attempted to stop alcohol cognitions. Associations between average daily craving and weekly consumption were seen. Depression and negative mood were associated with more frequent, stronger and longer lasting desires for alcohol. Conclusions. Results supported the distinction of automatic and controlled processes in craving, together with the importance of craving imagery. They were also consistent with prediction of consumption from cross-situational averages of craving, and with positive associations between craving and negative mood. However, this study’s retrospective reporting and correlational design require that its results be interpreted cautiously. Research using ecological momentary measures and laboratory manipulations is needed before confident inferences about causality can be made.

Theory and its role in mathematics education

The increased recognition of the theory in mathematics education is evident in numerous handbooks, journal articles, and other publications. For example, Silver and Herbst (2007) examined ―Theory in Mathematics Education Scholarship‖ in the Second Handbook of Research on Mathematics Teaching and Learning (Lester, 2007) while Cobb (2007) addressed ―Putting Philosophy to Work: Coping with Multiple Theoretical Perspectives‖ in the same handbook. And a central component of both the first and second editions of the Handbook of International Research in Mathematics Education (English, 2002; 2008) was ―advances in theory development.‖ Needless to say, the comprehensive second edition of the Handbook of Educational Psychology (Alexander & Winne, 2006) abounds with analyses of theoretical developments across a variety of disciplines and contexts. Numerous definitions of ―theory‖ appear in the literature (e.g., see Silver & Herbst, in Lester, 2007). It is not our intention to provide a ―one-size-fits-all‖ definition of theory per se as applied to our discipline; rather we consider multiple perspectives on theory and its many roles in improving the teaching and learning of mathematics in varied contexts.

Modulation of the SHBG signalling axis

Sex hormone-binding globulin (SHBG) is a homodimeric plasma glycoprotein that is the major sex steroid carrier-protein in the bloodstream and functions also as a key regulator of steroid bioavailability within target tissues, such as the prostate. Additionally, SHBG binds to prostatic cell membranes via the putative and unidentified SHBG receptor (RSHBG), activating a signal transduction pathway implicated in stimulating both proliferation and expression of prostate specific antigen (PSA) in prostate cell lines in vitro. A yeast-two hybrid assay suggested an interaction between SHBG and kallikrein-related protease (KLK) 4, which is a serine protease implicated in the progression of prostate cancer. The potential interaction between these two proteins was investigated in this PhD thesis to determine whether SHBG is a proteolytic substrate of KLK4 and other members of the KLK family including KLK3/PSA, KLK7 and KLK14. Furthermore, the effects from SHBG proteolytic degradation on SHBG-regulated steroid bioavailability and the activation of the putative RSHBG signal transduction pathway were examined in the LNCaP prostate cancer cell line. SHBG was found to be a proteolytic substrate of the trypsin-like KLK4 and KLK14 in vitro, yielding several proteolysis fragments. Both chymotrypsin-like PSA and KLK7 displayed insignificant proteolytic activity against SHBG. The kinetic parameters of SHBG proteolysis by KLK4 and KLK14 demonstrate a strong enzyme-substrate binding capacity, possessing a Km of 1.2 ± 0.7 µM and 2.1 ± 0.6 µM respectively. The catalytic efficiencies (kcat/Km) of KLK4 and KLK14 proteolysis of SHBG were 1.6 x 104 M-1s-1 and 3.8 x 104 M-1s-1 respectively, which were comparable to parameters previously reported for peptide substrates. N-terminal sequencing of the fragments revealed cleavage near the junction of the N- and C-terminal laminin globulin-like (G-like) domains of SHBG, resulting in the division of the two globulins and ultimately the full degradation of these fragments by KLK4 and KLK14 over time. Proteolytic fragments that may retain steroid binding were rapidly degraded by both proteases, while fragments containing residues beyond the steroid binding pocket were less degraded over the same period of time. Degradation of SHBG was inhibited by the divalent metal cations calcium and zinc for KLK4, and calcium, zinc and magnesium for KLK14. The human secreted serine protease inhibitors (serpins), α1-antitrypsin and α2-antiplasmin, inhibited KLK4 and KLK14 proteolysis of SHBG; α1-antichymotrypsin inhibited KLK4 but not KLK14 activity. The inhibition by these serpins was comparable and in some cases more effective than general trypsin protease inhibitors such as aprotinin and phenylmethanesulfonyl fluoride (PMSF). The binding of 5α-dihydrotestosterone (DHT) to SHBG modulated interactions with KLK4 and KLK14. Steroid-free SHBG was more readily digested by both enzymes than DHT-bound SHBG. Moreover, a binding interaction exists between SHBG and pro-KLK4 and pro-KLK14, with DHT strengthening the binding to pro-KLK4 only. The inhibition of androgen uptake by cultured prostate cancer cells, mediated by SHBG steroid-binding, was examined to assess whether SHBG proteolysis by KLK4 and KLK14 modulated this process. Proteolytic digestion eliminated the ability of SHBG to inhibit the uptake of DHT from conditioned media into LNCaP cells. Therefore, the proteolysis of SHBG by KLK4 and KLK14 increased steroid bioavailability in vitro, leading to an increased uptake of androgens by prostate cancer cells. Interestingly, different transcriptional responses of PSA and KLK2, which are androgen-regulated genes, to DHT-bounsd SHBG treatment were observed between low and high passage number LNCaP cells (lpLNCaP and hpLNCaP respectively). HpLNCaP cells treated with DHT-bound SHBG demonstrated a significant synergistic upregulation of PSA and KLK2 above DHT or SHBG treatment alone, which is similar to previously reported downstream responses from RSHBG-mediated signaling activation. As this result was not seen in lpLNCaP cells, only hpLNCaP cells were further investigated to examine the modulation of potential RSHBG activity by KLK4 and KLK14 proteolysis of SHBG. Contrary to reported results, no increase in intracellular cAMP was observed in hpLNCaP cells when treated with SHBG in the presence and absence of either DHT or estradiol. As a result, the modulation of RSHBG-mediated signaling activation could not be determined. Finally, the identification of the RSHBG from both breast (MCF-7) and prostate cancer (LNCaP) cell lines was attempted. Fluorescently labeled peptides corresponding to the putative receptor binding domain (RBD) of SHBG were shown to be internalized by MCF-7 cells. Crosslinking of the RBD peptide to the cell surfaces of both MCF-7 and LNCaP cells, demonstrated the interaction of the peptide with several targets. These targets were then captured using RBD peptides synthesized onto a hydrophilic scaffold and analysed by mass spectrometry. The samples captured by the RBD peptide returned statistically significantly matches for cytokeratin 8, 18 and 19 as well as microtubule-actin crosslinking factor 1, which may indicate a novel interaction between SHBG and these proteins, but ultimately failed to detect a membrane receptor potentially responsible for the putative RSHBG-mediated signaling. This PhD project has reported the proteolytic processing of SHBG by two members of the kallikrein family, KLK4 and KLK14. The effect of SHBG proteolysis by KLK4 and KLK14 on RSHBG-mediated signaling activation was unable to be determined as the reported signal transduction pathway was not activated after treatment with SHBG, in combination with either DHT or estradiol. However, the digestion of SHBG by these two proteases positively regulated androgen bioavailability to prostate cancer cells in vitro. The increased uptake of androgens is deleterious in prostate cancer due to the promotion of proliferation, metastasis, invasion and the inhibition of apoptosis. The increased bioavailability of androgens, from SHBG proteolysis by KLK4 and KLK14, may therefore promote both carcinogenesis and progression of prostate cancer. Finally, this information may contribute to the development of therapeutic treatment strategies for prostate cancer by inhibiting the proteolysis of SHBG, by KLK4 and KLK14, to prevent the increased uptake of androgens by hormone-dependent cancerous tissues.

Imaginary relish and exquisite torture : the elaborated intrusion theory of desire

The authors argue that human desire involves conscious cognition that has strong affective connotation and is potentially involved in the determination of appetitive behavior rather than being epiphenomenal to it. Intrusive thoughts about appetitive targets are triggered automatically by external or physiological cues and by cognitive associates. When intrusions elicit significant pleasure or relief, cognitive elaboration usually ensues. Elaboration competes with concurrent cognitive tasks through retrieval of target related information and its retention in working memory. Sensory images are especially important products of intrusion and elaboration because they simulate the sensory and emotional qualities of target acquisition. Desire images are momentarily rewarding but amplify awareness of somatic and emotional deficits. Effects of desires on behavior are moderated by competing incentives, target availability, and skills. The theory provides a coherent account of existing data and suggests new directions for research and treatment.

Critical Systems Theory: A Political Economy of Language, Thought, and Technology

An emergent form of political economy, facilitated by information and communication technologies (ICTs), is widely propagated as the apotheosis of unmitigated social, economic, and technological progress. Meanwhile, throughout the world, social degradation and economic inequality are increasing logarithmically. Valued categories of thought are, axiomatically, the basic commodities of the “knowledge economy”. Language is its means of exchange. This paper proposes a sociolinguistic method with which to critically engage the hyperbole of the “Information Age”. The method is grounded in a systemic social theory that synthesises aspects of autopoiesis and Marxist political economy. A trade policy statement is analysed to exemplify the sociolinguistically created aberrations that are today most often construed as social and political determinants.

Re-assessing streetkids : a critique of subculture theory

Focusing on the notion of street kids, the paper suggests that youth be viewed in an alternative way to the subculture theory associated with the Center for Contemporary Cultural Studies in Birmingham (CCCS). It is argued that not only is subculture theory an unsuitable mechanism for understanding homeless youth but also, and more importantly, is itself fundamentally problematic. It is suggested that the work of Michel Foucault necessitates a reevaluation of the domain assumptions underlying subculture theory and offers in its place a model that relocates street kids, and youth itself, as artifacts of a network of governmental strategies.

Education research and youth subculture theory

Recent theoretical developments (particularly those involving the work of Michel Foucault) have challenged the foundations upon which subcultural analysis is built. It is not the intention of this paper to take issue with the underpinning neo-Marxist assumptions concerning hegemony, consciousness and culture. Rather, the intention is simply to problematise the use of subculture theory in terms of its totalising, normalising and dichotomising nature.

Southern theory and its dynamics for postcolonial education

This paper discusses how the exploration of social texts and historical contexts from the global 'South', as put forward in Raewyn Connell's study 'Southern Theory' (2007), can improve the theoretical tools used in postcolonial education analysis. Connell analyses a selection of excellent and compelling social theory texts written by scholars in Africa, India, Iran, Latin America and Australia to show how they challenge and counter the silences, distortions and plain lies of dominant Western social theory. These texts of the global South do not mince words in laying bare the role of the institutions and elites of the West in the destruction, dispossession, and bloodshed involved in creating the world in which we live, and in perpetuating its catastrophes. The texts also reveal intense debates between scholars over their conceptualisations of local, national and global society. My paper argues that this kind of work is of vital importance to postcolonial studies in education. It helps education scholars to uncover the problematic assumptions and distortions of dominant education thought, and understand different ways of seeing. Postcolonial educators could use this to help both students and teacher unlearn many of our taught perceptions of the world, whether in the global North or the global South. Developing a countervailing social theory in education would sharpen our questioning of the structures of schooling as they relate to society, and tease out new dimensions of postcolonial leadership for education.

Applying Stafford and Warr’s Reconceptualization of Deterrence Theory to drug driving : can it predict those likely to offend?

In December 2007, random roadside drug testing commenced in Queensland, Australia. Subsequently, the aim of this study was to explore the preliminary impact of Queensland’s drug driving legislation and enforcement techniques by applying Stafford and Warr’s [Stafford, M. C., & Warr, M. (1993). A reconceptualization of general and specific deterrence. Journal of Research in Crime and Delinquency, 30, 123-135] reconceptualization of deterrence theory. Completing a comprehensive drug driving questionnaire were 899 members of the public, university students, and individuals referred to a drug diversion program. Of note was that approximately a fifth of participants reported drug driving in the past six months. Additionally, the analysis indicated that punishment avoidance and vicarious punishment avoidance were predictors of the propensity to drug drive in the future. In contrast, there were indications that knowing of others apprehended for drug driving was not a sufficient deterrent. Sustained testing and publicity of the legislation and countermeasure appears needed to increase the deterrent impact for drug driving.

Boys 'doing' and 'undoing' media education : new possibilities for theory and practice

The purpose of this study is to investigate how secondary school media educators might best meet the needs of students who prefer practical production work to ‘theory’ work in media studies classrooms. This is a significant problem for a curriculum area that claims to develop students’ media literacies by providing them with critical frameworks and a metalanguage for thinking about the media. It is a problem that seems to have become more urgent with the availability of new media technologies and forms like video games. The study is located in the field of media education, which tends to draw on structuralist understandings of the relationships between young people and media and suggests that students can be empowered to resist media’s persuasive discourses. Recent theoretical developments suggest too little emphasis has been placed on the participatory aspects of young people playing with, creating and gaining pleasure from media. This study contributes to this ‘participatory’ approach by bringing post structuralist perspectives to the field, which have been absent from studies of secondary school media education. I suggest theories of media learning must take account of the ongoing formation of students’ subjectivities as they negotiate social, cultural and educational norms. Michel Foucault’s theory of ‘technologies of the self’ and Judith Butler’s theories of performativity and recognition are used to develop an argument that media learning occurs in the context of students negotiating various ‘ethical systems’ as they establish their social viability through achieving recognition within communities of practice. The concept of ‘ethical systems’ has been developed for this study by drawing on Foucault’s theories of discourse and ‘truth regimes’ and Butler’s updating of Althusser’s theory of interpellation. This post structuralist approach makes it possible to investigate the ways in which students productively repeat and vary norms to creatively ‘do’ and ‘undo’ the various media learning activities with which they are required to engage. The study focuses on a group of year ten students in an all boys’ Catholic urban school in Australia who undertook learning about video games in a three-week intensive ‘immersion’ program. The analysis examines the ethical systems operating in the classroom, including formal systems of schooling, informal systems of popular cultural practice and systems of masculinity. It also examines the students’ use of semiotic resources to repeat and/or vary norms while reflecting on, discussing, designing and producing video games. The key findings of the study are that students are motivated to learn technology skills and production processes rather than ‘theory’ work. This motivation stems from the students’ desire to become recognisable in communities of technological and masculine practice. However, student agency is not only possible through critical responses to media, but through performative variation of norms through creative ethical practices as students participate with new media technologies. Therefore, the opportunities exist for media educators to create the conditions for variation of norms through production activities. The study offers several implications for media education theory and practice including: the productive possibilities of post structuralism for informing ways of doing media education; the importance of media teachers having the autonomy to creatively plan curriculum; the advantages of media and technology teachers collaborating to draw on a broad range of resources to develop curriculum; the benefits of placing more emphasis on students’ creative uses of media; and the advantages of blending formal classroom approaches to media education with less formal out of school experiences.