Knowledge Based Urban Development

The changing and challenging conditions of the 21st century have been significantly impacting our economy, society and built and natural environments. Today generation of knowledge—mostly in the form of technology and innovation—is seen as a panacea for the adaptation to changes and management of challenges (Yigitcanlar, 2010a). Making space and place that concentrate on knowledge generation, thus, has become a priority for many nations (van Winden, 2010). Along with this movement, concepts like knowledge cities and knowledge precincts are coined as places where citizenship undertakes a deliberate and systematic initiative for founding its development on the identification and sustainable balance of its shared value system, and bases its ability to create wealth on its capacity to generate and leverage its knowledge capabilities (Carrillo, 2006; Yigitcanlar, 2008a). In recent years, the term knowledge precinct (Hu & Chang, 2005) in its most contemporary interpretation evolved into knowledge community precinct (KCP). KCP is a mixed-use post-modern urban setting—e.g., flexible, decontextualized, enclaved, fragmented—including a critical mass of knowledge enterprises and advanced networked infrastructures, developed with the aim of collecting the benefits of blurring the boundaries of living, shopping, recreation and working facilities of knowledge workers and their families. KCPs are the critical building blocks of knowledge cities, and thus, building successful KCPs significantly contributes to the formation of prosperous knowledge cities. In the literature this type of development���a place containing economic prosperity, environmental sustainability, just socio‐spatial order and good governance—is referred as knowledge-based urban development (KBUD). This chapter aims to provide a conceptual understanding on KBUD and its contribution to the building of KCPs that supports the formation of prosperous knowledge cities.

The function of the RNA-binding protein TEL1 in moss reveals ancient regulatory mechanisms of shoot development

The shoot represents the basic body plan in land plants. It consists of a repeated structure composed of stems and leaves. Whereas vascular plants generate a shoot in their diploid phase, non-vascular plants such as mosses form a shoot (called the gametophore) in their haploid generation. The evolution of regulatory mechanisms or genetic networks used in the development of these two kinds of shoots is unclear. TERMINAL EAR1-like genes have been involved in diploid shoot development in vascular plants. Here, we show that disruption of PpTEL1 from the moss Physcomitrella patens, causes reduced protonema growth and gametophore initiation, as well as defects in gametophore development. Leafy shoots formed on ΔTEL1 mutants exhibit shorter stems with more leaves per shoot, suggesting an accelerated leaf initiation (shortened plastochron), a phenotype shared with the Poaceae vascular plants TE1 and PLA2/LHD2 mutants. Moreover, the positive correlation between plastochron length and leaf size observed in ΔTEL1 mutants suggests a conserved compensatory mechanism correlating leaf growth and leaf initiation rate that would minimize overall changes in plant biomass. The RNA-binding protein encoded by PpTEL1 contains two N-terminus RNA-recognition motifs, and a third C-terminus non-canonical RRM, specific to TEL proteins. Removal of the PpTEL1 C-terminus (including this third RRM) or only 16–18 amino acids within it seriously impairs PpTEL1 function, suggesting a critical role for this third RRM. These results show a conserved function of the RNA-binding PpTEL1 protein in the regulation of shoot development, from early ancestors to vascular plants, that depends on the third TEL-specific RRM.

The function of Bmps and Runx2 in normal tooth development and in the pathogenesis of cleidocranial dysplasia

The development of many embryonic organs is regulated by reciprocal and sequential epithelial-mesenchymal interactions. These interactions are mediated by conserved signaling pathways that are reiteratively used. Cleidocranial dysplasia (CCD) is a congenital syndrome where both bone and tooth development is affected. The syndrome is characterized by short stature, abnormal clavicles, general bone dysplasia, and supernumerary teeth. CCD is caused by mutations in RUNX2, a transcription factor that is a key regulator of osteoblast differentiation and bone formation. The first aim of this study was to analyse the expression of a family of key signal molecules, Bone morphogenetic protein (Bmp) at different stages of tooth development. Bmps have a variety of functions and they were originally discovered as signals inducing ectopic bone formation. We performed a comparative in situ hybridisation analysis of the mRNA expression of Bmp2-7 from initiation of tooth development to differentiation of dental hard tissues. The expression patterns indicated that the Bmps signal between the epithelial and mesenchymal tissues during initiation and morphogenesis of tooth development, as well as during the differentiation of odontoblasts and ameloblasts. Furthermore, they are also part of the signalling networks whereby the enamel knot regulates the patterning of tooth cusps. The second aim was to study the role of Runx2 during tooth development and thereby to gain better understanding of the pathogenesis of the tooth phenotype in CCD. We analysed the tooth phenotype of Runx2 knockout mice and examined the patterns and regulation of Runx2 gene expression.. The teeth of wild-type and Runx2 mutant mice were compared by several methods including in situ hybridisation, tissue culture, bead implantation experiments, and epithelial-mesenchymal recombination studies. Phenotypic analysis of Runx2 -/- mutant tooth development showed that teeth failed to advance beyond the bud stage. Runx2 expression was restricted to dental mesenchyme between the bud and early bell stages of tooth development and it was regulated by epithelial signals, in particular Fgfs. We searched for downstream targets of Runx2 by comparative in situ hybridisation analysis. The expression of Fgf3 was downregulated in the mesenchyme of Runx2 -/- teeth. Shh expression was absent from the enamel knot in the lower molars of Runx2 -/- and reduced in the upper molars. In conclusion, these studies showed that Runx2 regulates key epithelial-mesenchymal interactions that control advancing tooth morphogenesis and histodifferentiation of the epithelial enamel organ. In addition, in the upper molars of Runx2 mutants extra buddings occured at the palatal side of the tooth bud. We suggest that Runx2 acts as an inhibitor of successional tooth formation by preventing advancing development of the buds. Accordingly, we propose that RUNX2 haploinsuffiency in humans causes incomplete inhibition of successional tooth formation and as a result supernumerary teeth.

The social tasks of learning to become a physical education teacher: Considering the HPE subject department as a community of practice

Initial teacher education (ITE) students participate in various workplaces within schools and in doing so, form understandings about the numerous, and at times competing, expectations of teachers’ work. Through these experiences they form understandings about themselves as health and physical education (HPE) teachers. This paper examines the ways communities of practice within HPE subject department offices function as sites of workplace learning for student teachers. In particular this research focused on how ITE students negotiate tacit and contradictory expectations as well as social tasks during the practicum and the ways in which their understandings are mediated through participation in the workspace. Qualitative methods of survey and semi-structured interview were used to collect data on a cohort of student teachers during and following their major (10 week) practicum experience. Analysis was informed by theories of communities of practice (Wenger, 1998), workplace learning (Billett, 2001), and social task systems (Doyle, 1977). It was evident that considerable effort, attention, and energy was expended on various interrelated social tasks aimed at building positive relationships with their supervisor and other HPE teachers at the school. The social dynamics were highly nuanced and required a game-like approach. In our view the complexity that student teachers must negotiate in striving for an excellent evaluation warrants specific attention in physical education teacher education (PETE) programs. This study raises questions regarding our responsibilities in sending student teachers into contexts that might even be described as toxic. We offer some suggestions for how PETE might better support students going into practicum contexts that might be regarded as problematic workplaces.

Corporate social responsibilities of Indian public sector enterprises-a case study of Bharat Heavy Electricals Limited (BHEL)

The high level of public accountability attached to Public Sector Enterprises as a result of public ownership makes them socially responsible. The Committee of Public Undertakings in 1992 examined the issue relating to social obligations of Central Public Sector Enterprises and observed that ``being part of the `State', every Public Sector enterprise has a moral responsibility to play an active role in discharging the social obligations endowed on a welfare state, subject to the financial health of the enterprise''. It issued the Corporate Social Responsibility Guidelines in 2010 where all Central Public Enterprises, through a Board Resolution, are mandated to create a CSR budget as a specified percentage of net profit of the previous year. This paper examines the CSR activities of the biggest engineering public sector organization in India, Bharath Heavy Electricals Limited. The objectives are twofold, one, to develop a case study of the organization about the funds allocated and utilized for various CSR activities, and two, to examine its status with regard to other organizations, the 2010 guidelines, and the local socio-economic development. Secondary data analysis results show three interesting trends. One, it reveals increasing organizational social orientation with the formal guidelines in place. Two, Firms can no longer continue to exploit environmental resources and escape from their responsibilities by acting separate entities regardless of the interest of the society and Three the thrust of CSR in public sector is on inclusive growth, sustainable development and capacity building with due attention to the socio-economic needs of the neglected and marginalized sections of the society.

MicroRNA-132 is a physiological regulator of hematopoietic stem cell function and B-cell development

MicroRNAs are a class of small non-coding RNAs that negatively regulate gene expression. Several microRNAs have been implicated in altering hematopoietic cell fate decisions. Importantly, deregulation of many microRNAs can lead to deleterious consequences in the hematopoietic system, including the onset of cancer, autoimmunity, or a failure to respond effectively to infection. As such, microRNAs fine-tune the balance between normal hematopoietic output and pathologic consequences. In this work, we explore the role of two microRNAs, miR-132 and miR-125b, in regulating hematopoietic stem cell (HSC) function and B cell development. In particular, we uncover the role of miR-132 in maintaining the appropriate balance between self-renewal, differentiation, and survival in aging HSCs by buffering the expression of a critical transcription factor, FOXO3. By maintain this balance, miR-132 may play a critical role in preventing aging-associated hematopoietic conditions such as autoimmune disease and cancer. We also find that miR-132 plays a critical role in B cell development by targeting a key transcription factor, Sox4, that is responsible for the differentiation of pro-B cells into pre-B cells. We find that miR-132 regulates B cell apoptosis, and by delivering miR-132 to mice that are predisposed to developing B cell cancers, we can inhibit the formation of these cancers and improve the survival of these mice. In addition to miR-132, we uncovered the role of another critical microRNA, miR-125b, that potentiates hematopoietic stem cell function. We found that enforced expression of miR-125b causes an aggressive myeloid leukemia by downregulation of its target Lin28a. Importantly, miR-125b also plays a critical role in inhibiting the formation of pro-B cells. Thus, we have discovered two microRNAs with important roles in regulating normal hematopoiesis, and whose dregulation can lead to deleterious consequences such as cancer in the aging hematopoietic system. Both miR-132 and miR-125b may therefore be targeted for therapeutics to inhibit age-related immune diseases associated with the loss of HSC function and cancer progression.

O direito ao entretenimento na função social da cidade

O art. 6 da Constituição Federal estabelece que o lazer é um direito social. A referida proteção constitucional conquistada com a Carta Cidadã de 1988, somada a previsão internacional da Declaração Universal dos Direitos Humanos por si só ensejam a elaboração de estudo detalhado do tema. Além disso, a ascensão de uma nova classe média com maior poder de consumo, a efervescência da terceira revolução industrial e a eleição do Brasil, e especificamente da cidade do Rio de Janeiro, como sede de diversos eventos de entretenimento internacional, são os argumentos que introduzem o estudo a cidade e a satisfação do direito ao (do) entretenimento. Assim, a partir da conceituação de entretenimento à luz da comparação com as outras ciências humanas e o direito alienígena, enseja-se a propositura de um conceito próprio para o ordenamento jurídico pátrio, que delimita os deveres do Estado na satisfação deste direito, e na regulação e fomento da atividade econômica que circundam o lazer, denominada indústria do entretenimento. O estudo aborda ainda a compreensão de que a cidade pode ser concebida como oikos do entretenimento, permitindo uma análise das formas como as cidades devem comportar conteúdo mínimo que viabilize a satisfação do lazer. Ao final, tendo por paradigma a cidade do Rio de Janeiro, se analisa como determinadas cidade podem possuir características geográficas, históricas e culturais próprias que permitem que sua vocação econômica seja a satisfação do entretenimento em nível internacional.

Poder local, cidadania e participação popular no município de Maricá: uma análise crítica das regras do jogo

O tema que nos propomos a estudar é o Poder local, cidadania e participação popular no município de Maricá. A delimitação espaço temporal de nosso projeto situa-se na cidade de Maricá, localizada na Sub-região dos Lagos, no Estado do Rio de Janeiro, a partir do ano de 2009, tendo como pano de fundo as especificidades da formação social brasileira e as determinações estruturais resultantes da mundialização do capital. É importante ressaltar que o termo participação popular pertinente a este estudo refere-se à criação ou ampliação de canais institucionais para intervenção da população no controle social ou na construção do debate orçamentário nas cidades, que exigem estratégias políticas que são absolutamente fundamentais para a construção de uma nova sociedade pautada em princípios radicalmente democráticos.As contradições e as possibilidades da luta pelo direito à cidade, frente à ampliação mercantilização do espaço e a tradição clientelista na cidade de Maricá, foram os desafios que procuraremos responder nesta tese. Para tal, elencamos as seguintes hipóteses: 1) a disputa de projetos societários, a partir da luta de classes, pode ser identificada nas cidades através das propostas antagônicas de cidade-mercadoria e do direito à cidade, contradições estas que se reproduzem inclusive em governos municipais comprometidos com a ampliação dos canais de participação popular; 2) a gestão participativa municipal pode tanto contribuir para a subjetivação das classes subalternas no sentido das mesmas intervirem e até modificarem a esfera pública, quanto se tornar um espaço instrumental ao clientelismo e/ou associativismo local; 3) para evitar tal distorção é importante que agentes contestatórios da sociedade civil retomem o tensionamento de canais institucionais de participação popular nas cidades, enquanto estratégia de ampliação da esfera pública, visto que tais espaços têm sido ocupados por agentes muito mais colaborativos que conflituosos, despolitizando possibilidades, tais como: o orçamento participativo, audiências públicas e os Conselhos Municipais; 4) as cidades do CONLESTE, em especial o município de Maricá, tornaram-se foco do interesse da burguesia nacional e internacional, após as discussões em torno do COMPERJ e do Pré-sal, dificultando e/ou inviabilizado um direcionamento autônomo do poder local em torno das propostas engendradas pela participação popular na cidade, contexto que torna o urgente o tensionamento visando à possibilidade de garantia da função social da cidade, conforme preconiza a Carta Mundial de Direito à Cidade, em especial frente à especulação imobiliária.

O estudo prévio de impacto de vizinhança e sua exigibilidade para o exercício do direito de construir quando da criação do condomínio edilício à luz da Constituição

O presente estudo objetiva sublinhar o estudo prévio de impacto de vizinhança como instrumento de política urbana apto a conformar a autonomia privada do incorporador imobiliário no exercício do direito de construir o condomínio edilício a legalidade constitucional. O que justifica o debate é a necessidade de harmonizar,numa sociedade de risco, a liberdade de construir o condomínio edilício à proteção e não degradação do meio ambiente urbano, gerenciando os riscos e planejando a utilização e fruição dos recursos ambientais, apresentando um instrumento de política urbana que alie a livre iniciativa do incorporador imobiliário e a preservação ambiental urbana como meta. Nestes termos segue o problema do presente estudo:qual é o instrumento de política urbana que pode conformar a autonomia privada do incorporador imobiliário no exercício do direito de construir o condomínio edilício à legalidade constitucional?Para responder esta indagação buscou-se: escorçar o histórico dos aspectos jurídicos e econômicos na produção do condomínio edilício; relacionar o princípio do numerus clausus e da tipicidade nos direitos reais para distinguir o condomínio edilício como tipo de direito real; identificar o espaço para fixação do conteúdo do condomínio edilício pelo incorporador imobiliário na viabilização, instituição e constituição; sublinhar a legalidade constitucional como um método hermenêutico; identificar as premissas metodológicas da legalidade constitucional; identificar os valores constitucionais que irradiam no exercício do direito de construir o condomínio edilício na cidade; distinguir a noção contemporânea de vizinhança; sublinhar a disciplina jurídica do estudo prévio de impacto de vizinhança; e identificar os conteúdos dos fatores de investigação do estudo prévio de impacto de vizinhança, relacionando-os com a construção do condomínio edilício. A pesquisa teve um enfoque quali-quantitativo no tratamento dos dados levantados em censos e relatórios de pesquisa, segundo amostras estratificadas e de acessibilidade do universo pesquisado, com a utilização do método de procedimento descritivo, tendo como delineamento as bibliografias e documentos concernentes ao tema. Os resultados revelaram que a construção do condomínio edilício pode causar impactos na vizinhança; que o estudo prévio de impacto de vizinhança é o instrumento de política urbana necessário para conformar a autonomia privada do incorporador imobiliário, no exercício do direito de construir o condomínio edilício, a legalidade constitucional; que para exigi-lo depende de regulamentação legal municipal; e que é baixa esta regulamentação dentre os Municípios brasileiros.

The differences in the social competence of children who attend integrated junior infant classes and children who attend segregated learning environments

There are a number of reasons why this researcher has decided to undertake this study into the differences in the social competence of children who attend integrated Junior Infant classes and children who attend segregated learning environments. Theses reasons are both personal and professional. My personal reasons stem from having grown up in a family which included both an aunt who presented with Down Syndrome and an uncle who presented with hearing impairment. Both of these relatives' experiences in our education system are interesting. My aunt was considered ineducable while her brother - my uncle - was sent to Dublin (from Cork) at six years of age to be educated by a religious order. My professional reasons, on the other hand, stemmed from my teaching experience. Having taught in both special and integrated classrooms it became evident to me that there was somewhat 'suspicion' attached to integration. Parents of children without disabilities questioned whether this process would have a negative impact on their children's education. While parents of children with disabilities debated whether integrated settings met the specific needs of their children. On the other hand, I always questioned whether integration and inclusiveness meant the same thing. My research has enabled me to find many answers. Increasingly, children with special educational needs (SEN) are attending a variety of integrated and inclusive childcare and education settings. This contemporary practice of educating children who present with disabilities in mainstream classrooms has stimulated vast interest on the impact of such practices on children with identified disabilities. Indeed, children who present with disabilities "fare far better in mainstream education than in special schools" (Buckley, cited in Siggins, 2001,p.25). However, educators and practitioners in the field of early years education and care are concerned with meeting the needs of all children in their learning environments, while also upholding high academic standards (Putman, 1993). Fundamentally, therefore, integrated education must also produce questions about the impact of this practice on children without identified special educational needs. While these questions can be addressed from the various areas of child development (i.e. cognitive, physical, linguistic, emotional, moral, spiritual and creative), this research focused on the social domain. It investigates the development of social competence in junior infant class children without identified disabilities as they experience different educational settings.

Expression and function of the neurotrophic factors GDF5 and GDNF in the nigrostriatal system during development and in rat models of Parkinson's disease

Growth/differentiation factor 5 (GDF5) and glial cell line-derived neurotrophic factor (GDNF) are neurotrophic factors that promote the survival of midbrain dopaminergic neurons in vitro and in vivo. Both factors have potent neurotrophic and neuroprotective effects in rat models of Parkinson's disease (PD), and may represent promising new therapies for PD. The aim of the present study was to investigate the endogenous expression and function of GDF5 and GDNF in the nigrostriatal dopaminergic system during development and in rat models of PD. Examination of the temporal expression patterns of endogenous GDF5, GDNF, and their respective receptors, in the developing and adult nigrostriatal dopaminergic system suggest that these factors play important roles in promoting the survival and maturation of midbrain dopaminergic neurons during the period of postnatal programmed cell death. The relative levels of GDF5 and GDNF mRNAs in the midbrain and striatum, and their individual temporal expression patterns during development, suggest that their modes of actions are quite distinct in vivo. Furthermore, the sustained expression of GDF5, GDNF, and their receptors into adulthood suggest roles for these factors in the continued support and maintenance of mature nigrostriatal dopaminergic neurons. The present study found that endogenous GDF5, GDNF, and their receptors are differentially expressed in two 6-hydroxydopamine-induced lesion adult rat models of PD. In both terminal and axonal lesion models of PD, GDF5 mRNA levels in the striatum increased at 10 days post-lesion, while GDNF mRNA levels in the nigrostriatal system decreased at 10 and 28 days post-lesion. Thus, despite the fact that exogenous GDF5 and GDNF have similar effects on midbrain dopaminergic neurons in vitro and in vivo, their endogenous responses to a neurotoxic injury are quite distinct. These results highlight the importance of studying the temporal dynamic changes in neurotrophic factor expression during development and in animal models of PD.

Investigating the function of PINK1 in cancer development and pathogenesis

PTEN‐induced kinase 1 (PINK1) was identified initially in cancer cells as a gene up‐regulated by overexpression of the central tumour suppressor, PTEN. Loss‐of‐function mutations in PINK1 were discovered subsequently to cause autosomal recessive Parkinsonʹs disease (ARPD). Despite much research focusing on the proposed mechanism(s) through which loss of PINKI function causes neurodegeneration, few studies have focused on a direct role for this serine/threonine kinase in cancer biology. The focus of this thesis was to examine a direct role for PINK1 function in tumourigenesis. Initial studies showed that loss of PINK1 reduces tumour‐associated phenotypes including cell growth, colony formation and invasiveness, in several cell types in vitro, indicating a pro‐tumourigenic role for PINK1 in cancer. Furthermore, results revealed for the first time that PINK1 deletion, examined in mouse embryonic fibroblasts (MEFS) from PINK1 knock‐out animals, causes cell cycle defects, whereby cells arrest at in cytokinesis, giving rise to a highly significant increase in the number of multinucleated cells. This results in several key changes in the expression profile of cell cycle associated protein. In addition, PINK1‐deficient MEFs were found to resist cell cycle exit, with a proportion of cells remaining in proliferative phases upon removal of serum. The ability of cells to progress through mitosis conferred by PINK1 expression was independent of its kinase activity, while the cell cycle exit following serum withdrawal was kinase dependent. Investigations into the mechanism through which loss of PINK1 function gives rise to cell cycle defects revealed that dynamin related protein 1 (Drp1)‐mediated mitochondrial fission is enhanced in PINK1‐ deficient MEFs, and that increased expression of Drp1 on mitochondria and activation of Drp1 is highly significant in PINK1‐deficient multinucleated cells. Deregulated and increased levels and activation of mitochondrial fission via Drp1 was shown to be a major feature of cell cycle defects caused by PINK1 deletion, both during progression through G2/M and cell cycle exit following serum removal. Altered PINK1 localisation was also observed during progression of mitosis, and upon serum deprivation. Thus, PINK1 dissociated from the mitochondria during the mitotic phases and localised to mitochondria upon serum withdrawal. During serum withdrawal deletion of PINK1 disabled the ability of MEFs to increase mitochondrial membrane potential (ΔΨm), and increase autophagy. This was co‐incident with increased mitochondrial fission, and increased localisation of Drp1 to mitochondria following serum deprivation. Together, this indicates an inability of PINK1‐negative cells to respond protectively to this stress‐induced state, primarily via impaired mitochondrial function. In contrast, PINK1 overexpression was found to protect cells from DNA damage following treatment with oxidants. In addition, deletion of PINK1 blocked the ability of cells to re‐enter the cell cycle in response to insulin‐like growth factor‐1 (IGF‐1), a major cancer promoting agonistwhich acts primarily via PI3‐kinase/Akt activation. Furthermore, PINK1 mRNA expression was significantly increased following serum deprivation of MCF‐7 cells, and this was rendered more significant upon additional inhibition of PI3‐kinase. Conversely, IGF‐1 activation of PI3‐kinase/Akt causes a time‐dependent and significant reduction of PINK1 mRNA expression that was PI3‐kinase dependent. Together these results indicate that PINK1 expression is necessary for IGF‐1 signalling and is regulated reciprocally in the absence and presence of IGF‐1, via PI3‐kinase/Akt, a signalling system which has major tumour‐promoting capacity in cancer cell biology. The results of this thesis indicate PINK1 is a candidate tumour-promoting gene which has a significant function in the regulation of the cell cycle, and growth factor responses, at key cell cycle checkpoints, namely, during progression through G2/M and during exit of the cell cycle following removal of serum. Furthermore, the results reveal that the regulation of mitochondrial fission and Drp1 function is mechanistically important in the regulation of cell cycle control by PINK1. As deregulation of the cell cycle is linked to both tumourigenesis and neurodegeneration, the findings of this thesis are of importance not just for understanding cancer biology, but also in the context of PINK1‐associated neurodegeneration.