133 resultados para Top-down regulation


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Sleep loss, widespread in today’s society and associated with a number of clinical conditions, has a detrimental effect on a variety of cognitive domains including attention. This study examined the sequelae of sleep deprivation upon BOLD fMRI activation during divided attention. Twelve healthy males completed two randomized sessions; one after 27 h of sleep deprivation and one after a normal night of sleep. During each session, BOLD fMRI was measured while subjects completed a cross-modal divided attention task (visual and auditory). After normal sleep, increased BOLD activation was observed bilaterally in the superior frontal gyrus and the inferior parietal lobe during divided attention performance. Subjects reported feeling significantly more sleepy in the sleep deprivation session, and there was a trend towards poorer divided attention task performance. Sleep deprivation led to a down regulation of activation in the left superior frontal gyrus, possibly reflecting an attenuation of top-down control mechanisms on the attentional system. These findings have implications for understanding the neural correlates of divided attention and the neurofunctional changes that occur in individuals who are sleep deprived.

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Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of approximately 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

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Androgens and the androgen receptor (AR) play a crucial role in the initiation and progression of prostate cancer (PCa), regulating the expression of many PCa risk-associated genes. Iroquois Homeobox 4 (IRX4) has been recently identified with PCa risk and overexpressed in PCa. We observed a down-regulation of IRX4 expression in the cells undergoing epithelial to mesenchymal transition, suggesting its potential role in PCa progression and aim to delineate the androgenmediated regulation of IRX4 in PCa.

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Major South-East Asian city-regions have experienced considerable physical, economic and social transformations during the past three decades. The rapid pace of globalisation and economic restructuring has resulted in these city-regions receiving the full impact of urbanisation pressures. In an attempt to ease these pressures, city-regions such as Bangkok, Seoul, Tokyo, Taipei, Hong Kong, Singapore and Kuala Lumpur have advocate growth management approaches giving particular interest to urban sustainability. These approaches promote efforts to achieve the triple bottom line sustainability by balancing economic and social development, and environmental protection, and putting more emphasis on compact and optimum development of urban forms. This paper evaluates the case of two South-East Asian city-regions, Kuala Lumpur and Hong Kong, and assesses their experiences in managing their urban forms whilst promoting sustainable patterns of urban development. The findings show that sustainable urban development initiatives employing a top down approach has yielded encouraging results in these case study city-regions. However the need for a more concerted effort towards the overall sustainability agenda still remains vital.

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Principal Topic Although corporate entrepreneurship is of vital importance for long-term firm survival and growth (Zahra and Covin, 1995), researchers still struggle with understanding how to manage corporate entrepreneurship activities. Corporate entrepreneurship consists of three parts: innovation, venturing, and renewal processes (Guth and Ginsberg, 1990). Innovation refers to the development of new products, venturing to the creation of new businesses, and renewal to redefining existing businesses (Sharma, and Chrisman, 1999; Verbeke et al., 2007). Although there are many studies focusing on one of these aspects (cf. Burgelman, 1985; Huff et al., 1992), it is very difficult to compare the outcomes of these studies due to differences in contexts, measures, and methodologies. This is a significant lack in our understanding of CE, as firms engage in all three aspects of CE, making it important to compare managerial and organizational antecedents of innovation, venturing and renewal processes. Because factors that may enhance venturing activities may simultaneously inhibit renewal activities. The limited studies that did empirically compare the individual dimensions (cf. Zahra, 1996; Zahra et al., 2000; Yiu and Lau, 2008; Yiu et al., 2007) generally failed to provide a systematic explanation for potential different effects of organizational antecedents on innovation, venturing, and renewal. With this study we aim to investigate the different effects of structural separation and social capital on corporate entrepreneurship activities. The access to existing and the development of new knowledge has been deemed of critical importance in CE-activities (Floyd and Wooldridge, 1999; Covin and Miles, 2007; Katila and Ahuja, 2002). Developing new knowledge can be facilitated by structurally separating corporate entrepreneurial units from mainstream units (cf. Burgelman, 1983; Hill and Rothaermel, 2003; O'Reilly and Tushman, 2004). Existing knowledge and resources are available through networks of social relationships, defined as social capital (Nahapiet and Ghoshal, 1998; Yiu and Lau, 2008). Although social capital has primarily been studied at the organizational level, it might be equally important at top management level (Belliveau et al., 1996). However, little is known about the joint effects of structural separation and integrative mechanisms to provide access to social capital on corporate entrepreneurship. Could these integrative mechanisms for example connect the separated units to facilitate both knowledge creation and sharing? Do these effects differ for innovation, venturing, and renewal processes? Are the effects different for organizational versus top management team integration mechanisms? Corporate entrepreneurship activities have for example been suggested to take place at different levels. Whereas innovation is suggested to be a more bottom-up process, strategic renewal is a more top-down process (Floyd and Lane, 2000; Volberda et al., 2001). Corporate venturing is also a more bottom-up process, but due to the greater required resource commitments relative to innovation, it ventures need to be approved by top management (Burgelman, 1983). As such we will explore the following key research question in this paper: How do social capital and structural separation on organizational and TMT level differentially influence innovation, venturing, and renewal processes? Methodology/Key Propositions We investigated our hypotheses on a final sample of 240 companies in a variety of industries in the Netherlands. All our measures were validated in previous studies. We targeted a second respondent in each firm to reduce problems with single-rater data (James et al., 1984). We separated the measurement of the independent and the dependent variables in two surveys to create a one-year time lag and reduce potential common method bias (Podsakoff et al., 2003). Results and Implications Consistent with our hypotheses, our results show that configurations of structural separation and integrative mechanisms have different effects on the three aspects of corporate entrepreneurship. Innovation was affected by organizational level mechanisms, renewal by integrative mechanisms on top management team level and venturing by mechanisms on both levels. Surprisingly, our results indicated that integrative mechanisms on top management team level had negative effects on corporate entrepreneurship activities. We believe this paper makes two significant contributions. First, we provide more insight in what the effects of ambidextrous organizational forms (i.e. combinations of differentiation and integration mechanisms) are on venturing, innovation and renewal processes. Our findings show that more valuable insights can be gained by comparing the individual parts of corporate entrepreneurship instead of focusing on the whole. Second, we deliver insights in how management can create a facilitative organizational context for these corporate entrepreneurship activities.

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In Australia, a range of Federal Government services have been provided online for some time, but direct, online citizen consultation and involvement in processes of governance is relatively new. Moves towards more extensive citizen involvement in legislative processes are now being driven in a “top-down” fashion by government agencies, or in a “bottom-up” manner by individuals and third-sector organisations. This chapter focusses on one example from each of these categories, as well as discussing the presence of individual politicians in online social networking spaces. It argues that only a combination of these approaches can achieve effective consultation between citizens and policymakers. Existing at a remove from government sites and the frameworks for public communication which govern them, bottom-up consultation tools may provide a better chance for functioning, self-organising user communities to emerge, but they are also more easily ignored by governments not directly involved in their running. Top-down consultation tools, on the other hand, may seem to provide a more direct line of communication to relevant government officials, but for that reason are also more likely to be swamped by users who wish simply to register their dissent rather than engage in discussion. The challenge for governments, politicians, and user communities alike is to develop spaces in which productive and undisrupted exchanges between citizens and policymakers can take place.

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There are currently a number of issues of great importance affecting universities and the way in which their programs are now offered. Many issues are largely being driven top-down and impact both at a university-wide and at an individual discipline level. This paper provides a brief history of cartography and digital mapping education at the Queensland University of Technology (QUT). It also provides an overview of what is curriculum mapping and presents some interesting findings from the program review process. Further, this review process has triggered discussion and action for the review, mapping and embedding of graduate attributes within the spatial science major program. Some form of practical based learning is expected in vocationally oriented degrees that lead to professional accreditation and are generally regarded as a good learning exposure. With the restructure of academic programs across the Faculty of Built Environment and Engineering in 2006, spatial science and surveying students now undertake a formal work integrated learning unit. There is little doubt that students acquire the skills of their discipline (mapping science, spatial) by being immersed in the industry culture- learning how to process information and solve real-world problems within context. The broad theme of where geo-spatial mapping skills are embedded in this broad-based tertiary education course are examined with some focused discussion on the learning objectives, outcomes and examples of some student learning experiences

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Collaborative networks have come to form a large part of the public sector’s strategy to address ongoing and often complex social problems. The relational power of networks, with its emphasis on trust, reciprocity and mutuality provides the mechanism to integrate previously dispersed and even competitive entities into a collective venture(Agranoff 2003; Agranoff and McGuire 2003; Mandell 1994; Mandell and Harrington 1999). It is argued that the refocusing of a single body of effort to a collective contributes to reducing duplication and overlap of services, maximizes increasingly scarce resources and contributes to solving intractable or 'wicked’problems (Clarke and Stewart 1997). Given the current proliferation of collaborative networks and the fact that they are likely to continue for some time, concerns with the management and leadership of such arrangements for optimal outcomes are increasingly relevant. This is especially important for public sector managers who are used to working in a top-down, hierarchical manner. While the management of networks (Agranoff and McGuire 2001, 2003), including collaborative or complex networks (Kickert et al. 1997; Koppenjan and Klijn 2004), has been the subject of considerable attention, there has been much less explicit discussion on leadership approaches in this context. It is argued in this chapter that the traditional use of the terms ‘leader’ or ‘leadership’ does not apply to collaborative networks. There are no ‘followers’ in collaborative networks or supervisor-subordinate relations. Instead there are equal, horizontal relationships that are focused on delivering systems change. In this way the emergent organizational forms such as collaborative networks challenge older models of leadership. However despite the questionable relevance of old leadership styles to the contemporary work environment, no clear alternative has come along to take its place.

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To enhance and regulate cell affinity for poly (l-lactic acid) (PLLA) based materials, two hydrophilic ligands, poly (ethylene glycol) (PEG) and poly (l-lysine) (PLL), were used to develop triblock copolymers: methoxy-terminated poly (ethylene glycol)-block-poly (l-lactide)-block-poly (l-lysine) (MPEG-b-PLLA-b-PLL) in order to regulate protein absorption and cell adhesion. Bone marrow stromal cells (BMSCs) were cultured on different composition of MPEG-b-PLLA-b-PLL copolymer films to determine the effect of modified polymer surfaces on BMSC attachment. To understand the molecular mechanism governing the initial cell adhesion on difference polymer surfaces, the mRNA expression of 84 human extracellular matrix (ECM) and adhesion molecules was analysed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). It was found that down regulation of adhesion molecules was responsible for the impaired BMSC attachment on PLLA surface. MPEG-b-PLLA-b-PLL copolymer films improved significantly the cell adhesion and cytoskeleton expression by upregulation of relevant molecule genes significantly. Six adhesion genes (CDH1, ITGL, NCAM1, SGCE, COL16A1, and LAMA3) were most significantly influenced by the modified PLLA surfaces. In summary, polymer surfaces altered adhesion molecule gene expression of BMSCs, which consequently regulated cell initial attachment on modified PLLA surfaces.

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This abstract is a preliminary discussion of the importance of blending of Indigenous cultural knowledges with mainstream knowledges of mathematics for supporting Indigenous young people. This import is emphasised in the documents Preparing the Ground for Partnership (Priest, 2005), The Indigenous Education Strategic Directions 2008–2011 (Department of Education, Training and the Arts, 2007) and the National Goals for Indigenous Education (Department of Education, Employment and Work Relations, 2008). These documents highlight the contextualising of literacy and numeracy to students’ community and culture (see Priest, 2005). Here, Community describes “a culture that is oriented primarily towards the needs of the group. Martin Nakata (2007) describes contextualising to culture as about that which already exists, that is, Torres Strait Islander community, cultural context and home languages (Nakata, 2007, p. 2). Continuing, Ezeife (2002) cites Hollins (1996) in stating that Indigenous people belong to “high-context culture groups” (p. 185). That is, “high-context cultures are characterized by a holistic (top-down) approach to information processing in which meaning is “extracted” from the environment and the situation. Low-context cultures use a linear, sequential building block (bottom-up) approach to information processing in which meaning is constructed” (p.185). In this regard, students who use holistic thought processing are more likely to be disadvantaged in mainstream mathematics classrooms. This is because Westernised mathematics is presented as broken into parts with limited connections made between concepts and with the students’ culture. It potentially conflicts with how they learn. If this is to change the curriculum needs to be made more culture-sensitive and community orientated so that students know and understand what they are learning and for what purposes.

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Biomineralization is a process encompassing all mineral containing tissues produced within an organism. The most dynamic example of this process is the formation of the mollusk shell, comprising a variety of crystal phases and microstructures. The organic component incorporated within the shell is said to dictate this remarkable architecture. Subsequently, for the past decade considerable research have been undertaken to identify and characterize the protein components involved in biomineralization. Despite these efforts the general understanding of the process remains ambiguous. This study employs a novel molecular approach to further the elucidation of the shell biomineralization. A microarray platform has been custom generated (PmaxArray 1.0) from the pearl oyster Pinctada maxima. PmaxArray 1.0 consists of 4992 expressed sequence tags (ESTs) originating from the mantle, an organ involved in shell formation. This microarray has been used as the primary tool for three separate investigations in an effort to associate transcriptional gene expression from P. maxima to the process of shell biomineralization. The first investigation analyzes the spatial expression of ESTs throughout the mantle organ. The mantle was dissected into five discrete regions and each analyzed for gene expression with PmaxArray 1.0. Over 2000 ESTs were differentially expressed among the tissue sections, identifying five major expression regions. Three of these regions have been proposed to have shell formation functions belonging to nacre, prismatic calcite and periostracum. The spatial gene expression map was confirmed by in situ hybridization, localizing a subset of ESTs from each expression region to the same mantle area. Comparative sequence analysis of ESTs expressed in the proposed shell formation regions with the BLAST tool, revealed a number of the transcripts were novel while others showed significant sequence similarities to previously characterized shell formation genes. The second investigation correlates temporal EST expression during P. maxima larval ontogeny with transitions in shell mineralization during the same period. A timeline documenting the morphologicat microstructural and mineralogical shell characteristics of P. maxima throughout larval ontogeny has been established. Three different shell types were noted based on the physical characters and termed, prodissoconch I, prodissoconch 11 and dissoconch. PmaxArray 1.0 analyzed ESTs expression of animals throughout the larval development of P. maxima, noting up-regulation of 359 ESTs in association with the shell transitions from prodissoconch 1 to prodissoconch 11 to dissoconch. Comparative sequence analysis of these ESTs indicates a number of the transcripts are novel as well as showing significant sequence similarities between ESTs and known shell matrix associated genes and proteins. These ESTs are discussed in relation to the shell characters associated with their temporal expression. The third investigation uses PmaxArray 1.0 to analyze gene expression in the mantle tissue of P. maxima specimens exposed to sub-lethal concentrations of a shell-deforming toxin, tributyltin (TBT). The shell specific effects of TBT are used in this investigation to interpret differential expression of ESTs with respect to shell formation functions. A lethal and sublethal TBT concentration range was established for P. maxima, noting a concentration of 50 ng L- 1 TBT as sub-lethal over a 21 day period. Mantle tissue from P. maxima animals treated with 50 ng L- 1 TBT was assessed for differential EST expression with untreated control animals. A total of 102 ESTs were identified as differentially expressed in association with TBT exposure, comparative sequence identities included an up-regulation of immunity and detoxification related genes and down-regulation of several shell matrix genes. A number of transcripts encoding novel peptides were additionally identified. The potential actions of these genes are discussed with reference to TBT toxicity and shell biomineralization. This thesis has used a microarray platform to analyze gene expression in spatial, temporal and toxicity investigations, revealing the involvement of numerous gene transcripts in specific shell formation functions. Investigation of thousands of transcripts simultaneously has provided a holistic interpretation of the organic components regulating shell biomineralization.

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Networks form a key part of the infrastructure of contemporary governance arrangements and, as such, are likely to continue for some time. Networks can take many forms and be formed for many reasons. Some networks have been explicitly designed to generate a collective response to an issue; some arise from a top down perspective through mandate or coercion; while others rely more heavily on interpersonal relations and doing the right thing. In this paper, these three different perspectives are referred to as the “3I”s: Instrumental, Institutional or Interpersonal. It is proposed that these underlying motivations will affect the process dynamics within the different types of networks in different ways and therefore influence the type of outcomes achieved. This proposition is tested through a number of case studies. An understanding of these differences will lead to more effective design, management and clearer expectations of what can be achieved through networks.

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Purpose: The purpose of this paper is to explore two dimensions of leadership practices (i.e. teaching and learning and sources of power) used by two exemplary principals in mainland China against a background of education reform and to identify how broader contextual factors have shaped these two dimensions of their leadership.--------- Design/methodology/approach: An exploratory case study was used that drew upon semi-structured interviews, observations and document analysis. Interviews were conducted with two principals, six teachers from each of the two schools and a superintendent who was the supervisor of the two principals.---------- Findings: The findings reveal that there are some common elements in both of the leaders’ practices but also some subtle differences. Both leaders emphasise teaching and learning. One sees herself as curriculum expert; the other delegate teaching responsibilities. While both uses a top down approach, one principal uses an adversarial approach and the other a more facilitative approach.---------- Research limitations/implications: The study used a small sample size. It explored the leaders’ practices in the light of broader contextual factors rather than personal factors or gender-based factors Originality/value – Given the limited empirical research conducted on female principals in mainland China, this qualitative study provides insights into two dimensions of leadership used by two exemplary principals and explains their practices in the light of critical contextual factors such as contemporary and traditional Chinese culture and the school’s organisational context.

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Ecological networks are often represented as utopian webs of green meandering through cities, across states, through regions and even across a country (Erickson, 2006, p.28; Fabos, 2004, p.326; Walmsley, 2006). While this may be an inspiring goal for some in developed countries, the reality may be somewhat different in developing countries. China, in its shift to urbanisation and suburbanisation, is also being persuaded to adjust its planning schemes according to these aspirational representations of green spaces (Yu et al, 2006, p.237; Zhang and Wang, 2006, p.455). The failure of other countries to achieve regional goals of natural and cultural heritage protection on the ground in this way (Peterson et al, 2007; Ryan et al, 2006; von Haaren and Reich, 2006) suggests that there may be flaws in the underpinning concepts that are widely circulated in North American and Western European literature (Jongman et al, 2004; Walmsley, 2006). In China, regional open space networks, regional green infrastructure or regional ecological corridors as we know them in the West, are also likely to be problematic, at least in the foreseeable future. Reasons supporting this view can be drawn from lessons learned from project experience in landscape planning and related fields of study in China and overseas. Implementation of valuable regional green space networks is problematic because: • the concept of region as a spatial unit for planning green space networks is ambiguous and undefinable for practical purposes; • regional green space networks traditionally require top down inter-governmental cooperation and coordination which are generally hampered by inequalities of influence between and within government agencies; • no coordinating body with funding powers exists for regional green space development and infrastructure authorities are still in transition from engineering authorities; • like other infrastructure projects, green space is likely to become a competitive rather than a complementary resource for city governments; • stable long-term management, maintenance and uses of green space networks must fit into a ‘family’ social structure rather than a ‘public good’ social structure, particularly as rural and urban property rights are being re-negotiated with city governments; and • green space provision is a performance indicator of urban improvement in cities within the city hierarchy and remains quantitatively-based (land area, tree number and per capita share) rather than qualitatively-based with local people as the focus.