899 resultados para gene-environment interaction
Resumo:
The Pedestrian Interaction Patch Project (PIPP) seeks to exert influence over and encourage abnormal pedestrian behavior. By placing an unadvertised (and non recording) interactive video manipulation system and projection source in a high traffic public area, the PIPP allows pedestrians to privately (and publically) re-engage with a previously inactive physical environment, like a commonly used walkway or corridor. This system, the results of which are projected in real time on the architectural surface, inadvertently provides pedestrians with questions around preconceived notions of self and space. In an attempt to re-activate our relationship with the physical surrounds we occupy each day the PIPP creates a new set of memories to be recalled as we re-enter known environments once PIPP has moved on and as such re-enlivens our relationship with the everyday architecture we stroll past everyday. The PIPP environment is controlled using the software program Isadora, devised by Mark Coniglio at Troika Ranch, and contains a series of video manipulation patches that are designed to not only grab the pedestrians attention but to also encourage a sense of play and interaction between the architecture, the digital environment, the initially unsuspecting participant(s) and the pedestrian audience. The PIPP was included as part of the planned walking tour for the “Playing in Urban Spaces” seminar day, and was an installation that ran for the length of the symposium in a reclaimed pedestrian space that was encountered by both the participants and general public during the course of the day long event. Ideally once discovered PIPP encouraged pedestrians to return through the course of the seminar day to see if the environmental patches had changed or altered, and changed their standard route to include the PIPP installation or to avoid it, either way, encouraging an active response to the pathways normally traveled or newly discovered each day.
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Objective. Previous studies have shown the influence of subchondral bone osteoblasts (SBOs) on phenotypical changes of articular cartilage chondrocytes (ACCs) during the development of osteoarthritis (OA). The molecular mechanisms involved during this process remain elusive, in particular, the signal transduction pathways. The aim of this study was to investigate the in vitro effects of OA SBOs on the phenotypical changes in normal ACCs and to unveil the potential involvement of MAPK signaling pathways during this process. Methods. Normal and arthritic cartilage and bone samples were collected for isolation of ACCs and SBOs. Direct and indirect coculture models were applied to study chondrocyte hypertrophy under the influence of OA SBOs. MAPKs in the regulation of the cell–cell interactions were monitored by phosphorylated antibodies and relevant inhibitors. Results. OA SBOs led to increased hypertrophic gene expression and matrix calcification in ACCs by means of both direct and indirect cell–cell interactions. In this study, we demonstrated for the first time that OA SBOs suppressed p38 phosphorylation and induced ERK-1/2 signal phosphorylation in cocultured ACCs. The ERK-1/2 pathway inhibitor PD98059 significantly attenuated the hypertrophic changes induced by conditioned medium from OA SBOs, and the p38 inhibitor SB203580 resulted in the up-regulation of hypertrophic genes in ACCs. Conclusion. The findings of this study suggest that the pathologic interaction of OA SBOs and ACCs is mediated via the activation of ERK-1/2 phosphorylation and deactivation of p38 phosphorylation, resulting in hypertrophic differentiation of ACCs.
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In this paper, a static synchronous series compensator (SSSC), along with a fixed capacitor, is used to avoid torsional mode instability in a series compensated transmission system. A 48-step harmonic neutralized inverter is used for the realization of the SSSC. The system under consideration is the IEEE first benchmark model on SSR analysis. The system stability is studied both through eigenvalue analysis and EMTDC/PSCAD simulation studies. It is shown that the combination of the SSSC and the fixed capacitor improves the synchronizing power coefficient. The presence of the fixed capacitor ensures increased damping of small signal oscillations. At higher levels of fixed capacitor compensation, a damping controller is required to stabilize the torsional modes of SSR.
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Conifers are resistant to attack from a large number of potential herbivores or pathogens. Previous molecular and biochemical characterization of selected conifer defence systems support a model of multigenic, constitutive and induced defences that act on invading insects via physical, chemical, biochemical or ecological (multitrophic) mechanisms. However, the genomic foundation of the complex defence and resistance mechanisms of conifers is largely unknown. As part of a genomics strategy to characterize inducible defences and possible resistance mechanisms of conifers against insect herbivory, we developed a cDNA microarray building upon a new spruce (Picea spp.) expressed sequence tag resource. This first-generation spruce cDNA microarray contains 9720 cDNA elements representing c. 5500 unique genes. We used this array to monitor gene expression in Sitka spruce (Picea sitchensis) bark in response to herbivory by white pine weevils (Pissodes strobi, Curculionidae) or wounding, and in young shoot tips in response to western spruce budworm (Choristoneura occidentalis, Lepidopterae) feeding. Weevils are stem-boring insects that feed on phloem, while budworms are foliage feeding larvae that consume needles and young shoot tips. Both insect species and wounding treatment caused substantial changes of the host plant transcriptome detected in each case by differential gene expression of several thousand array elements at 1 or 2 d after the onset of treatment. Overall, there was considerable overlap among differentially expressed gene sets from these three stress treatments. Functional classification of the induced transcripts revealed genes with roles in general plant defence, octadecanoid and ethylene signalling, transport, secondary metabolism, and transcriptional regulation. Several genes involved in primary metabolic processes such as photosynthesis were down-regulated upon insect feeding or wounding, fitting with the concept of dynamic resource allocation in plant defence. Refined expression analysis using gene-specific primers and real-time PCR for selected transcripts was in agreement with microarray results for most genes tested. This study provides the first large-scale survey of insect-induced defence transcripts in a gymnosperm and provides a platform for functional investigation of plant-insect interactions in spruce. Induction of spruce genes of octadecanoid and ethylene signalling, terpenoid biosynthesis, and phenolic secondary metabolism are discussed in more detail.
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This workshop explores innovative approaches to understanding and cultivating sustainable food culture in urban environments via human-computer-interaction (HCI) design and ubiquitous technologies. We perceive the city as an intersecting network of people, place, and technology in constant transformation. Our 2009 OZCHI workshop, Hungry 24/7? HCI Design for Sustainable Food Culture, opened a new space for discussion on this intersection amongst researchers and practitioners from diverse backgrounds including academia, government, industry, and non-for-profit organisations. Building on the past success, this new instalment of the workshop series takes a more refined view on mobile human-food interaction and the role of interactive media in engaging citizens to cultivate more sustainable everyday human-food interactions on the go. Interactive media in this sense is distributed, pervasive, and embedded in the city as a network. The workshop addresses environmental, health, and social domains of sustainability by bringing together insights across disciplines to discuss conceptual and design approaches in orchestrating mobility and interaction of people and food in the city as a network of people, place, technology, and food.
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Fibre Bragg Grating (FBG) sensors have been installed along an existing line for the purposes of train detection and weight measurement. The results show fair accuracy and high resolution on the vertical force acted on track when the train wheels are rolling upon. While the sensors are already in place and data is available, further applications beyond train detection are explored. This study presents the analysis on the unique signatures from the data collected to characterise wheel-rail interaction for rail defect detection. Focus of this first stage of work is placed on the repeatability of signals from the same wheel-rail interactions while the rail is in healthy state. Discussions on the preliminary results and hence the feasibility of this condition monitoring application, as well as technical issues to be addressed in practice, are given.
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Agile ridesharing aims to utilise the capability of social networks and mobile phones to facilitate people to share vehicles and travel in real time. However the application of social networking technologies in local communities to address issues of personal transport faces significant design challenges. In this paper we describe an iterative design-based approach to exploring this problem and discuss findings from the use of an early prototype. The findings focus upon interaction, privacy and profiling. Our early results suggest that explicitly entering information such as ride data and personal profile data into formal fields for explicit computation of matches, as is done in many systems, may not be the best strategy. It might be preferable to support informal communication and negotiation with text search techniques.
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Corepressors play a crucial role in negative gene regulation and are defective in several diseases. BCoR is a corepressor for the BCL6 repressor protein. Here we describe and functionally characterize BCoR-L1, a homolog of BCoR. When tethered to a heterologous promoter, BCoR-L1 is capable of strong repression. Like other corepressors, BCoR-L1 associates with histone deacetylase (HDAC) activity. Specifically, BCoR-L1 coprecipitates with the Class II HDACs, HDAC4, HDAC5, and HDAC7, suggesting that they are involved in its role as a transcriptional repressor. BCoR-L1 also interacts with the CtBP corepressor through a CtBP-interacting motif in its amino terminus. Abrogation of the CtBP binding site within BCoR-L1 partially relieves BCoR-L1-mediated transcriptional repression. Furthermore, BCoR-L1 is located on the E-cadherin promoter, a known CtBP-regulated promoter, and represses the E-cadherin promoter activity in a reporter assay. The inhibition of BCoR-L1 expression by RNA-mediated interference results in derepression of E-cadherin in cells that do not normally express E-cadherin, indicating that BCoR-L1 contributes to the repression of an authentic endogenous CtBP target.
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It is widely held, through the Socratic tradition, that discussion is at the heart of learning. Moderated discussion forums have been shown to replicate the debate, argument and verbal defence of viewpoints that we have come to expect in face-to-face learning environments and that we generally accept to underpin learning. While much has been written about discussion forums in educational settings, particularly in how to moderate and promote effective interaction with students at a distance, this paper takes a different approach. It looks at how forums may be used to support face-to-face learning in the contemporary context of the massification of on-campus classes. Further to this, it will argue for discussion forums as an indicator of social presence in the learning environment. It will cautiously conclude that, through purposeful design, this form of asynchronous communication has a valuable role to play in creating a positive and supportive environment for students entering university. Discussion forums are tools with a versatility yet to be fully exploited.
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The molecular mechanism between atherosclerosis formation and periodontal pathogens is not clear although positive correlation between periodontal infections and cardiovascular diseases has been reported. Objective: To determine if atherosclerosis related genes were affected in foam cells during and after its formation by P. gingivalis lipopolysaccharide (LPS) stimulation. Methods: Macrophages from human THP-1 monocytes were treated with oxidized low density lipoprotein (oxLDL) to induce the formation of foam cells. P. gingivalis LPS was added to cultures of either oxLDL-induced macrophages or foam cells. The expression of atherosclerosis related genes was assayed by quantitative real time PCR and the protein production of granulocyte-macrophage colony-stimulating factor(GM-CSF), monocyte chemotactic protein-1 (MCP-1), IL-1β, IL-10 and IL-12 was determined by ELISA. Nuclear translocation of NF-κB P65 was detected by immunocytochemistry and western blot was used to evaluate IKB-α degradation to confirm the NF-κB pathway activation. Results: P. gingivalis LPS stimulated atherosclerosis related gene expression in foam cells and increased oxLDL induced expression of chemokines, adhesion molecules, growth factors, apoptotic genes, and nuclear receptors in macrophages. Transcription of the pro-inflammatory cytokines IL-1β and IL-12 was elevated in response to LPS in both macrophages and foam cells, whereas the anti-inflammatory cytokine IL-10 was not affected. Increased NF-κB pathway activation was also observed in LPS and oxLDL co-stimulated macrophages. Conclusion: P. gingivalis LPS appears to be an important factor in the development of atherosclerosis by stimulation of atherosclerosis related gene expression in both macrophages and foam cells via activation of the NF-κB pathway.
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Introduction and aims: For a scaffold material to be considered effective and efficient for tissue engineering it must be biocompatible as well as bioinductive. Silk fiber is a natural biocompatible material suitable for scaffold fabrication; however, silk is tissue-conductive and lacks tissue-inductive properties. One proposed method to make the scaffold tissue-inductive is to introduce plasmids or viruses encoding a specific growth factor into the scaffold. In this study, we constructed adenoviruses encoding bone morphogenetic protein-7 (BMP-7) and incorporated these into silk scaffolds. The osteo-inductive and new bone formation properties of these constructs were assessed in vivo in a critical-sized skull defect animal model. Materials and methods: Silk fibroin scaffolds containing adenovirus particles coding BMP-7 were prepared. The release of the adenovirus particles from the scaffolds was quantified by tissue-culture infective dose (TCID50) and the bioactivity of the released viruses was evaluated on human bone marrow mesenchymal stromal cells (BMSCs). To demonstrate the in vivo bone forming ability of the virus-carrying silk fibroin scaffold, the scaffold constructs were implanted into calvarial defects in SCID mice. Results: In vitro studies demonstrated that the virus-carrying silk fibroin scaffold released virus particles over a 3 week period while preserving their bioactivity. In vivo test of the scaffold constructs in critical-sized skull defect areas revealed that silk scaffolds were capable of delivering the adenovirus encoding BMP-7, resulting significantly enhanced new bone formation. Conclusions: Silk scaffolds carrying BMP-7 encoding adenoviruses can effectively transfect cells and enhance both in vitro and in vivo osteogenesis. The findings of this study indicate silk fibroin is a promising biomaterial for gene delivery to repair critical-sized bone defects.
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Interaction Design is a fast developing branch of Industrial Design. The availability of cheap microprocessors and sensor electronics allow interactions between people and products that were until recently impossible. This has added additional layers of complexity to the design process. Novice designers find it difficult to effectively juggle these complexities and typically tend to focus on one aspect at a time. They also tend to take a linear, step-by-step approach to the design process in contrast to expert designers who pursue “parallel lines of thought” whilst simultaneously co-evolving both problem and solution. (Lawson, 1993) This paper explores an approach that encourages designers (in this case novice designers) to take a parallel rather than linear approach to the design process. It also addresses the problem of social loafing that tends to occur in team activities.
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Cell based therapies require cells capable of self renewal and differentiation, and a prerequisite is the ability to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies is therefore an integral part of tissue engineering. Bone marrow is the most easily accessible source of mesenchymal stem cells (MSCs), and harbours two distinct populations of adult stem cells; namely hematopoietic stem cells (HSCs) and bone mesenchymal stem cells (BMSCs). Unlike HSCs, there are yet no rigorous criteria for characterizing BMSCs. Changing understanding about the pluripotency of BMSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to BMSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their in vitro study. Also, when BMSCs are cultured in vitro there is a loss of the in vivo microenvironment which results in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage number, characterized by the onset of senescence related changes. Accordingly, establishing protocols for generating large numbers of BMSCs without affecting their differentiation potential is necessary. The principal aims of this thesis were to identify potential molecular factors for characterizing BMSCs from osteoarthritic patients, and also to attempt to establish culture protocols favourable for generating large number of BMSCs, while at the same time retaining their proliferation and differentiation potential. Previously published studies concerning clonal cells have demonstrated that BMSCs are heterogeneous populations of cells at various stages of growth. Some cells are higher in the hierarchy and represent the progenitors, while other cells occupy a lower position in the hierarchy and are therefore more committed to a particular lineage. This feature of BMSCs was made evident by the work of Mareddy et al., which involved generating clonal populations of BMSCs from bone marrow of osteoarthritic patients, by a single cell clonal culture method. Proliferation potential and differentiation capabilities were used to group cells into fast growing and slow growing clones. The study presented here is a continuation of the work of Mareddy et al. and employed immunological and array based techniques to identify the primary molecular factors involved in regulating phenotypic characteristics exhibited by contrasting clonal populations. The subtractive immunization (SI) was used to generate novel antibodies against favourably expressed proteins in the fast growing clonal cell population. The difference between the clonal populations at the transcriptional level was determined using a Stem Cell RT2 Profiler TM PCR Array which focuses on stem cell pathway gene expression. Monoclonal antibodies (mAb) generated by SI were able to effectively highlight differentially expressed antigenic determinants, as was evident by Western blot analysis and confocal microscopy. Co-immunoprecipitation, followed by mass spectroscopy analysis, identified a favourably expressed protein as the cytoskeletal protein vimentin. The stem cell gene array highlighted genes that were highly upregulated in the fast growing clonal cell population. Based on their functions these genes were grouped into growth factors, cell fate determination and maintenance of embryonic and neural stem cell renewal. Furthermore, on a closer analysis it was established that the cytoskeletal protein vimentin and nine out of ten genes identified by gene array were associated with chondrogenesis or cartilage repair, consistent with the potential role played by BMSCs in defect repair and maintaining tissue homeostasis, by modulating the gene expression pattern to compensate for degenerated cartilage in osteoarthritic tissues. The gene array also presented transcripts for embryonic lineage markers such as FOXA2 and Sox2, both of which were significantly over expressed in fast growing clonal populations. A recent groundbreaking study by Yamanaka et al imparted embryonic stem cell (ESCs) -like characteristic to somatic cells in a process termed nuclear reprogramming, by the ectopic expression of the genes Sox2, cMyc and Oct4. The expression of embryonic lineage markers in adult stem cells may be a mechanism by which the favourable behaviour of fast growing clonal cells is determined and suggests a possible active phenomenon of spontaneous reprogramming in fast growing clonal cells. The expression pattern of these critical molecular markers could be indicative of the competence of BMSCs. For this reason, the expression pattern of Sox2, Oct4 and cMyc, at various passages in heterogeneous BMSCs population and tissue derived cells (osteoblasts and chondrocytes), was investigated by a real-time PCR and immunoflourescence staining. A strong nuclear staining was observed for Sox2, Oct4 and cMyc, which gradually weakened accompanied with cytoplasmic translocation after several passage. The mRNA and protein expression of Sox2, Oct4 and cMyc peaked at the third passage for osteoblasts, chondrocytes and third passage for BMSCs, and declined with each subsequent passage, indicating towards a possible mechanism of spontaneous reprogramming. This study proposes that the progressive decline in proliferation potential and multipotentiality associated with increased passaging of BMSCs in vitro might be a consequence of loss of these propluripotency factors. We therefore hypothesise that the expression of these master genes is not an intrinsic cell function, but rather an outcome of interaction of the cells with their microenvironment; this was evident by the fact that when removed from their in vivo microenvironment, BMSCs undergo a rapid loss of stemness after only a few passages. One of the most interesting aspects of this study was the integration of factors in the culture conditions, which to some extent, mimicked the in vivo microenvironmental niche of the BMSCs. A number of studies have successfully established that the cellular niche is not an inert tissue component but is of prime importance. The total sum of stimuli from the microenvironment underpins the complex interplay of regulatory mechanisms which control multiple functions in stem cells most importantly stem cell renewal. Therefore, well characterised factors which affect BMSCs characteristics, such as fibronectin (FN) coating, and morphogens such as FGF2 and BMP4, were incorporated into the cell culture conditions. The experimental set up was designed to provide insight into the expression pattern of the stem cell related transcription factors Sox2, cMyc and Oct4, in BMSCs with respect to passaging and changes in culture conditions. Induction of these pluripotency markers in somatic cells by retroviral transfection has been shown to confer pluripotency and an ESCs like state. Our study demonstrated that all treatments could transiently induce the expression of Sox2, cMyc and Oct4, and favourably affect the proliferation potential of BMSCs. The combined effect of these treatments was able to induce and retain the endogenous nuclear expression of stem cell transcription factors in BMSCs over an extended number of in vitro passages. Our results therefore suggest that the transient induction and manipulation of endogenous expression of transcription factors critical for stemness can be achieved by modulating the culture conditions; the benefit of which is to circumvent the need for genetic manipulations. In summary, this study has explored the role of BMSCs in the diseased state of osteoarthritis, by employing transcriptional profiling along with SI. In particular this study pioneered the use of primary cells for generating novel antibodies by SI. We established that somatic cells and BMSCs have a basal level of expression of pluripotency markers. Furthermore, our study indicates that intrinsic signalling mechanisms of BMSCs are intimately linked with extrinsic cues from the microenvironment and that these signals appear to be critical for retaining the expression of genes to maintain cell stemness in long term in vitro culture. This project provides a basis for developing an “artificial niche” required for reversion of commitment and maintenance of BMSC in their uncommitted homeostatic state.
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Increasingly scientists are using collections of software tools in their research. These tools are typically used in concert, often necessitating laborious and error-prone manual data reformatting and transfer. We present an intuitive workflow environment to support scientists with their research. The workflow, GPFlow, wraps legacy tools, presenting a high level, interactive web-based front end to scientists. The workflow backend is realized by a commercial grade workflow engine (Windows Workflow Foundation). The workflow model is inspired by spreadsheets and is novel in its support for an intuitive method of interaction enabling experimentation as required by many scientists, e.g. bioinformaticians. We apply GPFlow to two bioinformatics experiments and demonstrate its flexibility and simplicity.