899 resultados para Gene-Environment Interaction


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Portable water-filled barriers (PWFB) are roadside structures used to separate moving traffic from work-zones. Numerical PWFB modelling is preferred in the design stages prior to actual testing. This paper aims to study the fluid-structure interaction of PWFB under vehicular impact using several methods. The strategy to treat water as non-structural mass was proposed and the errors were investigated. It was found that water can be treated with the FEA-NSM model for velocities higher than 80kmh-1. However, full SPH/FEA model is still the best treatment for water and necessary for lower impact velocities. The findings in this paper can be used as guidelines for modelling and designing PWFB.

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Suicide is a serious public health issue that results from an interaction between multiple risk factors including individual vulnerabilities to complex feelings of hopelessness, fear, and stress. Although kinase genes have been implicated in fear and stress, including the consolidation and extinction of fearful memories, expression profiles of those genes in the brain of suicide victims are less clear. Using gene expression microarray data from the Online Stanley Genomics Database 1 and a quantitative PCR, we investigated the expression profiles of multiple kinase genes including the calcium calmodulin-dependent kinase (CAMK), the cyclin-dependent kinase, the mitogen-activated protein kinase (MAPK), and the protein kinase C (PKC) in the prefrontal cortex (PFC) of mood disorder patients died with suicide (N = 45) and without suicide (N = 38). We also investigated the expression pattern of the same genes in the PFC of developing humans ranging in age from birth to 49 year (N = 46). The expression levels of CAMK2B, CDK5, MAPK9, and PRKCI were increased in the PFC of suicide victims as compared to non-suicide controls (false discovery rate, FDR-adjusted p < 0.05, fold change >1.1). Those genes also showed changes in expression pattern during the postnatal development (FDR-adjusted p < 0.05). These results suggest that multiple kinase genes undergo age-dependent changes in normal brains as well as pathological changes in suicide brains. These findings may provide an important link to protein kinases known to be important for the development of fear memory, stress associated neural plasticity, and up-regulation in the PFC of suicide victims. More research is needed to better understand the functional role of these kinase genes that may be associated with the pathophysiology of suicide

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OBJECTIVE: This study explored gene expression differences in predicting response to chemoradiotherapy in esophageal cancer. PURPOSE:: A major pathological response to neoadjuvant chemoradiation is observed in about 40% of esophageal cancer patients and is associated with favorable outcomes. However, patients with tumors of similar histology, differentiation, and stage can have vastly different responses to the same neoadjuvant therapy. This dichotomy may be due to differences in the molecular genetic environment of the tumor cells. BACKGROUND DATA: Diagnostic biopsies were obtained from a training cohort of esophageal cancer patients (13), and extracted RNA was hybridized to genome expression microarrays. The resulting gene expression data was verified by qRT-PCR. In a larger, independent validation cohort (27), we examined differential gene expression by qRT-PCR. The ability of differentially-regulated genes to predict response to therapy was assessed in a multivariate leave-one-out cross-validation model. RESULTS: Although 411 genes were differentially expressed between normal and tumor tissue, only 103 genes were altered between responder and non-responder tumor; and 67 genes differentially expressed >2-fold. These included genes previously reported in esophageal cancer and a number of novel genes. In the validation cohort, 8 of 12 selected genes were significantly different between the response groups. In the predictive model, 5 of 8 genes could predict response to therapy with 95% accuracy in a subset (74%) of patients. CONCLUSIONS: This study has identified a gene microarray pattern and a set of genes associated with response to neoadjuvant chemoradiation in esophageal cancer. The potential of these genes as biomarkers of response to treatment warrants further investigation. Copyright © 2009 by Lippincott Williams & Wilkins.

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Several chronic infections known to be associated with malignancy have established oncogenic properties. However the existence of chronic inflammatory conditions that do not have an established infective cause and are associated with the development of tumours strongly suggests that the inflammatory process itself provides the prerequisite environment for the development of malignancy. This environment includes upregulation of mediators of the inflammatory response such as cyclo-oxygenase (COX)-2 leading to the production of inflammatory cytokines and prostaglandins which themselves may suppress cell mediated immune responses and promote angiogenesis. These factors may also impact on cell growth and survival signalling pathways resulting in induction of cell proliferation and inhibition of apoptosis. Furthermore, chronic inflammation may lead to the production of reactive oxygen species and metabolites such as malondialdehyde within the affected cells that may in turn induce DNA damage and mutations and, as a result, be carcinogenic. Here it is proposed that the conditions provided by a chronic inflammatory environment are so essential for the progression of the neoplastic process that therapeutic intervention aimed at inhibiting inflammation, reducing angiogenesis and stimulating cell mediated immune responses may have a major role in reducing the incidence of common cancers. © 2001 Cancer Research Campaign http://www.bjcancer.com.

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The non-canonical Wnt pathway, a regulator of cellular motility and morphology, is increasingly implicated in cancer metastasis. In a quantitative PCR array analysis of 84 Wnt pathway associated genes, both non-canonical and canonical pathways were activated in primary and metastatic tumors relative to normal prostate. Expression of the Wnt target gene PITX2 in a prostate cancer (PCa) bone metastasis was strikingly elevated over normal prostate (over 2,000-fold) and primary prostate cancer (over 200-fold). The elevation of PITX2 protein was also evident on tissue microarrays, with strong PITX2 immunostaining in PCa skeletal and, to a lesser degree, soft tissue metastases. PITX2 is associated with cell migration during normal tissue morphogenesis. In our studies, overexpression of individual PITX2A/B/C isoforms stimulated PC-3 PCa cell motility, with the PITX2A isoform imparting a specific motility advantage in the presence of non-canonical Wnt5a stimulation. Furthermore, PITX2 specific shRNA inhibited PC-3 cell migration toward bone cell derived chemoattractant. These experimental results support a pivotal role of PITX2A and non-canonical Wnt signaling in enhancement of PCa cell motility, suggest PITX2 involvement in homing of PCa to the skeleton, and are consistent with a role for PITX2 in PCa metastasis to soft and bone tissues. Our findings, which significantly expand previous evidence that PITX2 is associated with risk of PCa biochemical recurrence, indicate that variation in PITX2 expression accompanies and may promote prostate tumor progression and metastasis.

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We report on an alternative OCGM interface for a bulletin board, where a user can pin a note or a drawing, and actually shares contents. Exploiting direct and continuous manipulations, opposite to discrete gestures, to explore containers, the proposed interface supports a more natural and immediate interaction. It manages also the presence of different simultaneous users, allowing for the creation of local multimedia contents, the connection to social networks, providing a suitable working environment for cooperative and collaborative tasks in a multi-touch setup, such as touch-tables, interactive walls or multimedia boards

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We write in response to the letter by Liu et al. [1] commenting on our article, ‘‘Mesenchymal Stem Cells Regulate Angiogenesis According to Their Mechanical Environment’’ [2]. The study by Liu et al. demonstrates that the commonly used endogeneous reference gene (ERG), b-actin, is upregulated by mechanical loading, indicating a potential bias in the determined target gene expression when normalizing to b-actin, such as in our report on unchanged vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIF)-1a mRNA levels in mechanically loaded mesenchymal stem cells (MSCs).

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This paper uses finite element techniques to investigate the performance of buried tunnels subjected to surface blasts incorporating fully coupled Fluid Structure Interaction and appropriate material models which simulate strain rate effects. Modelling techniques are first validated against existing experimental results and then used to treat the blast induced shock wave propagation and tunnel response in dry and saturated sands. Results show that the tunnel buried in saturated sand responds earlier than that in dry sand. Tunnel deformations decrease with distance from explosive in both sands, as expected. In the vicinity of the explosive, the tunnel buried in saturated sand suffered permanent deformation in both axial and circumferential directions, whereas the tunnel buried in dry sand recovered from most of the axial deformation. Overall, response of the tunnel in saturated sand is more severe for a given blast event and shows the detrimental effect of pore water on the blast response of buried tunnels. The validated modelling techniques developed in this paper can be used to investigate the blast response of tunnels buried in dry and saturated sands.

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Rail steel bridges are vulnerable to high impact forces due to the passage of trains; unfortunately the determination of these transient impact forces is not straightforward as these are affected by a large number of parameters, including the wagon design, the wheel-rail contact and the design parameters of the bridge deck and track, as well as the operational parameters – wheel load and speed. To determine these impact forces, a detailed rail train-track/bridge dynamic interaction model has been developed, which includes a comprehensive train model using multi-body dynamics approach and a flexible track/bridge model using Euler– Bernoulli beam theory. Single and multi-span bridges have been modelled to examine their dynamic characteristics. From the single span bridge, the train critical speed is determined; the minimum distance of two peak loadings is found to affect the train critical speed. The impact factor and the dynamic characteristics are discussed.

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Playfulness, with non-intrusive elements, can be considered a useful resource for enhancing social awareness and community building within work organizations. Taking inspirations from the cultural probes approach, we developed organizational probes as a set of investigation tools that could provide useful information about employees’ everyday playful experiences within their work organizations. In an academic work environment, we applied our organizational probes over a period of three weeks. Based on the collected data we developed two design concepts for playful technologies in work environments.

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Lean construction and building information modeling (BIM) are quite different initiatives, but both are having profound impacts on the construction industry. A rigorous analysis of the myriad specific interactions between them indicates that a synergy exists which, if properly understood in theoretical terms, can be exploited to improve construction processes beyond the degree to which it might be improved by application of either of these paradigms independently. Using a matrix that juxtaposes BIM functionalities with prescriptive lean construction principles, 56 interactions have been identified, all but four of which represent constructive interaction. Although evidence for the majority of these has been found, the matrix is not considered complete but rather a framework for research to explore the degree of validity of the interactions. Construction executives, managers, designers, and developers of information technology systems for construction can also benefit from the framework as an aid to recognizing the potential synergies when planning their lean and BIM adoption strategies.

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Building with Building Information Modelling (BIM) changes design and production processes. But can BIM be used to support process changes designed according to lean production and lean construction principles? To begin to answer this question we provide a conceptual analysis of the interaction of lean construction and BIM for improving construction. This was investigated by compiling a detailed listing of lean construction principles and BIM functionalities which are relevant from this perspective. These were drawn from a detailed literature survey. A research framework for analysis of the interaction between lean and BIM was then compiled. The goal of the framework is to both guide and stimulate research; as such, the approach adopted up to this point is constructive. Ongoing research has identified 55 such interactions, the majority of which show positive synergy between the two.

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In Arabidopsis, the identity of perianth and reproductive organs are specified by antagonistic action of two floral homeotic genes, APETALA2 (AP2) and AGAMOUS (AG). AP2 is also negatively regulated by an evolutionary conserved interaction with a microRNA, miR172, and has additional roles in general plant development. A kiwifruit gene with high levels of homology to AP2 and AP2-like genes from other plant species was identified. The transcript was abundant in the kiwifruit flower, particularly petal, suggesting a role in floral organ identity. Splice variants were identified, all containing both AP2 domains, including a variant that potentially produces a shorter transcript without the miRNA172 targeting site. Increased AP2 transcript accumulation was detected in the aberrant flowers of the mutant 'Pukekohe dwarf' with multiple perianth whorls and extended petaloid features. In contrast to normal kiwifruit flowers, the aberrant flowers failed to accumulate miR172 in the developing whorls, although accumulation was detected at the base of the flower. An additional role during dormancy in kiwifruit was proposed based on AP2 transcript accumulation in axillary buds before and after budbreak.

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This study investigated the relationship between psychosocial risk factors and (1) neck symptoms and (2) neck pain and disability as measured by the neck disability index (NDI). Female office workers employed in local private and public organizations were invited to participate, with 333 completing a questionnaire. Data were collected on various risk factors including age, negative affectivity, history of previous neck trauma, physical work environment, and task demands. Sixty-one percent of the sample reported neck symptoms lasting greater than 8 days in the last 12 months. The mean NDI of the sample was 15.5 out of 100, indicating mild neck pain and disability. In a hierarchical multivariate logistic regression, low supervisor support was the only psychosocial risk factor identified with the presence of neck symptoms. Similarly, low supervisor support was the only factor associated with the score on the NDI. These associations remained after adjustment for potential confounders of age, negative affectivity, and physical risk factors. The interaction of job demands, decision authority, and supervisor support was significantly associated with the NDI in the final model and this association increased when those with previous trauma were excluded. Interestingly, and somewhat contrary to initial expectations, as job demands increased, high decision authority had an increasing effect on the NDI when supervisor support was low.