9 resultados para analysis and functional analysis

em Cambridge University Engineering Department Publications Database


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Cytosine methylation is important for transposon silencing and epigenetic regulation of endogenous genes, although the extent to which this DNA modification functions to regulate the genome is still unknown. Here we report the first comprehensive DNA methylation map of an entire genome, at 35 base pair resolution, using the flowering plant Arabidopsis thaliana as a model. We find that pericentromeric heterochromatin, repetitive sequences, and regions producing small interfering RNAs are heavily methylated. Unexpectedly, over one-third of expressed genes contain methylation within transcribed regions, whereas only approximately 5% of genes show methylation within promoter regions. Interestingly, genes methylated in transcribed regions are highly expressed and constitutively active, whereas promoter-methylated genes show a greater degree of tissue-specific expression. Whole-genome tiling-array transcriptional profiling of DNA methyltransferase null mutants identified hundreds of genes and intergenic noncoding RNAs with altered expression levels, many of which may be epigenetically controlled by DNA methylation.

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In this paper we demonstrate laser emission from emulsion-based polymer dispersed liquid crystals. Such lasers can be easily formed on single substrates with no alignment layers. Remarkably, it is shown that there can exist two radically different laser emission profiles, namely, photonic band-edge lasing and non-resonant random lasing. The emission is controlled by simple changes in the emulsification procedure. Low mixing speeds generate larger droplets that favor photonic band edge lasing with the requisite helical alignment produced by film shrinkage. Higher mixing speeds generate small droplets, which facilitate random lasing by a non-resonant scattering feedback process. Lasing thresholds and linewidth data are presented showing the potential of controllable linewidth lasing sources. Sequential and stacked layers demonstrate the possibility of achieving complex, simultaneous multi-wavelength and "white-light" laser output from a wide variety of substrates including glass, metallic, paper and flexible plastic. © 2011 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

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In this paper we demonstrate laser emission from emulsion-based polymer dispersed liquid crystals. Such lasers can be easily formed on single substrates with no alignment layers. Remarkably, it is shown that there can exist two radically different laser emission profiles, namely, photonic band-edge lasing and non-resonant random lasing. The emission is controlled by simple changes in the emulsification procedure. Low mixing speeds generate larger droplets that favor photonic band edge lasing with the requisite helical alignment produced by film shrinkage. Higher mixing speeds generate small droplets, which facilitate random lasing by a non-resonant scattering feedback process. Lasing thresholds and linewidth data are presented showing the potential of controllable linewidth lasing sources. Sequential and stacked layers demonstrate the possibility of achieving complex, simultaneous multi-wavelength and "white-light" laser output from a wide variety of substrates including glass, metallic, paper and flexible plastic. © 2011 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

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Understanding how and why changes propagate during engineering design is critical because most products and systems emerge from predecessors and not through clean sheet design. This paper applies change propagation analysis methods and extends prior reasoning through examination of a large data set from industry including 41,500 change requests, spanning 8 years during the design of a complex sensor system. Different methods are used to analyze the data and the results are compared to each other and evaluated in the context of previous findings. In particular the networks of connected parent, child and sibling changes are resolved over time and mapped to 46 subsystem areas. A normalized change propagation index (CPI) is then developed, showing the relative strength of each area on the absorber-multiplier spectrum between -1 and +1. Multipliers send out more changes than they receive and are good candidates for more focused change management. Another interesting finding is the quantitative confirmation of the "ripple" change pattern. Unlike the earlier prediction, however, it was found that the peak of cyclical change activity occurred late in the program driven by systems integration and functional testing. Patterns emerged from the data and offer clear implications for technical change management approaches in system design. Copyright © 2007 by ASME.

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Access to robust and information-rich human cardiac tissue models would accelerate drug-based strategies for treating heart disease. Despite significant effort, the generation of high-fidelity adult-like human cardiac tissue analogs remains challenging. We used computational modeling of tissue contraction and assembly mechanics in conjunction with microfabricated constraints to guide the design of aligned and functional 3D human pluripotent stem cell (hPSC)-derived cardiac microtissues that we term cardiac microwires (CMWs). Miniaturization of the platform circumvented the need for tissue vascularization and enabled higher-throughput image-based analysis of CMW drug responsiveness. CMW tissue properties could be tuned using electromechanical stimuli and cell composition. Specifically, controlling self-assembly of 3D tissues in aligned collagen, and pacing with point stimulation electrodes, were found to promote cardiac maturation-associated gene expression and in vivo-like electrical signal propagation. Furthermore, screening a range of hPSC-derived cardiac cell ratios identified that 75% NKX2 Homeobox 5 (NKX2-5)+ cardiomyocytes and 25% Cluster of Differentiation 90 OR (CD90)+ nonmyocytes optimized tissue remodeling dynamics and yielded enhanced structural and functional properties. Finally, we demonstrate the utility of the optimized platform in a tachycardic model of arrhythmogenesis, an aspect of cardiac electrophysiology not previously recapitulated in 3D in vitro hPSC-derived cardiac microtissue models. The design criteria identified with our CMW platform should accelerate the development of predictive in vitro assays of human heart tissue function.

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This paper reports a perspective investigation of computational modelling of blood fluid in microchannel devices as a preparation for future research on fluid-structure interaction (FSI) in biofluid mechanics. The investigation is carried out through two aspects, respectively on physical behaviours of blood flow in microchannels and appropriate methodology for modelling. The physics of blood flow is targeted to the challenges for describing blood flow in microchannels, including rheology of blood fluid, suspension features of red blood cells (RBCs), laminar hydrodynamic influence and effect of surface roughness. The analysis shows that due to the hyperelastic property of RBC and its comparable dimension with microchannels, blood fluid shows complex behaviours of two phase flow. The trajectory and migration of RBCs require accurate description of RBC deformation and interaction with plasma. Following on a discussion of modelling approaches, i.e. Eulerian method and Lagrangian method, the main stream modelling methods for multiphase flow are reviewed and their suitability to blood flow is analysed. It is concluded that the key issue for blood flow modelling is how to describe the suspended blood cells, modelled by Lagrangian method, and couple them with the based flow, modelled by Eulerian method. The multiphase flow methods are thereby classified based on the number of points required for describing a particle, as follows: (i) single-point particle methods, (ii) mutli-point particle methods, (iii) functional particle methods, and (iv) fluid particle methods. While single-point particle methods concentrate on particle dynamic movement, multipoint and functional particle methods can take into account particle mechanics and thus offer more detailed information for individual particles. Fluid particle methods provide good compromise between two phases, but require additional information for particle mechanics. For furthermore detailed description, we suggest to investigate the possibility using two domain coupling method, in which particles and base flow are modelled by two separated solvers. It is expected that this paper could clarify relevant issues in numerical modelling of blood flow in microchannels and induce some considerations for modelling blood flow using multiphase flow methods. © 2012 IEEE.

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In order to improve algal biofuel production on a commercial-scale, an understanding of algal growth and fuel molecule accumulation is essential. A mathematical model is presented that describes biomass growth and storage molecule (TAG lipid and starch) accumulation in the freshwater microalga Chlorella vulgaris, under mixotrophic and autotrophic conditions. Biomass growth was formulated based on the Droop model, while the storage molecule production was calculated based on the carbon balance within the algal cells incorporating carbon fixation via photosynthesis, organic carbon uptake and functional biomass growth. The model was validated with experimental growth data of C. vulgaris and was found to fit the data well. Sensitivity analysis showed that the model performance was highly sensitive to variations in parameters associated with nutrient factors, photosynthesis and light intensity. The maximum productivity and biomass concentration were achieved under mixotrophic nitrogen sufficient conditions, while the maximum storage content was obtained under mixotrophic nitrogen deficient conditions.

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In order to improve algal biofuel production on a commercial-scale, an understanding of algal growth and fuel molecule accumulation is essential. A mathematical model is presented that describes biomass growth and storage molecule (TAG lipid and starch) accumulation in the freshwater microalga Chlorella vulgaris, under mixotrophic and autotrophic conditions. Biomass growth was formulated based on the Droop model, while the storage molecule production was calculated based on the carbon balance within the algal cells incorporating carbon fixation via photosynthesis, organic carbon uptake and functional biomass growth. The model was validated with experimental growth data of C. vulgaris and was found to fit the data well. Sensitivity analysis showed that the model performance was highly sensitive to variations in parameters associated with nutrient factors, photosynthesis and light intensity. The maximum productivity and biomass concentration were achieved under mixotrophic nitrogen sufficient conditions, while the maximum storage content was obtained under mixotrophic nitrogen deficient conditions. © 2014 Elsevier Ltd.