Side channel spillways

Bibliography: pages 101-102.The design of side channel spillways has been discussed in detail by a number of investigators. In this thesis the most important works have been summarised, discussed and in some cases expanded in an attempt to give a concise account of the existing theories. Model tests were carried out on a side channel spillway of general type, as well as on the proposed Mtata dam spillway and the results are presented and discussed. Charts were drawn up and a procedure was recommended for the design of side channel spillways in an attempt to provide a designer with a simple method of design which he can use with confidence

Control of Fugitive Methane Emissions Through Combustion of Compressor Vent and Engine Crankcase Emissions

At compressor stations, fugitive methane emissions from compressor piston rod packing and engine crankcases are vented directly into the atmosphere. In an effort to reduce compression station carbon footprint, this study evaluates the feasibility of combusting the methane emissions into carbon dioxide and thus reduce the global warming potential. This study focuses on running simulations to determine the methane reduction from rebreathing engine crankcase and compressor vent gases into the air intake of a large bore, natural gas, 2-stroke engine. The methane reduction percentage is observed over a range of rebreathed gas mass flow rates, and rebreathed gas composition. It is extremely difficult to determine the composition of the engine blow-by gases in the crankcase, since the composition depends on a large variety of parameters. For this study, the emissions from the compressor was modeled as methane, and the emissions from the engine crankcase was modeled as products of combustion with a varying amount of methane concentrations. A sensitivity analysis was performed, and the observed pressure traces show that the engine performance is not affected by the addition of rebreathed gases. This insensitivity mainly results from the very small rebreathed flow rates compared to the air intake, and the adjustments made on engine parameters, boost pressure and fuel injection rate, to keep TER and the energy delivery rate the same. The simulations also showed that the net methane reduction percentage was approximately 52%, no matter the study test conditions. It was discovered that the methane reduction depends on the trapping ratio of the engine; since these engines generally have trapping ratios around 50%, the actual methane reduction tends to be small. A 52% reduction rate is not desirable; the hope is to increase the reduction rate closer to 100%. More importantly to note, a substantial amount of complexity would need to be added to a typical compressor station just to reduce methane emissions by 1 kg/hr. Thus, at present, the idea of rebreathing compressor and engine crank case gases for methane emission reduction is not feasible. Future studies should focus on routing the emissions to a 4-stroke engine, a waste heat recovery system, or other combustion devices with higher trapping ratios

Modelling polarity-driven laminar patterns in bilayer tissues with mixed signalling mechanisms

Recent advances in high-resolution experimental methods have highlighted the significance of cell signal pathway crosstalk and localised signalling activity in the development and disease of numerous biological systems. The investigation of multiple signal pathways often introduces different methods of cell-cell communication, i.e. contact-based or diffusive signalling, which generates both a spatial and temporal dependence on cell behaviours. Motivated by cellular mechanisms that control cell-fate decisions in developing bilayer tissues, we use dynamical systems coupled with multilayer graphs to analyse the role of signalling polarity and pathway crosstalk in fine-grain pattern formation of protein activity. Specifically, we study how multilayer graph edge structures and weights influence the layer-wise (laminar) patterning of cells in bilayer structures, which are commonly found in glandular tissues. We present sufficient conditions for existence, uniqueness and instability of homogeneous cell states in the large-scale spatially discrete dynamical system. Using methods of pattern templating by graph partitioning to generate quotient systems in combination with concepts from monotone dynamical systems, we exploit the extensive dimensionality reduction to provide existence conditions for the polarity required to induce fine-grain laminar patterns with multiple spatially dependent intracellular components. We then explore the spectral links between the quotient and large-scale dynamical systems to extend the laminar patterning criteria from existence to convergence for sufficiently large amounts of cellular polarity in the large-scale dynamical system, independent of spatial dimension and number of cells in the tissue

Wnt ligand and receptor patterning in the liver

In the liver, the tight spatiotemporal regulation of Wnt/β-catenin signaling is required to establish and maintain a metabolic form of tissue polarity termed zonation. In this review, we discuss the latest technologies applied in the study of liver zonation and provide a summary of the Wnt ligand and receptor expression patterns in the hepatic lobule. We further discuss the mechanisms, by which Wnt instructive cues might be spatially confined and propagated along the central vein-portal triad axis

A divergent canonical WNT-signaling pathway regulates microtubule dynamics: Dishevelled signals locally to stabilize microtubules

Dishevelled (DVL) is associated with axonal microtubules and regulates microtubule stability through the inhibition of the serine/threonine kinase, glycogen synthase kinase 3β (GSK-3β). In the canonical WNT pathway, the negative regulator Axin forms a complex with β-catenin and GSK-3β, resulting in β-catenin degradation. Inhibition of GSK-3β by DVL increases β-catenin stability and TCF transcriptional activation. Here, we show that Axin associates with microtubules and unexpectedly stabilizes microtubules through DVL. In turn, DVL stabilizes microtubules by inhibiting GSK-3β through a transcription- and β-catenin–independent pathway. More importantly, axonal microtubules are stabilized after DVL localizes to axons. Increased microtubule stability is correlated with a decrease in GSK-3β–mediated phosphorylation of MAP-1B. We propose a model in which Axin, through DVL, stabilizes microtubules by inhibiting a pool of GSK-3β, resulting in local changes in the phosphorylation of cellular targets. Our data indicate a bifurcation in the so-called canonical WNT-signaling pathway to regulate microtubule stability

Optimization and evaluation of T7 based RNA linear amplification protocols for cDNA microarray analysis

BACKGROUND: T7 based linear amplification of RNA is used to obtain sufficient antisense RNA for microarray expression profiling. We optimized and systematically evaluated the fidelity and reproducibility of different amplification protocols using total RNA obtained from primary human breast carcinomas and high-density cDNA microarrays. RESULTS: Using an optimized protocol, the average correlation coefficient of gene expression of 11,123 cDNA clones between amplified and unamplified samples is 0.82 (0.85 when a virtual array was created using repeatedly amplified samples to minimize experimental variation). Less than 4% of genes show changes in expression level by 2-fold or greater after amplification compared to unamplified samples. Most changes due to amplification are not systematic both within one tumor sample and between different tumors. Amplification appears to dampen the variation of gene expression for some genes when compared to unamplified poly(A)(+) RNA. The reproducibility between repeatedly amplified samples is 0.97 when performed on the same day, but drops to 0.90 when performed weeks apart. The fidelity and reproducibility of amplification is not affected by decreasing the amount of input total RNA in the 0.3–3 micrograms range. Adding template-switching primer, DNA ligase, or column purification of double-stranded cDNA does not improve the fidelity of amplification. The correlation coefficient between amplified and unamplified samples is higher when total RNA is used as template for both experimental and reference RNA amplification. CONCLUSION: T7 based linear amplification reproducibly generates amplified RNA that closely approximates original sample for gene expression profiling using cDNA microarrays

Cell permeable stapled peptide inhibitor of Wnt signaling that targets β-catenin protein‒protein interactions

The Wnt signaling pathway plays a critical role in cell proliferation and differentiation, thus it is often associated with diseases such as cancers. Unfortunately, although attractive, developing anti-cancer strategy targeting Wnt signaling has been challenging given that the most attractive targets are involved in protein-protein interactions (PPIs). Here, we develop a stapled peptide inhibitor that targets the interaction between β-catenin and T cell factor/lymphoid enhancer-binding factor transcription factors, which are crucially involved in Wnt signaling. Our integrative approach combines peptide stapling to optimize proteolytic stability, with lessons learned from cell-penetrating peptide (CPP) design to maximize cellular uptake resulting in NLS-StAx-h, a selective, cell permeable, stapled peptide inhibitor of oncogenic Wnt signaling that efficiently inhibits β-catenin-transcription factor interactions. We expect that this type of integrative strategy that endows stapled peptides with CPP features will be generally useful for developing inhibitors of intracellular PPIs

Modelling polarity-driven laminar patterns in bilayer tissues with mixed signalling mechanisms

Recent advances in high-resolution experimental methods have highlighted the significance of cell signal pathway crosstalk and localised signalling activity in the development and disease of numerous biological systems. The investigation of multiple signal pathways often introduces different methods of cell-cell communication, i.e. contact-based or diffusive signalling, which generates both a spatial and temporal dependence on cell behaviours. Motivated by cellular mechanisms that control cell-fate decisions in developing bilayer tissues, we use dynamical systems coupled with multilayer graphs to analyse the role of signalling polarity and pathway crosstalk in fine-grain pattern formation of protein activity. Specifically, we study how multilayer graph edge structures and weights influence the layer-wise (laminar) patterning of cells in bilayer structures, which are commonly found in glandular tissues. We present sufficient conditions for existence, uniqueness and instability of homogeneous cell states in the large-scale spatially discrete dynamical system. Using methods of pattern templating by graph partitioning to generate quotient systems, in combination with concepts from monotone dynamical systems, we exploit the extensive dimensionality reduction to provide existence conditions for the polarity required to induce fine-grain laminar patterns with multiple spatially dependent intracellular components. We then explore the spectral links between the quotient and large-scale dynamical systems to extend the laminar patterning criteria from existence to convergence for sufficiently large amounts of cellular polarity in the large-scale dynamical system, independent of spatial dimension and number of cells in the tissue

A general computational framework for COVID-19 modelling with applications to testing varied interventions in education environments

We construct a spatially-compartmental, individual-based model of the spread of SARS-CoV-2 in indoor spaces. The model can be used to predict the infection rates in a variety of locations when various non-pharmaceutical interventions (NPIs) are introduced. Tasked by the Welsh Government, we apply the model to secondary schools and to Further and Higher Education environments. Specifically, we consider student populations mixing in a classroom and in halls of residence. We focus on assessing the potential efficacy of Lateral Flow Devices (LFDs) when used in broad-based screens for asymptomatic infection or in ‘test-to-release’ scenarios in which individuals who have been exposed to infection are released from isolation after a negative LFD result. LFDs are also compared to other NPIs; we find that, although LFD testing can be used to mitigate the spread of SARS-CoV-2, it is more effective to invest in personal protective equipment, e.g., masks, and in increasing ventilation quality. In addition, we provide an open-access and user-friendly online applet that simulates the model, complete with user tutorials to encourage the use of the model to aid educational policy decisions as input infection data becomes available