641 research outputs found

    Generalized Stabilizing Conditions for Model Predictive Control

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    © 2015, The Author(s).This note addresses the tracking problem for model predictive control. It presents simple procedures for both linear and nonlinear constrained model predictive control when the desired equilibrium state is any point in a specified set. The resultant region of attraction is the union of the regions of attraction for each equilibrium state in the specified set and is therefore larger than that obtained when conventional model predictive control is employed

    Results from a set of three-dimensional numerical experiments of a hot Jupiter atmosphere

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    We present highlights from a large set of simulations of a hot Jupiter atmosphere, nominally based on HD 209458b, aimed at exploring both the evolution of the deep atmosphere, and the acceleration of the zonal flow or jet. We find the occurrence of a super-rotating equatorial jet is robust to changes in various parameters, and over long timescales, even in the absence of strong inner or bottom boundary drag. This jet is diminished in one simulation only, where we strongly force the deep atmosphere equator-to-pole temperature gradient over long timescales. Finally, although the eddy momentum fluxes in our atmosphere show similarities with the proposed mechanism for accelerating jets on tidally-locked planets, the picture appears more complex. We present tentative evidence for a jet driven by a combination of eddy momentum transport and mean flow.Comment: 26 pages, 22 Figures. Accepted for publication in Astronomy and Astrophysic

    Using the UM dynamical cores to reproduce idealised 3D flows

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    We demonstrate that both the current (New Dynamics), and next generation (ENDGame) dynamical cores of the UK Met Office global circulation model, the UM, reproduce consistently, the long-term, large-scale flows found in several published idealised tests. The cases presented are the Held-Suarez test, a simplified model of Earth (including a stratosphere), and a hypothetical tidally locked Earth. Furthermore, we show that using simplifications to the dynamical equations, which are expected to be justified for the physical domains and flow regimes we have studied, and which are supported by the ENDGame dynamical core, also produces matching long-term, large-scale flows. Finally, we present evidence for differences in the detail of the planetary flows and circulations resulting from improvements in the ENDGame formulation over New Dynamics.Comment: 34 Pages, 23 Figures. Accepted for publication in Geoscientific Model Development (pre-proof version

    ADAPTIVE MULTILEVEL SPLITTING IN MOLECULAR DYNAMICS SIMULATIONS

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    Adaptive Multilevel Splitting (AMS) is a replica-based rare event sampling method that has been used successfully in high-dimensional stochastic simulations to identify trajectories across a high potential barrier separating one metastable state from another, and to estimate the probability of observing such a trajectory. An attractive feature of AMS is that, in the limit of a large number of replicas, it remains valid regardless of the choice of reaction coordinate used to characterize the trajectories. Previous studies have shown AMS to be accurate in Monte Carlo simulations. In this study, we extend the application of AMS to molecular dynamics simulations and demonstrate its effectiveness using a simple test system. Our conclusion paves the way for useful applications, such as molecular dynamics calculations of the characteristic time of drug dissociation from a protein target

    COX-2 mRNA is increased in oesophageal mucosal cells by a proton pump inhibitor

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    Author version made available in accordance with the publisher's policy.Introduction: Barrett’s oesophagus develops in some individuals with gastro-oesophageal reflux, and is the precursor to oesophageal adenocarcinoma. Proton pump inhibitors (PPIs) suppress gastric acid production and are used to treat reflux. Clinical trials suggest that COX inhibitors might prevent oesophageal cancer, although PPIs could offset this by increasing COX-2 expression in Barrett’s oesophagus. To investigate this, we evaluated the impact of a PPI on COX expression in oesophageal mucosal cells. Methods: The effect of the PPI esomeprazole on COX-1 and COX-2 mRNA levels in oesophageal cells was determined. Oesophageal cell lines OE33 (adenocarcinoma derived) and HET-1A (immortalized squamous cells), and a control intestinal cell line - HT29 (colon carcinoma), were treated for 24 hours with increasing concentrations of the esomeprazole. Results: COX-2, but not COX-1, mRNA levels, dose dependently increased in OE33 and HET-1A cells vs. esomeprazole concentration. COX-2 mRNA levels did not increase in HT29 cells. Conclusions: Exposure to esomeprazole increases COX-2 mRNA in oesophageal cells. This might contribute to the lack of benefit for COX inhibitors for oesophageal cancer prevention in recent clinica

    microRNAs and Esophageal Cancer - Implications for Pathogenesis and Therapy

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    Author version made available in accordance with the publisher's policy.There are several microRNAs that have been consistently reported to be differentially expressed in esophageal squamous cell carcinoma vs. normal squamous tissue, with prognostic associations for miR-21 (invasion, positive nodes, decreased survival), miR-143 (disease recurrence, invasion depth), and miR-375 (inversely correlated with advanced stage, distant metastasis, poor overall survival, and disease-free survival). There is also evidence that miR-375 regulates gene expression associated with resistance to chemotherapy. Hence, microRNA expression assays have the potential to provide clinically relevant information about prognosis and potential response to chemotherapy in patients with esophageal squamous cell carcinoma. Results are inconsistent, however, for microRNAs across different studies for esophageal adenocarcinoma (EAC) vs. its precursor lesion Barrett’s esophagus. These inconsistencies may partly result from pathological and/or molecular heterogeneity in both Barrett’s esophagus and EAC, but may also result from differences in study designs or different choices of comparator tissues. Despite these inconsistencies, however, several mRNA/protein targets have been identified, the cancer related biology of some of these targets is well understood, and there are clinico-pathological associations for some of these mRNA targets. MicroRNAs also have potential for use in therapy for esophageal cancers. The development of new delivery methods, such as minicells and autologous microvesicles, and molecular modifications such as the addition of aromatic benzene pyridine analogs, have facilitated the exploration of the effects of therapeutic microRNAs in vivo. These approaches are producing encouraging results, with one technology in a phase I/IIa clinical trial

    Molecular biomarkers and ablative therapies for Barrett’s esophagus

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    Author version made available in accordance with the publisher's policy.Barrett’s esophagus is the major risk factor for esophageal adenocarcinoma. Endoscopic interventions which ablate Barrett’s esophagus mucosa lead to replacement with a new squamous (neosquamous) mucosa, but it can be difficult to achieve complete ablation. Knowing whether cancer is less likely to develop in neosquamous mucosa or residual Barrett’s esophagus after ablation is critical for determining the efficacy of treatment. This issue can be informed by assessing biomarkers that are associated with an increased risk of progression to adenocarcinoma. Although there are few post-ablation biomarker studies, evidence suggests that that neosquamous mucosa may have a reduced risk of adenocarcinoma in patients who have been treated for dysplasia or cancer, but some patients who do not have complete eradication of non-dysplastic Barrett’s esophagus may still be at risk. Biomarkers could be used to optimize endoscopic surveillance strategies following ablation, but this needs to be assessed by clinical studies and economic modeling

    Bayesian fitting of Taurus brown dwarf spectral energy distributions

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    We present derived stellar and disc parameters for a sample of Taurus brown dwarfs both with and without evidence of an associated disc. These parameters have been derived using an online fitting tool (http://bd-server.astro.ex.ac.uk/), which includes a statistically robust derivation of uncertainties, an indication of pa- rameter degeneracies, and a complete treatment of the input photometric and spectroscopic observations. The observations of the Taurus members with indications of disc presence have been fitted using a grid of theoretical models including detailed treatments of physical processes accepted for higher mass stars, such as dust sublimation, and a simple treatment of the accretion flux. This grid of models has been designed to test the validity of the adopted physical mechanisms, but we have also constructed models using parameterisation, for example semi-empirical dust sublimation radii, for users solely interested in parameter derivation and the quality of the fit. The parameters derived for the naked and disc brown dwarf systems are largely consistent with literature observations. However, our inner disc edge locations are consistently closer to the star than previous results and we also derive elevated accretion rates over non-SED based accretion rate derivations. For inner edge locations we attribute these differences to the detailed modelling we have performed of the disc structure, particularly at the crucial inner edge where departures in geometry from the often adopted vertical wall due to dust sublimation (and therefore accretion flux) can compensate for temperature (and therefore distance) changes to the inner edge of the dust disc. In the case of the elevated derived accretion rates, in some cases, this may be caused by the intrinsic stellar luminosities of the targets exceeding that predicted by the isochrones we have adopted.Comment: The paper contains 35 pages with 15 figures and 17 tables. Accepted for publication in MNRA
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