127 research outputs found

    Stability of quantized time-delay nonlinear systems: A Lyapunov-Krasowskii-functional approach

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    Lyapunov-Krasowskii functionals are used to design quantized control laws for nonlinear continuous-time systems in the presence of constant delays in the input. The quantized control law is implemented via hysteresis to prevent chattering. Under appropriate conditions, our analysis applies to stabilizable nonlinear systems for any value of the quantization density. The resulting quantized feedback is parametrized with respect to the quantization density. Moreover, the maximal allowable delay tolerated by the system is characterized as a function of the quantization density.Comment: 31 pages, 3 figures, to appear in Mathematics of Control, Signals, and System

    An ISS Small-Gain Theorem for General Networks

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    We provide a generalized version of the nonlinear small-gain theorem for the case of more than two coupled input-to-state stable (ISS) systems. For this result the interconnection gains are described in a nonlinear gain matrix and the small-gain condition requires bounds on the image of this gain matrix. The condition may be interpreted as a nonlinear generalization of the requirement that the spectral radius of the gain matrix is less than one. We give some interpretations of the condition in special cases covering two subsystems, linear gains, linear systems and an associated artificial dynamical system.Comment: 26 pages, 3 figures, submitted to Mathematics of Control, Signals, and Systems (MCSS

    Contextualizing time-series data: quantification of short-term regional variability in the San Pedro Channel using high-resolution in situ glider data

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    Oceanic time series have been instrumental in providing an understanding of biological, physical, and chemical dynamics in the oceans and how these processes change over time. However, the extrapolation of these results to larger oceanographic regions requires an understanding and characterization of local versus regional drivers of variability. Here we use high-frequency spatial and temporal glider data to quantify variability at the coastal San Pedro Ocean Time-series (SPOT) site in the San Pedro Channel (SPC) and provide insight into the underlying oceanographic dynamics for the site. The dataset could be described by a combination of four water column profile types that typified active upwelling, a surface bloom, warm-stratified low-nutrient conditions, and a subsurface chlorophyll maximum. On weekly timescales, the SPOT station was on average representative of 64&thinsp;% of profiles taken within the SPC. In general, shifts in water column profile characteristics at SPOT were also observed across the entire channel. On average, waters across the SPC were most similar to offshore profiles, suggesting that SPOT time series data would be more impacted by regional changes in circulation than local coastal events. These results indicate that high-resolution in situ glider deployments can be used to quantify major modes of variability and provide context for interpreting time series data, allowing for broader application of these datasets and greater integration into modeling efforts.</p

    Rapid appraisal of barriers to the diagnosis and management of patients with dementia in primary care: a systematic review

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    <p>Abstract</p> <p>Background</p> <p>The diagnosis of dementia in primary care is perceived as a problem across countries and systems, resulting in delayed recognition and adverse outcomes for patients and their carers. Improving its early detection is an area identified for development in the English National Dementia Strategy 2009; there are thought to be multiple benefits to the patient, family, and resources by doing this. The aim of this review was to carry out a rapid appraisal in order to inform the implementation of this policy.</p> <p>Method</p> <p>Publications in English up to August 2009 relating to barriers to the recognition of dementia, were identified by a broad search strategy, using electronic databases MEDLINE, EMBASE, and psycINFO. Exclusion criteria included non-English language, studies about pharmacological interventions or screening instruments, and settings without primary care.</p> <p>Results</p> <p>Eleven empirical studies were found: 3 quantitative, 6 qualitative, and 2 with mixed methodologies. The main themes from the qualitative studies were found to be lack of support, time constraints, financial constraints, stigma, diagnostic uncertainty, and disclosing the diagnosis. Quantitative studies yielded diverse results about knowledge, service support, time constraints, and confidence. The factors identified in qualitative and quantitative studies were grouped into 3 categories: patient factors, GP factors and system characteristics.</p> <p>Conclusion</p> <p>Much can still be done in the way of service development and provision, GP training and education, and the eradication of stigma attached to dementia, to improve the early detection and management of dementia. Implementation of dementia strategies should include attention to all three categories of barriers. Further research should focus on their interaction, using different methods from studies to date.</p

    Initiation of V(D)J Recombination by Dβ-Associated Recombination Signal Sequences: A Critical Control Point in TCRβ Gene Assembly

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    T cell receptor (TCR) β gene assembly by V(D)J recombination proceeds via successive Dβ-to-Jβ and Vβ-to-DJβ rearrangements. This two-step process is enforced by a constraint, termed beyond (B)12/23, which prohibits direct Vβ-to-Jβ rearrangements. However the B12/23 restriction does not explain the order of TCRβ assembly for which the regulation remains an unresolved issue. The initiation of V(D)J recombination consists of the introduction of single-strand DNA nicks at recombination signal sequences (RSSs) containing a 12 base-pairs spacer. An RSS containing a 23 base-pairs spacer is then captured to form a 12/23 RSSs synapse leading to coupled DNA cleavage. Herein, we probed RSS nicks at the TCRβ locus and found that nicks were only detectable at Dβ-associated RSSs. This pattern implies that Dβ 12RSS and, unexpectedly, Dβ 23RSS initiate V(D)J recombination and capture their respective Vβ or Jβ RSS partner. Using both in vitro and in vivo assays, we further demonstrate that the Dβ1 23RSS impedes cleavage at the adjacent Dβ1 12RSS and consequently Vβ-to-Dβ1 rearrangement first requires the Dβ1 23RSS excision. Altogether, our results provide the molecular explanation to the B12/23 constraint and also uncover a ‘Dβ1 23RSS-mediated’ restriction operating beyond chromatin accessibility, which directs Dβ1 ordered rearrangements

    Gene Expression Signature of DMBA-Induced Hamster Buccal Pouch Carcinomas: Modulation by Chlorophyllin and Ellagic Acid

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    Chlorophyllin (CHL), a water-soluble, semi-synthetic derivative of chlorophyll and ellagic acid (EA), a naturally occurring polyphenolic compound in berries, grapes, and nuts have been reported to exert anticancer effects in various human cancer cell lines and in animal tumour models. The present study was undertaken to examine the mechanism underlying chemoprevention and changes in gene expression pattern induced by dietary supplementation of chlorophyllin and ellagic acid in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model by whole genome profiling using pangenomic microarrays. In hamsters painted with DMBA, the expression of 1,700 genes was found to be altered significantly relative to control. Dietary supplementation of chlorophyllin and ellagic acid modulated the expression profiles of 104 and 37 genes respectively. Microarray analysis also revealed changes in the expression of TGFβ receptors, NF-κB, cyclin D1, and matrix metalloproteinases (MMPs) that may play a crucial role in the transformation of the normal buccal pouch to a malignant phenotype. This gene expression signature was altered on treatment with chlorophyllin and ellagic acid. Our study has also revealed patterns of gene expression signature specific for chlorophyllin and ellagic acid exposure. Thus dietary chlorophyllin and ellagic acid that can reverse gene expression signature associated with carcinogenesis are novel candidates for cancer prevention and therapy

    Review on computational methods for Lyapunov functions

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    Lyapunov functions are an essential tool in the stability analysis of dynamical systems, both in theory and applications. They provide sufficient conditions for the stability of equilibria or more general invariant sets, as well as for their basin of attraction. The necessity, i.e. the existence of Lyapunov functions, has been studied in converse theorems, however, they do not provide a general method to compute them. Because of their importance in stability analysis, numerous computational construction methods have been developed within the Engineering, Informatics, and Mathematics community. They cover different types of systems such as ordinary differential equations, switched systems, non-smooth systems, discrete-time systems etc., and employ di_erent methods such as series expansion, linear programming, linear matrix inequalities, collocation methods, algebraic methods, set-theoretic methods, and many others. This review brings these different methods together. First, the different types of systems, where Lyapunov functions are used, are briefly discussed. In the main part, the computational methods are presented, ordered by the type of method used to construct a Lyapunov function

    Effectiveness of an intervention to facilitate prompt referral to memory clinics in the United Kingdom: Cluster randomised controlled trial

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    Background Most people with dementia do not receive timely diagnosis, preventing them from making informed plans about their future and accessing services. Many countries have a policy to increase timely diagnosis, but trials aimed at changing general practitioner (GP) practice have been unsuccessful. We aimed to assess whether a GP’s personal letter, with an evidence-based leaflet about overcoming barriers to accessing help for memory problems—aimed at empowering patients and families—increases timely dementia diagnosis and patient presentation to general practice. Methods and finding Multicentre, cluster-randomised controlled trial with raters masked to an online computer-generated randomisation system assessing 1 y outcome. We recruited 22 general practices (August 2013–September 2014) and 13 corresponding secondary care memory services in London, Hertfordshire, and Essex, United Kingdom. Eligible patients were aged ≥70 y, without a known diagnosis of dementia, living in their own homes. There were 6,387 such patients in 11 intervention practices and 8,171 in the control practices. The primary outcome was cognitive severity on Mini Mental State Examination (MMSE). Main secondary outcomes were proportion of patients consulting their GP with suspected memory disorders and proportion of those referred to memory clinics. There was no between-group difference in cognitive severity at diagnosis (99 intervention, mean MMSE = 22.04, 95% confidence intervals (CIs) = 20.95 to 23.13; 124 control, mean MMSE = 22.59, 95% CI = 21.58 to 23.6; p = 0.48). GP consultations with patients with suspected memory disorders increased in intervention versus control group (odds ratio = 1.41; 95% CI = 1.28, 1.54). There was no between-group difference in the proportions of patients referred to memory clinics (166, 2.5%; 220, 2.7%; p = .077 respectively). The study was limited as we do not know whether the additional patients presenting to GPs had objective as well as subjective memory problems and therefore should have been referred. In addition, we aimed to empower patients but did not do anything to change GP practice. Conclusions Our intervention to access timely dementia diagnosis resulted in more patients presenting to GPs with memory problems, but no diagnoses increase. We are uncertain as to the reason for this and do not know whether empowering the public and targeting GPs would have resulted in a successful intervention. Future interventions should be targeted at both patients and GPs. Trial registration Current Controlled Trials ISRCTN1921687
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