H∞ and H2 norms of 2D mixed continuous-discrete-time systems via rationally-dependent complex Lyapunov functions

This paper addresses the problem of determining the H∞ and H2 norms of 2-D mixed continuous-discrete-time systems. The first contribution is to propose a novel approach based on the use of complex Lyapunov functions with even rational parametric dependence, which searches for upper bounds on the sought norms via linear matrix inequalities (LMIs). The second contribution is to show that the upper bounds provided are nonconservative by using Lyapunov functions in the chosen class with sufficiently large degree. The third contribution is to provide conditions for establishing the tightness of the upper bounds. The fourth contribution is to show how the numerical complexity of the proposed approach can be significantly reduced by proposing a new necessary and sufficient LMI condition for establishing positive semidefiniteness of even Hermitian matrix polynomials. This result is also exploited to derive an improved necessary and sufficient LMI condition for establishing exponential stability of 2-D mixed continuous-discrete-time systems. Some numerical examples illustrate the proposed approach. It is worth remarking that nonconservative LMI methods for determining the H∞and H2 norms of 2-D mixed continuous-discrete-time systems have not been proposed yet in the literature.postprin

The introduction of an holistic design approach through a teaching company scheme

Traditional design approaches separate the various functions of design such as material selection, performance modelling and tolerance specification into discrete entities. Whilst this allows more focused methods to be used at each stage, areas of conflict or benefit may be overlooked, and the designer is left to bring the loose ends together. This paper looks at a synthesis approach that draws upon a number of current design themes. The design process is considered along with various aspects such as product development, design-for-`X' methodologies and material selection. The need for the preservation of design knowledge and reasoning, the so called wh-? questions, within the process are considered along with various models of the design process. The paper draws these various aspects together to form a more holistic approach to design. The application of this technique within the Teaching Company Scheme is briefly discussed

Robust stability and performance analysis of 2D mixed continuous-discrete-time systems with uncertainty

postprin

Polynomial approximation of quasipolynomials based on digital filter design principles

This contribution is aimed at a possible procedure approximating quasipolynomials by polynomials. Quasipolynomials appear in linear time-delay systems description as a natural consequence of the use of the Laplace transform. Due to their infinite root spectra, control system analysis and synthesis based on such quasipolynomial models are usually mathematically heavy. In the light of this fact, there is a natural research endeavor to design a sufficiently accurate yet simple engineeringly acceptable method that approximates them by polynomials preserving basic spectral information. In this paper, such a procedure is presented based on some ideas of discrete-time (digital) filters designing without excessive math. Namely, the particular quasipolynomial is subjected to iterative discretization by means of the bilinear transformation first; consequently, linear and quadratic interpolations are applied to obtain integer powers of the approximating polynomial. Since dominant roots play a decisive role in the spectrum, interpolations are made in their very neighborhood. A simulation example proofs the algorithm efficiency. © Springer International Publishing Switzerland 2016

O6-methylguanine-DNA methyltransferase depletion and DNA damage in patients with melanoma treated with temozolomide alone or with lomeguatrib

We evaluated the pharmacodynamic effects of the O6-methylguanine-DNA methyltransferase (MGMT) inactivator lomeguatrib (LM) on patients with melanoma in two clinical trials. Patients received temozolomide (TMZ) for 5 days either alone or with LM for 5, 10 or 14 days. Peripheral blood mononuclear cells (PBMCs) were isolated before treatment and during cycle 1. Where available, tumour biopsies were obtained after the last drug dose in cycle 1. Samples were assayed for MGMT activity, total MGMT protein, and O6-methylguanine (O6-meG) and N7-methylguanine levels in DNA. MGMT was completely inactivated in PBMC from patients receiving LM, but detectable in those on TMZ alone. Tumours biopsied on the last day of treatment showed complete inactivation of MGMT but there was recovery of activity in tumours sampled later. Significantly more O6-meG was present in the PBMC DNA of LM/TMZ patients than those on TMZ alone. LM/TMZ leads to greater MGMT inactivation, and higher levels of O6-meG than TMZ alone. Early recovery of MGMT activity in tumours suggested that more protracted dosing with LM is required. Extended dosing of LM completely inactivated PBMC MGMT, and resulted in persistent levels of O6-meG in PBMC DNA during treatment

Glucocorticoid pharmacogenetics in pediatric idiopathic nephrotic syndrome

Idiopathic nephrotic syndrome represents the most common type of primary glomerular disease in children: glucocorticoids (GCs) are the first-line therapy, even if considerable interindividual differences in thepir efficacy and side effects have been reported. Immunosuppressive and anti-inflammatory effects of these drugs are mainly due to the GC-mediated transcription regulation of pro- and anti-inflammatory genes. This mechanism of action is the result of a complex multistep pathway that involves the glucocorticoid receptor and several other proteins, encoded by polymorphic genes. Aim of this review is to highlight the current knowledge on genetic variants that could affect GC response, particularly focusing on children with idiopathic nephrotic syndrome

The diagnostic accuracy of (18) F-FGD-PET/CT for cancer of the gallbladder: a retrospective study

Background Gallbladder cancer has a poor prognosis and imaging can have variable diagnostic accuracy. We assessed the ability of preoperative 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG-PET/CT) imaging to predict a postoperative histological diagnosis of gallbladder cancer. Method A retrospective analysis was undertaken in a cohort of patients, who had suspected gallbladder cancer on cross-sectional imaging and that underwent preoperative FDG-PET/CT scan. The discriminatory power of FDG-PET/CT was determined in receiver operator characteristic (ROC) analysis and diagnostic accuracy parameters were estimated at different thresholds of maximum standard unit value (SUVmax). Results Twenty-two patients were included in the study; 7 had malignant and 15 benign diagnoses. There was no statistically significant difference between the measured SUVmax between the two groups (p = 0.71). With an area under the curve of 0.486, the ROC curve did not indicate any discriminatory power of FDG-PET/CT at any potential threshold of SUVmax. Conclusion This study indicates that the diagnosis of primary gallbladder cancer cannot be accurately confirmed with FDG PET/CT scanning

Inhibition, flexibility, working memory and planning in autism spectrum disorders with and without comorbid ADHD-symptoms

<p>Abstract</p> <p>Background</p> <p>Recent studies have not paid a great deal of attention to comorbid attention-deficit/hyperactivity disorder (ADHD) symptoms in autistic children even though it is well known that almost half of children with autism spectrum disorder (ASD) suffer from hyperactivity, inattention and impulsivity. The goal of this study was to evaluate and compare executive functioning (EF) profiles in children with ADHD and in children with ASD with and without comorbid ADHD.</p> <p>Methods</p> <p>Children aged 6 to 18 years old with ADHD (n = 20) or ASD (High-Functioning autism or Asperger syndrome) with (n = 20) and without (n = 20) comorbid ADHD and a typically developing group (n = 20) were compared on a battery of EF tasks comprising inhibition, flexibility, working memory and planning tasks. A MANOVA, effect sizes as well as correlations between ADHD-symptomatology and EF performance were calculated. Age- and IQ-corrected z scores were used.</p> <p>Results</p> <p>There was a significant effect for the factor group (F = 1.55; dF = 42; p = .02). Post-hoc analysis revealed significant differences between the ADHD and the TD group on the inhibition task for false alarms (p = .01) and between the ADHD group, the ASD+ group (p = .03), the ASD- group (p = .02) and the TD group (p = .01) for omissions. Effect sizes showed clear deficits of ADHD children in inhibition and working memory tasks. Participants with ASD were impaired in planning and flexibility abilities. The ASD+ group showed compared to the ASD- group more problems in inhibitory performance but not in the working memory task.</p> <p>Conclusion</p> <p>Our findings replicate previous results reporting impairment of ADHD children in inhibition and working memory tasks and of ASD children in planning and flexibility abilities. The ASD + group showed similarities to the ADHD group with regard to inhibitory but not to working memory deficits. Nevertheless the heterogeneity of these and previous results shows that EF assessment is not useful for differential diagnosis between ADHD and ASD. It might be useful for evaluating strengths and weaknesses in individual children.</p

Nonsense Mediated Decay Resistant Mutations Are a Source of Expressed Mutant Proteins in Colon Cancer Cell Lines with Microsatellite Instability

BACKGROUND: Frameshift mutations in microsatellite instability high (MSI-High) colorectal cancers are a potential source of targetable neo-antigens. Many nonsense transcripts are subject to rapid degradation due to nonsense-mediated decay (NMD), but nonsense transcripts with a cMS in the last exon or near the last exon-exon junction have intrinsic resistance to nonsense-mediated decay (NMD). NMD-resistant transcripts are therefore a likely source of expressed mutant proteins in MSI-High tumours. METHODS: Using antibodies to the conserved N-termini of predicted mutant proteins, we analysed MSI-High colorectal cancer cell lines for examples of naturally expressed mutant proteins arising from frameshift mutations in coding microsatellites (cMS) by immunoprecipitation and Western Blot experiments. Detected mutant protein bands from NMD-resistant transcripts were further validated by gene-specific short-interfering RNA (siRNA) knockdown. A genome-wide search was performed to identify cMS-containing genes likely to generate NMD-resistant transcripts that could encode for antigenic expressed mutant proteins in MSI-High colon cancers. These genes were screened for cMS mutations in the MSI-High colon cancer cell lines. RESULTS: Mutant protein bands of expected molecular weight were detected in mutated MSI-High cell lines for NMD-resistant transcripts (CREBBP, EP300, TTK), but not NMD-sensitive transcripts (BAX, CASP5, MSH3). Expression of the mutant CREBBP and EP300 proteins was confirmed by siRNA knockdown. Five cMS-bearing genes identified from the genome-wide search and without existing mutation data (SFRS12IP1, MED8, ASXL1, FBXL3 and RGS12) were found to be mutated in at least 5 of 11 (45%) of the MSI-High cell lines tested. CONCLUSION: NMD-resistant transcripts can give rise to expressed mutant proteins in MSI-High colon cancer cells. If commonly expressed in primary MSI-High colon cancers, MSI-derived mutant proteins could be useful as cancer specific immunological targets in a vaccine targeting MSI-High colonic tumours