On local linearization of control systems

We consider the problem of topological linearization of smooth (C infinity or real analytic) control systems, i.e. of their local equivalence to a linear controllable system via point-wise transformations on the state and the control (static feedback transformations) that are topological but not necessarily differentiable. We prove that local topological linearization implies local smooth linearization, at generic points. At arbitrary points, it implies local conjugation to a linear system via a homeomorphism that induces a smooth diffeomorphism on the state variables, and, except at "strongly" singular points, this homeomorphism can be chosen to be a smooth mapping (the inverse map needs not be smooth). Deciding whether the same is true at "strongly" singular points is tantamount to solve an intriguing open question in differential topology

Implementation of behavioral systems

In this chapter, we study control by interconnection of a given linear differential system (the plant behavior) with a suitable controller. The problem formulations and their solutions are completely representation free, and specified only in terms of the system dynamics. A controller is a system that constrains the plant behavior through a certain set of variables. In this context, there are two main situations to be considered: either all the system variables are available for control, i.e., are control variables (full control) or only some of the variables are control variables (partial control). For systems evolving over a time domain (1D) the problems of implementability by partial (regular) interconnection are well understood. In this chapter, we study why similar results are not valid in themultidimensional (nD) case. Finally, we study two important classes of controllers, namely, canonical controllers and regular controllers

Accuracy of popular automatic QT Interval algorithms assessed by a 'Gold Standard' and comparison with a Novel method: computer simulation study

BACKGROUND: Accurate measurement of the QT interval is very important from a clinical and pharmaceutical drug safety screening perspective. Expert manual measurement is both imprecise and imperfectly reproducible, yet it is used as the reference standard to assess the accuracy of current automatic computer algorithms, which thus produce reproducible but incorrect measurements of the QT interval. There is a scientific imperative to evaluate the most commonly used algorithms with an accurate and objective 'gold standard' and investigate novel automatic algorithms if the commonly used algorithms are found to be deficient. METHODS: This study uses a validated computer simulation of 8 different noise contaminated ECG waveforms (with known QT intervals of 461 and 495 ms), generated from a cell array using Luo-Rudy membrane kinetics and the Crank-Nicholson method, as a reference standard to assess the accuracy of commonly used QT measurement algorithms. Each ECG contaminated with 39 mixtures of noise at 3 levels of intensity was first filtered then subjected to three threshold methods (T1, T2, T3), two T wave slope methods (S1, S2) and a Novel method. The reproducibility and accuracy of each algorithm was compared for each ECG. RESULTS: The coefficient of variation for methods T1, T2, T3, S1, S2 and Novel were 0.36, 0.23, 1.9, 0.93, 0.92 and 0.62 respectively. For ECGs of real QT interval 461 ms the methods T1, T2, T3, S1, S2 and Novel calculated the mean QT intervals(standard deviations) to be 379.4(1.29), 368.5(0.8), 401.3(8.4), 358.9(4.8), 381.5(4.6) and 464(4.9) ms respectively. For ECGs of real QT interval 495 ms the methods T1, T2, T3, S1, S2 and Novel calculated the mean QT intervals(standard deviations) to be 396.9(1.7), 387.2(0.97), 424.9(8.7), 386.7(2.2), 396.8(2.8) and 493(0.97) ms respectively. These results showed significant differences between means at >95% confidence level. Shifting ECG baselines caused large errors of QT interval with T1 and T2 but no error with Novel. CONCLUSION: The algorithms T2, T1 and Novel gave low coefficients of variation for QT measurement. The Novel technique gave the most accurate measurement of QT interval, T3 (a differential threshold method) was the next most accurate by a large margin. The objective and accurate 'gold standard' presented in this paper may be useful to assess new QT measurement algorithms. The Novel algorithm may prove to be more accurate and reliable method to measure the QT interval

Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions

Characterization of Neutralizing Profiles in HIV-1 Infected Patients from whom the HJ16, HGN194 and HK20 mAbs were Obtained

Several new human monoclonal antibodies (mAbs) with a neutralizing potential across different subtypes have recently been described. Three mAbs, HJ16, HGN194 and HK20, were obtained from patients within the HIV-1 cohort of the Institute of Tropical Medicine (ITM). Our aim was to generate immunization antibodies equivalent to those seen in plasma. Here, we describe the selection and characterization of patient plasma and their mAbs, using a range of neutralization assays, including several peripheral blood mononuclear cell (PBMC) based assays and replicating primary viruses as well as cell line based assays and pseudoviruses (PV). The principal criterion for selection of patient plasma was the activity in an ‘extended incubation phase’ PBMC assay. Neutralizing Abs, derived from their memory B cells, were then selected by ELISA with envelope proteins as solid phase. MAbs were subsequently tested in a high-throughput HOS-PV assay to assess functional neutralization. The present study indicates that the strong profiles in the patients' plasma were not solely due to antibodies represented by the newly isolated mAbs. Although results from the various assays were divergent, they by and large indicate that neutralizing Abs to other epitopes of the HIV-1 envelope are present in the plasma and synergy between Abs may be important. Thus, the spectrum of the obtained mAbs does not cover the range of cross-reactivity seen in plasma in these carefully selected patients irrespective of which neutralization assay is used. Nevertheless, these mAbs are relevant for immunogen discovery because they bind to the recombinant glycoproteins to which the immune response needs to be targeted in vivo. Our observations illustrate the remaining challenges required for successful immunogen design and development

The HOSTS Survey for Exozodiacal Dust: Preliminary results and future prospects

[abridged] The presence of large amounts of dust in the habitable zones of nearby stars is a significant obstacle for future exo-Earth imaging missions. We executed an N band nulling interferometric survey to determine the typical amount of such exozodiacal dust around a sample of nearby main sequence stars. The majority of our data have been analyzed and we present here an update of our ongoing work. We find seven new N band excesses in addition to the high confidence confirmation of three that were previously known. We find the first detections around Sun-like stars and around stars without previously known circumstellar dust. Our overall detection rate is 23%. The inferred occurrence rate is comparable for early type and Sun-like stars, but decreases from 71% [+11%/-20%] for stars with previously detected mid- to far-infrared excess to 11% [+9%/-4%] for stars without such excess, confirming earlier results at high confidence. For completed observations on individual stars, our sensitivity is five to ten times better than previous results. Assuming a lognormal luminosity function of the dust, we find upper limits on the median dust level around all stars without previously known mid to far infrared excess of 11.5 zodis at 95% confidence level. The corresponding upper limit for Sun-like stars is 16 zodis. An LBTI vetted target list of Sun-like stars for exo-Earth imaging would have a corresponding limit of 7.5 zodis. We provide important new insights into the occurrence rate and typical levels of habitable zone dust around main sequence stars. Exploiting the full range of capabilities of the LBTI provides a critical opportunity for the detailed characterization of a sample of exozodiacal dust disks to understand the origin, distribution, and properties of the dust.GMK is supported by the Royal Society as a Royal Society University Research Fellow. AS is partially supported by funding from the Center for Exoplanets and Habitable Worlds. The Center for Exoplanets and Habitable Worlds is supported by the Pennsylvania State University, the Eberly College of Science, and the Pennsylvania Space Grant Consortium. JMS is supported by NASA through Hubble Fellowship grant HSTHF2-51398.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Three-year randomised clinical trial to evaluate the clinical performance, quantitative and qualitative wear patterns of hybrid composite restorations

The aim of the study was to compare the clinical performance, quantitative and qualitative wear patterns of conventional hybrid (Tetric Ceram), micro-filled hybrid (Gradia Direct Posterior) and nano-hybrid (Tetric EvoCeram, TEC) posterior composite restorations in a 3-year randomised clinical trial. Sixteen Tetric Ceram, 17 TEC and 16 Gradia Direct Posterior restorations were placed in human molars and evaluated at baseline, 6, 12, 24 and 36 months of clinical service according to US Public Health Service criteria. The gypsum replicas at each recall were used for 3D laser scanning to quantify wear, and the epoxy resin replicas were observed under scanning electron microscope to study the qualitative wear patterns. After 3 years of clinical service, the three hybrid restorative materials performed clinically well in posterior cavities. Within the observation period, the nano-hybrid and micro-hybrid restorations evolved better in polishability with improved surface gloss retention than the conventional hybrid counterpart. The three hybrid composites showed enamel-like vertical wear and cavity-size dependant volume loss magnitude. Qualitatively, while the micro-filled and nano-hybrid composite restorations exhibited signs of fatigue similar to the conventional hybrid composite restorations at heavy occlusal contact area, their light occlusal contact areas showed less surface pitting after 3 years of clinical service