A new approach to adaptive control: no nonlinearities

In adaptive control the goal is to design a controller to control an uncertain system whose parameters may be changing with time. Typically the controller consists of an identifier (or tuner) which is used to adjust the parameters of a linear time-invariant (LTI) compensator, and under suitable assumptions on the plant model uncertainty it is proven that good asymptotic behaviour is achieved, such as model matching (for minimum phase systems) or stability. However, a typical adaptive controller does not track time-varying parameters very well, and it is often highly nonlinear, which can result in undesirable behaviour, such as large transients or a large control signal. Furthermore, most adaptive controllers provide only asymptotic tracking, with no ability to design for a pre-specified settling time.Here we propose an alternative approach, which yields a linear periodic controller. Rather than estimating the plant or compensator parameters, instead we estimate what the control signal would be if the plant parameters were known. In this paper we argue the utility of this approach and then examine the first order case in detail, including a simulation. We also explore the benefits and limitations of the approach.     

Coordination in networks: An economic equilibrium analysis

Networks utilizing modern communication technologies can offer competitive advantages to those using them wisely. But due to the existence of network effects, planning and operating cooperation networks is difficult. In this paper, the strategic situation of individual agents deciding on network participation is analysed. A systematic equilibrium analysis using computer-based simulations reveals principal solution scenarios for network agents and shows that network cooperation problems might frequently be not as difficult to resolve as often feared. In particular, strategic situations are identified showing that a majority of individuals might be better off getting the optimal solution from a central principal and that in many cases simple information intermediation can solve the start-up problem notorious in network economics.     

Growing a hypercubical output space in a self-organizing featuremap

Neural maps project data from an input space onto a neuron position in a (often lower dimensional) output space grid in a neighborhood preserving way, with neighboring neurons in the output space responding to neighboring data points in the input space. A map-learning algorithm can achieve an optimal neighborhood preservation only, if the output space topology roughly matches the effective structure of the data in the input space. We here present a growth algorithm, called the GSOM or growing self-organizing map, which enhances a widespread map self-organization process, Kohonen's self-organizing feature map (SOFM), by an adaptation of the output space grid during learning. The GSOM restricts the output space structure to the shape of a general hypercubical shape, with the overall dimensionality of the grid and its extensions along the different directions being subject of the adaptation. This constraint meets the demands of many larger information processing systems, of which the neural map can be a part. We apply our GSOM-algorithm to three examples, two of which involve real world data. Using recently developed methods for measuring the degree of neighborhood preservation in neural maps, we find the GSOM-algorithm to produce maps which preserve neighborhoods in a nearly optimal fashion.     

A Software Tool for Automatically Verified Operations on Intervals and Probability Distributions

We describe a software tool for performing automatically verified arithmetic operations on independent operands when the operands are intervals, or probability distribution functions, or one operand is an interval and the other is a distribution. Intervals and distributions are expressed using the same technique, so the algorithms do not need to distinguish between intervals and distributions in their operation. The tool can calculate common arithmetic operations with guaranteed results (as well as confidence limits on a distribution if the distribution is empirically estimated from samples).A previous paper [1] discusses the concepts, algorithms, and related work. Here we emphasize a software tool that implements the algorithms, interacts with the user via a graphical user interface, and saves, retrieves, and prints the results of its calculations.     

Simulation Study of Aspects of the Classical Hydrogen Atom Interacting with Electromagnetic Radiation: Elliptical Orbits

The present study examines the behavior of a classical charged point particle in near-elliptic orbits about an infinitely massive and oppositely charged nucleus, while acted upon by applied electromagnetic radiation. As recently shown for near-circular orbits, and now extended here to the elliptical case, rather surprising nonlinear dynamical effects are readily produced for this simple system. A broad range of stability-like conditions can be achieved by applying radiation to this classical atom. A perfect balance condition is examined, which requires an infinite number of plane waves representing harmonics of the orbital motion. By applying a scale factor to this radiation, stability-like conditions are produced where periodic variations in semimajor and semiminor axes occur for extended periods of time, before orbital decay eventually takes over due to the effects of radiation reaction. This work is expected to lead to both practical suggestions on experimental ideas involving controlling ionization and stabilization conditions, as well as hopefully aiding in theoretical explorations of stochastic electrodynamics.     

Specific Local Predictors That Reflect the Tropism of Endometriosis—A Multiple Immunohistochemistry Technique

Ectopic endometrial epithelium associates a wide spectrum of symptomatology. Their evolution can be influenced by inflammatory and vascular changes, that affect not only the structure and cell proliferation rate, but also symptoms. This prospective study involved tissue samples from surgically treated patients, stained using classical histotechniques and immunohistochemistry. We assessed ectopic endometrial glands (CK7+, CK20−), adjacent blood vessels (CD34+), estrogen/progesterone hormone receptors (ER+, PR+), inflammatory cells (CD3+, CD20+, CD68+, Tryptase+), rate of inflammatory cells (Ki67+) and oncoproteins (BCL2+, PTEN+, p53+) involved in the development of endometriosis/adenomyosis. A CK7+/CK20− expression profile was present in the ectopic epithelium and differentiated it from digestive metastases. ER+/PR+ were present in all cases analyzed. We found an increased vascularity (CD34+) in the areas with abdominal endometriosis and CD3+−:T-lymphocytes, CD20+−:B-lymphocytes, CD68+:macrophages, and Tryptase+: mastocytes were abundant, especially in cases with adenomyosis as a marker of proinflammatory microenvironment. In addition, we found a significantly higher division index-(Ki67+) in the areas with adenomyosis, and inactivation of tumor suppressor genes-p53+ in areas with neoplastic changes. The inflammatory/vascular/hormonal mechanisms trigger endometriosis progression and neoplastic changes increasing local pain. Furthermore, they may represent future therapeutic targets. Simultaneous-multiple immunohistochemical labelling represents a valuable technique for rapidly detecting cellular features that facilitate comparative analysis of the studied predictors.     

SK119, a Novel Shikonin Derivative,Leads to Apoptosis in Melanoma Cell Lines and Exhibits Synergistic Effects with Vemurafenib and Cobimetinib

Melanoma is a complex and heterogenous disease, displays the deadliest form of skin cancer, and accounts for approx. 80% of all skin cancer deaths. In this study, we reported on the synthesis and pharmacological effects of a novel shikonin derivative (SK119), which is active in a nano-molar range and exhibits several promising in vitro effects in different human melanoma cells. SK119 was synthesized from shikonin as part of our search for novel, promising shikonin derivatives. It was screened against a panel of melanoma and non-tumorigenic cell lines using XTT viability assays. Moreover, we studied its pharmacological effects using apoptosis and Western blot experiments. Finally, it was combined with current clinically used melanoma therapeutics. SK119 exhibited IC₅₀ values in a nano-molar range, induced apoptosis and led to a dose-dependent increase in the expression and protein phosphorylation of HSP27 and HSP90 in WM9 and MUG-Mel 2 cells. Combinatorial treatment, which is highly recommended in melanoma, revealed the synergistic effects of SK119 with vemurafenib and cobimetinib. SK119 treatment changed the expression levels of apoptosis genes and death receptor expression and exhibited synergistic effects with vemurafenib and cobimetinib in human melanoma cells. Further research indicates a promising potential in melanoma therapy.     

Exposure of Mice to Thirdhand Smoke Modulates In Vitro and In Vivo Platelet Responses

Smoking is a risk factor for a variety of deleterious conditions, such as cancer, respiratory disease and cardiovascular disease. Thrombosis is an important and common aspect of several cardiovascular disease states, whose risk is known to be increased by both first- and secondhand smoke. More recently, the residual cigarette smoke that persists after someone has smoked (referred to as thirdhand smoke or THS) has been gaining more attention, since it has been shown that it also negatively affects health. Indeed, we have previously shown that 6-month exposure to THS increases the risk of thrombogenesis. However, neither the time-dependence of THS-induced thrombus formation, nor its sex dependence have been investigated. Thus, in the present study, we investigated these issues in the context of a shorter exposure to THS, specifically 3 months, in male and female mice. We show that the platelets from 3-month THS-exposed mice exhibited enhanced activation by agonists. Moreover, we also show that mice of both sexes exposed to THS have decreased tail bleeding as well as decreased thrombus occlusion time. In terms of the role of sex, intersex disparities in thrombus development and hemostasis as well as in platelet aggregation were, interestingly, observed. Together, our findings show that exposing mice to THS for 3 months is sufficient to predispose them to thrombosis; which seems to be driven, at least in part, by an increased activity in platelets, and that it does not manifest equally in both sexes.     

Structural Abnormalities of the Optic Nerve and Retina in Huntington’s Disease Pre-Clinical and Clinical Settings

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein. HD-related pathological remodelling has been reported in HD mouse models and HD carriers. In this study, we studied structural abnormalities in the optic nerve by employing Spectral Domain Optical Coherence Tomography (SD-OCT) in pre-symptomatic HD carriers of Caucasian origin. Transmission Electron Microscopy (TEM) was used to investigate ultrastructural changes in the optic nerve of the well-established R6/2 mouse model at the symptomatic stage of the disease. We found that pre-symptomatic HD carriers displayed a significant reduction in the retinal nerve fibre layer (RNFL) thickness, including specific quadrants: superior, inferior and temporal, but not nasal. There were no other significant irregularities in the GCC layer, at the macula level and in the optic disc morphology. The ultrastructural analysis of the optic nerve in R6/2 mice revealed a significant thinning of the myelin sheaths, with a lamellar separation of the myelin, and a presence of myelonoid bodies. We also found a significant reduction in the thickness of myelin sheaths in peripheral nerves within the choroids area. Those ultrastructural abnormalities were also observed in HD photoreceptor cells that contained severely damaged membrane disks, with evident vacuolisation and swelling. Moreover, the outer segment of retinal layers showed a progressive disintegration. Our study explored structural changes of the optic nerve in pre- and clinical settings and opens new avenues for the potential development of biomarkers that would be of great interest in HD gene therapies.