Efficient construction of maximally localized photonic Wannier functions: locality criterion and initial conditions

Wannier function expansions are well suited for the description of photonic- crystal-based defect structures, but constructing maximally localized Wannier functions by optimizing the phase degree of freedom of the Bloch modes is crucial for the efficiency of the approach. We systematically analyze different locality criteria for maximally localized Wannier functions in two- dimensional square and triangular lattice photonic crystals, employing (local) conjugate-gradient as well as (global) genetic-algorithm-based, stochastic methods. Besides the commonly used second moment (SM) locality measure, we introduce a new locality measure, namely the integrated modulus (IM) of the Wannier function. We show numerically that, in contrast to the SM criterion, the IM criterion leads to an optimization problem with a single extremum, thus allowing for fast and efficient construction of maximally localized Wannier functions using local optimization techniques. We also present an analytical formula for the initial choice of Bloch phases, which under certain conditions represents the global maximum of the IM criterion and, thus, further increases the optimization efficiency in the general case

The effect of local or systemic tumor necrosis factor (TNF)-α inhibition on the immune response in experimental autoimmune uveoretinitis

In der hier vorliegenden experimentellen Arbeit wurde untersucht, inwieweit die lokale Inhibition von TNF-α den Verlauf der EAU als Modell für die humane endogene posteriore Uveitis verbessern kann und Einfluss auf zugrunde liegende immunologische Prozesse nimmt. Der durchgeführte TNF-α-Bioassay an L929-Zellen zeigte, dass der dabei eingesetzte humanisierte Wirkstoff Etanercept die biologische Aktivität auch von murinem TNF-α in vitro effektiv hemmen kann. Um zu überprüfen, ob Etanercept generell auch einen mildernden Einfluss auf den EAU-Verlauf hat, wurde der Wirkstoff zunächst systemisch angewendet. Dabei zeigte sich, dass der EAU-Schweregrad durch die systemische Behandlung mit Etanercept in der afferenten Phase des Modells signifikant verringert war. Dieser reduzierte EAU-Schweregrad in der Etanercept-Behandlungsgruppe war von einer verringerten antigenspezifischen Proliferation von Milzzellen und einer reduzierten antigenspezifischen Produktion von proinflammatorischen Th1-, Th2- sowie Th17-assoziierten Zytokinen durch Milzzellen begleitet. Die systemische Behandlung mit Etanercept in der efferenten Phase des Modells zeigte hingegen keinen reduzierenden Einfluss auf den EAU-Schweregrad sowie die antigenspezifische Proliferation von Milzzellen. Dies galt auch für die systemische Etanercept-Behandlung in dem EAU-Modell, das durch den adoptiven Transfer von IRBPp161-180-spezifischen und in vitro restimulierten Splenozyten induziert wurde. Die Ergebnisse zur systemischen TNF-α-Inhibition durch Etanercept signalisierten damit eine bedeutende Rolle von TNF-α in der Induktionsphase der EAU. Es kann gefolgert werden, dass Etanercept in erster Linie Einfluss auf die Generierung von uveitogenen Effektorzellen nimmt, nicht aber auf bereits aktivierte und differenzierte Effektorzellen wirkt. Zur lokalen Behandlung der EAU wurden intravitreale oder subkonjunktivale Wirkstoffapplikationen angewendet. Auch nach intravitrealen Injektionen von Etanercept in der afferenten Phase des Modells war der EAU-Schweregrad im Vergleich zur Kontrollgruppe signifikant geringer. Dabei ging die Reduktion des EAU-Schweregrades jedoch nicht mit einer verringerten antigenpezifischen Proliferation von Milzzellen einher. Bezüglich der antigenspezifischen Produktion von Zytokinen durch Milzzellen wurde nach der intravitrealen Etanercept-Applikation eine Reduktion des zentralen Th1-Zytokins IFN-γ beobachtet, während die Th2-assoziierten Zytokine IL-6 und IL-10 erhöht waren. Diese Ergebnisse sprechen für unterschiedliche Wirkmechanismen von Etanercept in Abhängigkeit der Applikationsroute. Der Wirkmechanismus der systemischen Etanercept-Applikation bestand eher in der allgemeinen Suppression der Generierung proinflammatorischer Effektorfunktionen, während die Ergebnisse zur intravitrealen Etanercept-Applikation eher einen immunmodulatorischen Wirkmechanismus aufzeigten. Die subkonjunktivale Etanercept-Injektion als weiterer lokaler Behandlungsansatz zeigte keinen verringernden Effekt auf den EAU-Schweregrad. Als Wirkstoffkontrolle zu Etanercept wurden gegen die mRNA von TNF-α gerichtete ASON eingesetzt. Es konnte jedoch kein verbessernder Einfluss auf den EAU-Verlauf nach lokaler Applikation beobachtet werden. Schlussendlich war die systemische Applikation von Etanercept effektiver zur Behandlung der EAU als die intravitreale Applikation. In diesem Zusammenhang wiesen die Experimente zur VCAID-Induktion in der hier vorliegenden Arbeit auf eine Beeinträchtigung des Immunprivilegs des Auges durch die intraokulare TNF-α-Inhibition mit Etanercept hin. Solche Einflüsse auf regulatorische Funktionen von TNF-α könnten damit einen limitierenden Faktor für den Wert der intravitrealen Etanercept-Applikation als lokalen Behandlungsansatz für eine autoimmune posteriore Uveitis darstellen.In the present experimental study the extent was determined to which local TNF-α inhibition ameliorates the course of an animal model of human posterior uveitis (experimental autoimmune uveoretinitis [EAU]) and it was investigated how this affects underlying immunopathological processes. In these experiments etanercept functioned as an antagonist to block TNF-α. A TNF-α bioassay with L929 cells showed that etanercept effectively inhibits the biological activity of murine TNF-α in vitro. The effect of etanercept on the course of EAU was initially analyzed by treating immunized mice systemically in the afferent phase. Here, EAU scores were significantly lower in the etanercept group, which was also accompanied by decreased antigen-specific proliferation of splenocytes. Furthermore, systemic etanercept treatment in the afferent phase lowered the antigen-specific production of various proinflammatory cytokines by splenocytes. In contrast, systemic etanercept treatment in the efferent phase had no reducing effect on EAU severity, nor did it decrease the antigen-specific proliferation of splenocytes as compared to control mice. This was also observed after systemic etanercept treatment of animals in which EAU was induced by adoptive transfer of uveitogenic splenocytes. These results for the systemic TNF-α inhibition by etanercept indicate that TNF-α has a predominant role in the immunopathologic processes of the induction phase of EAU, suggesting that etanercept affects the generation of uveitogenic effector cells rather than having an effect on already activated and differentiated effector cells. For local treatment, etanercept was injected intravitreally or subconjunctivally. After intravitreal etanercept treatment in the afferent phase, EAU scores were also significantly lower than those in the control group. However, the improved EAU scores were not associated with reduced antigen-specific proliferation of splenocytes. Regarding the antigen-specific cytokine response of splenocytes, the Th1 cytokine IFN-γ was reduced after intravitreal etanercept treatment, while the Th2 associated cytokines IL-6 and IL-10 were elevated. These results indicate that the mechanism of action may be different for systemic and intravitreal etanercept treatment. While systemic TNF-α inhibition using etanercept in the afferent phase suppressed proinflammatory effector functions, the mechanism underlying EAU improvement after intravitreal TNF-α inhibition seemed to be immunomodulation. The subconjunctival injection of etanercept as a further local treatment approach showed no ameliorating effect on the course of EAU at any time in this model. In further experiments, ASON binding to the mRNA of TNF-α were used as a drug control to etanercept. Independently of the applied treatment schedule, local ASON treatment had no ameliorating effect on the course of EAU. Finally, systemic administration of etanercept more effectively ameliorated EAU than intravitreal administration. In this context, the experiments concerning the induction of VCAID shown here indicate that intraocular TNF-α inhibition using etanercept impairs immune privilege of the eye. Interfering with such regulatory functions of local TNF-α may limit the value of intravitreal etanercept treatment for autoimmune posterior uveitis

Differences in long-term physical activity trajectories among individuals with chronic widespread pain : A secondary analysis of a randomized controlled trial

Funding Sources: The MUSICIAN trial was funded by Arthritis Research UK, Chesterfield, UK (Grant award number 17292) and the MELODIC study was funded by NHS Grampian Endowment Grant, Project No: 14/40.Peer reviewedPostprin

Distributed state estimation for uncertain Markov-type sensor networks with mode-dependent distributed delays

This the post-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2012 John Wiley & Sons, Ltd.In this paper, the distributed state estimation problem is investigated for a class of sensor networks described by uncertain discrete-time dynamical systems with Markovian jumping parameters and distributed time-delays. The sensor network consists of sensor nodes characterized by a directed graph with a nonnegative adjacency matrix that specifies the interconnection topology (or the distribution in the space) of the network. Both the parameters of the target plant and the sensor measurements are subject to the switches from one mode to another at different times according to a Markov chain. The parameter uncertainties are norm-bounded that enter into both the plant system as well as the network outputs. Furthermore, the distributed time-delays are considered, which are also dependent on the Markovian jumping mode. Through the measurements from a small fraction of the sensors, this paper aims to design state estimators that allow the nodes of the sensor network to track the states of the plant in a distributed way. It is verified that such state estimators do exist if a set of matrix inequalities is solvable. A numerical example is provided to demonstrate the effectiveness of the designed distributed state estimators.This work was supported in part by the Royal Society of the U.K., the National Natural Science Foundation of China under Grants 60804028 and 61028008, the Specialized Research Fund for the Doctoral Program of Higher Education for New Teachers in China under Grant 200802861044, the Teaching and Research Fund for Excellent Young Teachers at Southeast University of China, the International Science and Technology Cooperation Project of China under Grant No. 2009DFA32050, and the Alexander von Humboldt Foundation of Germany

Flavour Changing Neutral Currents, Weak-Scale Scalars and Rare Top Decays

We examine the decays $t\rightarrow c\gamma$ and $c Z^0$ in the Standard Model with an extra scalar doublet and no discrete symmetry preventing tree-level flavour changing neutral currents. The Yukawa couplings of the new scalars are assumed to be proportional to fermion masses, evading bounds on FCNC's from the light quark sector. These rare top decays may be visible at the SSC.Comment: (some wording changed, and several references added) 13 pages, 2 figures included, uses harvmac.tex and epsf.tex, UCSD/PTH 93-0