Schneller sehen durch Regelungstechnik - Moderne Bildgebung in der Nanotechnologie

Die Nanotechnologie, also die Wissenschaft von Untersuchungen und Manipulationen im Nanometermaßstab, wird als eine der Schlüsseltechnologien des 21. Jahrhunderts angesehen. Wichtige Komponenten dieses aktuellen Forschungszweiges sind das Rastertunnelmikroskop und das Rasterkraftmikroskop, die den Blick in die Nanowelt erlauben. Dieser Artikel gibt einen einführenden Einblick in die Bildgebung der Nanowelt und versucht, den Beitrag von Systemtheorie und Regelungstechnik für die Nanotechnologie anhand der Regelung von Rasterkraftmikroskopen allgemeinverständlich zu beschreiben

Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch

Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale.Comment: 14 pages, 4 figure

Mechanism of PP2A-mediated IKKβ dephosphorylation: a systems biological approach

BACKGROUND: Biological effects of nuclear factor-kappaB (NF kappaB) can differ tremendously depending on the cellular context. For example, NF kappaB induced by interleukin-1 (IL-1) is converted from an inhibitor of death receptor induced apoptosis into a promoter of ultraviolet-B radiation (UVB)-induced apoptosis. This conversion requires prolonged NF kappaB activation and is facilitated by IL-1 + UVB-induced abrogation of the negative feedback loop for NF kappaB, involving a lack of inhibitor of kappaB (I kappaB alpha) protein reappearance. Permanent activation of the upstream kinase IKK beta results from UVB-induced inhibition of the catalytic subunit of Ser-Thr phosphatase PP2A (PP2Ac), leading to immediate phosphorylation and degradation of newly synthesized I kappaB alpha. RESULTS: To investigate the mechanism underlying the general PP2A-mediated tuning of IKK beta phosphorylation upon IL-1 stimulation, we have developed a strictly reduced mathematical model based on ordinary differential equations which includes the essential processes concerning the IL-1 receptor, IKK beta and PP2A. Combining experimental and modelling approaches we demonstrate that constitutively active, but not post-stimulation activated PP2A, tunes out IKK beta phosphorylation thus allowing for I kappaB alpha resynthesis in response to IL-1. Identifiability analysis and determination of confidence intervals reveal that the model allows reliable predictions regarding the dynamics of PP2A deactivation and IKK beta phosphorylation. Additionally, scenario analysis is used to scrutinize several hypotheses regarding the mode of UVB-induced PP2Ac inhibition. The model suggests that down regulation of PP2Ac activity, which results in prevention of I kappaB alpha reappearance, is not a direct UVB action but requires instrumentality. CONCLUSION: The model developed here can be used as a reliable building block of larger NF kappa B models and offers comprehensive simplification potential for future modeling of NF kappa B signaling. It gives more insight into the newly discovered mechanisms for IKK deactivation and allows for substantiated predictions and investigation of different hypotheses. The evidence of constitutive activity of PP2Ac at the IKK complex provides new insights into the feedback regulation of NF kappa B, which is crucial for the development of new anti-cancer strategies

Smoking and mental illness: results from population surveys in Australia and the United States

<p>Abstract</p> <p>Background</p> <p>Smoking has been associated with a range of mental disorders including schizophrenia, anxiety disorders and depression. People with mental illness have high rates of morbidity and mortality from smoking related illnesses such as cardiovascular disease, respiratory diseases and cancer. As many people who meet diagnostic criteria for mental disorders do not seek treatment for these conditions, we sought to investigate the relationship between mental illness and smoking in recent population-wide surveys.</p> <p>Methods</p> <p>Survey data from the US National Comorbidity Survey-Replication conducted in 2001–2003, the 2007 Australian Survey of Mental Health and Wellbeing, and the 2007 US National Health Interview Survey were used to investigate the relationship between current smoking, ICD-10 mental disorders and non-specific psychological distress. Population weighted estimates of smoking rates by disorder, and mental disorder rates by smoking status were calculated.</p> <p>Results</p> <p>In both the US and Australia, adults who met ICD-10 criteria for mental disorders in the 12 months prior to the survey smoked at almost twice the rate of adults without mental disorders. While approximately 20% of the adult population had 12-month mental disorders, among adult smokers approximately one-third had a 12-month mental disorder – 31.7% in the US (95% CI: 29.5%–33.8%) and 32.4% in Australia (95% CI: 29.5%–35.3%). Female smokers had higher rates of mental disorders than male smokers, and younger smokers had considerably higher rates than older smokers. The majority of mentally ill smokers were not in contact with mental health services, but their rate of smoking was not different from that of mentally ill smokers who had accessed services for their mental health problem. Smokers with high levels of psychological distress smoked a higher average number of cigarettes per day.</p> <p>Conclusion</p> <p>Mental illness is associated with both higher rates of smoking and higher levels of smoking among smokers. Further, a significant proportion of smokers have mental illness. Strategies that address smoking in mental illness, and mental illness among smokers would seem to be important directions for tobacco control. As the majority of smokers with mental illness are not in contact with mental health services for their condition, strategies to address mental illness should be included as part of population health-based mental health and tobacco control efforts.</p

Hantaviren und Nagetiere in Deutschland: Das Netzwerk „Nagetier-übertragene Pathogene”

ZusammenfassungHantavirus-Infektionen sind in Deutschland seit etwa 25 Jahren bekannt. Die durchschnittliche Antikörperprävalenz in der Bevölkerung liegt bei ca. 1 bis 2%. Nach Einführung der Meldepflicht im Jahr 2001 sind jährlich durchschnittlich etwa 70 bis 240 Fälle gemeldet worden. Im Jahr 2005 und insbesondere im Jahr 2007 ist jedoch ein deutlicher Anstieg der Zahl der gemeldeten Fälle registriert worden. Die am meisten betroffenen Regionen lagen in den Bundesländern Baden-Württemberg, Bayern, Nordrhein-Westfalen und Niedersachsen. Im Gegensatz zur gut dokumentierten Situation beim Menschen ist die Kenntnis der geografischen Verbreitung und Häufigkeit von Hantavirus-Infektionen in den Nagetier-Reservoiren und deren Schwankungen sehr begrenzt. Aus diesem Grund wurde in Deutschland das Netzwerk „Nagetier-übertragene Pathogene“ etabliert, das interdisziplinäre Untersuchungen zur Nagetier-Populationsdynamik, Prävalenz und Evolution von Hantaviren und anderen Nagetier-assoziierten Zoonoseerregern und den zugrunde liegenden Mechanismen sowie deren Auswirkungen auf die Häufigkeit humaner Infektionen erlaubt. Ein Monitoring von Hantaviren in Nagetieren wurde in Endemiegebieten (Baden-Württemberg, Bayern, Nordrhein-Westfalen, Niedersachsen) und Regionen mit einer geringen Zahl humaner Fälle (Mecklenburg-Vorpommern, Brandenburg, Sachsen, Sachsen-Anhalt, Thüringen, Schleswig-Holstein, Hessen, Rheinland-Pfalz) initiiert. Insgesamt wurde eine breite geographische Verbreitung des Puumalavirus (PUUV) in Rötelmäusen und des Tulavirus in Microtus-Mäusen dokumentiert. Dobrava-Belgrad-Virus-positive Apodemus-Mäuse wurden bisher ausschließlich in Brandenburg, Mecklenburg-Vorpommern und Niedersachsen gefunden. In den Hantavirus-Ausbruchsgebieten in Baden-Württemberg, Bayern, Nordrhein-Westfalen und Niedersachsen wurde bei Rötelmäusen eine hohe PUUV-Prävalenz beobachtet. Initiale Longitudinalstudien in Nordrhein-Westfalen (Stadt Köln), Bayern (Niederbayern) und Niedersachsen (ländliche Region bei Osnabrück) zeigten ein stabiles Vorkommen des PUUV in den Rötelmaus-Populationen. Neben den Untersuchungen zu Hantaviren ist auch mit Studien zum Vorkommen von anderen Nagetier-assoziierten Zoonoseerregern begonnen worden. Die begonnenen Longitudinalstudien werden Schlussfolgerungen zur Evolution von Hantaviren und anderen Nagetierassoziierten Erregern und zu Veränderungen in deren Häufigkeit und Verbreitung ermöglichen. Diese Untersuchungen werden zukünftig eine verbesserte Risikoabschätzung für die Gefährdung der Bevölkerung ermöglichen, die auch die möglichen zukünftigen Klimawandel-bedingten Veränderungen in der Epidemiologie Nagetier-assoziierter Zoonoseerreger berücksichtigt

Stability of periodically time-varying systems: periodic Lyapunov functions

This paper proposes a novel approach to stability analysis of discrete-time nonlinear periodically time-varying systems. The contributions are as follows. Firstly, a relaxation of standard Lyapunov conditions is derived. This leads to a less conservative Lyapunov function that is required to decrease at each period rather than at each time instant. Secondly, for linear periodic systems with constraints, it is shown that compared to standard Lyapunov theory, the novel concept of periodic Lyapunov functions allows for the calculation of a larger estimate of the region of attraction. An example illustrates the effectiveness of the developed theory

Stabilizing linear model predictive control : on the enlargement of the terminal set

It is well known that a large terminal set leads to a large region where the MPC problem is feasible without the need for a long prediction horizon. This paper proposes a new method for the enlargement of the terminal set. Contrary to existing approaches, the method uses the convex hull of a trajectory as the basis for the construction. This trajectory may be any feasible trajectory of the system terminating in an invariant set around the origin and is not restricted to consist only of equilibrium points. The method is applied in an MPC scheme where the terminal set is calculated at initialization