when channels cooperate or capacitance varies

Die elektrische Signalverarbeitung in Nervenzellen basiert auf deren erregbarer Zellmembran. Üblicherweise wird angenommen, dass die in der Membran eingebetteten leitfähigen Ionenkanäle nicht auf direkte Art gekoppelt sind und dass die Kapazität des von der Membran gebildeten Kondensators konstant ist. Allerdings scheinen diese Annahmen nicht für alle Nervenzellen zu gelten. Im Gegenteil, verschiedene Ionenkanäle “kooperieren” und auch die Vorstellung von einer konstanten spezifischen Membrankapazität wurde kürzlich in Frage gestellt. Die Auswirkungen dieser Abweichungen auf die elektrischen Eigenschaften von Nervenzellen ist das Thema der folgenden kumulativen Dissertationsschrift. Im ersten Projekt wird gezeigt, auf welche Weise stark kooperative spannungsabhängige Ionenkanäle eine Form von zellulärem Kurzzeitspeicher für elektrische Aktivität bilden könnten. Solche kooperativen Kanäle treten in der Membran häufig in kleinen räumlich getrennte Clustern auf. Basierend auf einem mathematischen Modell wird nachgewiesen, dass solche Kanalcluster als eine bistabile Leitfähigkeit agieren. Die dadurch entstehende große Speicherkapazität eines Ensembles dieser Kanalcluster könnte von Nervenzellen für stufenloses persistentes Feuern genutzt werden -- ein Feuerverhalten von Nutzen für das Kurzzeichgedächtnis. Im zweiten Projekt wird ein neues Dynamic Clamp Protokoll entwickelt, der Capacitance Clamp, das erlaubt, Änderungen der Membrankapazität in biologischen Nervenzellen zu emulieren. Eine solche experimentelle Möglichkeit, um systematisch die Rolle der Kapazität zu untersuchen, gab es bisher nicht. Nach einer Reihe von Tests in Simulationen und Experimenten wurde die Technik mit Körnerzellen des *Gyrus dentatus* genutzt, um den Einfluss von Kapazität auf deren Feuerverhalten zu studieren. Die Kombination beider Projekte zeigt die Relevanz dieser oft vernachlässigten Facetten von neuronalen Membranen für die Signalverarbeitung in Nervenzellen.Electrical signaling in neurons is shaped by their specialized excitable cell membranes. Commonly, it is assumed that the ion channels embedded in the membrane gate independently and that the electrical capacitance of neurons is constant. However, not all excitable membranes appear to adhere to these assumptions. On the contrary, ion channels are observed to gate cooperatively in several circumstances and also the notion of one fixed value for the specific membrane capacitance (per unit area) across neuronal membranes has been challenged recently. How these deviations from the original form of conductance-based neuron models affect their electrical properties has not been extensively explored and is the focus of this cumulative thesis. In the first project, strongly cooperative voltage-gated ion channels are proposed to provide a membrane potential-based mechanism for cellular short-term memory. Based on a mathematical model of cooperative gating, it is shown that coupled channels assembled into small clusters act as an ensemble of bistable conductances. The correspondingly large memory capacity of such an ensemble yields an alternative explanation for graded forms of cell-autonomous persistent firing – an observed firing mode implicated in working memory. In the second project, a novel dynamic clamp protocol -- the capacitance clamp -- is developed to artificially modify capacitance in biological neurons. Experimental means to systematically investigate capacitance, a basic parameter shared by all excitable cells, had previously been missing. The technique, thoroughly tested in simulations and experiments, is used to monitor how capacitance affects temporal integration and energetic costs of spiking in dentate gyrus granule cells. Combined, the projects identify computationally relevant consequences of these often neglected facets of neuronal membranes and extend the modeling and experimental techniques to further study them

Network resilience

Many systems on our planet are known to shift abruptly and irreversibly from one state to another when they are forced across a "tipping point," such as mass extinctions in ecological networks, cascading failures in infrastructure systems, and social convention changes in human and animal networks. Such a regime shift demonstrates a system's resilience that characterizes the ability of a system to adjust its activity to retain its basic functionality in the face of internal disturbances or external environmental changes. In the past 50 years, attention was almost exclusively given to low dimensional systems and calibration of their resilience functions and indicators of early warning signals without considerations for the interactions between the components. Only in recent years, taking advantages of the network theory and lavish real data sets, network scientists have directed their interest to the real-world complex networked multidimensional systems and their resilience function and early warning indicators. This report is devoted to a comprehensive review of resilience function and regime shift of complex systems in different domains, such as ecology, biology, social systems and infrastructure. We cover the related research about empirical observations, experimental studies, mathematical modeling, and theoretical analysis. We also discuss some ambiguous definitions, such as robustness, resilience, and stability.Comment: Review chapter

A complex systems approach to education in Switzerland

The insights gained from the study of complex systems in biological, social, and engineered systems enables us not only to observe and understand, but also to actively design systems which will be capable of successfully coping with complex and dynamically changing situations. The methods and mindset required for this approach have been applied to educational systems with their diverse levels of scale and complexity. Based on the general case made by Yaneer Bar-Yam, this paper applies the complex systems approach to the educational system in Switzerland. It confirms that the complex systems approach is valid. Indeed, many recommendations made for the general case have already been implemented in the Swiss education system. To address existing problems and difficulties, further steps are recommended. This paper contributes to the further establishment complex systems approach by shedding light on an area which concerns us all, which is a frequent topic of discussion and dispute among politicians and the public, where billions of dollars have been spent without achieving the desired results, and where it is difficult to directly derive consequences from actions taken. The analysis of the education system's different levels, their complexity and scale will clarify how such a dynamic system should be approached, and how it can be guided towards the desired performance

SIMULATING SEISMIC WAVE PROPAGATION IN TWO-DIMENSIONAL MEDIA USING DISCONTINUOUS SPECTRAL ELEMENT METHODS

We introduce a discontinuous spectral element method for simulating seismic wave in 2- dimensional elastic media. The methods combine the flexibility of a discontinuous finite element method with the accuracy of a spectral method. The elastodynamic equations are discretized using high-degree of Lagrange interpolants and integration over an element is accomplished based upon the Gauss-Lobatto-Legendre integration rule. This combination of discretization and integration results in a diagonal mass matrix and the use of discontinuous finite element method makes the calculation can be done locally in each element. Thus, the algorithm is simplified drastically. We validated the results of one-dimensional problem by comparing them with finite-difference time-domain method and exact solution. The comparisons show excellent agreement

Vehicle and Traffic Safety

The book is devoted to contemporary issues regarding the safety of motor vehicles and road traffic. It presents the achievements of scientists, specialists, and industry representatives in the following selected areas of road transport safety and automotive engineering: active and passive vehicle safety, vehicle dynamics and stability, testing of vehicles (and their assemblies), including electric cars as well as autonomous vehicles. Selected issues from the area of accident analysis and reconstruction are discussed. The impact on road safety of aspects such as traffic control systems, road infrastructure, and human factors is also considered

Dynamical Models of biological networks

In der Molekularbiologie sind mathematische Modelle von regulatorischen und metabolischen Netzwerken essentiell, um von einer Betrachtung isolierter Komponenten und Interaktionen zu einer systemischen Betrachtungsweise zu kommen. Genregulatorische Systeme eignen sich besonders gut zur Modellierung, da sie experimentell leicht zugänglich und manipulierbar sind. In dieser Arbeit werden verschiedene genregulatorische Netzwerke unter Zuhilfenahme von mathematischen Modellen analysiert. Weiteres wird ein Modell einer in silico Zelle vorgestellt und diskutiert. Zunächst werden zwei zyklische genregulatorische Netzwerke - der klassische Repressilator und ein Repressilator mit zusätzlicher Autoaktivierung – im Detail mit analytischen Methoden untersucht. Um den Einfluß zufällig schwankender Molekülzahlen auf die Dynamik der beiden Systeme zu untersuchen, werden stochastische Modelle erstellt und die beiden oszillierenden Systeme verglichen. Weiteres werden mögliche Auswirkungen von Genduplikationen auf ein einfaches genregulatorisches Netzwerk untersucht. Dazu wird zunächst ein kleines Netzwerk von GATA Transkriptionsfaktoren, das eine zentrale Rolle in der Regulation des Stickstoffmetabolismus in Hefe spielt, modelliert und das Modell mit experimentellen Daten verglichen, um Parameterregionen einschränken zu können. Außerdem werden potentielle Topologien genregulatorischer Netzwerke von GATA Transkriptionsfaktoren in verwandten Fungi mittels sequenzbasierender Methoden gesucht und verglichen. Im letzten Teil der Arbeit wird MiniCellSim vorgestellt, ein Modell einer selbständigen in silico Zelle. Es erlaubt ein dynamisches System, das eine Protozelle mit einem genregulatorischen Netzwerk, einem einfachen Metabolismus und einer Zellmembran beschreibt, aus einer Sequenz abzuleiten. Nachdem alle Parameter, die zur Berechnung des dynamischen Systems benötigt werden, ohne zusätzliche Eingabe nur aus der Sequenzinformation abgeleitet werden, kann das Modell für Studien zur Evolution von genregulatorischen Netzwerken verwendet werden.In this thesis different types of gene regulatory networks are analysed using mathematical models. Further a computational framework of a novel, self-contained in silico cell model is described and discussed. At first the behaviour of two cyclic gene regulatory systems - the classical repressilator and a repressilator with additional auto-activation - are inspected in detail using analytical bifurcation analysis. To examine the behaviour under random fluctuations, stochastic versions of the systems are created. Using the analytical results sustained oscillations in the stochastic versions are obtained, and the two oscillating systems compared. In the second part of the thesis possible implications of gene duplication on a simple gene regulatory system are inspected. A model of a small network formed by GATA-type transcription factors, central in nitrogen catabolite repression in yeast, is created and validated against experimental data to obtain approximate parameter values. Further, topologies of potential gene regulatory networks and modules consisting of GATA-type transcription factors in other fungi are derived using sequence-based approaches and compared. The last part describes MiniCellSim, a model of a self-contained in silico cell. In this framework a dynamical system describing a protocell with a gene regulatory network, a simple metabolism, and a cell membrane is derived from a string representing a genome. All the relevant parameters required to compute the time evolution of the dynamical system are calculated from within the model, allowing the system to be used in studies of evolution of gene regulatory and metabolic networks

Life Sciences Program Tasks and Bibliography for FY 1997

This document includes information on all peer reviewed projects funded by the Office of Life and Microgravity Sciences and Applications, Life Sciences Division during fiscal year 1997. This document will be published annually and made available to scientists in the space life sciences field both as a hard copy and as an interactive internet web page

Advanced Modeling and Research in Hybrid Microgrid Control and Optimization

This book presents the latest solutions in fuel cell (FC) and renewable energy implementation in mobile and stationary applications. The implementation of advanced energy management and optimization strategies are detailed for fuel cell and renewable microgrids, and for the multi-FC stack architecture of FC/electric vehicles to enhance the reliability of these systems and to reduce the costs related to energy production and maintenance. Cyber-security methods based on blockchain technology to increase the resilience of FC renewable hybrid microgrids are also presented. Therefore, this book is for all readers interested in these challenging directions of research