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Showing 41 to 47 of 47 (0.022 seconds)Spelling suggestions: "subject:"feedbackloop"" "subject:"feedbackloops""
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Death is Not the End: The Role of Reactive Oxygen Species in Driving Apoptosis-induced ProliferationFogarty, Caitlin E. 02 June 2015 (has links)
Apoptosis-induced proliferation (AiP) is a compensatory mechanism to maintain tissue size and morphology following unexpected cell loss during normal development, and may also be a contributing factor to cancer growth and drug resistance. In apoptotic cells, caspase-initiated signaling cascades lead to the downstream production of mitogenic factors and the proliferation of neighboring surviving cells. In epithelial Drosophila tissues, the Caspase-9 homolog Dronc drives AiP via activation of Jun N-terminal kinase (JNK); however, the specific mechanisms of JNK activation remain unknown. Using a model of sustained AiP that produces a hyperplastic phenotype in Drosophila eye and head tissue, I have found that caspase-induced activation of JNK during AiP depends on extracellular reactive oxygen species (ROS) generated by the NADPH oxidase Duox. I found these ROS are produced early in the death-regeneration process by undifferentiated epithelial cells that have initiated the apoptotic cascade. I also found that reduction of these ROS by mis-expression of extracellular catalases was sufficient to reduce the frequency of overgrowth associated with our model of AiP. I further observed that extracellular ROS attract and activate Drosophila macrophages (hemocytes), which may in turn trigger JNK activity in epithelial cells by signaling through the TNF receptor Grindelwald. We propose that signaling back and forth between epithelial cells and hemocytes by extracellular ROS and Grindelwald drives compensatory proliferation within the epithelium, and that in cases of persistent signaling, such as in our sustained model of AiP, hemocytes play a tumor promoting role, driving overgrowth.
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Beyond standard assumptions on neural excitability / when channels cooperate or capacitance variesPfeiffer, Paul Elias 24 August 2023 (has links)
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.
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Applying Artificial Neural Networks to Reduce the Adaptation Space in Self-Adaptive Systems : an exploratory workButtar, Sarpreet Singh January 2019 (has links)
Self-adaptive systems have limited time to adjust their configurations whenever their adaptation goals, i.e., quality requirements, are violated due to some runtime uncertainties. Within the available time, they need to analyze their adaptation space, i.e., a set of configurations, to find the best adaptation option, i.e., configuration, that can achieve their adaptation goals. Existing formal analysis approaches find the best adaptation option by analyzing the entire adaptation space. However, exhaustive analysis requires time and resources and is therefore only efficient when the adaptation space is small. The size of the adaptation space is often in hundreds or thousands, which makes formal analysis approaches inefficient in large-scale self-adaptive systems. In this thesis, we tackle this problem by presenting an online learning approach that enables formal analysis approaches to analyze large adaptation spaces efficiently. The approach integrates with the standard feedback loop and reduces the adaptation space to a subset of adaptation options that are relevant to the current runtime uncertainties. The subset is then analyzed by the formal analysis approaches, which allows them to complete the analysis faster and efficiently within the available time. We evaluate our approach on two different instances of an Internet of Things application. The evaluation shows that our approach dramatically reduces the adaptation space and analysis time without compromising the adaptation goals.
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An investigation into the integration of qualitative and quantitative techniques for addressing systemic complexity in the context of organisational strategic decision-makingMcLucas, Alan Charles, Civil Engineering, Australian Defence Force Academy, UNSW January 2001 (has links)
System dynamics modelling has been used for around 40 years to address complex, systemic, dynamic problems, those often described as wicked. But, system dynamics modelling is not an exact science and arguments about the most suitable techniques to use in which circumstances, continues. The nature of these wicked problems is investigated through a series of case studies where poor situational awareness among stakeholders was identified. This was found to be an underlying cause for management failure, suggesting need for better ways of recognising and managing wicked problem situations. Human cognition is considered both as a limitation and enabler to decision-making in wicked problem environments. Naturalistic and deliberate decision-making are reviewed. The thesis identifies the need for integration of qualitative and quantitative techniques. Case study results and a review of the literature led to identification of a set of principles of method to be applied in an integrated framework, the aim being to develop an improved way of addressing wicked problems. These principles were applied to a series of cases in an action research setting. However, organisational and political barriers were encountered. This limited the exploitation and investigation of cases to varying degrees. In response to a need identified in the literature review and the case studies, a tool is designed to facilitate analysis of multi-factorial, non-linear causality. This unique tool and its use to assist in problem conceptualisation, and as an aid to testing alternate strategies, are demonstrated. Further investigation is needed in relation to the veracity of combining causal influences using this tool and system dynamics, broadly. System dynamics modelling was found to have utility needed to support analysis of wicked problems. However, failure in a particular modelling project occurred when it was found necessary to rely on human judgement in estimating values to be input into the models. This was found to be problematic and unacceptably risky for sponsors of the modelling effort. Finally, this work has also identified that further study is required into: the use of human judgement in decision-making and the validity of system dynamics models that rely on the quantification of human judgement.
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Enhanching the Human-Team Awareness of a RobotWåhlin, Peter January 2012 (has links)
The use of autonomous robots in our society is increasing every day and a robot is no longer seen as a tool but as a team member. The robots are now working side by side with us and provide assistance during dangerous operations where humans otherwise are at risk. This development has in turn increased the need of robots with more human-awareness. Therefore, this master thesis aims at contributing to the enhancement of human-aware robotics. Specifically, we are investigating the possibilities of equipping autonomous robots with the capability of assessing and detecting activities in human teams. This capability could, for instance, be used in the robot's reasoning and planning components to create better plans that ultimately would result in improved human-robot teamwork performance. we propose to improve existing teamwork activity recognizers by adding intangible features, such as stress, motivation and focus, originating from human behavior models. Hidden markov models have earlier been proven very efficient for activity recognition and have therefore been utilized in this work as a method for classification of behaviors. In order for a robot to provide effective assistance to a human team it must not only consider spatio-temporal parameters for team members but also the psychological.To assess psychological parameters this master thesis suggests to use the body signals of team members. Body signals such as heart rate and skin conductance. Combined with the body signals we investigate the possibility of using System Dynamics models to interpret the current psychological states of the human team members, thus enhancing the human-awareness of a robot. / Användningen av autonoma robotar i vårt samhälle ökar varje dag och en robot ses inte längre som ett verktyg utan som en gruppmedlem. Robotarna arbetar nu sida vid sida med oss och ger oss stöd under farliga arbeten där människor annars är utsatta för risker. Denna utveckling har i sin tur ökat behovet av robotar med mer människo-medvetenhet. Därför är målet med detta examensarbete att bidra till en stärkt människo-medvetenhet hos robotar. Specifikt undersöker vi möjligheterna att utrusta autonoma robotar med förmågan att bedöma och upptäcka olika beteenden hos mänskliga lag. Denna förmåga skulle till exempel kunna användas i robotens resonemang och planering för att ta beslut och i sin tur förbättra samarbetet mellan människa och robot. Vi föreslår att förbättra befintliga aktivitetsidentifierare genom att tillföra förmågan att tolka immateriella beteenden hos människan, såsom stress, motivation och fokus. Att kunna urskilja lagaktiviteter inom ett mänskligt lag är grundläggande för en robot som ska vara till stöd för laget. Dolda markovmodeller har tidigare visat sig vara mycket effektiva för just aktivitetsidentifiering och har därför använts i detta arbete. För att en robot ska kunna ha möjlighet att ge ett effektivt stöd till ett mänskligtlag måste den inte bara ta hänsyn till rumsliga parametrar hos lagmedlemmarna utan även de psykologiska. För att tyda psykologiska parametrar hos människor förespråkar denna masteravhandling utnyttjandet av mänskliga kroppssignaler. Signaler så som hjärtfrekvens och hudkonduktans. Kombinerat med kroppenssignalerar påvisar vi möjligheten att använda systemdynamiksmodeller för att tolka immateriella beteenden, vilket i sin tur kan stärka människo-medvetenheten hos en robot. / <p>The thesis work was conducted in Stockholm, Kista at the department of Informatics and Aero System at Swedish Defence Research Agency.</p>
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An investigation into the integration of qualitative and quantitative techniques for addressing systemic complexity in the context of organisational strategic decision-makingMcLucas, Alan Charles, Civil Engineering, Australian Defence Force Academy, UNSW January 2001 (has links)
System dynamics modelling has been used for around 40 years to address complex, systemic, dynamic problems, those often described as wicked. But, system dynamics modelling is not an exact science and arguments about the most suitable techniques to use in which circumstances, continues. The nature of these wicked problems is investigated through a series of case studies where poor situational awareness among stakeholders was identified. This was found to be an underlying cause for management failure, suggesting need for better ways of recognising and managing wicked problem situations. Human cognition is considered both as a limitation and enabler to decision-making in wicked problem environments. Naturalistic and deliberate decision-making are reviewed. The thesis identifies the need for integration of qualitative and quantitative techniques. Case study results and a review of the literature led to identification of a set of principles of method to be applied in an integrated framework, the aim being to develop an improved way of addressing wicked problems. These principles were applied to a series of cases in an action research setting. However, organisational and political barriers were encountered. This limited the exploitation and investigation of cases to varying degrees. In response to a need identified in the literature review and the case studies, a tool is designed to facilitate analysis of multi-factorial, non-linear causality. This unique tool and its use to assist in problem conceptualisation, and as an aid to testing alternate strategies, are demonstrated. Further investigation is needed in relation to the veracity of combining causal influences using this tool and system dynamics, broadly. System dynamics modelling was found to have utility needed to support analysis of wicked problems. However, failure in a particular modelling project occurred when it was found necessary to rely on human judgement in estimating values to be input into the models. This was found to be problematic and unacceptably risky for sponsors of the modelling effort. Finally, this work has also identified that further study is required into: the use of human judgement in decision-making and the validity of system dynamics models that rely on the quantification of human judgement.
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Cantilever properties and noise figures in high-resolution non-contact atomic force microscopyLübbe, Jannis Ralph Ulrich 03 April 2013 (has links)
Different methods for the determination of cantilever properties in non-contact atomic force microscopy (NC-AFM) are under investigation. A key aspect is the determination of the cantilever stiffness being essential for a quantitative NC-AFM data analysis including the extraction of the tip-surface interaction force and potential. Furthermore, a systematic analysis of the displacement noise in the cantilever oscillation detection is performed with a special focus on the thermally excited cantilever oscillation. The propagation from displacement noise to frequency shift noise is studied under consideration of the frequency response of the PLL demodulator.
The effective Q-factor of cantilevers depends on the internal damping of the cantilever as well as external influences like the ambient pressure and the quality of the cantilever fixation.
While the Q-factor has a strong dependence on the ambient pressure between vacuum and ambient pressure yielding a decrease by several orders of magnitude, the pressure dependence of the resonance frequency is smaller than 1% for the same pressure range.
On the other hand, the resonance frequency highly depends on the mass of the tip at the end of the cantilever making its reliable prediction from known cantilever dimensions difficult.
The cantilever stiffness is determined with a high-precision static measurement method and compared to dimensional and dynamic methods. Dimensional methods suffer from the uncertainty of the measured cantilever dimensions and require a precise knowledge its material properties. A dynamic method utilising the measurement of the thermally excited cantilever displacement noise to obtain cantilever properties allows to characterise unknown cantilevers but requires an elaborative measurement equipment for spectral displacement noise analysis.
Having the noise propagation in the NC-AFM system fully characterised, a proposed method allows for spring constant determination from the frequency shift noise at the output of the PLL demodulator with equipment already being available in most NC-AFM setups.
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