Realistic Single Cell Modeling – from Experiment to Simulation

This tutorial gives a step by step explanation of how one uses experimental data to construct a biologically realistic multicompartmental model. Special emphasis is given on the many ways that this process can be imprecise. The tutorial is intended for both experimentalists who want to get into computer modeling and for computer scientists who use abstract neural network models but are curious about biological realistic modeling. The tutorial is not dependent on the use of a specific simulation engine, but rather covers the kind of data needed for constructing a model, how they are used, and potential pitfalls in the process.

Computer Simulation of Crowd Dynamics and Destructive Crowd Behavior

The social processes that lead to destructive behavior in celebratory crowds can be studied through an agent-based computer simulation. Riots are an increasingly common outcome of sports celebrations, and pose the potential for harm to participants, bystanders, property, and the reputation of the groups with whom participants are associated. Rioting cannot necessarily be attributed to the negative emotions of individuals, such as anger, rage, frustration and despair. For instance, the celebratory behavior (e.g., chanting, cheering, singing) during UConn’s “Spring Weekend” and after the 2004 NCAA Championships resulted in several small fires and overturned cars. Further, not every individual in the area of a riot engages in violence, and those who do, do not do so continuously. Instead, small groups carry out the majority of violent acts in relatively short-lived episodes. Agent-based computer simulations are an ideal method for modeling complex group-level social phenomena, such as celebratory gatherings and riots, which emerge from the interaction of relatively “simple” individuals. By making simple assumptions about individuals’ decision-making and behaviors and allowing actors to affect one another, behavioral patterns emerge that cannot be predicted by the characteristics of individuals. The computer simulation developed here models celebratory riot behavior by repeatedly evaluating a single algorithm for each individual, the inputs of which are affected by the characteristics of nearby actors. Specifically, the simulation assumes that (a) actors possess 1 of 5 distinct social identities (group memberships), (b) actors will congregate with actors who possess the same identity, (c) the degree of social cohesion generated in the social context determines the stability of relationships within groups, and (d) actors’ level of aggression is affected by the aggression of other group members. Not only does this simulation provide a systematic investigation of the effects of the initial distribution of aggression, social identification, and cohesiveness on riot outcomes, but also an analytic tool others may use to investigate, visualize and predict how various individual characteristics affect emergent crowd behavior.

Simulation of Freight Trains Equipped with Partially Filled Tank Containers and Related Resonance Phenomenon

To study the fluid motion-vehicle dynamics interaction, a model of four, liquid filled two-axle container freight wagons was set up. The railway vehicle has been modelled as a multi-body system (MBS). To include fluid sloshing, an equivalent mechanical model has been developed and incorporated. The influence of several factors has been studied in computer simulations, such as track defects, curve negotiation, train velocity, wheel wear, liquid and solid wagonload, and container baffles. SIMPACK has been used for MBS analysis, and ANSYS for liquid sloshing modelling and equivalent mechanical systems validation. Acceleration and braking manoeuvres of the freight train set the liquid cargo into motion. This longitudinal sloshing motion of the fluid cargo inside the tanks initiated a swinging motion of some components of the coupling gear. The coupling gear consists of UIC standard traction hooks and coupling screws that are located between buffers. One of the coupling screws is placed in the traction hook of the opposite wagon thus joining the two wagons, whereas the unused coupling screw rests on a hanger. Simulation results showed that, for certain combinations of type of liquid, filling level and container dimensions, the liquid cargo could provoke an undesirable, although not hazardous, release of the unused coupling screw from its hanger. The coupling screw's release was especially obtained when a period of acceleration was followed by an abrupt braking manoeuvre at 1 m/s2. It was shown that a resonance effect between the liquid's oscillation and the coupling screw's rotary motion could be the reason for the coupling screw's undesired release. Possible solutions to avoid the phenomenon are given.Acceleration and braking manoeuvres of the freight train set the liquid cargo into motion. This longitudinal sloshing motion of the fluid cargo inside the tanks initiated a swinging motion of some components of the coupling gear. The coupling gear consists of UIC standard traction hooks and coupling screws that are located between buffers. One of the coupling screws is placed in the traction hook of the opposite wagon thus joining the two wagons, whereas the unused coupling screw rests on a hanger. This paper reports on a study of the fluid motion-train vehicle dynamics interaction. In the study, a model of four, liquid-filled two-axle container freight wagons was developed. The railway vehicle has been modeled as a multi-body system (MBS). To include fluid sloshing, an equivalent mechanical model has been developed and incorporated. The influence of several factors has been studied in computer simulations, such as track defects, curve negotiation, train velocity, wheel wear, liquid and solid wagonload, and container baffles. A simulation program was used for MBS analysis, and a finite element analysis program was used for liquid sloshing modeling and equivalent mechanical systems validation. Acceleration and braking maneuvers of the freight train set the liquid cargo into motion. This longitudinal sloshing motion of the fluid cargo inside the tanks initiated a swinging motion of some components of the coupling gear. Simulation results showed that, for certain combinations of type of liquid, filling level and container dimensions, the liquid cargo could provoke an undesirable, although not hazardous, release of an unused coupling screw from its hanger. It was shown that a resonance effect between the liquid's oscillation and the coupling screw's rotary motion could be the reason for the coupling screw's undesired release. Solutions are suggested to avoid the resonance problem, and directions for future research are given.

Simulation, Design and Analysis of Air-Breathing Combined-Cycle Engines for High Speed Propulsion

Desde la aparición del turborreactor, el motor aeróbico con turbomaquinaria ha demostrado unas prestaciones excepcionales en los regímenes subsónico y supersónico bajo. No obstante, la operación a velocidades superiores requiere sistemas más complejos y pesados, lo cual ha imposibilitado la ejecución de estos conceptos. Los recientes avances tecnológicos, especialmente en materiales ligeros, han restablecido el interés por los motores de ciclo combinado. La simulación numérica de estos nuevos conceptos es esencial para estimar las prestaciones de la planta propulsiva, así como para abordar las dificultades de integración entre célula y motor durante las primeras etapas de diseño. Al mismo tiempo, la evaluación de estos extraordinarios motores requiere una metodología de análisis distinta. La tesis doctoral versa sobre el diseño y el análisis de los mencionados conceptos propulsivos mediante el modelado numérico y la simulación dinámica con herramientas de vanguardia. Las distintas arquitecturas presentadas por los ciclos combinados basados en sendos turborreactor y motor cohete, así como los diversos sistemas comprendidos en cada uno de ellos, hacen necesario establecer una referencia común para su evaluación. Es más, la tendencia actual hacia aeronaves "más eléctricas" requiere una nueva métrica para juzgar la aptitud de un proceso de generación de empuje en el que coexisten diversas formas de energía. A este respecto, la combinación del Primer y Segundo Principios define, en un marco de referencia absoluto, la calidad de la trasferencia de energía entre los diferentes sistemas. Esta idea, que se ha estado empleando desde hace mucho tiempo en el análisis de plantas de potencia terrestres, ha sido extendida para relacionar la misión de la aeronave con la ineficiencia de cada proceso involucrado en la generación de empuje. La metodología se ilustra mediante el estudio del motor de ciclo combinado variable de una aeronave para el crucero a Mach 5. El diseño de un acelerador de ciclo combinado basado en el turborreactor sirve para subrayar la importancia de la integración del motor y la célula. El diseño está limitado por la trayectoria ascensional y el espacio disponible en la aeronave de crucero supersónico. Posteriormente se calculan las prestaciones instaladas de la planta propulsiva en función de la velocidad y la altitud de vuelo y los parámetros de control del motor: relación de compresión, relación aire/combustible y área de garganta. ABSTRACT Since the advent of the turbojet, the air-breathing engine with rotating machinery has demonstrated exceptional performance in the subsonic and low supersonic regimes. However, the operation at higher speeds requires further system complexity and weight, which so far has impeded the realization of these concepts. Recent technology developments, especially in lightweight materials, have restored the interest towards combined-cycle engines. The numerical simulation of these new concepts is essential at the early design stages to compute a first estimate of the engine performance in addition to addressing airframe-engine integration issues. In parallel, a different analysis methodology is required to evaluate these unconventional engines. The doctoral thesis concerns the design and analysis of the aforementioned engine concepts by means of numerical modeling and dynamic simulation with state-of-the-art tools. A common reference is needed to evaluate the different architectures of the turbine and the rocket-based combined-cycle engines as well as the various systems within each one of them. Furthermore, the actual trend towards more electric aircraft necessitates a common metric to judge the suitability of a thrust generation process where different forms of energy coexist. In line with this, the combination of the First and the Second Laws yields the quality of the energy being transferred between the systems on an absolute reference frame. This idea, which has been since long applied to the analysis of on-ground power plants, was extended here to relate the aircraft mission with the inefficiency of every process related to the thrust generation. The methodology is illustrated with the study of a variable- combined-cycle engine for a Mach 5 cruise aircraft. The design of a turbine-based combined-cycle booster serves to highlight the importance of the engine-airframe integration. The design is constrained by the ascent trajectory and the allocated space in the supersonic cruise aircraft. The installed performance of the propulsive plant is then computed as a function of the flight speed and altitude and the engine control parameters: pressure ratio, air-to-fuel ratio and throat area.

Short-term electricity price forecasting using wavelet and SVM techniques

In deregulated electricity market, modeling and forecasting the spot price present a number of challenges. By applying wavelet and support vector machine techniques, a new time series model for short term electricity price forecasting has been developed in this paper. The model employs both historical price and other important information, such as load capacity and weather (temperature), to forecast the price of one or more time steps ahead. The developed model has been evaluated with the actual data from Australian National Electricity Market. The simulation results demonstrated that the forecast model is capable of forecasting the electricity price with a reasonable forecasting accuracy.

Multiscale modelling:approaches and challenges

Multiscale systems that are characterized by a great range of spatial–temporal scales arise widely in many scientific domains. These range from the study of protein conformational dynamics to multiphase processes in, for example, granular media or haemodynamics, and from nuclear reactor physics to astrophysics. Despite the diversity in subject areas and terminology, there are many common challenges in multiscale modelling, including validation and design of tools for programming and executing multiscale simulations. This Theme Issue seeks to establish common frameworks for theoretical modelling, computing and validation, and to help practical applications to benefit from the modelling results. This Theme Issue has been inspired by discussions held during two recent workshops in 2013: ‘Multiscale modelling and simulation’ at the Lorentz Center, Leiden (http://www.lorentzcenter.nl/lc/web/2013/569/info.php3?wsid=569&venue=Snellius), and ‘Multiscale systems: linking quantum chemistry, molecular dynamics and microfluidic hydrodynamics’ at the Royal Society Kavli Centre. The objective of both meetings was to identify common approaches for dealing with multiscale problems across different applications in fluid and soft matter systems. This was achieved by bringing together experts from several diverse communities.

Passivity Framework for Modeling, Composing and Mitigating Cyber Attacks

Thesis (Ph.D.)--University of Washington, 2016-08

Design, modelling, simulation and integration of cyber physical systems: methods and applications

The main drivers for the development and evolution of Cyber Physical Systems (CPS) are the reduction of development costs and time along with the enhancement of the designed products. The aim of this survey paper is to provide an overview of different types of system and the associated transition process from mechatronics to CPS and cloud-based (IoT) systems. It will further consider the requirement that methodologies for CPS-design should be part of a multi-disciplinary development process within which designers should focus not only on the separate physical and computational components, but also on their integration and interaction. Challenges related to CPS-design are therefore considered in the paper from the perspectives of the physical processes, computation and integration respectively. Illustrative case studies are selected from different system levels starting with the description of the overlaying concept of Cyber Physical Production Systems (CPPSs). The analysis and evaluation of the specific properties of a sub-system using a condition monitoring system, important for the maintenance purposes, is then given for a wind turbine.

Physical Design Methodologies for Low Power and Reliable 3D ICs

As the semiconductor industry struggles to maintain its momentum down the path following the Moore's Law, three dimensional integrated circuit (3D IC) technology has emerged as a promising solution to achieve higher integration density, better performance, and lower power consumption. However, despite its significant improvement in electrical performance, 3D IC presents several serious physical design challenges. In this dissertation, we investigate physical design methodologies for 3D ICs with primary focus on two areas: low power 3D clock tree design, and reliability degradation modeling and management. Clock trees are essential parts for digital system which dissipate a large amount of power due to high capacitive loads. The majority of existing 3D clock tree designs focus on minimizing the total wire length, which produces sub-optimal results for power optimization. In this dissertation, we formulate a 3D clock tree design flow which directly optimizes for clock power. Besides, we also investigate the design methodology for clock gating a 3D clock tree, which uses shutdown gates to selectively turn off unnecessary clock activities. Different from the common assumption in 2D ICs that shutdown gates are cheap thus can be applied at every clock node, shutdown gates in 3D ICs introduce additional control TSVs, which compete with clock TSVs for placement resources. We explore the design methodologies to produce the optimal allocation and placement for clock and control TSVs so that the clock power is minimized. We show that the proposed synthesis flow saves significant clock power while accounting for available TSV placement area. Vertical integration also brings new reliability challenges including TSV's electromigration (EM) and several other reliability loss mechanisms caused by TSV-induced stress. These reliability loss models involve complex inter-dependencies between electrical and thermal conditions, which have not been investigated in the past. In this dissertation we set up an electrical/thermal/reliability co-simulation framework to capture the transient of reliability loss in 3D ICs. We further derive and validate an analytical reliability objective function that can be integrated into the 3D placement design flow. The reliability aware placement scheme enables co-design and co-optimization of both the electrical and reliability property, thus improves both the circuit's performance and its lifetime. Our electrical/reliability co-design scheme avoids unnecessary design cycles or application of ad-hoc fixes that lead to sub-optimal performance. Vertical integration also enables stacking DRAM on top of CPU, providing high bandwidth and short latency. However, non-uniform voltage fluctuation and local thermal hotspot in CPU layers are coupled into DRAM layers, causing a non-uniform bit-cell leakage (thereby bit flip) distribution. We propose a performance-power-resilience simulation framework to capture DRAM soft error in 3D multi-core CPU systems. In addition, a dynamic resilience management (DRM) scheme is investigated, which adaptively tunes CPU's operating points to adjust DRAM's voltage noise and thermal condition during runtime. The DRM uses dynamic frequency scaling to achieve a resilience borrow-in strategy, which effectively enhances DRAM's resilience without sacrificing performance. The proposed physical design methodologies should act as important building blocks for 3D ICs and push 3D ICs toward mainstream acceptance in the near future.

Investigating output accuracy for a discrete event simulation model and an agent based simulation model

In this paper, we investigate output accuracy for a Discrete Event Simulation (DES) model and Agent Based Simulation (ABS) model. The purpose of this investigation is to find out which of these simulation techniques is the best one for modelling human reactive behaviour in the retail sector. In order to study the output accuracy in both models, we have carried out a validation experiment in which we compared the results from our simulation models to the performance of a real system. Our experiment was carried out using a large UK department store as a case study. We had to determine an efficient implementation of management policy in the store’s fitting room using DES and ABS. Overall, we have found that both simulation models were a good representation of the real system when modelling human reactive behaviour.

Modelling and analysing cargo screening processes: a project outline

The efficiency of current cargo screening processes at sea and air ports is unknown as no benchmarks exists against which they could be measured. Some manufacturer benchmarks exist for individual sensors but we have not found any benchmarks that take a holistic view of the screening procedures assessing a combination of sensors and also taking operator variability into account. Just adding up resources and manpower used is not an effective way for assessing systems where human decision-making and operator compliance to rules play a vital role. For such systems more advanced assessment methods need to be used, taking into account that the cargo screening process is of a dynamic and stochastic nature. Our project aim is to develop a decision support tool (cargo-screening system simulator) that will map the right technology and manpower to the right commodity-threat combination in order to maximize detection rates. In this paper we present a project outline and highlight the research challenges we have identified so far. In addition we introduce our first case study, where we investigate the cargo screening process at the ferry port in Calais.

Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting

The use of neuromodulation as a treatment for major depressive disorder (MDD) has recently attracted renewed interest due to development of other non-pharmacological therapies besides electroconvulsive therapy (ECT) such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). METHOD: We convened a working group of researchers to discuss the updates and key challenges of neuromodulation use for the treatment of MDD. RESULTS: The state-of-art of neuromodulation techniques was reviewed and discussed in four sections: [1] epidemiology and pathophysiology of MDD; [2] a comprehensive overview of the neuromodulation techniques; [3] using neuromodulation techniques in MDD associated with non-psychiatric conditions; [4] the main challenges of neuromodulation research and alternatives to overcome them. DISCUSSION: ECT is the first-line treatment for severe depression. TMS and tDCS are strategies with a relative benign profile of side effects; however, while TMS effects are comparable to antidepressant drugs for treating MDD; further research is needed to establish the role of tDCS. DBS and VNS are invasive strategies with a possible role in treatment-resistant depression. In summary, MDD is a chronic and incapacitating condition with a high prevalence; therefore clinicians should consider all the treatment options including invasive and non-invasive neuromodulation approaches.

Gene Expression Complex Networks: Synthesis, Identification, and Analysis

Thanks to recent advances in molecular biology, allied to an ever increasing amount of experimental data, the functional state of thousands of genes can now be extracted simultaneously by using methods such as cDNA microarrays and RNA-Seq. Particularly important related investigations are the modeling and identification of gene regulatory networks from expression data sets. Such a knowledge is fundamental for many applications, such as disease treatment, therapeutic intervention strategies and drugs design, as well as for planning high-throughput new experiments. Methods have been developed for gene networks modeling and identification from expression profiles. However, an important open problem regards how to validate such approaches and its results. This work presents an objective approach for validation of gene network modeling and identification which comprises the following three main aspects: (1) Artificial Gene Networks (AGNs) model generation through theoretical models of complex networks, which is used to simulate temporal expression data; (2) a computational method for gene network identification from the simulated data, which is founded on a feature selection approach where a target gene is fixed and the expression profile is observed for all other genes in order to identify a relevant subset of predictors; and (3) validation of the identified AGN-based network through comparison with the original network. The proposed framework allows several types of AGNs to be generated and used in order to simulate temporal expression data. The results of the network identification method can then be compared to the original network in order to estimate its properties and accuracy. Some of the most important theoretical models of complex networks have been assessed: the uniformly-random Erdos-Renyi (ER), the small-world Watts-Strogatz (WS), the scale-free Barabasi-Albert (BA), and geographical networks (GG). The experimental results indicate that the inference method was sensitive to average degree k variation, decreasing its network recovery rate with the increase of k. The signal size was important for the inference method to get better accuracy in the network identification rate, presenting very good results with small expression profiles. However, the adopted inference method was not sensible to recognize distinct structures of interaction among genes, presenting a similar behavior when applied to different network topologies. In summary, the proposed framework, though simple, was adequate for the validation of the inferred networks by identifying some properties of the evaluated method, which can be extended to other inference methods.