Gene electrotransfer into murine skeletal muscle: A systematic analysis of parameters for long-term gene expression

Skeletal muscle is an attractive target tissue for delivery of therapeutic genes, since it is well vascularized, easily accessible, and has a high capacity for protein synthesis. For efficient transfection in skeletal muscle, several protocols have been described, including delivery of low voltage electric pulses and a combination of high and low voltage electric pulses. The aim of this study was to determine the influence of different parameters of electrotransfection on short-term and long-term transfection efficiency in murine skeletal muscle, and to evaluate histological changes in the treated tissue. Different parameters of electric pulses, different time lags between plasmid DNA injection and application of electric pulses, and different doses of plasmid DNA were tested for electrotransfection of tibialis cranialis muscle of C57BI/6 mice using DNA plasmid encoding green fluorescent protein (GFP). Transfection efficiency was assessed on frozen tissue sections one week after electrotransfection using a fluorescence microscope and also noninvasively, followed by an in vivo imaging system using a fluorescence stereo microscope over a period of several months. Histological changes in muscle were evaluated immediately or several months after electrotransfection by determining infiltration of inflammatory mononuclear cells and presence of necrotic muscle fibers. The most efficient electrotransfection into skeletal muscle of C57BI/6 mice in our experiments was achieved when one high voltage (HV) and four low voltage (LV) electric pulses were applied 5 seconds after the injection of 30 μg of plasmid DNA. This protocol resulted in the highest short-term as well as long-term transfection. The fluorescence intensity of the transfected area declined after 2-3 weeks, but GFP fluorescence was still detectable 18 months after electrotransfection. Extensive inflammatory mononuclear cell infiltration was observed immediately after the electrotransfection procedure using the described parameters, but no necrosis or late tissue damage was observed. This study showed that electric pulse parameters, time lag between the injection of DNA and application of electric pulses, and dose of plasmid DNA affected the duration of transgene expression in murine skeletal muscle. Therefore, transgene expression in muscle can be controlled by appropriate selection of electrotransfection protocol.

Results from the farm

This paper reports on a large, long-term mobile wireless sensor network deployment. The trial was part of an animal study involving 45 animals. During the trial, 15 animals were equipped with wireless sensor nodes for a week. The paper discusses various issues with such a deployment including electronic design, software design, animal ethics clearance, logistics, and wearable computing equipment for animals. The paper also presents some preliminary analysis of the data obtained from the deployment, both from the perspective of network parameters and animal movement behavior.

Monitoring and analysis of internet traffic targeting unused address spaces

Today’s evolving networks are experiencing a large number of different attacks ranging from system break-ins, infection from automatic attack tools such as worms, viruses, trojan horses and denial of service (DoS). One important aspect of such attacks is that they are often indiscriminate and target Internet addresses without regard to whether they are bona fide allocated or not. Due to the absence of any advertised host services the traffic observed on unused IP addresses is by definition unsolicited and likely to be either opportunistic or malicious. The analysis of large repositories of such traffic can be used to extract useful information about both ongoing and new attack patterns and unearth unusual attack behaviors. However, such an analysis is difficult due to the size and nature of the collected traffic on unused address spaces. In this dissertation, we present a network traffic analysis technique which uses traffic collected from unused address spaces and relies on the statistical properties of the collected traffic, in order to accurately and quickly detect new and ongoing network anomalies. Detection of network anomalies is based on the concept that an anomalous activity usually transforms the network parameters in such a way that their statistical properties no longer remain constant, resulting in abrupt changes. In this dissertation, we use sequential analysis techniques to identify changes in the behavior of network traffic targeting unused address spaces to unveil both ongoing and new attack patterns. Specifically, we have developed a dynamic sliding window based non-parametric cumulative sum change detection techniques for identification of changes in network traffic. Furthermore we have introduced dynamic thresholds to detect changes in network traffic behavior and also detect when a particular change has ended. Experimental results are presented that demonstrate the operational effectiveness and efficiency of the proposed approach, using both synthetically generated datasets and real network traces collected from a dedicated block of unused IP addresses.

A circuit-breaker restrike diagnostic algorithm using ATP and wavelet transforms

Circuit breaker restrikes are unwanted occurrence, which can ultimately lead to breaker. Before 2008, there was little evidence in the literature of monitoring techniques based on restrike measurement and interpretation produced during switching of capacitor banks and shunt reactor banks. In 2008 a non-intrusive radiometric restrike measurement method, as well a restrike hardware detection algorithm was developed. The limitations of the radiometric measurement method are a band limited frequency response as well as limitations in amplitude determination. Current detection methods and algorithms required the use of wide bandwidth current transformers and voltage dividers. A novel non-intrusive restrike diagnostic algorithm using ATP (Alternative Transient Program) and wavelet transforms is proposed. Wavelet transforms are the most common use in signal processing, which is divided into two tests, i.e. restrike detection and energy level based on deteriorated waveforms in different types of restrike. A ‘db5’ wavelet was selected in the tests as it gave a 97% correct diagnostic rate evaluated using a database of diagnostic signatures. This was also tested using restrike waveforms simulated under different network parameters which gave a 92% correct diagnostic responses. The diagnostic technique and methodology developed in this research can be applied to any power monitoring system with slight modification for restrike detection.

Improving voltage profile of residential distribution systems using rooftop PVs and Battery Energy Storage systems

Large number of rooftop Photovoltaics (PVs) have turned traditional passive networks into active networks with intermittent and bidirectional power flow. A community based distribution network grid reinforcement process is proposed to address technical challenges associated with large integration of rooftop PVs. Probabilistic estimation of intermittent PV generation is considered. Depending on the network parameters such as the R/X ratio of distribution feeder, either reactive control from PVs or coordinated control of PVs and Battery Energy Storage (BES) has been proposed. Determination of BES capacity is one of the significant outcomes from the proposed method and several factors such as variation in PV installed capacity as well as participation from community members are analyzed. The proposed approach is convenient for the community members providing them flexibility of managing their integrated PV and BES systems

Smart coordinated distribution system control to enable high level penetration of rooftop PVs

This thesis addresses voltage violation problem, the most critical issue associated with high level penetration of photovoltaic (PV) in electricity distribution network. A coordinated control algorithm using the reactive power from PV inverter and integrated battery energy storage has been developed and investigated in different network scenarios in the thesis. Probable variations associated with solar generation, end-user participation and network parameters are also considered. Furthermore, a unified data model and well-defined communication protocol to ensure the smooth coordination between all the components during the operation of the algorithm is described. Finally this thesis incorporated the uncertainties of solar generation using probabilistic load flow analysis.

An intelligent network control system for plug-in electric vehicles and the associate communication mechanism

The development of an intelligent plug-in electric vehicle (PEV) network is an important research topic in the smart grid environment. An intelligent PEV network enables a flexible control of PEV charging and discharging activities and hence PEVs can be utilized as ancillary service providers in the power system concerned. Given this background, an intelligent PEV network architecture is first developed, and followed by detailed designs of its application layers, including the charging and discharging controlling system, mobility and roaming management, as well as communication mechanisms associated. The presented architecture leverages the philosophy in mobile communication network buildup

Characterising anomalous events using change point correlation on unsolicited network traffic

Monitoring unused or dark IP addresses offers opportunities to extract useful information about both on-going and new attack patterns. In recent years, different techniques have been used to analyze such traffic including sequential analysis where a change in traffic behavior, for example change in mean, is used as an indication of malicious activity. Change points themselves say little about detected change; further data processing is necessary for the extraction of useful information and to identify the exact cause of the detected change which is limited due to the size and nature of observed traffic. In this paper, we address the problem of analyzing a large volume of such traffic by correlating change points identified in different traffic parameters. The significance of the proposed technique is two-fold. Firstly, automatic extraction of information related to change points by correlating change points detected across multiple traffic parameters. Secondly, validation of the detected change point by the simultaneous presence of another change point in a different parameter. Using a real network trace collected from unused IP addresses, we demonstrate that the proposed technique enables us to not only validate the change point but also extract useful information about the causes of change points.

Network jamming : distributed performance using generative music

Generative music systems can be performed by manipulating the values of their algorithmic parameters, and their semi-autonomous nature provides an opportunity for coordinated interaction amongst a network of systems, a practice we call Network Jamming. This paper outlines the characteristics of this networked performance practice and discusses the types of mediated musical relationships and ensemble configurations that can arise. We have developed and tested the jam2jam network jamming software over recent years. We describe this system, draw from our experiences with it, and use it to illustrate some characteristics of Network Jamming.

On the optimal capacity expansion of electric power systems

The analysis of investment in the electric power has been the subject of intensive research for many years. The efficient generation and distribution of electrical energy is a difficult task involving the operation of a complex network of facilities, often located over very large geographical regions. Electric power utilities have made use of an enormous range of mathematical models. Some models address time spans which last for a fraction of a second, such as those that deal with lightning strikes on transmission lines while at the other end of the scale there are models which address time horizons consisting of ten or twenty years; these usually involve long range planning issues. This thesis addresses the optimal long term capacity expansion of an interconnected power system. The aim of this study has been to derive a new, long term planning model which recognises the regional differences which exist for energy demand and which are present in the construction and operation of power plant and transmission line equipment. Perhaps the most innovative feature of the new model is the direct inclusion of regional energy demand curves in the nonlinear form. This results in a nonlinear capacity expansion model. After review of the relevant literature, the thesis first develops a model for the optimal operation of a power grid. This model directly incorporates regional demand curves. The model is a nonlinear programming problem containing both integer and continuous variables. A solution algorithm is developed which is based upon a resource decomposition scheme that separates the integer variables from the continuous ones. The decompostion of the operating problem leads to an interactive scheme which employs a mixed integer programming problem, known as the master, to generate trial operating configurations. The optimum operating conditions of each trial configuration is found using a smooth nonlinear programming model. The dual vector recovered from this model is subsequently used by the master to generate the next trial configuration. The solution algorithm progresses until lower and upper bounds converge. A range of numerical experiments are conducted and these experiments are included in the discussion. Using the operating model as a basis, a regional capacity expansion model is then developed. It determines the type, location and capacity of additional power plants and transmission lines, which are required to meet predicted electicity demands. A generalised resource decompostion scheme, similar to that used to solve the operating problem, is employed. The solution algorithm is used to solve a range of test problems and the results of these numerical experiments are reported. Finally, the expansion problem is applied to the Queensland electricity grid in Australia.

On the optimal capacity expansion of electric power systems

The analysis of investment in the electric power has been the subject of intensive research for many years. The efficient generation and distribution of electrical energy is a difficult task involving the operation of a complex network of facilities, often located over very large geographical regions. Electric power utilities have made use of an enormous range of mathematical models. Some models address time spans which last for a fraction of a second, such as those that deal with lightning strikes on transmission lines while at the other end of the scale there are models which address time horizons consisting of ten or twenty years; these usually involve long range planning issues. This thesis addresses the optimal long term capacity expansion of an interconnected power system. The aim of this study has been to derive a new, long term planning model which recognises the regional differences which exist for energy demand and which are present in the construction and operation of power plant and transmission line equipment. Perhaps the most innovative feature of the new model is the direct inclusion of regional energy demand curves in the nonlinear form. This results in a nonlinear capacity expansion model. After review of the relevant literature, the thesis first develops a model for the optimal operation of a power grid. This model directly incorporates regional demand curves. The model is a nonlinear programming problem containing both integer and continuous variables. A solution algorithm is developed which is based upon a resource decomposition scheme that separates the integer variables from the continuous ones. The decompostion of the operating problem leads to an interactive scheme which employs a mixed integer programming problem, known as the master, to generate trial operating configurations. The optimum operating conditions of each trial configuration is found using a smooth nonlinear programming model. The dual vector recovered from this model is subsequently used by the master to generate the next trial configuration. The solution algorithm progresses until lower and upper bounds converge. A range of numerical experiments are conducted and these experiments are included in the discussion. Using the operating model as a basis, a regional capacity expansion model is then developed. It determines the type, location and capacity of additional power plants and transmission lines, which are required to meet predicted electicity demands. A generalised resource decompostion scheme, similar to that used to solve the operating problem, is employed. The solution algorithm is used to solve a range of test problems and the results of these numerical experiments are reported. Finally, the expansion problem is applied to the Queensland electricity grid in Australia

Network protocols and predictive control strategies for distributed real-time control applications

A trend in design and implementation of modern industrial automation systems is to integrate computing, communication and control into a unified framework at different levels of machine/factory operations and information processing. These distributed control systems are referred to as networked control systems (NCSs). They are composed of sensors, actuators, and controllers interconnected over communication networks. As most of communication networks are not designed for NCS applications, the communication requirements of NCSs may be not satisfied. For example, traditional control systems require the data to be accurate, timely and lossless. However, because of random transmission delays and packet losses, the control performance of a control system may be badly deteriorated, and the control system rendered unstable. The main challenge of NCS design is to both maintain and improve stable control performance of an NCS. To achieve this, communication and control methodologies have to be designed. In recent decades, Ethernet and 802.11 networks have been introduced in control networks and have even replaced traditional fieldbus productions in some real-time control applications, because of their high bandwidth and good interoperability. As Ethernet and 802.11 networks are not designed for distributed control applications, two aspects of NCS research need to be addressed to make these communication networks suitable for control systems in industrial environments. From the perspective of networking, communication protocols need to be designed to satisfy communication requirements for NCSs such as real-time communication and high-precision clock consistency requirements. From the perspective of control, methods to compensate for network-induced delays and packet losses are important for NCS design. To make Ethernet-based and 802.11 networks suitable for distributed control applications, this thesis develops a high-precision relative clock synchronisation protocol and an analytical model for analysing the real-time performance of 802.11 networks, and designs a new predictive compensation method. Firstly, a hybrid NCS simulation environment based on the NS-2 simulator is designed and implemented. Secondly, a high-precision relative clock synchronization protocol is designed and implemented. Thirdly, transmission delays in 802.11 networks for soft-real-time control applications are modeled by use of a Markov chain model in which real-time Quality-of- Service parameters are analysed under a periodic traffic pattern. By using a Markov chain model, we can accurately model the tradeoff between real-time performance and throughput performance. Furthermore, a cross-layer optimisation scheme, featuring application-layer flow rate adaptation, is designed to achieve the tradeoff between certain real-time and throughput performance characteristics in a typical NCS scenario with wireless local area network. Fourthly, as a co-design approach for both a network and a controller, a new predictive compensation method for variable delay and packet loss in NCSs is designed, where simultaneous end-to-end delays and packet losses during packet transmissions from sensors to actuators is tackled. The effectiveness of the proposed predictive compensation approach is demonstrated using our hybrid NCS simulation environment.

The sample complexity of pattern classification with neural networks: the size of the weights is more important than the size of the network

Sample complexity results from computational learning theory, when applied to neural network learning for pattern classification problems, suggest that for good generalization performance the number of training examples should grow at least linearly with the number of adjustable parameters in the network. Results in this paper show that if a large neural network is used for a pattern classification problem and the learning algorithm finds a network with small weights that has small squared error on the training patterns, then the generalization performance depends on the size of the weights rather than the number of weights. For example, consider a two-layer feedforward network of sigmoid units, in which the sum of the magnitudes of the weights associated with each unit is bounded by A and the input dimension is n. We show that the misclassification probability is no more than a certain error estimate (that is related to squared error on the training set) plus A3 √((log n)/m) (ignoring log A and log m factors), where m is the number of training patterns. This may explain the generalization performance of neural networks, particularly when the number of training examples is considerably smaller than the number of weights. It also supports heuristics (such as weight decay and early stopping) that attempt to keep the weights small during training. The proof techniques appear to be useful for the analysis of other pattern classifiers: when the input domain is a totally bounded metric space, we use the same approach to give upper bounds on misclassification probability for classifiers with decision boundaries that are far from the training examples.