Spatiotemporal investigations of DNA damage repair using microbeams

Cellular response to radiation damage is made by a complex network of pathways and feedback loops whose spatiotemporal organisation is still unclear despite its decisive role in determining the fate of the damaged cell. Revealing the dynamic sequence of the repair proteins is therefore critical in understanding how the DNA repair mechanisms work. There are also still open questions regarding the possible movement of damaged chromatin domains and its role as trigger for lesion recognition and signalling in the DNA repair context. The single-cell approach and the high spatial resolution offered by microbeams provide the perfect tool to study and quantify the dynamic processes associated with the induction and repair of DNA damage. We have followed the development of radiation-induced foci for three DNA damage markers (i.e. γ-H2AX, 53BP1 and hSSB1) using normal fibroblasts (AG01522), human breast adenocarcinoma cells (MCF7) and human fibrosarcoma cells (HT1080) stably transfected with yellow fluorescent protein fusion proteins following irradiation with the QUB X-ray microbeam (carbon X-rays <2 µm spot). The size and intensity of the foci has been analysed as a function of dose and time post-irradiation to investigate the dynamics of the above-mentioned DNA repair processes and monitor the remodelling of chromatin structure that the cell undergoes to deal with DNA damage.

Multiple human single-stranded DNA binding proteins function in genome maintenance : structural, biochemical and functional analysis

DNA exists predominantly in a duplex form that is preserved via specific base pairing. This base pairing affords a considerable degree of protection against chemical or physical damage and preserves coding potential. However, there are many situations, e.g. during DNA damage and programmed cellular processes such as DNA replication and transcription, in which the DNA duplex is separated into two singlestranded DNA (ssDNA) strands. This ssDNA is vulnerable to attack by nucleases, binding by inappropriate proteins and chemical attack. It is very important to control the generation of ssDNA and protect it when it forms, and for this reason all cellular organisms and many viruses encode a ssDNA binding protein (SSB). All known SSBs use an oligosaccharide/oligonucleotide binding (OB)-fold domain for DNA binding. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating strand-exchange proteins and helicases, and mediation of protein–protein interactions. Recently two additional human SSBs have been identified that are more closely related to bacterial and archaeal SSBs. Prior to this it was believed that replication protein A, RPA, was the only human equivalent of bacterial SSB. RPA is thought to be required for most aspects of DNA metabolism including DNA replication, recombination and repair. This review will discuss in further detail the biological pathways in which human SSBs function.

Involvement of Exo1b in DNA damage-induced apoptosis

Apoptosis is essential for the maintenance of inherited genomic integrity. During DNA damage-induced apoptosis, mechanisms of cell survival, such as DNA repair are inactivated to allow cell death to proceed. Here, we describe a role for the mammalian DNA repair enzyme Exonuclease 1 (Exo1) in DNA damage-induced apoptosis. Depletion of Exo1 in human fibroblasts, or mouse embryonic fibroblasts led to a delay in DNA damage-induced apoptosis. Furthermore, we show that Exo1 acts upstream of caspase-3, DNA fragmentation and cytochrome c release. In addition, induction of apoptosis with DNA-damaging agents led to cleavage of both isoforms of Exo1. The cleavage of Exo1 was mapped to Asp514, and shown to be mediated by caspase-3. Expression of a caspase-3 cleavage site mutant form of Exo1, Asp514Ala, prevented formation of the previously observed fragment without any affect on the onset of apoptosis. We conclude that Exo1 has a role in the timely induction of apoptosis and that it is subsequently cleaved and degraded during apoptosis, potentially inhibiting DNA damage repair.

Performance comparison of VSC-based shunt and series compensators used for load voltage control in distribution systems

In this paper, the performance of voltage-source converter-based shunt and series compensators used for load voltage control in electrical power distribution systems has been analyzed and compared, when a nonlinear load is connected across the load bus. The comparison has been made based on the closed-loop frequency resopnse characteristics of the compensated distribution system. A distribution static compensator (DSTATCOM) as a shunt device and a dynamic voltage restorer (DVR) as a series device are considered in the voltage-control mode for the comparison. The power-quality problems which these compensator address include voltage sags/swells, load voltage harmonic distortions, and unbalancing. The effect of various system parameters on the control performance of the compensator can be studied using the proposed analysis. In particular, the performance of the two compensators are compared with the strong ac supply (stiff source) and weak ac-supply (non-still source) distribution system. The experimental verification of the analytical results derived has been obtained using a laboratory model of the single-phase DSTATCOM and DVR. A generalized converter topology using a cascaded multilevel inverter has been proposed for the medium-voltage distribution system. Simulation studies have been performed in the PSCAD/EMTDC software to verify the results in the three-phase system.

Effects of reduced contrast on the perception and control of speed when driving

Misperception of speed under low-contrast conditions has been identified as a possible contributor to motor vehicle crashes in fog. To test this hypothesis, we investigated the effects of reduced contrast on drivers’ perception and control of speed while driving under real-world conditions. Fourteen participants drove around a 2.85 km closed road course under three visual conditions: clear view and with two levels of reduced contrast created by diffusing filters on the windscreen and side windows. Three dependent measures were obtained, without view of the speedometer, on separate laps around the road course: verbal estimates of speed; adjustment of speed to instructed levels (25 to 70 km h-1); and estimation of minimum stopping distance. The results showed that drivers traveled more slowly under low-contrast conditions. Reduced contrast had little or no effect on either verbal judgments of speed or estimates of minimum stopping distance. Speed adjustments were significantly slower under low-contrast than clear conditions, indicating that, contrary to studies of object motion, drivers perceived themselves to be traveling faster under conditions of reduced contrast. Under real-world driving conditions, drivers’ ability to perceive and control their speed was not adversely affected by large variations in the contrast of their surroundings. These findings suggest that perceptions of self-motion and object motion involve neural processes that are differentially affected by variations in stimulus contrast as encountered in fog.

The role of vision in obese and normal-weight children's gait control

Previous research has suggested that perceptual-motor difficulties may account for obese children's lower motor competence; however, specific evidence is currently lacking. Therefore, this study examined the effect of altered visual conditions on spatiotemporal and kinematic gait parameters in obese versus normal-weight children. Thirty-two obese and normal-weight children (11.2 ± 1.5 years) walked barefoot on an instrumented walkway at constant self-selected speed during LIGHT and DARK conditions. Three-dimensional motion analysis was performed to calculate spatiotemporal parameters, as well as sagittal trunk segment and lower extremity joint angles at heel-strike and toe-off. Self-selected speed did not significantly differ between groups. In the DARK condition, all participants walked at a significantly slower speed, decreased stride length, and increased stride width. Without normal vision, obese children had a more pronounced increase in relative double support time compared to the normal-weight group, resulting in a significantly greater percentage of the gait cycle spent in stance. Walking in the DARK, both groups showed greater forward tilt of the trunk and restricted hip movement. All participants had increased knee flexion at heel-strike, as well as decreased knee extension and ankle plantarflexion at toe-off in the DARK condition. The removal of normal vision affected obese children's temporal gait pattern to a larger extent than that of normal-weight peers. Results suggest an increased dependency on vision in obese children to control locomotion. Next to the mechanical problem of moving excess mass, a different coupling between perception and action appears to be governing obese children's motor coordination and control.

Individual differences in the visual control of intercepting a penalty kick in association football

Recent perceptual-motor studies have revealed variations in learning trajectories of novices. Despite such observation, relatively little attention has been paid to studying individual differences in experienced performers’ perceptual-motor behaviors. The present study examined individual differences for a visual anticipation task. Experienced association football goalkeepers attempted to intercept penalty kicks taken with deceptive and non-deceptive kicking actions. Data revealed that differences in the action capabilities of goalkeepers affected the timing and accuracy of movement response behaviors. Faster goalkeepers tended to wait until later before initiating movement in comparison with slower goalkeepers. The study of affordances in sport environments offers a theoretical framework with which to overcome some of the reported methodological limitations in the visual anticipation literature.

A sense of control : virtual communities for people with mobility impairments

The purpose of this book is to show why we should be concerned about virtual communities for people with physical, or more particularly mobility, impairments. The well-being model through a virtual community introduced here goes towards advancing the work begun by others, by adding for example a socio-political component. The model presented here provides practical insights into how strategic community investment can support people with disabilities and their families. Virtual communities are about engagement, quality of life and support, not just about information. The role of information technology in building and raising community capacity and social capital in socially and economically disadvantaged communities is also examined. Practical insights are offered into community support for people with chronic illness.

Hysteresis modeling of Magneto-Rheological (MR) fluid damper by self tuning fuzzy control

Magneto-rheological (MR) fluid damper is a semi-active control device that has recently received more attention by the vibration control community. But inherent nonlinear hysteresis character of magneto-rheological fluid dampers is one of the challenging aspects for utilizing this device to achieve high system performance. So the development of accurate model is necessary to take the advantage their unique characteristics. Research by others [3] has shown that a system of nonlinear differential equations can successfully be used to describe the hysteresis behavior of the MR damper. The focus of this paper is to develop an alternative method for modeling a damper in the form of centre average fuzzy interference system, where back propagation learning rules are used to adjust the weight of network. The inputs for the model are used from the experimental data. The resulting fuzzy interference system is satisfactorily represents the behavior of the MR fluid damper with reduced computational requirements. Use of the neuro-fuzzy model increases the feasibility of real time simulation.

Access control : allocating resources to selfish agents

The ultimate goal of an authorisation system is to allocate each user the level of access they need to complete their job - no more and no less. This proves to be challenging in an organisational setting because on one hand employees need enough access to perform their tasks, while on the other hand more access will bring about an increasing risk of misuse - either intentionally, where an employee uses the access for personal benefit, or unintentionally through carelessness, losing the information or being socially engineered to give access to an adversary. With the goal of developing a more dynamic authorisation model, we have adopted a game theoretic framework to reason about the factors that may affect users’ likelihood to misuse a permission at the time of an access decision. Game theory provides a useful but previously ignored perspective in authorisation theory: the notion of the user as a self-interested player who selects among a range of possible actions depending on their pay-offs.

Can the contra-lateral limb be used as a control with respect to analyses of bone remodelling?

Bone loss may result from remodelling initiated by implant stress protection. Quantifying remodelling requires bone density distributions which can be obtained from computed tomography scans. Pre-operative scans of large animals however are rarely possible. This study aimed to determine if the contra-lateral bone is a suitable control for the purpose of quantifying bone remodelling. CT scans of 8 pairs of ovine tibia were used to determine the likeness of left and right bones. The deviation between the outer surfaces of the bone pairs was used to quantify geometric similarity. The density differences were determined by dividing the bones into discrete volumes along the shaft of the tibia. Density differences were also determined for fractured and contra-lateral bone pairs to determine the magnitude of implant related remodelling. Left and right ovine tibiae were found to have a high degree of similarity with differences of less than 1.0 mm in the outer surface deviation and density difference of less than 5% in over 90% of the shaft region. The density differences (10–40%) as a result of implant related bone remodelling were greater than left-right differences. Therefore, for the purpose of quantifying bone remodelling in sheep, the contra-lateral tibia may be considered an alternative to a pre-operative control.

A crash avoidance framework for heavy equipment control systems using 3D imaging sensors

This paper presents a preliminary crash avoidance framework for heavy equipment control systems. Safe equipment operation is a major concern on construction sites since fatal on-site injuries are an industry-wide problem. The proposed framework has potential for effecting active safety for equipment operation. The framework contains algorithms for spatial modeling, object tracking, and path planning. Beyond generating spatial models in fractions of seconds, these algorithms can successfully track objects in an environment and produce a collision-free 3D motion trajectory for equipment.

Local adjustment and global adaptation of control periods for QoC management of control systems

Linking real-time schedulability directly to the Quality of Control (QoC), the ultimate goal of a control system, a hierarchical feedback QoC management framework with the Fixed Priority (FP) and the Earliest-Deadline-First (EDF) policies as plug-ins is proposed in this paper for real-time control systems with multiple control tasks. It uses a task decomposition model for continuous QoC evaluation even in overload conditions, and then employs heuristic rules to adjust the period of each of the control tasks for QoC improvement. If the total requested workload exceeds the desired value, global adaptation of control periods is triggered for workload maintenance. A sufficient stability condition is derived for a class of control systems with delay and period switching of the heuristic rules. Examples are given to demonstrate the proposed approach.

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.

Variable structure control for power systems stabilization

The application of variable structure control (VSC) for power systems stabilization is studied in this paper. It is the application, aspects and constraints of VSC which are of particular interest. A variable structure control methodology has been proposed for power systems stabilization. The method is implemented using thyristor controlled series compensators. A three machine power system is stabilized using a switching line control for large disturbances which becomes a sliding control as the disturbance becomes smaller. The results demonstrate the effectiveness of the methodology proposed as an useful tool to suppress the oscillations in power systems.