A variant of the breast cancer type 2 susceptibility protein (BRC) repeat is essential for the RECQL5 Helicase to interact with RAD51 Recombinase for genome stabilization

The BRC repeat is a structural motif in the tumor suppressor BRCA2 (breast cancer type 2 susceptibility protein), which promotes homologous recombination (HR) by regulating RAD51 recombinase activity. To date, the BRC repeat has not been observed in other proteins, so that its role in HR is inferred only in the context of BRCA2. Here, we identified a BRC repeat variant, named BRCv, in the RECQL5 helicase, which possesses anti-recombinase activity in vitro and suppresses HR and promotes cellular resistance to camptothecin-induced replication stress in vivo. RECQL5-BRCv interacted with RAD51 through two conserved motifs similar to those in the BRCA2-BRC repeat. Mutations of either motif compromised functions of RECQL5, including association with RAD51, inhibition of RAD51-mediated D-loop formation, suppression of sister chromatid exchange, and resistance to camptothecin-induced replication stress. Potential BRCvs were also found in other HR regulatory proteins, including Srs2 and Sgs1, which possess anti-recombinase activities similar to that of RECQL5. A point mutation in the predicted Srs2-BRCv disrupted the ability of the protein to bind RAD51 and to inhibit D-loop formation. Thus, BRC is a common RAD51 interaction module that can be utilized by different proteins to either promote HR, as in the case of BRCA2, or to suppress HR, as in RECQL5.

Data collection techniques

The objective of this chapter is to provide an overview of traffic data collection that can and should be used for the calibration and validation of traffic simulation models. There are big differences in availability of data from different sources. Some types of data such as loop detector data are widely available and used. Some can be measured with additional effort, for example, travel time data from GPS probe vehicles. Some types such as trajectory data are available only in rare situations such as research projects.

Robust control scheme for a microgrid with PFC capacitor connected

Capacitors are widely used for power-factor correction (PFC) in power systems. When a PFC capacitor is installed with a certain load in a microgrid, it may be in parallel with the filter capacitor of the inverter interfacing the utility grid and the local distributed-generation unit and, thus, change the effective filter capacitance. Another complication is the possibility of occurrence of resonance in the microgrid. This paper conducts an in-depth investigation of the effective shunt-filter-capacitance variation and resonance phenomena in a microgrid due to a connection of a PFC capacitor. To compensate the capacitance-parameter variation, an Hinfin controller is designed for the voltage-source- inverter voltage control. By properly choosing the weighting functions, the synthesized Hinfin controller would exhibit high gains at the vicinity of the line frequency, similar to traditional high- performance P+ resonant controller and, thus, would possess nearly zero steady-state error. However, with the robust Hinfin controller, it will be possible to explicitly specify the degree of robustness in face of parameter variations. Furthermore, a thorough investigation is carried out to study the performance of inner current-loop feedback variables under resonance conditions. It reveals that filter-inductor current feedback is more effective in damping the resonance. This resonance can be further attenuated by employing the dual-inverter microgrid conditioner and controlling the series inverter as a virtual resistor affecting only harmonic components without interference with the fundamental power flow. And finally, the study in this paper has been tested experimentally using an experimental microgrid prototype.

The complete mitochondrial genome of the yellow coaster, Acraea issoria (Lepidoptera: Nymphalidae: Heliconiinae: Acraeini): sequence, gene organization and a unique tRNA translocation event

In this paper, the complete mitochondrial genome of Acraea issoria (Lepidoptera: Nymphalidae: Heliconiinae: Acraeini) is reported; a circular molecule of 15,245 bp in size. For A. issoria, genes are arranged in the same order and orientation as the complete sequenced mitochondrial genomes of the other lepidopteran species, except for the presence of an extra copy of tRNAIle(AUR)b in the control region. All protein-coding genes of A. issoria mitogenome start with a typical ATN codon and terminate in the common stop codon TAA, except that COI gene uses TTG as its initial codon and terminates in a single T residue. All tRNA genes possess the typical clover leaf secondary structure except for tRNASer(AGN), which has a simple loop with the absence of the DHU stem. The sequence, organization and other features including nucleotide composition and codon usage of this mitochondrial genome were also reported and compared with those of other sequenced lepidopterans mitochondrial genomes. There are some short microsatellite-like repeat regions (e.g., (TA)9, polyA and polyT) scattered in the control region, however, the conspicuous macro-repeats units commonly found in other insect species are absent.

A hierarchical model of goal directed navigation selects trajectories in a visual environment

We have developed a Hierarchical Look-Ahead Trajectory Model (HiLAM) that incorporates the firing pattern of medial entorhinal grid cells in a planning circuit that includes interactions with hippocampus and prefrontal cortex. We show the model’s flexibility in representing large real world environments using odometry information obtained from challenging video sequences. We acquire the visual data from a camera mounted on a small tele-operated vehicle. The camera has a panoramic field of view with its focal point approximately 5 cm above the ground level, similar to what would be expected from a rat’s point of view. Using established algorithms for calculating perceptual speed from the apparent rate of visual change over time, we generate raw dead reckoning information which loses spatial fidelity over time due to error accumulation. We rectify the loss of fidelity by exploiting the loop-closure detection ability of a biologically inspired, robot navigation model termed RatSLAM. The rectified motion information serves as a velocity input to the HiLAM to encode the environment in the form of grid cell and place cell maps. Finally, we show goal directed path planning results of HiLAM in two different environments, an indoor square maze used in rodent experiments and an outdoor arena more than two orders of magnitude larger than the indoor maze. Together these results bridge for the first time the gap between higher fidelity bio-inspired navigation models (HiLAM) and more abstracted but highly functional bio-inspired robotic mapping systems (RatSLAM), and move from simulated environments into real-world studies in rodent-sized arenas and beyond.

CFD simulations of flow and heat transfer through the porous interface of a metal foam heat exchanger

This paper offers numerical modelling of a waste heat recovery system. A thin layer of metal foam is attached to a cold plate to absorb heat from hot gases leaving the system. The heat transferred from the exhaust gas is then transferred to a cold liquid flowing in a secondary loop. Two different foam PPI (Pores Per Inch) values are examined over a range of fluid velocities. Numerical results are then compared to both experimental data and theoretical results available in the literature. Challenges in getting the simulation results to match those of the experiments are addressed and discussed in detail. In particular, interface boundary conditions specified between a porous layer and a fluid layer are investigated. While physically one expects much lower fluid velocity in the pores compared to that of free flow, capturing this sharp gradient at the interface can add to the difficulties of numerical simulation. The existing models in the literature are modified by considering the pressure gradient inside and outside the foam. Comparisons against the numerical modelling are presented. Finally, based on experimentally-validated numerical results, thermo-hydraulic performance of foam heat exchangers as waste heat recovery units is discussed with the main goal of reducing the excess pressure drop and maximising the amount of heat that can be recovered from the hot gas stream.

Blood transfer devices for malaria rapid diagnostic tests : evaluation of accuracy, safety and ease of use

Background: Malaria rapid diagnostic tests (RDTs) are increasingly used by remote health personnel with minimal training in laboratory techniques. RDTs must, therefore, be as simple, safe and reliable as possible. Transfer of blood from the patient to the RDT is critical to safety and accuracy, and poses a significant challenge to many users. Blood transfer devices were evaluated for accuracy and precision of volume transferred, safety and ease of use, to identify the most appropriate devices for use with RDTs in routine clinical care. Methods: Five devices, a loop, straw-pipette, calibrated pipette, glass capillary tube, and a new inverted cup device, were evaluated in Nigeria, the Philippines and Uganda. The 227 participating health workers used each device to transfer blood from a simulated finger-prick site to filter paper. For each transfer, the number of attempts required to collect and deposit blood and any spilling of blood during transfer were recorded. Perceptions of ease of use and safety of each device were recorded for each participant. Blood volume transferred was calculated from the area of blood spots deposited on filter paper. Results: The overall mean volumes transferred by devices differed significantly from the target volume of 5 microliters (p < 0.001). The inverted cup (4.6 microliters) most closely approximated the target volume. The glass capillary was excluded from volume analysis as the estimation method used is not compatible with this device. The calibrated pipette accounted for the largest proportion of blood exposures (23/225, 10%); exposures ranged from 2% to 6% for the other four devices. The inverted cup was considered easiest to use in blood collection (206/ 226, 91%); the straw-pipette and calibrated pipette were rated lowest (143/225 [64%] and 135/225 [60%] respectively). Overall, the inverted cup was the most preferred device (72%, 163/227), followed by the loop (61%, 138/227). Conclusions: The performance of blood transfer devices varied in this evaluation of accuracy, blood safety, ease of use, and user preference. The inverted cup design achieved the highest overall performance, while the loop also performed well. These findings have relevance for any point-of-care diagnostics that require blood sampling.

Optimisation methods for coupled thermodynamic and 1D design of radial-inflow turbines

Optimisation is a fundamental step in the turbine design process, especially in the development of non-classical designs of radial-inflow turbines working with high-density fluids in low-temperature Organic Rankine Cycles (ORCs). The present work discusses the simultaneous optimisation of the thermodynamic cycle and the one-dimensional design of radial-inflow turbines. In particular, the work describes the integration between a 1D meanline preliminary design code adapted to real gases and the performance estimation approach for radial-inflow turbines in an established ORC cycle analysis procedure. The optimisation approach is split in two distinct loops; the inner operates on the 1D design based on the parameters received from the outer loop, which optimises the thermodynamic cycle. The method uses parameters including brine flow rate, temperature and working fluid, shifting assumptions such as head and flow coefficients into the optimisation routine. The discussed design and optimisation method is then validated against published benchmark cases. Finally, using the same conditions, the coupled optimisation procedure is extended to the preliminary design of a radial-inflow turbine with R143a as working fluid in realistic geothermal conditions and compared against results from commercially-available software RITAL from Concepts-NREC.

Informal e-learning : the case of small business owners

Purpose - The purpose of this paper is to investigate the use of an informal online discussion forum (ODF) to encourage voluntary participation and promote double-loop learning by small business owners (SBOs). Design/methodology/approach - A qualitative methodology was used where data gathered from three sources, the ODF posts, in-depth interviews with participants and a focus group with non-participants. These were analysed to evaluate learning of SBOs in an ODF. Findings - This research provides evidence that an ODF for SBOs supports double-loop learning; however, participation could not be assumed simply by the online availability of the discussion resource. Research limitations/implications - Few SBOs participated in the ODF which is consistent with research finding SBOs are a difficult group to engage in learning. Four forms of data were analysed to strengthen results. Practical implications - Caution should be exercised when considering investment in e-learning for SBOs. Originality/value - Evidence showing e-learning through an informal voluntary ODF can promote deep learning for SBOs.

Controller design for variable-speed permanent magnet wind turbine generators interfaced with Z-source inverter

Increased awareness of environmental concerns has caused greater interest in developing power sources based on renewable technologies, such as wind. Due to the intermittent nature of the wind speed, output voltage and frequency of the direct driven permanent magnet synchronous generators (PMSG) are normally unsteady. Recently proposed Z-source inverter has been considered as a potential solution for grid interfacing wind power generators, thanks to buck-boost function that the single stage Z-source inverter can offer. Two control methodologies, namely unified controller for isolated operation and a multi-loop controller for grid interfaced operation are investigated in this paper. Theoretical analysis of these two control schemes is presented and experimental results to verify the effectiveness of the control method are also included.

Robotic explosive charging in mining and construction applications

Describes the development and testing of a robotic system for charging blast holes in underground mining. The automation system supports four main tactical functions: detection of blast holes; teleoperated arm pose control; automatic arm pose control; and human-in-the-loop visual servoing. We present the system architecture, and analyse the major components, Hole detection is crucial for automating the process, and we discuss theoretical and practical aspects in detail. The sensors used are laser range finders and cameras installed in the end effector. For automatic insertion, we consider image processing techniques to support visual servoing the tool to the hole. We also discuss issues surrounding the control of heavy-duty mining manipulators, in particular, friction, stiction, and actuator saturation.

Real-time decision making by driverless city vehicles : a discrete event driven approach

This thesis addresses the topic of real-time decision making by driverless (autonomous) city vehicles, i.e. their ability to make appropriate driving decisions in non-simplified urban traffic conditions. After addressing the state of research, and explaining the research question, the thesis presents solutions for the subcomponents which are relevant for decision making with respect to information input (World Model), information output (Driving Maneuvers), and the real-time decision making process. TheWorld Model is a software component developed to fulfill the purpose of collecting information from perception and communication subsystems, maintaining an up-to-date view of the vehicle’s environment, and providing the required input information to the Real-Time Decision Making subsystem in a well-defined, and structured way. The real-time decision making process consists of two consecutive stages. While the first decision making stage uses a Petri net to model the safetycritical selection of feasible driving maneuvers, the second stage uses Multiple Criteria Decision Making (MCDM) methods to select the most appropriate driving maneuver, focusing on fulfilling objectives related to efficiency and comfort. The complex task of autonomous driving is subdivided into subtasks, called driving maneuvers, which represent the output (i.e. decision alternatives) of the real-time decision making process. Driving maneuvers are considered as implementations of closed-loop control algorithms, each capable of maneuvering the autonomous vehicle in a specific traffic situation. Experimental tests in both a 3D simulation and real-world experiments attest that the developed approach is suitable to deal with the complexity of real-world urban traffic situations.

Shared autonomy for close-quarters navigation and control of a VTOL platform

This thesis presents an approach for a vertical infrastructure inspection using a vertical take-off and landing (VTOL) unmanned aerial vehicle and shared autonomy. Inspecting vertical structure such as light and power distribution poles is a difficult task. There are challenges involved with developing such an inspection system, such as flying in close proximity to a target while maintaining a fixed stand-off distance from it. The contributions of this thesis fall into three main areas. Firstly, an approach to vehicle dynamic modeling is evaluated in simulation and experiments. Secondly, EKF-based state estimators are demonstrated, as well as estimator-free approaches such as image based visual servoing (IBVS) validated with motion capture ground truth data. Thirdly, an integrated pole inspection system comprising a VTOL platform with human-in-the-loop control, (shared autonomy) is demonstrated. These contributions are comprehensively explained through a series of published papers.

Future perfect

"Future Perfect" is a solo artist exhibition featuring a 9 channel video installation, which is comprised of looped computer animation projections. In the first room, the big one, there are nine projections of looped computer animations. Many of these look like representations of gallery spaces containing sculptures, including rotating interpenetrating discs, bouncing coloured coffins, and jostling cardboard cubes (the cubes are blank, then covered in drawings, then covered in photographic imagery). In one video, a man and a woman walk towards one another but never get together. In the second room, an animated video on a flatscreen suggests an origin story. The subtitles tell how, in Russia, my great-grandfather made a joke about Stalin's child bride that cost him his life. That one isn’t a loop; it has a beginning, middle, and end. Lying on the floor, in front of the video, are two slightly crumpled mural prints of photographs of the ocean. There's also a clear Perspex cloud shape on a wall. Viewers will see themselves reflected in it, as if it were a distant hovering mirage. The first room of the exhibition, where objects are set in perpetual motion, is about departure. The second room registers some sense of arrival. The future perfect implies looking back on something that hasn't happened yet; future and past are conflated and the present is somehow deferred. The future perfect combines anticipation and reflection, and it relates to my interest in combining 3-D animation with other mediums like drawing, painting, and shot video. In my work, the virtual and actual coexist in tension, just like experience and expectation in the future perfect.

Epigenetics and migraine; complex mitochondrial interactions contributing to disease susceptibility

Migraine is a common neurological disorder classified by the World Health Organisation (WHO) as one of the top twenty most debilitating diseases in the developed world. Current therapies are only effective for a proportion of sufferers and new therapeutic targets are desperately needed to alleviate this burden. Recently the role of epigenetics in the development of many complex diseases including migraine has become an emerging topic. By understanding the importance of acetylation, methylation and other epigenetic modifications, it then follows that this modification process is a potential target to manipulate epigenetic status with the goal of treating disease. Bisulphite sequencing and methylated DNA immunoprecipitation have been used to demonstrate the presence of methylated cytosines in the human D-loop of mitochondrial DNA (mtDNA), proving that the mitochondrial genome is methylated. For the first time, it has been shown that there is a difference in mtDNA epigenetic status between healthy controls and those with disease, especially for neurodegenerative and age related conditions. Given co-morbidities with migraine and the suggestive link between mitochondrial dysfunction and the lowered threshold for triggering a migraine attack, mitochondrial methylation may be a new avenue to pursue. Creative thinking and new approaches are needed to solve complex problems and a systems biology approach, where multiple layers of information are integrated is becoming more important in complex disease modelling.