The improvement of micro-electronic component production operations by the application of cranfield developed precision engineering techniques

From an examination of the Cranfield Universal Measuring Machine certain features were selected. These features were linked together with some of the manufacturing and assembly operations used to make dual-in-line integrated circuits. The result was a group of design specifications for automatic machines to effect substantial improvements in productivity in those manufacturing operations. The report describes the preliminary work which culminated in the preparation of specifications, discussions with manufacturers and changes which were made as a result of these discussions. The report concludes with a number of proposals for continuing the main work and suggests certain additional, separate, investigations which, it is thought, would produce information of value to the semi-conductor industry

Results of REXUS12's Suaineadh Experiment : Deployment of a spinning space web in micro gravity conditions

On the 19th of March 2012, the Suaineadh experiment was launched onboard the sounding rocket REXUS12 (Rocket Experiments for University Students) from the Swedish launch base ESRANGE in Kiruna. The Suaineadh experiment served as a technology demonstrator for a space web deployed by a spinning assembly. The deployment of this web is a stepping stone for the development of ever larger structures in space. Such a structure could serve as a substructure for solar arrays, transmitters and/or antennas. The team was comprised of students from the University of Strathclyde (Glasgow, UK), the University of Glasgow (Glasgow, UK) and the Royal Institute of Technology (Stockholm, Sweden), designing, manufacturing and testing the experiment over the past 24 months. Following launch, the experiment was ejected from the ejection barrel located within the nosecone of the rocket. Centrifugal forces acting upon the space webs spinning assembly were used to stabilise the experiment’s platform. A specifically designed spinning reaction wheel, with an active control method, was used. Once the experiment’s motion was controlled, a 2 m by 2 m space web is released. Four daughter sections situated in the corners of the square web served as masses to stabilise the web due to the centrifugal forces acting on them. The four daughter sections contained inertial measurement units (IMUs). Each IMU provided acceleration and velocity measurements in all three directions. Through this, the positions of the four corners could be found through integration with respect to known time of the accelerations and rotations. Furthermore, four cameras mounted on the central hub section captured high resolution imagery of the deployment process. After the launch of REXUS12, the recovery helicopter was unable to locate the ejected experiment, but 22 pictures were received over the wireless connection between the experiment and the rocket. The last received picture was taken at the commencement of web deployment. Inspection of these pictures allowed the assumption that the experiment was fully functional after ejection, but perhaps through tumbling of either the experiment or the rocket, the wireless connection was interrupted. A recovery mission in the middle of August was only able to find the REXUS12 motor and the payload impact location

Weighted network modules

The inclusion of link weights into the analysis of network properties allows a deeper insight into the (often overlapping) modular structure of real-world webs. We introduce a clustering algorithm (CPMw, Clique Percolation Method with weights) for weighted networks based on the concept of percolating k-cliques with high enough intensity. The algorithm allows overlaps between the modules. First, we give detailed analytical and numerical results about the critical point of weighted k-clique percolation on (weighted) Erdos-Renyi graphs. Then, for a scientist collaboration web and a stock correlation graph we compute three-link weight correlations and with the CPMw the weighted modules. After reshuffling link weights in both networks and computing the same quantities for the randomised control graphs as well, we show that groups of 3 or more strong links prefer to cluster together in both original graphs.Comment: 19 pages, 7 figure

Live-cell imaging to detect phosphatidylserine externalization in brain endothelial cells exposed to ionizing radiation: Implications for the treatment of brain arteriovenous malformations

© 2016 AANS. Objective Stereotactic radiosurgery (SRS) is an established intervention for brain arteriovenous malformations (AVMs). The processes of AVM vessel occlusion after SRS are poorly understood. To improve SRS efficacy, it is important to understand the cellular response of blood vessels to radiation. The molecular changes on the surface of AVM endothelial cells after irradiation may also be used for vascular targeting. This study investigates radiation-induced externalization of phosphatidylserine (PS) on endothelial cells using live-cell imaging. methods An immortalized cell line generated from mouse brain endothelium, bEnd.3 cells, was cultured and irradiated at different radiation doses using a linear accelerator. PS externalization in the cells was subsequently visualized using polarity-sensitive indicator of viability and apoptosis (pSIVA)-IANBD, a polarity-sensitive probe. Live-cell imaging was used to monitor PS externalization in real time. The effects of radiation on the cell cycle of bEnd.3 cells were also examined by flow cytometry. results Ionizing radiation effects are dose dependent. Reduction in the cell proliferation rate was observed after exposure to 5 Gy radiation, whereas higher radiation doses (15 Gy and 25 Gy) totally inhibited proliferation. In comparison with cells treated with sham radiation, the irradiated cells showed distinct pseudopodial elongation with little or no spreading of the cell body. The percentages of pSIVA-positive cells were significantly higher (p = 0.04) 24 hours after treatment in the cultures that received 25-and 15-Gy doses of radiation. This effect was sustained until the end of the experiment (3 days). Radiation at 5 Gy did not induce significant PS externalization compared with the sham-radiation controls at any time points (p > 0.15). Flow cytometric analysis data indicate that irradiation induced growth arrest of bEnd.3 cells, with cells accumulating in the G2 phase of the cell cycle. coNclusioNs Ionizing radiation causes remarkable cellular changes in endothelial cells. Significant PS externalization is induced by radiation at doses of 15 Gy or higher, concomitant with a block in the cell cycle. Radiation-induced markers/targets may have high discriminating power to be harnessed in vascular targeting for AVM treatment

The Suaineadh Project : a stepping stone towards the deployment of large flexible structures in space

The Suaineadh project aims at testing the controlled deployment and stabilization of space web. The deployment system is based on a simple yet ingenious control of the centrifugal force that will pull each of the four daughters sections apart. The four daughters are attached onto the four corners of a square web, and will be released from their initial stowed configuration attached to a central hub. Enclosed in the central hub is a specifically designed spinning reaction wheel that controls the rotational speed with a closed loop control fed by measurements from an onboard inertial measurement sensor. Five other such sensors located within the web and central hub provide information on the surface curvature of the web, and progression of the deployment. Suaineadh is currently at an advanced stage of development: all the components are manufactured with the subsystems integrated and are presently awaiting full integration and testing. This paper will present the current status of the Suaineadh project and the results of the most recent set of tests. In particular, the paper will cover the overall mechanical design of the system, the electrical and sensor assemblies, the communication and power systems and the spinning wheel with its control system

Known mutator alleles do not markedly increase mutation rate in clinical Saccharomyces cerevisiae strains

Natural selection has the potential to act on all phenotypes, including genomic mutation rate. Classic evolutionary theory predicts that in asexual populations, mutator alleles, which cause high mutation rates, can fix due to linkage with beneficial mutations. This phenomenon has been demonstrated experimentally and may explain the frequency of mutators found in bacterial pathogens. By contrast, in sexual populations, recombination decouples mutator alleles from beneficial mutations, preventing mutator fixation. In the facultatively sexual yeast Saccharomyces cerevisiae, segregating alleles of MLH1 and PMS1 have been shown to be incompatible, causing a high mutation rate when combined. These alleles had never been found together naturally, but were recently discovered in a cluster of clinical isolates. Here we report that the incompatible mutator allele combination only marginally elevates mutation rate in these clinical strains. Genomic and phylogenetic analyses provide no evidence of a historically elevated mutation rate. We conclude that the effect of the mutator alleles is dampened by background genetic modifiers. Thus, the relationship between mutation rate and microbial pathogenicity may be more complex than once thought. Our findings provide rare observational evidence that supports evolutionary theory suggesting that sexual organisms are unlikely to harbour alleles that increase their genomic mutation rate

Mutations in two global regulators lower individual mortality in Escherichia coli

There has been considerable investigation into the survival of bacterial cells under stress conditions, but little is known about the causes of mortality in the absence of exogenous stress. That there is a basal frequency of cell death in such populations may reflect that it is either impossible to avoid all lethal events, or alternatively, that it is too costly. Here, through a genetic screen in the model organism Escherichia coli, we identify two mutants with lower frequencies of mortality: rssB and fliA. Intriguingly, these two genes both affect the levels of different sigma factors within the cell. The rssB mutant displays enhanced resistance to multiple external stresses, possibly indicating that the cell gains its increased vitality through elevated resistance to spontaneous, endogenous stresses. The loss of fliA does not result in elevated stress resistance; rather, its survival is apparently due to a decreased physical stress linked to the insertion of the flagellum through the membrane and energy saved through the loss of the motor proteins. The identification of these two mutants implies that reducing mortality is not impossible; rather, due to its cost, it is subject to trade-offs with other traits that contribute to the competitive success of the organism

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation