Ultimate and practical limits of fluid-based mass detection with suspended microchannel resonators

Suspended microchannel resonators (SMRs) are an innovative approach to fluid-based microelectromechanical mass sensing that circumvents complete immersion of the sensor. By embedding the fluidics within the device itself, vacuum-based operation of the resonator becomes possible. This enables frequency shift-based mass detection with high quality factors, and hence sensitivity comparable to vacuum-based micromechanical resonators. Here we present a detailed analysis of the sensitivity of these devices, including consideration of fundamental and practical noise limits, and the important role of binding kinetics in sensing.We demonstrate that these devices show significant promise for protein detection. For larger, biologically-important targets such as rare whole virions, the required analysis time to flow sufficient sample through the sensor can become prohibitively long unless large parallel arrays of sensors or preconcentrators are employed

Rubble & Honey

RUBBLE & HONEY is a collection of poems unified by its use of language driven lyricism to recount personal narratives in the life of the poet. The poems in this manuscript depict the landscapes of California, Florida, Mississippi, the South Downs of England, and Anglesey off the northwest coast of Wales. The manuscript engages with these physical spaces, how the speaker reacts to the natural world and how these locations can reflect the internal. The collection is broken into four sections: the first two explore parting, firstly from a relationship and then revisiting the poet’s childhood landscape of Sussex, England; the third is a rebirth of sorts after the exploration of these losses, a joyous look at the world that is tentative but hopeful; and the fourth section revisits the themes of the first from a more distanced perspective

Elevated expression of artemis in human fibroblast cells is associated with cellular radiosensitivity and increased apoptosis

Copyright @ 2012 Nature Publishing GroupThis article has been made available through the Brunel Open Access Publishing Fund.Background: The objective of this study was to determine the molecular mechanism(s) responsible for cellular radiosensitivity in two human fibroblast cell lines 84BR and 175BR derived from two cancer patients. Methods: Clonogenic assays were performed following exposure to increasing doses of gamma radiation to confirm radiosensitivity. γ-H2AX foci assays were used to determine the efficiency of DNA double strand break (DSB) repair in cells. Quantitative-PCR (Q-PCR) established the expression levels of key DNA DSB repair proteins. Imaging flow cytometry using Annexin V-FITC was used to compare artemis expression and apoptosis in cells. Results: Clonogenic cellular hypersensitivity in the 84BR and 175BR cell lines was associated with a defect in DNA DSB repair measured by the γ-H2AX foci assay. Q-PCR analysis and imaging flow cytometry revealed a two-fold overexpression of the artemis DNA repair gene which was associated with an increased level of apoptosis in the cells before and after radiation exposure. Over-expression of normal artemis protein in a normal immortalised fibroblast cell line NB1-Tert resulted in increased radiosensitivity and apoptosis. Conclusion: We conclude elevated expression of artemis is associated with higher levels of DNA DSB, radiosensitivity and elevated apoptosis in two radio-hypersensitive cell lines. These data reveal a potentially novel mechanism responsible for radiosensitivity and show that increased artemis expression in cells can result in either radiation resistance or enhanced sensitivity.This work was supported in part by The Vidal Sassoon Foundation USA. This article is made available through the Brunel Open Access Publishing Fund

The stochastic dynamics of micron and nanoscale elastic cantilevers in fluid: fluctuations from dissipation

The stochastic dynamics of micron and nanoscale cantilevers immersed in a viscous fluid are quantified. Analytical results are presented for long slender cantilevers driven by Brownian noise. The spectral density of the noise force is not assumed to be white and the frequency dependence is determined from the fluctuation-dissipation theorem. The analytical results are shown to be useful for the micron scale cantilevers that are commonly used in atomic force microscopy. A general thermodynamic approach is developed that is valid for cantilevers of arbitrary geometry as well as for arrays of multiple cantilevers whose stochastic motion is coupled through the fluid. It is shown that the fluctuation-dissipation theorem permits the calculation of stochastic quantities via straightforward deterministic methods. The thermodynamic approach is used with deterministic finite element numerical simulations to quantify the autocorrelation and noise spectrum of cantilever fluctuations for a single micron scale cantilever and the cross-correlations and noise spectra of fluctuations for an array of two experimentally motivated nanoscale cantilevers as a function of cantilever separation. The results are used to quantify the noise reduction possible using correlated measurements with two closely spaced nanoscale cantilevers.Comment: Submitted to Nanotechnology April 26, 200

Comparative advantages of mechanical biosensors

Mechanical interactions are fundamental to biology. Mechanical forces of chemical origin determine motility and adhesion on the cellular scale, and govern transport and affinity on the molecular scale. Biological sensing in the mechanical domain provides unique opportunities to measure forces, displacements and mass changes from cellular and subcellular processes. Nanomechanical systems are particularly well matched in size with molecular interactions, and provide a basis for biological probes with single-molecule sensitivity. Here we review micro- and nanoscale biosensors, with a particular focus on fast mechanical biosensing in fluid by mass- and force-based methods, and the challenges presented by non-specific interactions. We explain the general issues that will be critical to the success of any type of next-generation mechanical biosensor, such as the need to improve intrinsic device performance, fabrication reproducibility and system integration. We also discuss the need for a greater understanding of analyte–sensor interactions on the nanoscale and of stochastic processes in the sensing environment

Does additional monitoring status increase the reporting of adverse drug reactions? An interrupted time series analysis of EudraVigilance data:An interrupted time series analysis of EudraVigilance data

Purpose: To evaluate the impact of including a medicine in the list of medicinal products subject to additional monitoring (AM) on the reporting of adverse drug reactions (ADRs) in the european economic area (EEA).Methods: Interrupted time series using the monthly number of EEA ADR reports in EudraVigilance during 12 months before and after the addition to AM list. The main outcome was the change (%) in reporting of ADRs with step change as the a priori impact model. Further time series analysis was performed using Joinpoint Regression.Results: The analysis included 11 active substances. No significant immediate (step change) increase of reporting was identified for any product at time of addition to AM list. We identified a significant gradual increase of ADR reporting after addition to AM list (slope change) for two out of five new products—boceprevir (10% per month, 95% confidence interval (CI) 3%–18%) and denosumab-Xgeva (13% per month, 95% CI 4%–22%). No change was identified for Prolia, another denosumab-containing product not subject to AM. No significant increase was identified for any product included in the AM list due to the requirement to conduct a PASS. Conversely, a gradual decrease in reporting was identified for natalizumab (−5% per month; 95% CI −10% to −1%), rivaroxaban (−5%; −8 to −3%), and varenicline (−16%; −21 to −10%). The results were corroborated by the Joinpoint analyses, which yielded similar results.Conclusions: We identified limited evidence that reporting of ADRs increased modestly and gradually for some new products and not for products with PASS requirement.</p

Establishing and supporting educational research in engineering from a local and national perspective

This paper describes an action research approach to supporting an improvement in the educational research skills of engineering academics in the UK. Two engineering education centres based at Loughborough University (the engCETL which is funded to support academics based at the university and the Engineering Subject Centre which has a national remit) have worked collaboratively to develop resources, including guides, workshops and other events and have started to disseminate this work internationally. In response to an identified need to develop understanding and to facilitate collaborative opportunities, a Special Interest Group has been established that will promote high quality educational research and provide the UK voice for international research communities. This is work in progress and there will be further evaluation undertaken of the impact of these developments. The aim is to establish a selfsustaining community of researchers as there is limited funding for engineering education research in the UK

The US Food and Drug Administration-European Medicines Agency Collaboration in Pharmacovigilance: Common Objectives and Common Challenges

Abstract On 19 February 2014, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) announced the formation of a cluster on pharmacovigilance topics. The cluster is designed to complement, and not replace, other international activities in this field. It builds upon years of interactions between the two agencies. The creation of the cluster formalizes this longstanding and productive relationship and facilitates more systematic exchange of information and expertise