Assessing the Viability of Complex Electrical Impedance Tomography (EIT) with a Spatially Distributed Sensor Array for Imaging of River Bed Morphology: a Proof of Concept (Study)

This report was produced as part of a NERC funded ‘Connect A’ project to establish a new collaborative partnership between the University of Worcester (UW) and Q-par Angus Ltd. The project aim was to assess the potential of using complex Electrical Impedance Tomography (EIT) to image river bed morphology. An assessment of the viability of sensors inserted vertically into the channel margins to provide real-time or near real-time monitoring of bed morphology is reported. Funding has enabled UW to carry out a literature review of the use of EIT and existing methods used for river bed surveys, and outline the requirements of potential end-users. Q-par Angus has led technical developments and assessed the viability of EIT for this purpose. EIT is one of a suite of tomographic imaging techniques and has already been used as an imaging tool for medical analysis, industrial processing and geophysical site survey work. The method uses electrodes placed on the margins or boundary of the entity being imaged, and a current is applied to some and measured on the remaining ones. Tomographic reconstruction uses algorithms to estimate the distribution of conductivity within the object and produce an image of this distribution from impedance measurements. The advantages of the use of EIT lie with the inherent simplicity, low cost and portability of the hardware, the high speed of data acquisition for real-time or near real-time monitoring, robust sensors, and the object being monitored is done so in a non-invasive manner. The need for sophisticated image reconstruction algorithms, and providing images with adequate spatial resolution are key challenges. A literature review of the use of EIT suggests that to date, despite its many other applications, to the best of our knowledge only one study has utilised EIT for river survey work (Sambuelli et al 2002). The Sambuelli (2002) study supported the notion that EIT may provide an innovative way of describing river bed morphology in a cost effective way. However this study used an invasive sensor array, and therefore the potential for using EIT in a non-invasive way in a river environment is still to be tested. A review of existing methods to monitor river bed morphology indicates that a plethora of techniques have been applied by a range of disciplines including fluvial geomorphology, ecology and engineering. However, none provide non-invasive, low costs assessments in real-time or near real-time. Therefore, EIT has the potential to meet the requirements of end users that no existing technique can accomplish. Work led by Q-par Angus Ltd. has assessed the technical requirements of the proposed approach, including probe design and deployment, sensor array parameters, data acquisition, image reconstruction and test procedure. Consequently, the success of this collaboration, literature review, identification of the proposed approach and potential applications of this technique have encouraged the authors to seek further funding to test, develop and market this approach through the development of a new environmental sensor

Zeeman Slowers for Strontium based on Permanent Magnets

We present the design, construction, and characterisation of longitudinal- and transverse-field Zeeman slowers, based on arrays of permanent magnets, for slowing thermal beams of atomic Sr. The slowers are optimised for operation with deceleration related to the local laser intensity (by the parameter $\epsilon$), which uses more effectively the available laser power, in contrast to the usual constant deceleration mode. Slowing efficiencies of up to $\approx$ $18$ $$ are realised and compared to those predicted by modelling. We highlight the transverse-field slower, which is compact, highly tunable, light-weight, and requires no electrical power, as a simple solution to slowing Sr, well-suited to spaceborne application. For $^{88}$Sr we achieve a slow-atom flux of around $6\times 10^9$ atoms$\,$s$^{-1}$ at $30$ ms$^{-1}$, loading approximately $5\times 10^8$ atoms in to a magneto-optical-trap (MOT), and capture all isotopes in approximate relative natural abundances

ACA Implementation Monitoring and Tracking Site Visit Report: Colorado

Assesses Colorado's progress in implementing federal healthcare reform legislation, including ongoing planning for the health insurance exchange, enrollment and subsidy determination, and Medicaid expansion, as well as work remaining on insurance reforms

A Phase I/II Study of a 72-h Continuous Infusion of Etoposide in Advanced Soft Tissue Sarcoma

Purpose. The study was performed to assess the antitumour activity and toxicity of a 72-h continuous infusion of single-agent etoposide as second-line treatment for patients with locally advanced or metastatic soft tissue sarcoma (STS), following reports of substantial activity using this schedule of etoposide administration as first-line treatment in combination with ifosfamide

Directed evolution and targeted mutagenesis to murinize listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model

BACKGROUND: Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. RESULTS: We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26), multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlA(m) murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlA(m)*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlA(m)* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlA(m) strain. CONCLUSIONS: We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced entry into human cells as previously observed. This murinized L. monocytogenes strain will provide a useful tool for the analysis of the gastrointestinal phase of listeriosis

Development of multiple strain competitive index assays for Listeria monocytogenes using pIMC; a new site-specific integrative vector

<p>Abstract</p> <p>Background</p> <p>The foodborne, gram-positive pathogen, <it>Listeria monocytogenes</it>, is capable of causing lethal infections in compromised individuals. In the post genomic era of <it>L. monocytogenes </it>research, techniques are required to identify and validate genes involved in the pathogenicity and environmental biology of the organism. The aim here was to develop a widely applicable method to tag <it>L. monocytogenes </it>strains, with a particular emphasis on the development of multiple strain competitive index assays.</p> <p>Results</p> <p>We have constructed a new site-specific integrative vector, pIMC, based on pPL2, for the selection of <it>L. monocytogenes </it>from complex samples. The pIMC vector was further modified through the incorporation of IPTG inducible markers (antibiotic and phenotypic) to produce a suite of four vectors which allowed the discrimination of multiple strains from a single sample. We were able to perform murine infection studies with up to four EGDe isolates within a single mouse and showed that the tags did not impact upon growth rate or virulence. The system also allowed the identification of subtle differences in virulence between strains of <it>L. monocytogenes </it>commonly used in laboratory studies.</p> <p>Conclusion</p> <p>This study has developed a competitive index assay that can be broadly applied to all <it>L. monocytogenes </it>strains. Improved statistical robustness of the data was observed, resulting in fewer mice being required for virulence assays. The competitive index assays provide a powerful method to analyse the virulence or fitness of <it>L. monocytogenes </it>in complex biological samples.</p

A Critical Role for OX40 in T Cell–mediated Immunopathology during Lung Viral Infection

Respiratory infections are the third leading cause of death worldwide. Illness is caused by pathogen replication and disruption of airway homeostasis by excessive expansion of cell numbers. One strategy to prevent lung immune–mediated damage involves reducing the cellular burden. To date, antiinflammatory strategies have affected both antigen-specific and naive immune repertoires. Here we report a novel form of immune intervention that specifically targets recently activated T cells alone. OX40 (CD134) is absent on naive T cells but up-regulated 1–2 d after antigen activation. OX40–immunoglobulin fusion proteins block the interaction of OX40 with its ligand on antigen-presenting cells and eliminate weight loss and cachexia without preventing virus clearance. Reduced proliferation and enhanced apoptosis of lung cells accompanied the improved clinical phenotype. Manipulation of this late costimulatory pathway has clear therapeutic potential for the treatment of dysregulated lung immune responses