32 research outputs found

    Erythrosensors Cellular Characterization

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    For diabetics, continuous glucose monitoring, and the resulting tighter control of glucose levels, ameliorates serious complications from hypoglycemia and hyperglycemia. Today, diabetics measure their blood glucose levels multiple times a day by finger pricks, or use implantable monitoring devices. Still, glucose and other analytes in the blood fluctuate throughout the day and the current monitoring methods are invasive, immunogenic, and/or present biodegradation problems. Using carrier erythrocytes loaded with a fluorescent sensor, we seek to develop a biodegradable, efficient, and potentially cost effective method for long-term monitoring of blood analytes. We aim to reintroduce sensor-loaded erythrocytes to the bloodstream and conserve the erythrocytes lifetime of 120 days in the circulatory system. Here, the efficiency of two loading procedures is compared. Hypotonic dilution employs hypotonic buffer to create transient pores in the erythrocyte membrane, allowing dye entrance and a hypertonic buffer to restore tonicity. Electroporation relies on controlled electrical pulses that results in reversible pores formation to allow cargo entrance. As part of the cellular characterization of loaded erythrocytes, size and hemoglobin content was evaluated. Cell recovery and fluorescence per cell measurements also render optimal loading conditions. Furthermore, AFM and confocal microscopy protocols were implemented to evaluate morphological changes induced by hypotonic dilution. The development of a suitable protocol to engineer carrier erythrocytes has profound and lasting implications in the erythrocytes’ lifespan and sensing capabilities

    From neglected waste to protected space: An administrative history of Mojave National Preserve

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    The Mojave National Preserve, a unit of the National Park Service, was created in 1994 in southeastern California. Its 1.6 million acres were used historically for extractive industries such as mining and ranching, and its recent history was shaped by the land\u27s proximity to urban Los Angeles. The preserve was the fruit of a long political battle between environmental activists and conservative opponents, and the park\u27s final administrative form and subsequent management was indelibly altered by the compromises made during the legislative fight. The park\u27s subsequent history, including innovative planning efforts, a 1995 attempt by opponents to eliminate the preserve\u27s budget, and day to day management of Mojave\u27s extensive resources, highlight the unique features and history of the area, as well as the flexible institutional culture forged in the park\u27s early struggle for survival

    The Internet of Things (You Don’t Own) under Bourgeois Law: An Integrated Tactic to Rebalance Intellectual Property

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    First paragraph: It is a commonly held view that intellectual property (IP) is a policy bargain whereby exclusive rights and monopolies are granted as a reward to intellectual labour and investments in order to incentivise innovation and creativity. The idea that IP rights (IPRs) would be a necessary incentive has been largely debunked. Law and economics studies demonstrated that IP is just another product of capitalism aimed at creating new enclosures of the ‘commons.’ This notwithstanding, a number of national and international laws have kept expanding its scope and augmenting the relevant level of protection. Most IP-stemming monopolies are temporary on paper but end up producing revenues that are regarded as rents on a virtually permanent basis. The elevation of IP to perpetual rent is rendered possible by complex strategies that rely on cumulation of IPRs, factual control over data and service, contracts, and technical protection measures. Favoured by a legal environment that is ‘heavily tilted in favour of IP rent-seekers,’ IP has become the key ideological device of rentier capitalism. Traditionally, the phenomenon of rentiers refers to the fact that landowners would exploit their monopoly power over the land to impose a rent that was a monopoly price. As noted by Marx in The Poverty of Philosophy , ‘[r]ent, in the Ricardian sense, is patriarchal agriculture transformed into commercial industry, industrial capital applied to land, the town bourgeoisie transplanted into the country.’ Marx and Ricardo could not foresee that new forms of rent-seeking would become an essential component of capitalism: rent-seeking through IPRs. The IoT is pivotal to rentier capitalism as it generates ‘new sources of rent, new infrastructures of rentier relations, and new mechanisms of extraction and enclosure.’ While the IoT is not rentier in nature, the historically existing IoT is indeed rentier also thanks to IP abuses. According to Jathan Sadowski, data extraction, capital convergence, and digital enclosure are the main mechanisms of rentier capitalism. 9 IP is key to digital enclosure, as instantiated by the use of software licenses to control access and collecting rents over the physical world, regardless of the ownership of the underlying tangible assets

    Application of genetic algorithm to wireless communications

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    Wireless communication is one of the most active areas of technology development of our time. Like all engineering endeavours, the subject of the wireless communication also brings with it a whole host of complex design issues, concerning network design, signal detection, interference cancellation, and resource allocation, to name a few. Many of these problems have little knowledge of the solution space or have very large search space, which are known as non-deterministic polynomial (NP) -hard or - complete and therefore intractable to solution using analytical approaches. Consequently, varied heuristic methods attempts have been made to solve them ranging from simple deterministic algorithms to complicated random-search methods. Genetic alcyorithm (GA) is an adaptive heuristic search algorithm premised on the evolutionary ideas of evolution and natural selection, which has been successfully applied to a variety of complicated problems arising from physics, engineering, biology, economy or sociology. Due to its outstanding search strength and high designable components, GA has attracted great interests even in the wireless domain. This dissertation is devoted to the application of GA to solve various difficult problems spotlighted from the wireless systems. These problems have been mathematically formulated in the constrained optimisation context, and the main work has been focused on developing the problem-specific GA approaches, which incorporate many modifications to the traditional GA in order to obtain enhanced performance. Comparative results lead to the conclusion that the proposed GA approaches are generally able to obtain the optimal or near-optimal solutions to the considered optimisation problems provided that the appropriate representation, suitable fitness function, and problem-specific operators are utilised. As a whole, the present work is largely original and should be of great interest to the design of practical GA approaches to solve realistic problems in the wireless communications systems.EThOS - Electronic Theses Online ServiceBritish Council (ORS) : Newcastle UniversityGBUnited Kingdo

    COMPUTATIONAL STUDIES TO UNDERSTAND THE ROLE OF ALLOSTERY IN COPPER REGULATION IN Mycobacterium tuberculosis AND IN THE DESIGN OF HPV VACCINES

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    Thesis (Ph.D.) - Indiana University, Chemistry, 2015Allostery is defined as the change in the structure, function or activity of a specific site on a protein, due to the binding of a substrate or effecter on a different site of the same protein. This phenomenon has been observed and studied in two different protein systems of therapeutic importance. CsoR protein in Mycobacterium tuberculosis adopts classical allostery to regulate the concentration of Cu(I) inside the cell. Cu(I) is speculated to bind in an unusual trigonal planar geometry with two cysteines and one histidine. When CsoR is bound to copper an overall structural change (allostery) is envisioned and its affinity to DNA is lost. In the current computational exploration we focus on the binding mode of Cu(I) and identify different protonation states of copper bound cysteines. MD simulations were performed on the apo and copper bound form with a starting structure from QM/MM calculations to predict the allosteric structural transition. The dynamic properties of the capsid of the human papillomavirus (HPV) type 16 were also examined using classical molecular dynamics simulations. The allostery identified in the components of the HPV is non-classical because the mean structure of the epitope carrying loops remains unchanged as the result of allosteric effect, but the structural fluctuations are altered significantly, which in turn changes the biochemical reactivity profile of the epitopes. Exploiting this novel insight, a new vaccine design strategy is proposed, where a relatively small virus fragment is deposited on a silica nanoparticle in such a way that the fluctuations of the h4 helix are suppressed. The structural and dynamic properties of the epitope carrying loops on this hybrid nanoparticle match the characteristics of epitopes found on the full virus like particle precisely, suggesting that these nanoparticles may serve as potent, cost-effective and safe alternatives to traditionally developed vaccines

    User-appropriate viewer for high resolution interactive engagement with 3D digital cultural artefacts.

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    The core mission of museums and cultural institutions is the preservation, study and presentation of cultural heritage content. In this technological age, the creation of digital datasets and archives has been widely adopted as one way of seeking to achieve some or all of these goals. However, there are many challenges with the use of these data, and in particular the large numbers of 3D digital artefacts that have been produced using methods such as non- contact laser scanning. As public expectation for more open access to information and innovative digital media increases, there are many issues that need to be rapidly addressed. The novel nature of 3D datasets and their visualisation presenting unique issues that impede use and dissemination. Key questions include the legal issues associated with 3D datasets created from cultural artefacts; the complex needs of users who are interacting with them; a lack of knowledge to texture and assess the visual quality of the datasets; and how the visual quality of the presented dataset relates to the perceptual experience of the user. This engineering doctorate, based on an industrial partnership with the National Museums of Liverpool and Conservation Technologies, investigates these questions and offers new ways of working with 3D cultural heritage datasets. The research outcomes in the thesis provide an improved understanding of the complexity of intellectual property law in relation to 3D cultural heritage datasets and how this impacts dissemination of these types of data. It also provides tools and techniques that can be used to understand the needs of a user when interacting with 3D cultural content. Additionally, the results demonstrate the importance of the relationship between texture and polygonal resolution and how this can affect the perceived visual experience of a visitor. It finds that there is an acceptable cost to texture and polygonal resolution to offer the best perceptual experience with 3D digital cultural heritage. The results also demonstrate that a non-textured mesh may be as highly received as a high resolution textured mesh. The research presented provides methodologies and guidelines to improve upon the dissemination and visualisation of 3D cultural content; enhancing and communicating the significance of their 3D collections to their physical and virtual visitors. Future opportunities and challenges for disseminating and visualising 3D cultural content are also discussed

    A Comparative Law Perspective on Intermediaries\u27 Direct Liability in Cloud Computing Context -- A Proposal for China

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    This dissertation is motivated by two questions: How does the emergence of cloud-computing technology impact major countries’ copyright law regarding the issue of intermediaries’ direct liability? What should Chinese legislature body learn from those countries regarding this issue? Answering the first question lays a foundation for answering the second question. Usually, a cloud-computing intermediary’s specific activity may possess risk of violating a copyright holder’s right of reproduction, right of communication to the public and right of distribution. Comparatively, that intermediary can raise defenses under the exhaustion doctrine and the fair use doctrine. Analysis on these two topics consists of two parts. The first part examines copyright law in major countries or regional organizations such as the U.S., Japan or the European Union. The second part is an analysis of current related Chinese legislation and a proposal for China. This dissertation examines relevant international copyright treaties, major countries’ related legislature documents and related cases. This dissertation offers a thorough legal analysis how cloud-computing technology affects copyright worldwide. The proposal at the end consists of two parts. The first part provides four general legislature advices for China. The second part focuses on how China’s legislature should adjust copyright owner’s exclusive rights and intermediaries’ defense theories to react the impact brought by the cloud-computing technology

    Understanding the genomics and specialised metabolites of the biopesticidal bacterium Burkholderia ambifaria

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    Burkholderia ambifaria is a versatile bacterium frequently isolated from the environment in association with the rhizosphere of important crops species, and occasionally found as an opportunistic pathogen of cystic fibrosis patients. B. ambifaria strains were exploited successfully as biological pesticides during the 1990s, but declined in popularity following concerns over the pathogenicity of associated species in the Burkhlderia cepacia complex. A collection of environmentally and clinically sourced B. ambifaria strains were sequenced with the purpose of developing a deeper understanding of the biopesticide. Comparative genomics were combined with in vitro metabolite analyses, antagonism assays, and agriculturally relevant biological control assays to determine the contribution of antimicrobial metabolites to biocontrol. Genome mining for biosynthetic gene clusters (BGCs) revealed a considerable specialised metabolite potential, and multiple BGCs associated with characterised antimicrobials. Regulatory gene mining of quorum sensing associated luxR genes revealed an uncharacterised LuxRI system linked to an unknown BGC. Insertional mutagenesis and mass spectrometry confirmed the BGC as the biosynthetic origin of the historical Burkholderia polyyne metabolite cepacin. Comparison of the B. ambifaria BCC0191 wild-type with the cepacin-deficient mutant highlighted the importance of cepacin in the biological control of Pythium ultimum with a Pisum sativum crop model. The biocontrol phenotype was maintained following the deletion of the third replicon, and subsequent virulence testing in a murine respiratory inhalation model demonstrated a reduced persistence compared to the wild-type. This study systematically defined the specialised metabolite biosynthetic potential of B. ambifaria, and demonstrated the importance of the polyyne cepacin in biological control. Maintenance of biocontrol and loss of virulence following third-replicon deletion presents an opportunity to attenuate B. ambifaria and address the pathogenicity concerns that led to the decline of B. ambifaria as a biopesticide
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