1,423 research outputs found

    Ruthenium metallotherapeutics: a targeted approach to combatting multidrug resistant pathogens

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    The discovery of antibiotics revolutionised healthcare practice. However due to overuse, inappropriate use, widespread prophylaxis therapy and the lack of new developments, the threat of antimicrobial resistance is now a major global threat to health. By 2050, it is estimated that mortality due to antimicrobial resistant infections will exceed 10 million people per annum, superseding cancer as the leading cause of global mortality. The use of drug repurposing to identify potential therapies which combat antimicrobial resistance is one potential solution. Metals have been used as antimicrobial agents throughout the history of medicine for a broad range of applications, including the use of Silver as an antimicrobial agent which dates back to antiquity. More recently, Ruthenium metallotherapeutic complexes have been shown to exhibit highly active antimicrobial properties by targeting a range of bacterial species, and in contrast to traditional antibiotics, these compounds are thought to elicit antibacterial activity at multiple sites within the bacterial cell, which may reduce the possibility of resistance evolution. This study aimed to evaluate the antimicrobial activity of a series of Ruthenium metallotherapeutic complexes against multidrug-resistant bacterial pathogens, with a focus on use within wound care applications. Antimicrobial susceptibility assays identified two lead candidates, Hexaammineruthenium (III) chloride and [Chlorido(η6-p-cymene)(N-(4-chlorophenyl)pyridine-2-carbothioamide) ruthenium (II)] chloride which demonstrated activity against Pseudomonas aeruginosa and Staphylococcus aureus respectively with MIC values ranging between 4 μg mL-1 and 16 μg mL-1. Furthermore, Hexaammineruthenium (III) chloride demonstrated antibiofilm activity in both a time and concentration-dependent manner. Synergy studies combining lead complexes with antibiotics demonstrated the potential for use as resistance breakers. Subsequent in vitro infection modelling using scratch assays with skin cell lines, coupled with a 3D full thickness skin wound infection model was used to determine potential applied applications of Hexaammineruthenium (III) chloride for use as topical antimicrobial agent against P. aeruginosa infections. Antimicrobial mechanistic studies demonstrated that Hexaammineruthenium (III) chloride targeted the bacterial cell ultrastructure of P. aeruginosa strain PAO1 as cell perturbations were observed when treated cells were analysed by scanning electron microscopy. Furthermore, exposure of P. aeruginosa PAO1 to Hexaammineruthenium (III) chloride also resulted in a concentration dependent membrane depolarisation, which further supported the antimicrobial mechanistic role. Finally, global changes in gene expression following exposure of P. aeruginosa strain PAO1 to Hexaammineruthenium (III) chloride were explored by RNA sequencing. Genes involved in ribosome function, cofactor biosynthesis and membrane fusion were downregulated, which provided a further insight into the wider mechanisms of antibacterial activity. The research conducted in the present study indicated the potential use of Hexaammineruthenium (III) chloride (and derivatives) as a potential treatment option for chronic wounds infected with P. aeruginosa, which could be applied as either a direct treatment or used within antimicrobial wound care applications

    Sociotechnical Imaginaries, the Future and the Third Offset Strategy

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    Strategies for defending the Principle of Identity of Indiscernibles: a critical survey and a new approach

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    The Principle of Identity of Indiscernibles (PII) is the focus of much controversy in the history of Metaphysics and in contemporary Physics. Many questions rover the debate about its truth or falsehood, for example, to which objects the principle applies? Which properties can be counted as discerning properties? Is the principle necessary? In other words, which version of the principle is the correct and is this version true? This thesis aims to answer this questions in order to show that PII is a necessarily true principle of metaphysics. To accomplish this task, the reader will find, in this thesis, an encyclopaedical introduction to the history of PII and to the reasons it matters so much, followed by a presentation of the most famous arguments against it and the defences used against these arguments. Then, the reader finds in-depth discussion of the minutiae involved in postulating the principle as to make clear what is in fact being attacked and defended. With these preliminaries solved, a deeper analysis of these defences is presented aiming to discover which is the most appropriate example to use against the attacks to the principle. This analysis allowed a classification of these defences in four families with different strategies within them. Finally, with these defensive strategies at hand we are able to confront alleged counterexamples to PII in Mathematics with the intention to test these defences

    Cognitive Machine Individualism in a Symbiotic Cybersecurity Policy Framework for the Preservation of Internet of Things Integrity: A Quantitative Study

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    This quantitative study examined the complex nature of modern cyber threats to propose the establishment of cyber as an interdisciplinary field of public policy initiated through the creation of a symbiotic cybersecurity policy framework. For the public good (and maintaining ideological balance), there must be recognition that public policies are at a transition point where the digital public square is a tangible reality that is more than a collection of technological widgets. The academic contribution of this research project is the fusion of humanistic principles with Internet of Things (IoT) technologies that alters our perception of the machine from an instrument of human engineering into a thinking peer to elevate cyber from technical esoterism into an interdisciplinary field of public policy. The contribution to the US national cybersecurity policy body of knowledge is a unified policy framework (manifested in the symbiotic cybersecurity policy triad) that could transform cybersecurity policies from network-based to entity-based. A correlation archival data design was used with the frequency of malicious software attacks as the dependent variable and diversity of intrusion techniques as the independent variable for RQ1. For RQ2, the frequency of detection events was the dependent variable and diversity of intrusion techniques was the independent variable. Self-determination Theory is the theoretical framework as the cognitive machine can recognize, self-endorse, and maintain its own identity based on a sense of self-motivation that is progressively shaped by the machine’s ability to learn. The transformation of cyber policies from technical esoterism into an interdisciplinary field of public policy starts with the recognition that the cognitive machine is an independent consumer of, advisor into, and influenced by public policy theories, philosophical constructs, and societal initiatives

    Sensing Collectives: Aesthetic and Political Practices Intertwined

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    Are aesthetics and politics really two different things? The book takes a new look at how they intertwine, by turning from theory to practice. Case studies trace how sensory experiences are created and how collective interests are shaped. They investigate how aesthetics and politics are entangled, both in building and disrupting collective orders, in governance and innovation. This ranges from populist rallies and artistic activism over alternative lifestyles and consumer culture to corporate PR and governmental policies. Authors are academics and artists. The result is a new mapping of the intermingling and co-constitution of aesthetics and politics in engagements with collective orders

    Modern meat: the next generation of meat from cells

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    Modern Meat is the first textbook on cultivated meat, with contributions from over 100 experts within the cultivated meat community. The Sections of Modern Meat comprise 5 broad categories of cultivated meat: Context, Impact, Science, Society, and World. The 19 chapters of Modern Meat, spread across these 5 sections, provide detailed entries on cultivated meat. They extensively tour a range of topics including the impact of cultivated meat on humans and animals, the bioprocess of cultivated meat production, how cultivated meat may become a food option in Space and on Mars, and how cultivated meat may impact the economy, culture, and tradition of Asia

    Digital agriculture: research, development and innovation in production chains.

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    Digital transformation in the field towards sustainable and smart agriculture. Digital agriculture: definitions and technologies. Agroenvironmental modeling and the digital transformation of agriculture. Geotechnologies in digital agriculture. Scientific computing in agriculture. Computer vision applied to agriculture. Technologies developed in precision agriculture. Information engineering: contributions to digital agriculture. DIPN: a dictionary of the internal proteins nanoenvironments and their potential for transformation into agricultural assets. Applications of bioinformatics in agriculture. Genomics applied to climate change: biotechnology for digital agriculture. Innovation ecosystem in agriculture: Embrapa?s evolution and contributions. The law related to the digitization of agriculture. Innovating communication in the age of digital agriculture. Driving forces for Brazilian agriculture in the next decade: implications for digital agriculture. Challenges, trends and opportunities in digital agriculture in Brazil

    (b2023 to 2014) The UNBELIEVABLE similarities between the ideas of some people (2006-2016) and my ideas (2002-2008) in physics (quantum mechanics, cosmology), cognitive neuroscience, philosophy of mind, and philosophy (this manuscript would require a REVOLUTION in international academy environment!)

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    (b2023 to 2014) The UNBELIEVABLE similarities between the ideas of some people (2006-2016) and my ideas (2002-2008) in physics (quantum mechanics, cosmology), cognitive neuroscience, philosophy of mind, and philosophy (this manuscript would require a REVOLUTION in international academy environment!
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