797 research outputs found

    The initiation and evolution of ignimbrite faults, Gran Canaria, Spain

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    Understanding how faults initiate and fault architecture evolves is central to predicting bulk fault zone properties such as fault zone permeability and mechanical strength. The study of faults at the Earth’s surface and at near-surface levels is significant for the development of high level nuclear waste repositories, and CO2 sequestration facilities. Additionally, with growing concern over water resources, understanding the impact faults have on contaminant transport between the unsaturated and saturated zone has become increasingly important. The proposal of a high-level nuclear waste repository in the tuffs of Yucca Mountain, Nevada has stimulated interest into research on the characterisation of brittle deformation in non-welded to densely welded tuffs and the nature of fluid flow in these faults and fractures. The majority of research on the initiation and development of faults has focussed on shear faults in overall compressional stress regimes. Dilational structures have been examined in compressional settings e.g. overlapping faults generating extensional oversteps, or in normal faults cutting mechanical layered stratigraphy. Previous work has shown the affect mechanical stratigraphy has on fault dip angle; competent layers have steeply dipping segments and less competent layers have shallowly dipping segments. Displacement is accommodated by shear failure of the shallow segments and hybrid failure of the steeply dipping segments. As the fault walls of the shear failure segment slip past each other the walls of the hybrid failure segment are displaced horizontally as well as vertically thus forming dilation structures such as pull-aparts or extensional bends. Work on truly extensional faults has been at the kilometre scale of fissure swarms in rift systems where the focus is on fault geometry and direction of fault propagation. This study examines dilational faults with offsets of centimetres to 10’s of meters within moderately and densely welded ignimbrite units on the caldera island of Gran Canaria, Spain. Through the investigation of fault populations within different ignimbrite units I have examined how the fault architecture changes with accumulated displacement, identified the factors controlling fault core evolution and using these observations developed a new model for the initiation and growth of dilational faults in ignimbrites. The faults in this study do not have a linear correlation of increasing fault core thickness with displacement. Fault core width varies along fault dip and the largest offset faults have the narrowest fault cores. Furthermore, the damage zone joint frequency shows a limited increase with increasing displacement and faults and joints are sub-parallel. From these observations I have developed a new model for fault initiation and evolution in which the petrophysical properties of the host rock are the primary control on fault architecture. Faults initiate on existing sub-parallel joints and grow by the incorporation of material from joint surfaces and joint bound slabs. The growth of the fault depends on the joint spacing and the competency of the host rock. In densely welded ignimbrites, joint spacing is controlled by sub-layers within the ignimbrite unit which are formed by flattening and stretching of fiamme. In moderately welded ignimbrites, fiamme and lithic inclusions in the ash matrix act as sites of joint initiation; the greater the abundance of such flaws the higher the joint frequency. Whether fault growth is promoted or inhibited depends to some extent on the competency of the material. Faults cutting ash-rich friable units have narrow fault cores regardless of displacement. This suggests that the material is easily abraded in the fault core inhibiting fracturing of the host rock and incorporation of new material. Hence host rock fabric and composition have an important influence on fault architecture in these ignimbrite units. The other influence on fault evolution is the tensile stress regime in which faulting occurs. The faults in this study form by hybrid failure and so have both vertical and horizontal displacements. The dilation of existing joints causes slip on the joints and allows material to fall into the joint forming a fault core. This work identifies distinct differences between the mechanism of dilational fault initiation and resultant fault architecture compared to that of shear faults. The observations made in this study indicate that the host rock petrophysical properties, stress regime at time of faulting (tensile or compressive) and confining pressure are primary influences on fault architecture and not displacement; contradicting the widely accepted fault thickness-displacement scaling relationship. I suggest that the architecture of dilational faults can be predicted by examining the host rock properties and using the data from this study have developed a framework that illustrates how ignimbrite host rock properties may affect deformation structures. Such frameworks for individual lithologies may be more useful in predicting fault zone properties as opposed to global scaling relationships. The results of this study have implications for conceptual models of fluid flow based on fault architectures predicted using the thickness-displacement relationship

    Experienced tutors' deployment of thinking skills and what might be entailed in enhancing such skills

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    In the context of research that reports weaknesses in adults' critical thinking skills, the primary aim was to examine adults' use of critical thinking skills that are described in taxonomies and to identify areas for development. Position papers written by an opportunity sample of 32 experienced adult educators formed the data for a descriptive sample survey design intended to reveal participants' use of critical thinking skills. Each 6000-word paper was written during a development programme that supported such skills. A content analysis of the papers revealed that when participants drew on personal and published ideas about learning to derive their proposals for change, they accepted the ideas uncritically, thereby implying that they might find it difficult to help learners to examine ideas critically. The evidence supports research that implies that critical thinking skills are unlikely to develop unless overall course design privileges the development of epistemological understanding (King and Kitchener 1994, Kuhn 1999). A fundamental assumption underlying the study is that this understanding influences effective citizenship and personal development, as well as employability. A proposition that merits attention in future research is that the development of epistemological understanding is largely neglected in current curricula in formal post-16 education

    Can non-viral technologies knockdown the barriers to siRNA delivery and achieve the next generation of cancer therapeutics?

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    Cancer is one of the most wide-spread diseases of modern times, with an estimated increase in the number of patients diagnosed worldwide, from 11.3 million in 2007 to 15.5 million in 2030 (www.who.int). In many cases, due to the delay in diagnosis and high increase of relapse, survival rates are low. Current therapies, including surgery, radiation and chemotherapy, have made significant progress, but they have many limitations and are far from ideal. Although immunotherapy has recently offered great promise as a new approach in cancer treatment, it is still very much in its infancy and more information on this approach is required before it can be widely applied. For these reasons effective, safe and patient-acceptable cancer therapy is still largely an unmet clinical need. Recent knowledge of the genetic basis of the disease opens up the potential for cancer gene therapeutics based on siRNA. However, the future of such gene-based therapeutics is dependent on achieving successful delivery. Extensive research is ongoing regarding the design and assessment of non-viral delivery technologies for siRNA to treat a wide range of cancers. Preliminary results on the first human Phase I trial for solid tumours, using a targeted non-viral vector, illustrate the enormous therapeutic benefits once the issue of delivery is resolved. In this review the genes regulating cancer will be discussed and potential therapeutic targets will be identified. The physiological and biochemical changes caused by tumours, and the potential to exploit this knowledge to produce bio-responsive ‘smart’ delivery systems, will be evaluated. This review will also provide a critical and comprehensive overview of the different non-viral formulation strategies under investigation for siRNA delivery, with particular emphasis on those designed to exploit the physiological environment of the disease site. In addition, a section of the review will be dedicated to pre-clinical animal models used to evaluate the stability, safety and efficacy of the delivery systems

    Combination of electroporation delivered metabolic modulators with low-dose chemotherapy in osteosarcoma

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    Background: Osteosarcoma accounts for roughly 60% of all malignant bone tumors in children and young adults. The five-year survival rate for localized tumors after surgery and chemotherapy is approximately 70% whilst it drastically reduces to 15–30% in metastatic cases. Metabolic modulation is known to increase sensitivity of cancers to chemotherapy. A novel treatment strategy in Osteosarcoma is needed to battle this devastating malady. Results: Electroporation-delivered metabolic modulators were more effective in halting the cell cycle of Osteosarcoma cells and this negatively affects their ability to recover and proliferate, as shown in colony formation assays. Electroporation-delivered metabolic modulators increase the sensitivity of Osteosarcoma cells to chemotherapy and this combination reduces their survivability. Conclusion: This novel treatment approach highlights the efficacy of electroporation in the delivery of metabolic modulators in Osteosarcoma cells, and increased sensitivity to chemotherapy allowing for a lower dose to be therapeutic. Methods: Metabolic modulations of two Osteosarcoma cell lines were performed with clinically available modulators delivered using electroporation, and its combination with low-dose Cisplatin. The effects of Dicholoroacetic acid, 2-Deoxy-D-glucose and Metformin on cell cycle and recovery of Osteosarcoma cells were assessed. Their sensitivity to chemotherapy was also assessed when treated in combination with electroporation-delivered metabolic modulators

    Identifying success factors in crowdsourced geographic information use in government

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    Crowdsourcing geographic information in government is focusing on projects that are engaging people who are not government officials and employees in collecting, editing and sharing information with governmental bodies. This type of projects emerged in the past decade, due to technological and societal changes - such as the increased use of smartphones, combined with growing levels of education and technical abilities to use them by citizens. They also flourished due to the need for updated data in relatively quick time when financial resources are low. They range from recording the experience of feeling an earthquake to recording the location of businesses during the summer time. 50 cases of projects in which crowdsourced geographic information was used by governmental bodies across the world are analysed. About 60% of the cases were examined in 2014 and in 2017, to allow for comparison and identification of success and failure. The analysis looked at different aspects and their relationship to success: the drivers to start a project; scope and aims; stakeholders and relationships; inputs into the project; technical and organisational aspect; and problems encountered. The main key factors of the case studies were analysed with the use of Qualitative Comparative Analysis (QCA) which is an analytical method that combines quantitative and qualitative tools in sociological research. From the analysis, we can conclude that there is no “magic bullet” or a perfect methodology for a successful crowdsourcing in government project. Unless the organisation has reached maturity in the area of crowdsourcing, identifying a champion and starting a project that will not address authoritative datasets directly is a good way to ensure early success and start the process of organisational learning on how to run such projects. Governmental support and trust is undisputed. If the choice is to use new technologies, this should be accompanied by an investment of appropriate resources within the organisation to ensure that the investment bear fruits. Alternatively, using an existing technology that was successful elsewhere and investing in training and capacity building is another path for success. We also identified the importance of intermediary Non-Governmental Organizations (NGOs) with the experience and knowledge in working with crowdsourcing within a partnership. These organizations have the knowledge and skills to implement projects at the boundary between government and the crowd, and therefore can offer the experience to ensure better implementation. Changes and improvement of public services, or a focus on environmental monitoring can be a good basis for a project. Capturing base mapping is a good point to start, too. The recommendation of the report address organisational issues, resources, and legal aspects

    Expressional changes in stemness markers post electrochemotherapy in pancreatic cancer cells

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    Pancreatic cancer is one of the most lethal cancers with high metastatic potential and strong chemoresistance. The capability of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. Cancer stem cells exhibit great tumorigenicity and are closely correlated with drug resistance and tumor recurrence. The aim of our study was to illustrate electrochemotherapy as an effective treatment for pancreatic cancer along with the expression change in stemness genes (Nanog, Sox2 and Oct3/4) in pancreatic cancer cells post electrochemotherapy with bleomycin, cisplatin and oxaliplatin. Our results showed the enhanced expression of Nanog and decreased expression level of Oct3/4 after electrochemotherpy. We thus propose that these stemness markerS may have important roles in the initiation and/or recurrence of pancreatic cancer, and consequently may serve as important molecular diagnostics and/or therapeutic targets for the development of novel treatment strategies in pancreatic cancer patients. In conclusion, targeting these stemness factors could potentially improve electrochemotherapy as a treatment and preventing recurrence
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