4,617 research outputs found
Investigation of ancient proteins in archaeological material
Although several studies have positively identified dairy proteins from ancient dental calculus, other dietary protein identifications are exceedingly rare. The manuscripts included in this thesis include the identification of 20 different dietary proteins that could be taxonomically identified to the species level from 10 different species. One of our primary goals for this thesis was to evaluate any potential biases in our dietary protein recovery, and to gain a deeper understanding of the factors that influence dietary protein preservation within dental calculus. Although our sample sizes are small, we did find evidence of biases in the types of proteins we have recovered thus far. All proteins identified were potential allergens with IgE binding sites, low monomer molecular weight, resistance to changes in pH and temperature, and resistance to degradation through enzymatic proteolysis. The identified proteins primarily had functions in host defense or storage
\u27The Ghostly Language of the Ancient Earth\u27: The Idea of Nature in Deep Time (Flyer)
In 1799 William Wordsworth imagined his younger self standing beneath the rocks of his native mountains listening to the âghostly language of the ancient earthâ. I also try to hear the echoes that come out of the deep past and decipher what we can learn from them about the entangling of the human and natural worlds and the origins of the idea of Nature.
Professor Ashley currently teaches medieval, world and environmental history at Newcastle University, UK. He has published on diverse matters, including the Vikings, ninth-century astronomy and Captain James Cook. He is currently researching the role of climate change in the early middle ages and the ecological impacts of the Vikings in the North Atlantic
Impact Of Host Factors On The Adaptive Immune Response To Aav Gene Therapy
Impact of host factor on the adaptive immune response to AAV gene therapy
Scott Ashley
James Wilson
Adaptive immune responses to the transgene product remain an active area of concern for the gene therapy field. How host factors can influence the activation of the immune system is an important consideration in the development of gene therapy for different genetic disorders. One factor considered by many to shape the adaptive immune response is an individualâs genotype. Nonsense mutations were thought to result in an absence of tolerance to a replacement protein provided by gene therapy, due to a lack of antigen presentation during T cell development and negative selection. In this work we demonstrated that a class of nonsense mutations, premature termination codons (PTC), found in ornithine transcarbamylase deficiency (OTC) patients do not inhibit antigen presentation of C-terminal epitopes. We further found that these PTC containing OTC genes were able to induce anergy in a model of peripheral tolerance. These results change how we think about the relationship between the genotype and immune response, which indicate that individuals with PTC mutations may be less at risk of an adverse immune response attenuating the effects of gene therapy. We also identified vector factors that influence the adaptive immune response, activation of TLR9 and the tissues targeted for transduction and expression of the transgene. To investigate how inflammatory signaling might impact the outcome of adaptive immune responses; we use the transgenic OT-1 mouse model to interrogate how TLR9, the primary sensing molecule for vector DNA, can activate cytotoxic T cells against the transgene product OTC. These results confirm an important role for TLR9 induced inflammation being necessary for transgene specific T cell activation. To investigate the influence of TLR9 signaling and tissue targets on the humoral response, we used a mouse model of Mucopolysaccharidosis type I (MPS1) disease, and measured antibody generation to the secreted transgene product alpha-L-iduronidase (IDUA). We report that TLR9 signaling is also instrumental for the formation of anti-IDUA antibodies, as is expression of the transgene from the muscle. This work describes a novel process by which tolerance to a peptide located downstream of a PTC can be induced. This insight can help us better define the risks associated with an adaptive immune response based on an individualâs personal mutation. We also defined important vector factors which are important for activation of an adaptive immune response, and this knowledge could be exploited to generate safer gene therapy delivery methods
Overcoming the Obstacles to Sustainability in Ghana
For several decades following its independence from Great Britain, Ghanaâs policies continued to promote over-extraction of natural resources to the detriment of its economy and rural communities. Agricultural and forestry policy has gradually evolved to foster more sustainable and equitable practices, as in building partnerships with the private sector to fund infrastructure improvements. Policy has recently recognized the dire need to adopt agricultural practices and means of forest resource extraction that are compatible with ecological stewardship. However, many shortcomings are still apparent. Large logging operations completely disregard forestry regulations with impunity, whereas rural sustenance extractors are severely punished in the rare event that policy is actually enforced. Although the severe disadvantages that agricultural policies had imposed in the 1960s have been partially alleviated, much improvement is still needed. Recent agricultural policy has recognized the lack of funding available to invest in more efficient and higher-yielding agricultural practices, but partnerships with the actual lending institutions do not exist. The scarcity of crucial inputs, such as fertilizer and technical assistance remains a major problem in the agricultural sector, as the soils are becoming rapidly depleted, leading to declining crop yields and further encroachment on the 20 percent of forests remaining. Overly ambitious targets and unrealistic policies require more careful and detailed formulation so that Ghanaâs resources can be managed effectively before famine sweeps the food-insecure country once more
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Trade association strategies for providing technology intelligence to small and medium sized enterprises - A study of UK technology foresight processes
This thesis was submitted for the degree of Master of Philosophy and awarded by Brunel University.In the UK many industries are suffering as a result of business being lost to competition abroad. Raising the technical content of a companyâs product or service may enable them to increase its competitiveness and hence retain or even increase business. A Trade Association exists to represent the interests of its members. One way that this can be realized is by provision of technical information to its members to support raising the technical content of their membersâ products or services.
The provision of technical information entails sourcing information, collecting it
and then disseminating it in an appropriate format. Ways of undertaking this are
identified. The factors that are likely to influence the provision of technical
information are determined. This is so that a Trade Association can build upon its
strengths, diminish weaknesses, exploit opportunities and avoid threats. A strategy for provision of engineering technical information to trade association members was given. Four mechanisms were implemented on a test-bed Trade Association; utilising information technology communication capabilities, newsletters, collaborations and conferences.
Feedback and parameters were used to assess the strategy chosen for implementation on the test-bed. Taking this into consideration a revised strategy was established that can be adapted and applied by Trade Associations who wish to provide such a service in the future
The Back Road to Murfreesboro
This project was conceived as a multi-form, multi-media piece in which each work of fiction, poetry, or photography is fully intended to both stand on its own and contribute to an overall feeling for the entire collection. It is in the juxtaposition of these various works that the audience can gain a greater appreciation for the entire collection as well as for each individual piece contained within.
This collection explores the dissatisfaction and alienation of contemporary life, and depicts characters, objects, and settings that are all in some way disconnected or empty. The overall stance is negative, of frustrated desire, in the hope that it may serve as a warning call against what is shown
Generalizations of the Abstract Boundary singularity theorem
The Abstract Boundary singularity theorem was first proven by Ashley and
Scott. It links the existence of incomplete causal geodesics in strongly
causal, maximally extended spacetimes to the existence of Abstract Boundary
essential singularities, i.e., non-removable singular boundary points. We give
two generalizations of this theorem: the first to continuous causal curves and
the distinguishing condition, the second to locally Lipschitz curves in
manifolds such that no inextendible locally Lipschitz curve is totally
imprisoned. To do this we extend generalized affine parameters from
curves to locally Lipschitz curves.Comment: 24 page
The Use of Reflective Questioning as a Peer Coaching Strategy in an Asynchronous Online Cognitive Apprenticeship
The cognitive apprenticeship framework melds situated, authentic learning with social learning theory. The learning strategies included in a cognitive apprenticeship are modeling, coaching, scaffolding, articulation, reflection, and exploration. Previous research indicates that the most beneficial strategy for the learner is coaching, and is also the most time-consuming strategy for the instructor. However, no previous research has been conducted to determine which coaching strategies can be utilized in order to lessen the burden on the instructor, while being beneficial to the learner.
The purpose of this study was to explore the use of guided reflective questions as a strategy for enhancing cognitive presence in peer dyad groups. These dyads were created in order to provide a platform for peer coaching in an online, asynchronous professional development course designed using the cognitive apprenticeship framework for the professional development of professional programming librarians and paraprofessional programmers.
The current study found a significant difference in cognitive presence levels between the control and treatment groups, and no significant difference in learning outcomes between the two groups. Additionally, the study highlighted the challenges faced by participants, such as lack of time to devote to professional development and lack of peer engagement from their peer coach. Participants also valued the fresh perspectives that they experienced during peer interactions and the availability of resources that were provided during the course. Discussion of the results highlights constraints, limitations, challenges, and positive aspects of participation in an asynchronous online cognitive apprenticeship. Discussion of the results also sheds light on questions worthy of future research in order to develop best practices for the use of cognitive apprenticeships in professional development and online contexts
Critical Landscape Planning during the Belt and Road Initiative
This open access book traces the development of landscapes along the 414-kilometer ChinaâLaos Railway, one of the first infrastructure projects implemented under Chinaâs Belt and Road Initiative (BRI) and which is due for completion at the end of 2021. Written from the perspective of landscape architecture and intended for planners and related professionals engaged in the development and conservation of these landscapes, this book provides history, planning pedagogy and interdisciplinary framing for working alongside the often-opaque planning, design and implementation processes of large-scale infrastructure. It complicates simplistic notions of development and urbanization frequently reproduced in the LaosâChina frontier region. Many of the projects and sites investigated in this book are recent âfirstsâ in Laos: Laosâs first wildlife sanctuary for trafficked endangered species, its first botanical garden and its first planting plan for a community forest. Most often the agents and accomplices of neoliberal development, the planning and design professions, including landscape architecture, have little dialogue with either the mainstream natural sciences or critical social sciences that form the discourse of projects in Laos and comparable contexts. Covering diverse conceptions and issues of development, including cultural and scientific knowledge exchanges between Laos and China, nature tourism, connectivity and new town planning, this book also features nine planning proposals for Laos generated through this research initiative since the railway's groundbreaking in 2016. Each proposal promotes a wider "landscape approach" to development and deploys landscape architectureâs spatial and ecological acumen to synthesize critical development studies with the planner's capacity, if not naive predilection, to intervene on the ground. Ultimately, this book advocates the cautious engagement of the professionally oriented built-environment disciplines, such as regional planning, civil engineering and landscape architecture, with the landscapes of development institutions and environmental NGOs
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