6,121 research outputs found

    Analysis of quantification methods used for cell viability, cell morphology, and synaptic formation in modeling HIV associated dementia in primary neuronal cultures.

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    Change is inevitable, changes in neuronal function occur in physiologic and pathologic processes. The ability to reliably analyze and quantify those changes in neuronal morphology and function has been an important part of technical developments in Neuroscience. A key innovation in the Neuroscience was the development of primary neuronal cultures. Primary neuronal cultures allow neurons to be dissociated and studied as individual components. The study of specific pathologic processes associated with neurodegeneration have benefited greatly from the development and characterization of dissociated primary neuronal cultures. Human Immunodeficiency Virus can lead to a neurodegenerative process. Establishing a consistent model for studying the effects of HIV infection in the brain has provided a unique challenge. The use of analysis of quantification of neuronal changes in dissociated primary neurons modeling HIV dementia has proven useful. As the study of this disorder continues the characterization of the model system will become increasing important. This review will focus on analysis of specific techniques used to quantify specific changes in neurons in this model system. As this field moves forward it will be important to specifically focus on techniques involved in cell viability, morphologic changes, and synaptic formatio

    Charge environments around phosphorylation sites in proteins

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    Background: Phosphorylation is a central feature in many biological processes. Structural analyses have identified the importance of charge-charge interactions, for example mediating phosphorylation-driven allosteric change and protein binding to phosphopeptides. Here, we examine computationally the prevalence of charge stabilisation around phosphorylated sites in the structural database, through comparison with locations that are not phosphorylated in the same structures. Results: A significant fraction of phosphorylated sites appear to be electrostatically stabilised, largely through interaction with sidechains. Some examples of stabilisation across a subunit interface are evident from calculations with biological units. When considering the immediately surrounding environment, in many cases favourable interactions are only apparent after conformational change that accompanies phosphorylation. A simple calculation of potential interactions at longer-range, applied to non-phosphorylated structures, recovers the separation exhibited by phosphorylated structures. In a study of sites in the Phospho.ELM dataset, for which structural annotation is provided by non-phosphorylated proteins, there is little separation of the known phospho-acceptor sites relative to background, even using the wider interaction radius. However, there are differences in the distributions of patch polarity for acceptor and background sites in the Phospho.ELM dataset. Conclusion: In this study, an easy to implement procedure is developed that could contribute to the identification of phospho-acceptor sites associated with charge-charge interactions and conformational change. Since the method gives information about potential anchoring interactions subsequent to phosphorylation, it could be combined with simulations that probe conformational change. Our analysis of the Phospho.ELM dataset also shows evidence for mediation of phosphorylation effects through (i) conformational change associated with making a solvent inaccessible phospho-acceptor site accessible, and (ii) modulation of protein-protein interactions

    Advanced heat receiver conceptual design study

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    Solar Dynamic space power systems are candidate electrical power generating systems for future NASA missions. One of the key components of the solar dynamic power system is the solar receiver/thermal energy storage (TES) subsystem. Receiver development was conducted by NASA in the late 1960's and since then a very limited amount of work has been done in this area. Consequently the state of the art (SOA) receivers designed for the IOC space station are large and massive. The objective of the Advanced Heat Receiver Conceptual Design Study is to conceive and analyze advanced high temperature solar dynamic Brayton and Stirling receivers. The goal is to generate innovative receiver concepts that are half of the mass, smaller, and more efficient than the SOA. It is also necessary that these innovative receivers offer ease of manufacturing, less structural complexity and fewer thermal stress problems. Advanced Brayton and Stirling receiver storage units are proposed and analyzed in this study which can potentially meet these goals

    China's absorptive State: research, innovation and the prospects for China-UK collaboration

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    China's innovation system is advancing so rapidly in multiple directions that the UK needs to develop a more ambitious and tailored strategy, able to maximise opportunities and minimise risks across the diversity of its innovation links to China. For the UK, the choice is not whether to engage more deeply with the Chinese system, but how. This report analyses the policies, prospects and dilemmas for Chinese research and innovation over the next decade. It is designed to inform a more strategic approach to supporting China-UK collaboration

    How to make a comet

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    The primary mandate of NASA is the study of the nature and origin of the solar system. The study of the comets provide information about conditions and processes at the beginning of the solar system. Short period comets and their relatives, the near Earth asteroids may prove to be second only to the sun in importance to the long term survival of civilization for two reasons. The short period comets and the near Earth asteroids are a possible candidate for the cause of mass extinctions of life on Earth; and they may provide the material means for the expansion of civilization into the solar system and beyond. The comets and near Earth asteroids almost certainly represent the most primitive material of the solar system, still tantalizingly unavailable until spacecraft bring first-hand information. In the meantime comets must be studied by remote means. Laboratory investigations using synthetic cometary materials may add to the knowledge of these interesting objects. Experimentation on comet synthesis is briefly discussed

    Gender Differences of African American Adolescents When Exposed to Race Related Stress

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    For African Americans, issues of discrimination, oppression, and belonging to a minority group may significantly impact their identity formation, and their cognitive and subjective beliefs regarding racial issues. Racism-related stress as it affects African American adolescents has become an area of concern for African American researchers. Racism related stress can be characterized as the negative psychological or physiological response to a perceived instance of a racism related attitude or behavior. African American adolescents, because of their race, continue to be subjected to various social stressors that lead to negative stress that depletes them of their abilities to cope in response. Without the ability to effectively cope with threatening life episodes African American adolescents experience more stressful and negative lifestyles. This study examined: (a) whether there are gender differences with regards to race related stress, (b) the association of SES and race related stress, (c) the association of the type of neighborhood one lives in and race related stress, and (d) the association of which parent(s) the adolescent lives with and race related stress. Independent samples T-tests and Analysis of Variance were conducted to determine if there was a difference in gender with regard to race related stress. A significant difference was found with regards to the overall stress measure, as well as on the individual and collective subscales. Pearson-product moment correlations coefficients were conducted to determine the relations among demographic variables and race related stress. A significant positive relation was found between SES and family dynamic and race related stress

    Patterns and drivers of long term spatio-temporal change in a rural savanna landscape

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    A dissertation submitted to the Faculty of Science, University of the Witwatersrand, in fulfilment of the requirements for the degree of Master of Science 17th August 2015 in Johannesburg, South AfricaEcosystem services provide a vital lifeline to millions of people living in rural areas. The poorest people in these areas depend upon the natural resource base in their surroundings to provide these services. With growing populations in rural areas of South Africa, the natural resource base is under considerable pressure; however, uncovering the dynamics of vegetation in these systems has proven difficult. While much attention has been given to savanna ecology, long term studies on the patterns and drivers of woody biomass are few. We used 65 years of aerial imagery (from 1944 to 2009) over 31 953 ha of rural savanna in a communal rangeland in South Africa to determine the abundance of woody canopy cover. This data were captured at hectare resolution, giving a fine enough level of detail for local level analysis. We also captured data for five potential drivers for change at this resolution, in order to analyse these drivers for their relative importance in determining woody canopy cover throughout the study period. Surprisingly, while individual sites showed varied trends in the amounts of woody canopy cover through time, when pooled across all sites the total woody canopy cover increased over the 65 year period. Disturbance gradients were found around some of the villages, but only in 2009, suggesting that the drivers of disturbance gradients in these systems may have only operated sufficiently to produce disturbance gradients in recent years. A hot spot analysis (hot spots indicate cells that have similarly high values beyond what would be expected in a random distribution, with cold spots indicating the inverse) revealed an increase in both hot and cold spots through time, but with a low persistence of both through time. High canopy cover cells are presumed to be the result of bush encroachment, while low canopy cover cells are presumed to be the result of harvesting of trees for fuelwood or clearing for fields. The low persistence of hot and cold spots points to a system in continual change, with patches of hot and cold spots appearing and disappearing, and therefore drivers of change operating in short periods of time. MAP (Mean Annual Precipitation), and not an anthropogenic driver, was found to be the most important driver for woody canopy cover throughout the study period, with MAP up to 670 mm having a predictable pattern of hot and cold spots through time. Higher MAP was shown to have a non-linear and unpredictable pattern of hot and cold spots through time, indicating that low precipitation may produce a system where woody canopy cover is less influenced by other drivers and is more stable when acted upon by other drivers. This research demonstrates the value of a long term dataset, and the applicability of our methods for monitoring woody canopy cover. As such, it may well serve as a baseline for woody canopy cover in communal savanna rangeland systems, with the methodology employed here suitable for an early warning detection system for sudden changes in the woody canopy cover

    A Muse of Fire – British Trench Warfare Munitions, their Invention, Manufacture and Tactical Employment on the Western Front, 1914–18

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    The emergence of static warfare on the Western Front in late 1914, encouraged the reinvention of devices associated with siege warfare and the invention of hitherto unknown munitions. These munitions included hand and rifle grenades and trench mortars and their ammunition. At the outbreak of war, the British effectively possessed none of these devices and lacked an infrastructure by which they could be quickly designed, manufactured and supplied to the BEF. The British met this challenge with considerable success and the subsequent proliferation of trench warfare munitions had profound consequences for the evolution of British tactics on the Western Front. This thesis examines the processes by which these devices were invented, developed into manufacturable devices and supplied to the BEF. It considers their novelty in respect to similar devices from the American Civil War and the Russo-Japanese War. It looks at how their technical evolution affected tactical developments. The thesis discusses the relationship between the technical characteristics of these devices and the evolution of their tactical employment on the Western Front. It also considers how the characteristics of certain munitions, such as the Stokes mortar and the Mills grenade, directly effected tactics. It argues that the tactical employment of these munitions was dependent upon their functionality, utility and reliability. The present thesis provides a different model of trench warfare conducted by the British during the First World War and thereby demonstrates the significance of the novel munitions under discussion and the role they played in changing infantry warfare. This thesis also provides a different view of the Ministry of Munitions from that usually offered and argues that certain aspects of the Ministry’s role in providing the BEF with munitions has been overstated by virtue of its having underplayed the work of the War Office, while overlooking that conducted by the Royal Engineers in France

    Predicting and preventing tuberculosis

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    Background. To end tuberculosis, a substantial expansion of active case-finding and tuberculosis preventive treatment is urgently needed. Furthermore, these biomedical interventions, which form the backbone of the global tuberculosis response, should be integrated with socioeconomic interventions to address the poverty-related risk factors principally driving tuberculosis incidence. This research aimed to inform the implementation and integration of these interventions for contacts of patients with tuberculosis. Methods. The research was divided into three phases, all of which were undertaken in Lima, Peru: i) FUNDAMENTALS. A cohort study characterising tuberculosis epidemiology and case-finding among adult contacts of patients with infectious tuberculosis. An individual-level risk score predicting tuberculosis was derived and validated in a separate cohort. ii) CRESIPT. The score was integrated within a community randomised trial of socioeconomic supported for tuberculosis-affected households (the CRESIPT study). The impact of this intervention on access to healthcare and long-term health outcomes of contacts was evaluated. iii) POST-CRESIPT. Experiences during the CRESIPT study informed the derivation of a household-level risk score predicting tuberculosis. This score was derived using data from one cohort and validated in a separate cohort. Results. The first phase demonstrated that: adult contacts of patients with TB have a high and prolonged risk of tuberculosis; active case-finding can make an important contribution to tuberculosis case-finding; and tuberculosis can be predicted using a simple individual-level score. The second phase demonstrated that integrating this score with socioeconomic support achieved large increases in the proportions of contacts who completed active case-finding and tuberculosis preventive treatment; and reduced the risk of tuberculosis by approximately 40%. The third phase demonstrated that tuberculosis can be predicted using a simple household-level score. Conclusions. The research presented in this thesis provides rigorous evidence to support a novel, transformative, and holistic approach to the management of contacts of patients with tuberculosis.Open Acces
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