Investigation of molecular mechanisms of lkb1 function in dictyostelium development and stress responses and the function of superoxide dismutase c (sodc) in chemotaxis

The serine/threonine kinase LKB1 is a regulator of critical events including development and stress responses in metazoans. The current study was undertaken to determine the function of LKB1 in Dictyostelium. During multicellular development and in response to stress insult, an apparent increase in the DdLKB1 kinase activity was observed. Depletion of DdLKB1 with a knockdown construct led to aberrant development; a severe reduction in prespore cell differentiation and a precocious induction of prestalk cells, which were reminiscent of cells lacking GSK3, a well known cell-fate switch. Furthermore, DdLKB1 depleted cells displayed lower GSK3 activity than wild type cells in response to cAMP stimulation during development and failed to activate AMPK, a well known LKB1 target in mammals, in response to cAMP and stress insults. These results suggest that DdLKB1 positively regulates both GSK3 and AMPK during Dictyostelium development, and DdLKB1 is necessary for AMPK activation during stress response regulation. No apparent GSK3 activation was observed in response to stress insults. Spatial and temporal regulation of phosphatidylinositol-(3,4,5)-triphosphate (PIP3) along the membrane of polarized cells is important for efficient chemotaxis. A REMI screen for PIP3 suppressors in the absence of stimulation led to the identification of SodC as PIP3 regulator. Consistent with their higher PIP3 levels, sodC- cells showed defects in chemotaxis and exhibited higher intra-cellular superoxide levels. Protein localization studies along with observations from GPI specific PI-PLC treatment of wild-type cells suggested that SodC is a GPI anchored outer-membrane protein. SodC showed superoxide dismutase activity in vitro, and motility defects of sodC- cells can be rescued by expressing the intact SodC but not by the mutant SodC, which has point mutations that affect its dismutase function. Treatment of sodC- cells with LY294002, a pharmacological inhibitor of PI3K, partially rescued the polarization and chemoattractant sensing defects but not motility defects. Consistent with increased intracellular superoxide levels, sodC- cells also exhibited higher basal Ras activity, an upstream regulator of PI3K, which can be suppressed by a cell permeable superoxide scavenger, XTT, indicating that SodC is important in regulation of intracellular superoxide levels thereby regulating the Ras activity and PIP3 levels at the membrane.

Landscape of fear : a social history of the missile during the early years of the cold war, 1950-1965

The missile's significance has been central to national security since the Soviet launching of Sputnik, and became increasingly important throughout the years of the Cold War. Much has been written about missile technology, but little has been written about how the development and deployment of this weapon affected Americans. The missile was developed to both deter war but also to win war. Its presence, however, was not always reassuring. Three areas of the United States are studied to evaluate the social implications of the missile during these pivotal years: San Francisco, home of multiple Nike installations; of Cape Canaveral, Florida, the nation's primary missile test center; the Great Plains, the location of the largest ICBM concentration in the country. Interviews were conducted, tours of facilities were taken, and local newspapers were reviewed. In conjunction with national newspapers and magazines and public opinion polls, this information provided a local social context for missile history. Nationally and locally, Americans both feared and praised the new technology. They were anxious for government funding in their cities and often felt that the danger the missile brought to their communities by making it as a Soviet target was justified in the larger cause for national security.

Social determinants of dental treatment needs in Brazilian adults

Background The chronic cumulative nature of caries makes treatment needs a severe problem in adults. Despite the fact that oral diseases occur in social contexts, there are few studies using multilevel analyses focusing on treatment needs. Thus, considering the importance of context in explaining oral health related inequalities, this study aims to evaluate the social determinants of dental treatment needs in 35–44 year old Brazilian adults, assessing whether inequalities in needs are expressed at individual and contextual levels. Methods The dependent variables were based on the prevalence of normative dental treatment needs in adults: (a) restorative treatment; (b) tooth extraction and (c) prosthetic treatment. The independent variables at first level were household income, formal education level, sex and race. At second level, income, sanitation, infrastructure and house conditions. The city-level variables were the Human Development Index (HDI) and indicators related to health services. Exploratory analysis was performed evaluating the effect of each level through calculating Prevalence Ratios (PR). In addition, a three-level multilevel modelling was constructed for all outcomes to verify the effect of individual characteristics and also the influence of context. Results In relation to the need for restorative treatment, the main factors implicated were related to individual socioeconomic position, however the city-level contextual effect should also be considered. Regarding need for tooth extraction, the contextual effect does not seem to be important and, in relation to the needs for prosthetic treatment, the final model showed effect of individual-level and city-level. Variables related to health services did not show significant effects. Conclusions Dental treatment needs related to primary care (restoration and tooth extraction) and secondary care (prosthesis) were strongly associated with individual socioeconomic position, mainly income and education, in Brazilian adults. In addition to this individual effect, a city-level contextual effect, represented by HDI, was also observed for need for restorations and prosthesis, but not for tooth extractions. These findings have important implications for the health policy especially for financing and planning, since the distribution of oral health resources must consider the inequalities in availability and affordability of dental care for all.

Patricia Harris, Former United States Secretary of Housing and Urban Development

General note: Title and date provided by Bettye Lane.

Patricia Roberts Harris, Former United States Secretary of Housing and Urban Development

General note: Title and date provided by Bettye Lane.

Dunn County and Watford City, North Dakota: A case study of the fiscal effects of Bakken shale development

The Bakken region of North Dakota and Montana has experienced perhaps the greatest effects of increased oil and gas development in the United States, with major implications for local governments. Though development of the Bakken began in the early 2000s, large-scale drilling and population growth dramatically affected the region from roughly 2008 through today. This case study examines the local government fiscal benefits and challenges experienced by Dunn County and Watford City, which lie near the heart of the producing region. For both local governments, the initial growth phase presented major fiscal challenges due to rapidly expanding service demands and insufficient revenue. In the following years, these challenges eased as demand for services slowed due to declining industry activity and state tax policies redirected more funds to localities. Looking forward, both local governments describe their fiscal health as stronger because of the Bakken boom, though higher debt loads and an economy heavily dependent on the volatile oil and gas industry each pose challenges for future fiscal stability.

A strategy-based framework for assessing the flood resilience of cities – the Hamburg case study

Climate change and continuous urbanization contribute to an increased urban vulnerability towards flooding. Only relying on traditional flood control measures is recognized as inadequate, since the damage can be catastrophic if flood controls fail. The idea of a flood-resilient city – one which can withstand or adapt to a flood event without being harmed in its functionality – seems promising. But what does resilience actually mean when it is applied to urban environments exposed to flood risk, and how can resilience be achieved? This paper presents a heuristic framework for assessing the flood resilience of cities, for scientists and policy-makers alike. It enriches the current literature on flood resilience by clarifying the meaning of its three key characteristics – robustness, adaptability and transformability – and identifying important components to implement resilience strategies. The resilience discussion moves a step forward, from predominantly defining resilience to generating insight into “doing” resilience in practice. The framework is illustrated with two case studies from Hamburg, showing that resilience, and particularly the underlying notions of adaptability and transformability, first and foremost require further capacity-building among public as well as private stakeholders. The case studies suggest that flood resilience is currently not enough motivation to move from traditional to more resilient flood protection schemes in practice; rather, it needs to be integrated into a bigger urban agenda.

Who is in charge? An L2 Discourse Intonation Study on Four Prosodic Parameters to Exert the Pragmatic Function of Dominance and Control in the Context of L2 Non-specialist Public Speaking

This paper reports the findings from a study of the learning of English intonation by Spanish speakers within the discourse mode of L2 oral presentation. The purpose of this experiment is, firstly, to compare four prosodic parameters before and after an L2 discourse intonation training programme and, secondly, to confirm whether subjects, after the aforementioned L2 discourse intonation training, are able to match the form of these four prosodic parameters to the discourse-pragmatic function of dominance and control. The study designed the instructions and tasks to create the oral and written corpora and Brazil’s Pronunciation for Advanced Learners of English was adapted for the pedagogical aims of the present study. The learners’ pre- and post-tasks were acoustically analysed and a pre / post- questionnaire design was applied to interpret the acoustic analysis. Results indicate most of the subjects acquired a wider choice of the four prosodic parameters partly due to the prosodically-annotated transcripts that were developed throughout the L2 discourse intonation course. Conversely, qualitative and quantitative data reveal most subjects failed to match the forms to their appropriate pragmatic functions to express dominance and control in an L2 oral presentation.

Falls and the Social Isolation of Older Adults in the National Health and Aging Trends Study

Thesis (Ph.D.)--University of Washington, 2016-08

Review Pages: Planning for Livable and Safe Cities: Energy, Pollution and the Degradation of the Urban Environment

Starting from the relationship between urban planning and mobility management, TeMA has gradually expanded the view of the covered topics, always remaining in the groove of rigorous scientific in-depth analysis. During the last two years a particular attention has been paid on the Smart Cities theme and on the different meanings that come with it. The last section of the journal is formed by the Review Pages. They have different aims: to inform on the problems, trends and evolutionary processes; to investigate on the paths by highlighting the advanced relationships among apparently distant disciplinary fields; to explore the interaction’s areas, experiences and potential applications; to underline interactions, disciplinary developments but also, if present, defeats and setbacks. Inside the journal the Review Pages have the task of stimulating as much as possible the circulation of ideas and the discovery of new points of view. For this reason the section is founded on a series of basic’s references, required for the identification of new and more advanced interactions. These references are the research, the planning acts, the actions and the applications, analysed and investigated both for their ability to give a systematic response to questions concerning the urban and territorial planning, and for their attention to aspects such as the environmental sustainability and the innovation in the practices. For this purpose the Review Pages are formed by five sections (Web Resources; Books; Laws; Urban Practices; News and Events), each of which examines a specific aspect of the broader information storage of interest for TeMA.

Uma cidade diversa e complementar

Dissertação para obtenção do grau de Mestre em Arquitetura, apresentada na Universidade de Lisboa - Faculdade de Arquitetura.

Análisis crítico de la planificación urbana de la Ciudad de Cuenca

Las ciudades de todo el mundo deben mantener un entorno urbano habitable. Nueva York y Barcelona fueron una vez ejemplos a seguir, pero la visión urbana de expansión durante las últimas décadas ha dado lugar a un paradigma que comprende pobremente las tendencias de desarrollo de finales del siglo 20 e inicios del siglo 21. La planificación urbana insuficientemente pondera las aspiraciones de los ciudadanos y las funciones socioeconómicas de la ciudad, generando desequilibrios, caracterizados por el aumento de congestiones de tráfico, injusticia social y económica, y degradación medioambiental. En el caso de la ciudad de Cuenca, el desarrollo urbano ilustra claramente una expansión deficientemente controlada con graves fricciones en los mercados de trabajo y de vivienda, con pocos espacios verdes dentro y alrededor de la ciudad, como fue en el pasado. Este estudio intenta ilustrar la discrepancia entre la teoría y la práctica en el campo de la planificación urbana utilizando como caso de estudio a la ciudad andina de Cuenca. Mientras que la nueva doctrina de planificación urbana habla de un intrincado equilibrio entre las funciones socioeconómicas y ambientales en el espacio urbano, la ciudad se ve cada día más desorganizada. Además, para explicar la situación actual de la planificación de la ciudad de Cuenca, basada en razones teóricas y filosóficas, se identificaron las deficiencias en la planificación urbana. Las buenas prácticas de diseño y planificación urbana deben basarse en una buena comprensión del carácter dinámico y complejo de las ciudades. Con el manuscrito el autor tiene como objetivo impulsar la discusión científica sobre la planificación urbana desde la visión medioambiental y sustentable.

Creativity, Clusters and the Competitive Advantage of Cities

Purpose – This paper aims to marry Michael Porter’s industrial cluster theory of traded and local clusters to Richard Florida’s occupational approach of creative and routine workers to gain a better understanding of the process of economic development. Design/methodology/approach – Combining these two approaches, four major industrial-occupational categories are identified. The shares of US employment in each – creative-in-traded, creative-in-local, routine-in-traded and routine-in-local – are calculated, and a correlation analysis is used to examine the relationship of each to regional economic development indicators. Findings – Economic growth and development is positively related to employment in the creative-in-traded category. While metros with a higher share of creative-in-traded employment enjoy higher wages and incomes overall, these benefits are not experienced by all worker categories. The share of creative-in-traded employment is also positively and significantly associated with higher inequality. After accounting for higher median housing costs, routine workers in both traded and local industries are found to be relatively worse off in metros with high shares of creative-in-traded employment, on average. Social implications – This work points to the imperative for the US Government and industry to upgrade routine jobs, which make up the majority of all employment, by increasing the creative content of this work. Originality/value – The research is among the first to systematically marry the industry and occupational approaches to clusters and economic development.