The administration route is decisive for the ability of the vaccine adjuvant CAF09 to induce antigen-specific CD8+ T-cell responses:the immunological consequences of the biodistribution profile

A prerequisite for vaccine-mediated induction of CD8+ T-cell responses is the targeting of dendritic cell (DC) subsets specifically capable of cross-presenting antigen epitopes to CD8+ T cells. Administration of a number of cationic adjuvants via the intraperitoneal (i.p.) route has been shown to result in strong CD8+ T-cell responses, whereas immunization via e.g. the intramuscular (i.m.) or subcutaneous (s.c.) routes often stimulate weak CD8+ T-cell responses. The hypothesis for this is that self-drainage of the adjuvant/antigen to the lymphoid organs, which takes place upon i.p. immunization, is required for the subsequent activation of cross-presenting lymphoid organ-resident CD8α+ DCs. In contrast, s.c. or i.m. immunization usually results in the formation of a depot at the site of injection (SOI), which hinders the self-drainage and targeting of the vaccine to cross-presenting CD8α+ DCs. We investigated this hypothesis by correlating the biodistribution pattern and the adjuvanticity of the strong CD8+ T-cell inducing liposomal cationic adjuvant formulation 09 (CAF09), which is composed of dimethyldioctadecylammonium bromide/monomycoloyl glycerol liposomes with polyinosinic:polycytidylic acid electrostatically adsorbed to the surface. Biodistribution studies with radiolabeled CAF09 and a surface-adsorbed model antigen [ovalbumin (OVA)] showed that a significantly larger fraction of the vaccine dose localized in the draining lymph nodes (dLNs) and the spleen 6 h after i.p. immunization, as compared to after i.m. immunization. Studies with fluorescently labelled OVA + CAF09 demonstrated a preferential association of OVA + CAF09 to DCs/monocytes, as compared to macrophages and B cells, following i.p. immunization. Administration of OVA + CAF09 via the i.p. route did also result in DC activation, whereas no DC activation could be measured within the same period with unadjuvanted OVA and OVA + CAF09 administered via the s.c. or i.m. routes. In the dLNs, the highest level of activated, cross-presenting CD8α+ DCs was detected at 24 h post immunization, whereas an influx of activated, migrating and cross-presenting CD103+ DCs to the dLNs could be measured after 48 h. This suggests that the CD8α+ DCs are activated by self-draining OVA + CAF09 in the lymphoid organs, whereas the CD103+ DCs are stimulated by the OVA + CAF09 at the SOI. These results support the hypothesis that the self-drainage of OVA + CAF09 to the draining LNs is required for the activation of CD8α+ DCs, while the migratory CD103+ DCs may play a role in sustaining the subsequent induction of strong CD8+ T-cell responses.

The Political Economy of Climate Adaptation and Environmental Health: The Case of Ethiopia

The environment affects our health, livelihoods, and the social and political institutions within which we interact. Indeed, nearly a quarter of the global disease burden is attributed to environmental factors, and many of these factors are exacerbated by global climate change. Thus, the central research question of this dissertation is: How do people cope with and adapt to uncertainty, complexity, and change of environmental and health conditions? Specifically, I ask how institutional factors, risk aversion, and behaviors affect environmental health outcomes. I further assess the role of social capital in climate adaptation, and specifically compare individual and collective adaptation. I then analyze how policy develops accounting for both adaptation to the effects of climate and mitigation of climate-changing emissions. In order to empirically test the relationships between these variables at multiple levels, I combine multiple methods, including semi-structured interviews, surveys, and field experiments, along with health and water quality data. This dissertation uses the case of Ethiopia, Africa’s second-most populous nation, which has a large rural population and is considered very vulnerable to climate change. My fieldwork included interviews and institutional data collection at the national level, and a three-year study (2012-2014) of approximately 400 households in 20 villages in the Ethiopian Rift Valley. I evaluate the theoretical relationships between households, communities, and government in the process of adaptation to environmental stresses. Through my analyses, I demonstrate that water source choice varies by individual risk aversion and institutional context, which ultimately has implications for environmental health outcomes. I show that qualitative measures of trust predict cooperation in adaptation, consistent with social capital theory, but that measures of trust are negatively related with private adaptation by the individual. Finally, I describe how Ethiopia had some unique characteristics, significantly reinforced by international actors, that led to the development of an extensive climate policy, and yet with some challenges remaining for implementation. These results suggest a potential for adaptation through the interactions among individuals, communities, and government in the search for transformative processes when confronting environmental threats and climate change.

Challenges in the Management of Geriatric Obesity in High Risk Populations.

The global prevalence of obesity in the older adult population is growing, an increasing concern in both the developed and developing countries of the world. The study of geriatric obesity and its management is a relatively new area of research, especially pertaining to those with elevated health risks. This review characterizes the state of science for this "fat and frail" population and identifies the many gaps in knowledge where future study is urgently needed. In community dwelling older adults, opportunities to improve both body weight and nutritional status are hampered by inadequate programs to identify and treat obesity, but where support programs exist, there are proven benefits. Nutritional status of the hospitalized older adult should be optimized to overcome the stressors of chronic disease, acute illness, and/or surgery. The least restrictive diets tailored to individual preferences while meeting each patient's nutritional needs will facilitate the energy required for mobility, respiratory sufficiency, immunocompentence, and wound healing. Complications of care due to obesity in the nursing home setting, especially in those with advanced physical and mental disabilities, are becoming more ubiquitous; in almost all of these situations, weight stability is advocated, as some evidence links weight loss with increased mortality. High quality interdisciplinary studies in a variety of settings are needed to identify standards of care and effective treatments for the most vulnerable obese older adults.

The development of novel chiral tethers for controlling intramolecular aryl-aryl coupling and their application in the synthesis of gomisin M1 and analogues

The primary focus of this thesis was the development of a novel chiral tether that could be used to control axial chirality around a newly formed aryl-aryl bond, and the extension of this methodology to the model synthesis of gomisin M1. In chapter 1, a review detailing the use of chiral tethers in the synthesis of atropisomers is discussed. The use of a variety of chiral molecules including 1,2-diols, 1,3-diols and other diol-based tethers, as well as amine-based and miscellaneous tethers are detailed. In chapter 2, the rationale behind the design of our novel molecular tethers, along with the subsequent synthesis of three chiral 1,3-diol-based tethers, is outlined. The method by which the enantiopurity of these diols was determined is also reviewed. This chapter also includes the attempted Mitsunobu and intramolecular couplings in the model synthesis of BINOL. Chapter 3 discusses the synthesis of suitable aryl halide substrates, and their employment in the attempted tether-controlled asymmetric model synthesis of gomisin M1. A comprehensive investigation into the attempted intramolecular biaryl coupling of these tethered substrates is also included. The non-stereoselective model synthesis of gomisin M1 is outlined in chapter 4. The installation of the desired biaryl linkage and the subsequent attempted intramolecular McMurry couplings are discussed. The impact of different protecting groups in the molecule on the intramolecular McMurry reaction is also outlined. Chapter 5 details the full experimental procedures, including spectroscopic and analytical data for the compounds prepared during this research.

Fundamental studies of the application of wheat for malting and brewing

Wheat (Triticum aestivum L.) has a long tradition as a raw material for the production of malt and beer. While breeding and cultivation efforts for barley have been highly successful in creating agronomically and brew- technical optimal specialty cultivars that have become well established as brewing barley varieties, the picture is completely different for brewing wheat. An increasing wheat beer demand results in a rising amount of raw material. Wheat has been - and still is – grown almost exclusively for the baking industry. It is this high demand that defines most of the wheat breeding objectives; and these objectives are generally not favourable in brewing industry. It is of major interest to screen wheat varieties for brewing processability and to give more focus to wheat as a brewing cereal. To obtain fast and reliable predications about the suitability of wheat cultivars a new mathematical method was developed in this work. The method allows a selection based on generally accepted quality characteristics. As selection criteria the parameters raw protein, soluble nitrogen, Kolbach index, extract and viscosity were chosen. During a triannual cultivation series, wheat varieties were evaluated on their suitability for brewing as well as stability to environmental conditions. To gain a fundamental understanding of the complex malting process, microstructural changes were evaluated and visualized by confocal laser scanning and scanning electron microscopy. Furthermore, changes observed in the micrographs were verified and endorsed by metabolic changes using established malt attributes. The degradation and formation of proteins during malting is essential for the final beer quality. To visualise fundamental protein changes taking place during malting, samples of each single process step were analysed and fractioned according their solubility. Protein fractions were analysed using a Lab-on-a-chip technique as well as OFFgel analysis. In general, a different protein distribution of wheat compared to barley or oat could be confirmed. During the malting process a degradation of proteins to small peptides and amino acids could be observed in all four Osborn fractions. Furthermore, in this study a protein profiling was performed to evaluate changes during the mashing process as well as the influence of grist composition. Differences in specific protein peaks and profile were detected for all samples during mashing. This study investigated the suitability of wheat for malting and brewing industry and closed the scientifical gap of amylolytic, cytolytic and proteolytic changes during malting and mashing.

THE IMPORTANCE OF MHC-INDEPENDENT NATURAL KILLER CELL RECEPTORS IN THE IMMUNOREGULATION OF MURINE PREGNANCY

Numerous leukocyte populations are essential for pregnancy success. Uterine natural killer (uNK) cells are chief amongst these leukocytes and represent a unique lineage with limited cytotoxicity but abundant angiokine production. They possess a distinct phenotype of activating and inhibitory receptors that recognize major histocompatibility complex (MHC) molecules, such as the killer immunoglobulin like receptors (KIRs; mouse Ly49), and MHC-independent activating receptors, including the aryl hydrocarbon receptor (AHR) and natural cytotoxicity receptor 1 (NCR1). While the roles of MHC-dependent receptors are widely addressed in pregnancy, MHC-independent receptors are relatively unstudied. This thesis investigated the roles of MHC-independent receptors in promotion of mouse pregnancy and characterized early leukocyte interactions in the presence and absence of NCR1. It was hypothesized that loss of MHC-independent receptors impairs uNK cell development resulting in aberrations in leukocyte function and decidual vasculature. Implantation sites from Ahr-/- and Ncr1Gfp/Gfp mice were assessed using whole mount in situ immunohistochemistry (WM-IHC) and histochemical techniques. Leukocyte interactions identified during preliminary WM-IHC studies were confirmed as immune synapses. The novel identification of immune synapses in early mouse pregnancy compelled further examination of leukocyte conjugates in wildtype C57BL/6 and Ncr1Gfp/Gfp mice. In Ahr-/- and Ncr1Gfp/Gfp mice, receptor loss resulted in reduced uNK cell diameters, impaired decidual vasculature, and failures in spiral artery remodeling. Ahr-/- mice had severe fertility deficits whereas Ncr1Gfp/Gfp mice had increased fetal resorption indicating differing receptor requirements in pregnancy success. NCR1 loss primarily affected uNK cell maturation and function as identified by alterations in granule ultrastructure, lytic protein expression, and angiokine production. Leukocyte conjugates were frequent in early C57BL/6 decidua basalis and included uNK cells conjugating first with antigen presenting cells and then with T cells. Overall conjugate formation was reduced in the absence of NCR1, but specific uNK cell conjugations were unaffected by receptor loss. While KIR-MHC interactions are associated with numerous pregnancy complications in humans, the role of other uNK cell receptors are not well characterized. These results illustrate the importance of MHC-independent receptors in uNK cell activation during early pregnancy in mice and encourage further studies of pregnancy complications that may occur independently of maternal KIR-MHC contributions.

The Art of Change Movement: an anti-oppressive Social Work initiative

This article presents the Art of Change Movement (Movimiento Arte del Cambio), which has developed out of a project of the Association of Social Workers Without Boundaries (Asociación Trabajadores/as Sociales Sin Fronteras), with the collaboration of the Faculty of Social Work at Universidad de Granada and of education professionals, incorporating theatrical creativity and musical expression as pedagogical and social intervention tools. The aim is for the initiative to become another instrument in the fight against oppression. Through a laboratory for collective creativity involving students and professionals from social work and other social science disciplines, the movement seeks social transformation through artistic expression, based on political commitment and sustainable development that empowers participants.

The expansion of soybean cultivation in Campeche, México: Problematic and perspectives

The soybean is the grain in which greater food dependency has Mexico, reason why as of 2008, the government has promoted his culture, granting excellent subsidies, as much to producers as to buyers of the grain, thus contributing to a recent process of expansion in certain states, as it happens in Campeche. The objetive of this article is the analysis of the characteristics and effects of those supports, as well as of the rest of factors that until today they have taken to the producers of the mentioned state to initiate or to expand the cultivation of the soybean. The findings of the investigation reveal that although the producers have improved their levels of income, the process is vulnerable, as it depends on variables like the governmental supports, the international prices of the soybean and exchange rate. Although the study of the negative effects of genetically modified soybeans (GM) in other areas (environment, biodiversity, deforestation, human and animal health) is not the purpose of this investigation, some information will be provided, as on the conflict between soybean producers and beekeepers in the state of Campeche.

The Continuous Plankton Recorder survey: How can long-term phytoplankton datasets contribute to the assessment of Good Environmental Status?

Phytoplankton are crucial to marine ecosystem functioning and are important indicators of environmental change. Phytoplankton data are also essential for informing management and policy, particularly in supporting the new generation of marine legislative drivers, which take a holistic ecosystem approach to management. The Marine Strategy Framework Directive (MSFD) seeks to achieve Good Environmental Status (GES) of European seas through the implementation of such a management approach. This is a regional scale directive which recognises the importance of plankton communities in marine ecosystems; plankton data at the appropriate spatial, temporal and taxonomic scales are therefore required for implementation. The Continuous Plankton Recorder (CPR) survey is a multidecadal, North Atlantic basin scale programme which routinely records approximately 300 phytoplankton taxa. Because of these attributes, the survey plays a key role in the implementation of the MSFD and the assessment of GES in the Northeast Atlantic region. This paper addresses the role of the CPR's phytoplankton time-series in delivering GES through the development and informing of MSFD indicators, the setting of targets against a background of climate change and the provision of supporting information used to interpret change in non-plankton indicators. We also discuss CPR data in the context of other phytoplankton data types that may contribute to GES, as well as explore future possibilities for the use of new and innovative applications of CPR phytoplankton datasets in delivering GES. Efforts must be made to preserve long-term time series, such as the CPR, which supply vital ecological information used to informed evidence-based environmental policy.

The Continuous Plankton Recorder survey: How can long-term phytoplankton datasets contribute to the assessment of Good Environmental Status?

Phytoplankton are crucial to marine ecosystem functioning and are important indicators of environmental change. Phytoplankton data are also essential for informing management and policy, particularly in supporting the new generation of marine legislative drivers, which take a holistic ecosystem approach to management. The Marine Strategy Framework Directive (MSFD) seeks to achieve Good Environmental Status (GES) of European seas through the implementation of such a management approach. This is a regional scale directive which recognises the importance of plankton communities in marine ecosystems; plankton data at the appropriate spatial, temporal and taxonomic scales are therefore required for implementation. The Continuous Plankton Recorder (CPR) survey is a multidecadal, North Atlantic basin scale programme which routinely records approximately 300 phytoplankton taxa. Because of these attributes, the survey plays a key role in the implementation of the MSFD and the assessment of GES in the Northeast Atlantic region. This paper addresses the role of the CPR's phytoplankton time-series in delivering GES through the development and informing of MSFD indicators, the setting of targets against a background of climate change and the provision of supporting information used to interpret change in non-plankton indicators. We also discuss CPR data in the context of other phytoplankton data types that may contribute to GES, as well as explore future possibilities for the use of new and innovative applications of CPR phytoplankton datasets in delivering GES. Efforts must be made to preserve long-term time series, such as the CPR, which supply vital ecological information used to informed evidence-based environmental policy.

The activity of the feminist online publications: challenges for the transmission of the feminist culture in Spain

Traditionally, big media corporations have contributed to hiding the women’s movement itself, as well as its main claims and topics of discussion (Marx, Myra y Hess, 1995; Rhode, 1995; Mendes, 2011). This has led the feminist movement to develop its own media generally print publications, usually, with a very specialized character and reduced audience. This is similar to what has occurred with quality main stream media, asthese publications have had to adapt themselves to a new communicatiion context, because of the financial crisis and  technological evolution. Feminist media has found in the Internet an excellent opportunity to access citizens and communicate their messages. , In view of this scene of change and renovation,  this article offers the results of a qualitative analysis focused on the experiences of four feminist online media sites edited in Spain: Pikaramagazine.com, Proyecto-kahlo.com, Mujeresenred.net and Laindependent.cat. Besides exploring the characteristics and content of these sites, the article pays attention to the virality of their contents spread through Facebook and Twitter. The onclusion estimates their social impact, insofar as they symbolize the specialization, diversification and dialogue promoted by the Web.

Resolving conflict in bipolar societies: The fate of political settlements in Fiji and Northern Ireland

Ethnically divided societies that might be described as ‘balanced bicommunal’ (where there are two communities, each of which comes close to representing half of the population) pose a particular challenge to conventional principles of collective decision-making, and commonly threaten political stability. This article analyses the experience of two such societies – Northern Ireland and Fiji – with a view to exploring whether there are common processes in the route by which political stability has been pursued. We assess the manner in which a distinctive relationship with Great Britain and its political culture has interacted with local conditions to produce a highly competitive, bipolar party system. This leads to consideration of the devices that have been adopted in an effort to bridge the gap between the communities: the Fiji constitution as amended in 1997, and Northern Ireland’s Good Friday Agreement of 1998. We focus, in particular, on the use of unusual (preferential voting) formulas for the election of parliamentarians and of an inclusive principle in the selection of ministers, and consider the contribution of these institutional devices to the attainment of political stability. We find that, in both cases, the intervention of forces from outside the political system had a decisive impact, though in very different ways. In addition to being underpinned by solid institutional design, for political settlements to work effectively, some minimal level of trust between rival elites is required.

The Type of Behavior and the Role of Relationship Length in Mate Choice for Prosociality Among Physically Attractive Individuals

Two further key aspects of prosociality as a sexual signal are explored here. Firstly, the context in which it is used (in particular relationship length), and, second, also the different types of prosocial behaviors that exist in social interactions. Therefore, this commentary can show why prosocial behaviors are biased towards physically attractive individuals, as they can gain valuable information from them.

The challenges of integrating biodiversity and ecosystem services monitoring and evaluation at a landscape-scale wetland restoration project in the UK

There is an increasing emphasis on the restoration of ecosystem services as well as of biodiversity, especially where restoration projects are planned at a landscape scale. This increase in the diversity of restoration aims has a number of conceptual and practical implications for the way that restoration projects are monitored and evaluated. Landscape-scale projects require monitoring of not only ecosystem services and biodiversity but also of ecosystem processes since these can underpin both. Using the experiences gained at a landscape-scale wetland restoration project in the UK, we discuss a number of issues that need to be considered, including the choice of metrics for monitoring ecosystem services and the difficulties of assessing the interactions between ecosystem processes, biodiversity, and ecosystem services. Particular challenges that we identify, using two pilot data sets, include the decoupling of monetary metrics used for monitoring ecosystem services from biophysical change on the ground and the wide range of factors external to a project that influence the monitoring results. We highlight the fact that the wide range of metrics necessary to evaluate the ecosystem service, ecosystem process, and biodiversity outcomes of landscape-scale projects presents a number of practical challenges, including the need for high levels of varied expertise, high costs, incommensurate monitoring outputs, and the need for careful management of monitoring results, especially where they may be used in making decisions about the relative importance of project aims.

Greener methodology for the synthesis of alpha-diazocarbonyl compounds and a novel approach to dioxinone derivatives

This thesis outlines a more environmentally benign approach to diazo transfer, and the investigation of the reactivity of -diazocarbonyl compounds when subjected to transition metal and lanthanide catalysis. Extensive studies were carried out to find the optimum conditions for a greener diazo transfer methodology, and this was also applied to a continuous process for the synthesis of -diazo--ketoesters. The first chapter includes a literature review of the synthesis and subsequent reactivity of -diazocarbonyl compounds. An overview of the applications of flow chemistry for the synthesis of hazardous intermediates is also included. The applications of lanthanide catalysts in organic synthesis is also discussed. The second chapter outlines the extensive studies undertaken to determine the optimum conditions for a greener diazo transfer methodology, including base and solvent studies. Use of water as a viable solvent for diazo transfer was successfully investigated. Diazo transfer to a range of -diazo--ketoesters was achieved using 5 mol% triethylamine or DMAP in water with high conversions. Polystyrene-supported benzenesulfonyl azide as an alternative diazo transfer reagent was also explored, as well as investigations into cheaper generation of this safer reagent. This polymer-supported benzenesulfonyl azide was used with 25 mol% of base in water to achieve successful diazo transfer to a range of -diazo--ketoesters. The third chapter describes the application of the new methodology developed in Chapter 2 to a continuous processing approach. Various excellent conditions were identified for both batch and flow reactions. A series of -diazo--ketoesters were synthesised with excellent conversions using 25 mol% triethylamine in 90:10 acetone water using flow chemistry. Successful diazo transfer was also achieved using a polymer-supported benzenesulfonyl azide in water under flow conditions. The fourth chapter discusses the reactivity of -diazo--ketoesters under transition metal and lanthanide catalysis. This chapter describes the synthesis of a range of -ketoesters via transesterification, which were used to synthesise a range of novel -diazo--ketoesters that were used in subsequent decomposition reactions. A novel route to dioxinones via rhodium(II) catalysis is reported. Attempted OH and SH insertion reactions in the presence of various lanthanide(II) catalysts are outlined, leading to some unexpected and interesting rearrangement products. The experimental details, including spectroscopic and analytical data for all compounds prepared, are reported at the end of each chapter.