The synthesis of chemical tools for studying sphingolipid metabolism

Sphingolipids are important membrane compounds with a variety of functions. In mammalian cells, different enzymes are involved in the metabolism of sphingolipids, but interruption of this metabolism process leads to different diseases. To study the functions of sphingolipids and there related diseases, analogues of sphingolipids are needed. This thesis focuses on such sphingolipids analogues, and specifically on the design and synthesis of stable isotope encoded sphingolipids.Bio-organic Synthesi

Efects of lactation room quality on working mothers’ feelings and thoughts related to breastfeeding and work::a randomized controlled trial and a feld experiment

Background: The challenging combination of breastfeeding and work is one of the main reasons for early breastfeeding cessation. Although the availability of a lactation room (defined as a private space designated for milk expression or breastfeeding) is important in enabling the combination of breastfeeding and work, little is known about the effects of lactation room quality on mothers’ feelings and thoughts related to breastfeeding and work. We hypothesized that a high-quality lactation room (designed using the Theory of Supportive Design) would cause mothers to experience less stress, have more positive thoughts about milk expression at work, perceive more organizational support, and report more subjective well-being, than a low-quality lactation room. Methods: In an online randomized controlled trial (Study 1), Dutch mothers (N = 267) were shown either a high-quality or a low-quality lactation room (using pictures and descriptions for the manipulation) and were then asked about their feelings and thoughts. In a subsequent field experiment (Study 2) we modified the lactations rooms in a large organization in Groningen, the Netherlands, to manipulate lactation room quality, and asked mothers (N = 61) who used either a high-quality or low-quality lactation room to fill out surveys to assess the dependent variables. Results: The online study showed that mothers exposed to the high-quality lactation room anticipated less stress, more positive cognitions about milk expression at work, more perceived organizational support, and more subjective well-being than mothers exposed to the low-quality lactation room (p < 0.05). Moreover, the effect of lactation room quality on perceived organizational support was especially pronounced for mothers who were higher in environmental sensitivity. The field experiment showed that use of the high-quality room led to less reported stress than use of the low-quality room (p < 0.05). We also found that mothers who were higher in environmental sensitivity perceived more control over milk expression at work and experienced more subjective well-being in the high-quality condition than in the low-quality condition (p < 0.05). Conclusion: The current studies show that not only the availability, but also the quality of lactation rooms is important in facilitating the combination of breastfeeding and work

Assessment and comparison of extreme sea levels and waves during the 2013/2014 storm season in two UK coastal regions

The extreme sea levels and waves experienced around the UK's coast during the 2013/2014 winter caused extensive coastal flooding and damage. In such circumstances, coastal managers seek to place such extremes in relation to the anticipated standards of flood protection, and the long-term recovery of the natural system. In this context, return periods are often used as a form of guidance. We therefore provide these levels for the winter storms, as well as discussing their application to the given data sets and case studies (two UK case study sites: Sefton, northwest England; and Suffolk, east England). We use tide gauge records and wave buoy data to compare the 2013/2014 storms with return periods from a national dataset, and also generate joint probabilities of sea level and waves, incorporating the recent events. The UK was hit at a national scale by the 2013/2014 storms, although the return periods differ with location. We also note that the 2013/2014 high water and waves were extreme due to the number of events, as well as the extremity of the 5 December 2013 "Xaver" storm, which had a very high return period at both case study sites. Our return period analysis shows that the national scale impact of this event is due to its coincidence with spring high tide at multiple locations as the tide and storm propagated across the continental shelf. Given that this event is such an outlier in the joint probability analyses of these observed data sets, and that the season saw several events in close succession, coastal defences appear to have provided a good level of protection. This type of assessment should be recorded alongside details of defence performance and upgrade, with other variables (e.g. river levels at estuarine locations) included and appropriate offsetting for linear trends (e.g. mean sea level rise) so that the storm-driven component of coastal flood events can be determined. Local offsetting of the mean trends in sea level allows long-term comparison of storm severity and also enables an assessment of how sea level rise is influencing return levels over time, which is important when considering long-term coastal resilience in strategic management plans

Assessment and comparison of extreme sea levels and waves during the 2013/14 storm season in two UK coastal regions

The extreme sea levels and waves experienced around the UK's coast during the 2013/14 winter caused extensive coastal flooding and damage. Coastal managers seek to place such extremes in relation to the anticipated standards of flood protection, and the long-term recovery of the natural system. In this context, return periods are often used as a form of guidance. This paper provides these levels for the winter storms, and discusses their application to the given data sets for two UK case study sites: Sefton, northwest England, and Suffolk, east England. Tide gauge records and wave buoy data were used to compare the 2013/14 storms with return periods from a national data set, and also joint probabilities of sea level and wave heights were generated, incorporating the recent events. The 2013/14 high waters and waves were extreme due to the number of events, as well as the extremity of the 5 December 2013 "Xaver" storm, which had a high return period at both case study sites. The national-scale impact of this event was due to its coincidence with spring high tide at multiple locations. Given that this event is such an outlier in the joint probability analyses of these observed data sets, and that the season saw several events in close succession, coastal defences appear to have provided a good level of protection. This type of assessment could in the future be recorded alongside defence performance and upgrade. Ideally other variables (e.g. river levels at estuarine locations) would also be included, and with appropriate offsetting for local trends (e.g. mean sea-level rise) so that the storm-driven component of coastal flood events can be determined. This could allow long-term comparison of storm severity, and an assessment of how sea-level rise influences return levels over time, which is important for consideration of coastal resilience in strategic management plans

Lymphoid Microenvironments in the Thymus and Lymph Node

The three-dimensional architecture of the thymus and mesenteric lymph node reveals several different stromal cell types important in the development and function of T cells. In the thymic cortex, T cells proliferate and differentiate in a meshwork of epithelial-reticular cells. They then migrate towards the medulla where they may interact with interdigitating cells. T cells migrate from the thymus through perivascular spaces, surrounding large vessels at the cortico-medullary boundary. In this area also large thymic cystic cavities are found, their function remains at present unclear. Mature selected T cells leave the thymus most probably by the venous bloodstream, to enter peripheral lymph nodes. Upon entering the lymph node they cross the wall of high endothelial venules. On the other hand, lymph enters the node by afferent lymphatics draining into various types of sinuses. Here, macrophages are strategically located to phagocytose and process antigen. These cells then expose antigen to T cells and B cells within the lymph node parenchyma, thus creating a microenvironment for the onset of an immune response. The various microenvironments important in T cell development and T cell function are shown in this paper using scanning electron microscopy as a dissecting tool. We discuss our morphological findings in the light of recent data on the physiology of T cell differentiation and function