285 research outputs found

    Adria Palace on Jungmann Square

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    The segment features the Rondocubist Adria Palace (palác Adria) on the corner of Národní and Jungmannova streets. The building was commissioned in 1924 by the Italian insurance company Riunione Adriatica di Sicurta and was designed by architects Josef Zasch and Pavel Janák. A shot of the palace and its surroundings with the Josef Jungmann monument by sculptor Václav Levý. Shots of the insurance company's administrative building on the other side of the street which was designed by Fritz Lehmann and built in 1930-32

    Redesigning Adria Caravans for a Circular Economy

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    This project started with the following assignment: redesign the Adria Action caravan to fit in a circular economy and to have less CO2 emissions. However, the outcome of this project is not a redesign of a caravan but a framework for Adria to work towards (partial) circular As an example of the functioning of this framework, a redesign of the bathroom floor was done.To get to know the particular caravan and the caravan industry an analysis of the context was conducted. An eco-analysis on material basis of the Action caravan was done and visits to experts in the industry, repairmen and a caravan recycling company, were made. The main conclusions from the analysis were that the structural body has the most value, both economically as environmentally, and therefore needs to be used for a longer time. There already is an effort made but it is complicated due to components that are hard to repair and due to a lack of support and instructions and availability of spare parts. In the caravan industry and this company there is also little standardization which means there are a lot of unique parts. This makes it hard to find fitting components and to reuse perfectly good components in other vehicles. The successful business of repair and recycling companies shows that there is value after the sale of the caravan but it is made unnecessary complex to retain this value by the organization of the caravan companies.The framework shows that designing caravans for a circular economy involves more aspects than just redesigning the individual parts for reuse, repair and recycling possibilities. There are different levels on which actions can take place and to become completely circular, these levels must work together. First, analytical capabilities, such as LCA and hot spot mapping, are needed to assess the current condition of the caravans and evaluate improvements. To do this, a different way of documenting will be required within Adria. Next, with this objective way of assessing the caravan, focus points can be found and components can be redesigned using the circular economy ideals. Those adjustments can then again be evaluated.One of the focus points found is the bathroom floor. It is a critical part because it protects the frame from moisture, the bathroom is not functional without the floor and it is very difficult to disassemble and reassemble the floor. At the moment, the floor is being repaired with polyurethane, which restores the value of the caravan at that time, but the repair makes the component non-recyclable and therefore no longer part of the circular economy. It is more sustainable to replace the tray as a whole. So when redesigning the tray, it was looked at how this can be done easier. It requires minor adjustments to the part and larger adjustments at a company level. On a company level, some variables should be agreed on as a fixed standard. This makes future designs backward compatible and therefore makes it easy and cost-efficient to produce an extra part when a customer orders it, enabling the replacement of the tray.Integrated Product Desig

    Activation of PPARγ and δ by dietary punicic acid ameliorates intestinal inflammation in mice

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    The goal of the present study was to elucidate the mechanisms of immunoregulation by which dietary punicic acid (PUA) prevents or ameliorates experimental inflammatory bowel disease (IBD). The expression of PPARγ and δ, their responsive genes and pro-inflammatory cytokines was assayed in the colonic mucosa. Immune cell-specific PPARγ null, PPARδ knockout and wild-type mice were treated with PUA and challenged with 2·5 % dextran sodium sulphate (DSS). The prophylactic efficacy of PUA was examined in an IL-10− / −  model of IBD. The effect of PUA on the regulatory T-cell (Treg) compartment was also examined in mice with experimental IBD. PUA ameliorated spontaneous pan-enteritis in IL-10− / −  mice and DSS colitis, up-regulated Foxp3 expression in Treg and suppressed TNF-α, but the loss of functional PPARγ or δ impaired these anti-inflammatory effects. At the cellular level, the macrophage-specific deletion of PPARγ caused a complete abrogation of the protective effect of PUA, whereas the deletion of PPARδ or intestinal epithelial cell-specific PPARγ decreased its anti-inflammatory efficacy. We provide in vivo molecular evidence demonstrating that PUA ameliorates experimental IBD by regulating macrophage and T-cell function through PPARγ- and δ-dependent mechanisms.</jats:p

    Abscisic Acid: A Novel Nutraceutical for Glycemic Control

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    Abscisic acid is naturally present in fruits and vegetables, and it plays an important role in managing glucose homeostasis in humans. According to the latest U.S. dietary survey, about 92% of the population might have a deficient intake of ABA due to their deficient intake of fruits and vegetables. This review summarizes the in vitro, preclinical, mechanistic, and human translational findings obtained over the past 15 years in the study of the role of ABA in glycemic control. In 2007, dietary ABA was first reported to ameliorate glucose tolerance and obesity-related inflammation in mice. The most recent findings regarding the topic of ABA and its proposed receptor lanthionine synthetase C-like 2 in glycemic control and their interplay with insulin and glucagon-like peptide-1 suggest a major role for ABA in the physiological response to a glucose load in humans. Moreover, emerging evidence suggests that the ABA response might be dysfunctional in diabetic subjects. Follow on intervention studies in healthy individuals show that low-dose dietary ABA administration exerts a beneficial effect on the glycemia and insulinemia profiles after oral glucose load. These recent findings showing benefits in humans, together with extensive efficacy data in mouse models of diabetes and inflammatory disease, suggest the need for reference ABA values and its possible exploitation of the glycemia-lowering effects of ABA for preventative purposes. Larger clinical studies on healthy, prediabetic, and diabetic subjects are needed to determine whether addressing the widespread dietary ABA deficiency improves glucose control in humans

    Immunoregulatory Actions of Epithelial Cell PPAR γ at the Colonic Mucosa of Mice with Experimental Inflammatory Bowel Disease

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    BACKGROUND: Peroxisome proliferator-activated receptors are nuclear receptors highly expressed in intestinal epithelial cells (IEC) and immune cells within the gut mucosa and are implicated in modulating inflammation and immune responses. The objective of this study was to investigate the effect of targeted deletion of PPAR gamma in IEC on progression of experimental inflammatory bowel disease (IBD). METHODOLOGY/PRINCIPAL FINDINGS: In the first phase, PPAR gamma flfl; Villin Cre- (VC-) and PPAR gamma flfl; Villin Cre+ (VC+) mice in a mixed FVB/C57BL/6 background were challenged with 2.5% dextran sodium sulfate (DSS) in drinking water for 0, 2, or 7 days. VC+ mice express a transgenic recombinase under the control of the Villin-Cre promoter that causes an IEC-specific deletion of PPAR gamma. In the second phase, we generated VC- and VC+ mice in a C57BL/6 background that were challenged with 2.5% DSS. Mice were scored on disease severity both clinically and histopathologically. Flow cytometry was used to phenotypically characterize lymphocyte and macrophage populations in blood, spleen and mesenteric lymph nodes. Global gene expression analysis was profiled using Affymetrix microarrays. The IEC-specific deficiency of PPAR gamma in mice with a mixed background worsened colonic inflammatory lesions, but had no effect on disease activity (DAI) or weight loss. In contrast, the IEC-specific PPAR gamma null mice in C57BL/6 background exhibited more severe inflammatory lesions, DAI and weight loss in comparison to their littermates expressing PPAR gamma in IEC. Global gene expression profiling revealed significantly down-regulated expression of lysosomal pathway genes and flow cytometry results demonstrated suppressed production of IL-10 by CD4+ T cells in mesenteric lymph nodes (MLN) of IEC-specific PPAR gamma null mice. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that adequate expression of PPAR gamma in IEC is required for the regulation of mucosal immune responses and prevention of experimental IBD, possibly by modulation of lysosomal and antigen presentation pathways

    Transdisciplinary Strategies to Study the Mechanisms of CD4+ T cell Differentiation and Heterogeneity

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    CD4+ T cells mediate and orchestrate a tremendous panoply of lymphoid cell subsets in the human immune system. CD4+ T cells are able to differentiate into either effector pro-inflammatory or regulatory anti-inflammatory subsets depending on the cytokine milieu in their environment. This complex process is mediated through a variety of cytokines and soluble factors. Yet, the mechanisms of action underlying the process of differentiation and plasticity of this interesting immune subset are incompletely understood. To gain a better understanding of the CD4+ T cell differentiation and function, here we present an array of different strategies to model and validate CD4+ T cell differentiation and heterogeneity. The approaches presented here vary from ordinary-differential equation-based to agent-based simulations, from data-driven to theory-based approaches, and from intracellular mathematical to tissue-level or cellular modeling. The knowledge generated throughout this dissertation exemplifies how a combination of computational modeling with experimental immunology can efficiently advance the scene on CD4+ T cell differentiation. In this thesis I present i) an overview on CD4+ T cell differentiation and an introduction to which computational strategies have been adopted in the field to tackle with this problem, ii) ODE-based modeling and predictions on Th17 plasticity modulated by PPARγ, iii) ODE- and ABM-based cellular level modeling of immune responses towards Helicobacter pylori and the role of CD4+ T cell subsets on it, iv) Intracellular strategies to validate a potential therapeutic target within a CD4+ T cell to treat H. pylori infection, and finally v) data-driven strategies to model Th17 differentiation based on sequencing or microarray data to generate novel predictions on specific components. I present both mathematical and computational work as well as experimental work, in vitro and in vivo with animal models, to demonstrate how computational immunology and immunoinformatics can help, not only in understanding this complex process, but also in the development of immune therapeutics for infectious, allergic and immune-mediated diseases.Ph. D

    Obergefell v. Hodges and Support for Same-Sex Marriage: Changes in National and State Public Opinion

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    Title: Obergefell v. Hodges and Support for Same-Sex Marriage: Changes in National and State Public Opinion Author: Adria Neal Department: Political Science Mentor: Laura Moyer, Ph.D Abstract: Many have argued that Supreme Court decisions on culture war issues, issues that cause conflict between conservative and liberal values, stifle public progression on the very problems they are meant to resolve. They often cite political and electoral backlash following a decision as evidence of this stagnation. However, this backlash may not be representative of widespread public opinion. In order to understand the relationship between Court decisions and public opinion, changes in opinion on culture war issues following a Supreme Court ruling must be measured. This study utilized national and state survey data in order to examine this relationship. It measured changes in support for same-sex marriage nationwide as well as in the state of Kentucky following the Court’s decision in Obergefell v. Hodges. Changes in support for same-sex marriage among various racial groups and political parties are also assessed. Changes in nationwide support following Obergefell did not reach significance and changes in support on the state level, following the ruling, also could not be determined because of differences in survey question wording. However, findings showed that other significant same-sex marriage court decisions have preceded changes in overall support for same-sex marriage. Also, the gaps in support between racial groups and parties changed following these rulings, suggesting that groups have differing reactions to Court involvement. Research conducted after Kim Davis’s refusal to issue marriage licenses to same-sex couples suggested that Kentuckians are willing to acquiesce with the Court’s decision in Obergefell, despite widespread disapproval of same-sex marriage. Future research should utilize survey data with consistent questions before and after the Court’s ruling and should control for other variables in order to isolate the effect of Court decisions

    The Cub, the Parson, the Doctor: James Boswell, Laurence Sterne, and Samuel Johnson in London

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    Samuel Johnson (1709-1784) was the dominant literary figure of the later eighteenth century. He was most famed in his day as the author of the first comprehensive Dictionary of the English Language, but he would be eventually celebrated in equal measure as a great moral sage, essayist, poet, critic, conversationalist, and the second most quoted person in the English language after Shakespeare. Laurence Sterne (1713-1768) was an Irish-born Anglican clergyman who achieved instant celebrity as the author of one of the most wildly innovative comic novels in English, The Life and Opinions of Tristram Shandy, Gentleman. Though the novel is now considered a key work in the evolution of the novel and a precursor to postmodernist experiments in self-reflexive writing, not every reader has responded favourably to its dizzying novelties. Samuel Johnson, who likely never met Sterne, notoriously if incorrectly predicted that the novel‘s popularity would fade. James Boswell (1740-1795) also aimed to become a great literary author of the period but his reputation did not fare as well as Johnson‘s or Sterne‘s. A generation after his death, he had come to be seen as a buffoon who had needled his way into the company of the powerful and talented while displaying little talent or with himself. The 19th-century essayist Lord Macaulay pronounced him “one of the smallest men who ever lived [...] a man of the meanest and feeblest intellect [...] shallow and pedantic, a bigot and a sot [...] a common butt in the taverns of London.” Yet Boswell kept meticulous records of his conversations with the eminent writers and thinkers of his age, and from these records were produced not only a remarkable series of journals, unmatched in their detail and directness, but equally one indisputable masterpiece, his Life of Johnson, which is generally regarded as the greatest biography in English. In this ambitious and exhaustively researched paper, Adria Young gathers pretty much all evidence available (and there‘s not much of it) connecting Sterne to Johnson, with Boswell emerging as a go-between connecting these two very different personalities. But more than showing how their lives may have intersected, Young develops a lively and suggestive argument about how Boswell, always in search of a father-figure, ultimately shed the exuberant Sterne‘s early influence in favour of Johnson‘s sturdier guidance. -Dr. Trevor Ros
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